Standards of medical care in diabetes—2015

January 2015 Volume 38, Supplement 1

Standards of Medical Care in Diabetes—2015

S1 Introduction

S3 Professional Practice Committee

S4 Standards of Medical Care in Diabetes—2015:Summary of Revisions

S5 1. Strategies for Improving Care

Diabetes Care ConceptsCare Delivery SystemsWhen Treatment Goals Are Not Met

S8 2. Classification and Diagnosis of Diabetes

ClassificationDiagnostic Tests for DiabetesCategories of Increased Risk for Diabetes

(Prediabetes)Type 1 DiabetesType 2 DiabetesGestational Diabetes MellitusMonogenic Diabetes SyndromesCystic Fibrosis–Related Diabetes

S17 3. Initial Evaluation and Diabetes ManagementPlanning

Medical EvaluationManagement PlanCommon Comorbid Conditions

S20 4. Foundations of Care: Education, Nutrition,Physical Activity, Smoking Cessation,Psychosocial Care, and Immunization

Diabetes Self-management Education and SupportMedical Nutrition TherapyPhysical ActivitySmoking CessationPsychosocial Assessment and CareImmunization

S31 5. Prevention or Delay of Type 2 Diabetes

Lifestyle ModificationsPharmacological InterventionsDiabetes Self-management Education and Support

S33 6. Glycemic Targets

Assessment of Glycemic ControlA1C GoalsHypoglycemiaIntercurrent Illness

S41 7. Approaches to Glycemic Treatment

Pharmacological Therapy for Type 1 DiabetesPharmacological Therapy for Type 2 DiabetesBariatric Surgery

S49 8. Cardiovascular Disease and Risk Management

Hypertension/Blood Pressure ControlDyslipidemia/Lipid ManagementAntiplatelet AgentsCoronary Heart Disease

S58 9. Microvascular Complications and Foot Care

NephropathyRetinopathyNeuropathyFoot Care

S67 10. Older Adults

Treatment GoalsHypoglycemiaPharmacological Therapy

S70 11. Children and Adolescents

Type 1 DiabetesType 2 DiabetesPsychosocial Issues

S77 12. Management of Diabetes in Pregnancy

Diabetes in PregnancyPreconception CounselingGlycemic Targets in PregnancyPregnancy and Antihypertensive DrugsManagement of Gestational Diabetes MellitusManagement of Pregestational Type 1 Diabetes

and Type 2 Diabetes in PregnancyPostpartum Care

S80 13. Diabetes Care in the Hospital, Nursing Home,and Skilled Nursing Facility

Hyperglycemia in the HospitalGlycemic Targets in Hospitalized PatientsAntihyperglycemic Agents in Hospitalized PatientsPreventing HypoglycemiaDiabetes Care Providers in the HospitalSelf-management in the HospitalMedical Nutrition Therapy in the HospitalBedside Blood Glucose MonitoringDischarge PlanningDiabetes Self-management Education

S86 14. Diabetes Advocacy

Advocacy Position Statements

S88 Professional Practice Committee for the Standardsof Medical Care in Diabetes—2015

S90 Index

This issue is freely accessible online at care.diabetesjournals.org.

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IntroductionDiabetes Care 2015;38(Suppl. 1):S1–S2 | DOI: 10.2337/dc15-S001

Diabetes is a complex, chronic illness re-quiring continuous medical care withmultifactorial risk-reduction strategiesbeyond glycemic control. Ongoing pa-tient self-management education andsupport are critical to preventing acutecomplications and reducing the risk oflong-term complications. Significantevidence exists that supports a rangeof interventions to improve diabetesoutcomes.The American Diabetes Association’s

(ADA’s) “Standards of Medical Care inDiabetes” is intended to provide cli-nicians, patients, researchers, payers,and other interested individuals withthe components of diabetes care, gen-eral treatment goals, and tools to eval-uate the quality of care. The Standardsof Care recommendations are not in-tended to preclude clinical judgmentand must be applied in the context ofexcellent clinical care, with adjustmentsfor individual preferences, comorbid-ities, and other patient factors. Formore detailed information about man-agement of diabetes, please refer toMedical Management of Type 1 Diabetes(1) and Medical Management of Type 2Diabetes (2).The recommendations include screen-

ing, diagnostic, and therapeutic actionsthat are known or believed to favor-ably affect health outcomes of patientswith diabetes. Many of these interven-tions have also been shown to be cost-effective (3).The ADA strives to improve and update

the Standards of Care to ensure that clini-cians, health plans, and policy makers cancontinue to rely on them as the most au-thoritative and current guidelines for di-abetes care.

ADA STANDARDS, STATEMENTS,AND REPORTS

The ADA has been actively involved inthe development and dissemination ofdiabetes care standards, guidelines, andrelated documents for over 20 years.ADA’s clinical practice recommenda-tions are viewed as important resourcesfor health care professionals who carefor people with diabetes. ADA’s “Stan-dards of Medical Care in Diabetes,”position statements, and scientificstatements undergo a formal reviewprocess by ADA’s Professional PracticeCommittee (PPC) and the ExecutiveCommittee of the Board of Directors.The Standards and all ADA position state-ments, scientific statements, andconsensusreports are available on the Association’sWeb site at http://professional.diabetes.org/adastatements.

“Standards of Medical Care in Diabetes”Standards of Care: ADA position state-ment that provides key clinical practicerecommendations. The PPC performs anextensive literature search and updatesthe Standards annually based on thequality of new evidence.

ADA Position StatementA position statement is an official ADApoint of view or belief that contains clinicalor research recommendations. Positionstatements are issuedon scientific ormed-ical issues related to diabetes. They arepublished in ADA journals and other scien-tific/medical publications. ADA positionstatements are typically based on a sys-tematic review or other review of pub-lished literature. Position statementsundergo a formal review process. Theyare updated annually or as needed.

ADA Scientific StatementA scientific statement is an officialADA point of view or belief that may ormay not contain clinical or research rec-ommendations. Scientific statementscontain scholarly synopsis of a topic re-lated to diabetes. Workgroup reportsfall into this category. Scientific state-ments are published in the ADA journalsand other scientific/medical publications,as appropriate. Scientific statements alsoundergo a formal review process.

Consensus ReportA consensus report contains a compre-hensive examination by an expert panel(i.e., consensus panel) of a scientific ormedical issue related to diabetes. A con-sensus report is not an ADA position andrepresents expert opinion only. The cat-egory may also include task force andexpert committee reports. The needfor a consensus report arises when clini-cians or scientists desire guidance ona subject for which the evidence is con-tradictory or incomplete. A consensusreport is typically developed immedi-ately following a consensus conferencewhere the controversial issue is exten-sively discussed. The report representsthe panel’s collective analysis, evalua-tion, and opinion at that point in timebased in part on the conference pro-ceedings. A consensus report does notundergo a formal ADA review process.

GRADING OF SCIENTIFIC EVIDENCE

Since the ADA first began publishingpractice guidelines, there has been con-siderable evolution in the evaluation ofscientific evidence and in the develop-ment of evidence-based guidelines.In 2002, we developed a classification

“Standards of Medical Care in Diabetes” was originally approved in 1988. Most recent review/revision: October 2014.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered.

Diabetes Care Volume 38, Supplement 1, January 2015 S1

INTR

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system to grade the quality of scienti-fic evidence supporting ADA recommen-dations for all new and revised ADAposition statements. A recent analysisof the evidence cited in the Standardsof Care found steady improvement inquality over the past 10 years, with lastyear’s Standards for the first time havingthe majority of bulleted recommenda-tions supported by A- or B-level evi-dence (4). A grading system (Table 1)developed by ADA and modeled afterexisting methods was used to clarify

and codify the evidence that forms thebasis for the recommendations.

ADA recommendations are assignedratings of A, B, or C, depending on thequality of evidence. Expert opinion E is aseparate category for recommendationsin which there is no evidence from clin-ical trials, in which clinical trials maybe impractical, or in which there is con-flicting evidence. Recommendationswith an A rating are based on largewell-designed clinical trials or well-done meta-analyses. Generally, these

recommendations have the best chanceof improving outcomes when applied tothe population to which they are appro-priate. Recommendations with lowerlevels of evidencemay be equally impor-tant but are not as well supported.

Of course, evidence is only one com-ponent of clinical decision making. Clini-cians care for patients, not populations;guidelines must always be interpretedwith the individual patient in mind.Individual circumstances, such as co-morbid and coexisting diseases, age, ed-ucation, disability, and, above all,patients’ values and preferences, mustbe considered and may lead to differenttreatment targets and strategies. Also,conventional evidence hierarchies, suchas the one adapted by the ADA, maymiss nuances important in diabetescare. For example, although there is ex-cellent evidence from clinical trials sup-porting the importance of achievingmultiple risk factor control, the optimalway to achieve this result is less clear. Itis difficult to assess each component ofsuch a complex intervention.

References1. Kaufman FR (Ed.). Medical Management ofType 1 Diabetes, 6th ed. Alexandria, VA, Amer-ican Diabetes Association, 20122. Burant CF (Ed.). Medical Management ofType 2 Diabetes, 7th ed. Alexandria, VA, Amer-ican Diabetes Association, 20123. Li R, Zhang P, Barker LE, Chowdhury FM,Zhang X. Cost-effectiveness of interventions toprevent and control diabetesmellitus: a system-atic review. Diabetes Care 2010;33:1872–18944. Grant RW, Kirkman MS. Trends in the evi-dence level for the American Diabetes Associa-tion’s “Standards of Medical Care in Diabetes”from 2005 to 2014. Diabetes Care 2015;38:6–8

Table 1—ADA evidence-grading system for “Standards of Medical Care in Diabetes”

Level ofevidence Description

A Clear evidence from well-conducted, generalizable randomized controlledtrials that are adequately powered, includingc Evidence from a well-conducted multicenter trialc Evidence from a meta-analysis that incorporated quality ratings in theanalysis

Compelling nonexperimental evidence; i.e., “all or none” rule developed bythe Centre for Evidence-Based Medicine at the University of Oxford

Supportive evidence from well-conducted randomized controlled trials thatare adequately powered, includingc Evidence from a well-conducted trial at one or more institutionsc Evidence from a meta-analysis that incorporated quality ratings in theanalysis

B Supportive evidence from well-conducted cohort studiesc Evidence from a well-conducted prospective cohort study or registryc Evidence from a well-conducted meta-analysis of cohort studies

Supportive evidence from a well-conducted case-control study

C Supportive evidence from poorly controlled or uncontrolled studiesc Evidence from randomized clinical trials with one or more major or threeor more minor methodological flaws that could invalidate the results

c Evidence from observational studies with high potential for bias (such ascase series with comparison with historical controls)

c Evidence from case series or case reportsConflicting evidence with the weight of evidence supporting the

recommendation

E Expert consensus or clinical experience

S2 Introduction Diabetes Care Volume 38, Supplement 1, January 2015

Professional Practice CommitteeDiabetes Care 2015;38(Suppl. 1):S3 | DOI: 10.2337/dc15-S002

The Professional Practice Committee(PPC) of the American Diabetes Associa-tion (ADA) is responsible for the “Stan-dards of Medical Care in Diabetes”position statement, referred to as the“Standards of Care.” The PPC is a multidis-ciplinary expert committee comprised ofphysicians, diabetes educators, registereddietitians, and others who have expertisein a range of areas, including adult andpediatric endocrinology, epidemiology,public health, lipid research, hypertension,and preconception and pregnancy care.Appointment to the PPC is based on excel-lence in clinical practice and/or research.While the primary role of the PPC is toreview and update the Standards ofCare, it is also responsible for overseeingthe review and revisions of ADA’s positionstatements and scientific statements.All members of the PPC are required

to disclose potential conflicts of interestwith industry and/or other relevant or-ganizations. These disclosures are dis-cussed at the onset of each Standardsof Care revision meeting. Members ofthe committee, their employer, andtheir disclosed conflicts of interest arelisted in the “Professional Practice Com-mittee for the Standards of MedicalCare in Diabetesd2015” table (seep. S88).For the current revision, PPC mem-

bers systematically searched MEDLINE

for human studies related to each sec-tion and published since 1 January 2014.Recommendations were revised basedon new evidence or, in some cases, toclarify the prior recommendation ormatch the strength of the wording tothe strength of the evidence. A table link-ing the changes in recommendations tonew evidence can be reviewed at http://professional.diabetes.org/SOC. As forall position statements, the Standardsof Care position statement was reviewedand approved by the Executive Committeeof ADA’s Board of Directors, which in-cludes health care professionals, scientists,and lay people.

Feedback from the larger clinicalcommunity was valuable for the 2015revision of the Standards of Care. Read-ers who wish to comment on the Stan-dards of Medical Care in Diabetesd2015are invited to do so at http://professional.diabetes.org/SOC.

The ADA funds development of theStandards of Care and all ADA positionstatements out of its general revenuesand does not use industry support forthese purposes.

The PPC would like to thank the fol-lowing individuals who provided their ex-pertise in reviewing and/or consulting withthe committee: Donald R. Coustan, MD;Stephanie Dunbar, MPH, RD; Robert H.Eckel, MD; Henry N. Ginsberg, MD;

Edward W. Gregg, PhD; Silvio E. Inzucchi,MD; Mark E. Molitch, MD; John M.Morton, MD; Robert E. Ratner, MD;Linda M. Siminerio, RN, PhD, CDE; andKatherine R. Tuttle, MD.

Members of the PPC

Richard W. Grant, MD, MPH (Chair)*

Thomas W. Donner, MD

Judith E. Fradkin, MD

Charlotte Hayes, MMSc, MS, RD, CDE,ACSM CES

William H. Herman, MD, MPH

William C. Hsu, MD

Eileen Kim, MD

Lori Laffel, MD, MPH

Rodica Pop-Busui, MD, PhD

Neda Rasouli, MD*

Desmond Schatz, MD

Joseph A. Stankaitis, MD, MPH*

Tracey H. Taveira, PharmD, CDOE,CVDOE

Deborah J. Wexler, MD*

*Subgroup leaders

ADA Staff

Jane L. Chiang, MD

Erika Gebel Berg, PhD

©2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered.


PROFESSIO

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ECOMMITTEE

Standards of Medical Care in Diabetesd2015:Summary of RevisionsDiabetes Care 2015;38(Suppl. 1):S4 | DOI: 10.2337/dc15-S003

GENERAL CHANGES

Diabetes Care Supplement 1 was previ-ously called Clinical Practice Recommen-dations and included the “Standards ofMedical Care in Diabetes” and keyAmerican Diabetes Association (ADA)position statements. The supplementhas been renamed Standards of MedicalCare in Diabetes (“Standards”) andcontains a single ADA position state-ment that provides evidence-based clin-ical practice recommendations fordiabetes care.Whereas the “Standards of Medical

Care in Diabetesd2015” should stillbe viewed as a single document, it hasbeen divided into 14 sections, each in-dividually referenced, to highlight im-portant topic areas and to facilitatenavigation.The supplement now includes an in-

dex to help readers find information onparticular topics.

SECTION CHANGES

Although the levels of evidence for sev-eral recommendations have been up-dated, these changes are not includedbelow as the clinical recommendationshave remained the same. Changes in ev-idence level from, for example, C to E arenot noted below. The “Standards ofMedical Care in Diabetesd2015” con-tains, in addition tomanyminor changesthat clarify recommendations or reflectnew evidence, the following more sub-stantive revisions.

Section 2. Classification andDiagnosis of DiabetesThe BMI cut point for screening over-weight or obese Asian Americans for pre-diabetes and type 2 diabetes was changedto 23 kg/m2 (vs. 25 kg/m2) to reflectthe evidence that this population is at anincreased risk for diabetes at lower BMIlevels relative to the general population.

Section 4. Foundations of Care:Education, Nutrition, Physical Activity,Smoking Cessation, Psychosocial Care,and ImmunizationThe physical activity section was revisedto reflect evidence that all individuals,including those with diabetes, shouldbe encouraged to limit the amount oftime they spend being sedentary bybreaking up extended amounts of time(.90 min) spent sitting.

Due to the increasing use of e-cigarettes,the Standards were updated to make clearthat e-cigarettes are not supported as analternative to smoking or to facilitatesmoking cessation.

Immunization recommendations wererevised to reflect recentCenters forDiseaseControl and Prevention guidelines re-garding PCV13 and PPSV23 vaccinationsin older adults.

Section 6. Glycemic TargetsThe ADA now recommends a premealblood glucose target of 80–130 mg/dL,rather than 70–130 mg/dL, to better re-flect new data comparing actual averageglucose levels with A1C targets.

To provide additional guidance on thesuccessful implementation of continuousglucose monitoring (CGM), the Standardsincludenewrecommendationsonassessinga patient’s readiness for CGM and onproviding ongoing CGM support.

Section 7. Approaches to GlycemicTreatmentThe type 2 diabetes management algo-rithm was updated to reflect all of thecurrently available therapies for diabe-tes management.

Section 8. Cardiovascular Disease andRisk ManagementThe recommended goal for diastolicblood pressure was changed from 80mmHg to 90 mmHg for most peoplewith diabetes and hypertension to better

reflect evidence from randomized clinicaltrials. Lower diastolic targets may still beappropriate for certain individuals.

Recommendations for statin treat-ment and lipid monitoring were revisedafter consideration of 2013 AmericanCollege of Cardiology/American HeartAssociation guidelines on the treatmentof blood cholesterol. Treatment initia-tion (and initial statin dose) is nowdriven primarily by risk status ratherthan LDL cholesterol level.

With consideration for the newstatin treatment recommendations, theStandards now provide the followinglipid monitoring guidance: a screeninglipid profile is reasonable at diabetes di-agnosis, at an initial medical evaluationand/or at age 40 years, and periodicallythereafter.

Section 9. MicrovascularComplications and Foot CareTo better target those at high risk forfoot complications, the Standards em-phasize that all patients with insensatefeet, foot deformities, or a history offoot ulcers have their feet examined atevery visit.

Section 11. Children and AdolescentsTo reflect new evidence regarding therisks and benefits of tight glycemic con-trol in children and adolescents with di-abetes, the Standards now recommenda target A1C of ,7.5% for all pediatricage-groups; however, individualization isstill encouraged.

Section 12. Management of Diabetesin PregnancyThis new section was added to theStandards to provide recommendationsrelated to pregnancy and diabetes, in-cluding recommendations regardingpreconception counseling, medications,blood glucose targets, and monitoring.

©2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered.

S4 Diabetes Care Volume 38, Supplement 1, January 2015

SUMMARYOFREV

ISIONS

1. Strategies for Improving CareDiabetes Care 2015;38(Suppl. 1):S5–S7 | DOI: 10.2337/dc15-S004

Recommendations

c A patient-centered communication style that incorporates patient prefer-ences, assesses literacy and numeracy, and addresses cultural barriers tocare should be used. B

c Treatment decisions should be timely and founded on evidence-based guide-lines that are tailored to individual patient preferences, prognoses, andcomorbidities. B

c Care should be aligned with components of the Chronic Care Model (CCM) toensure productive interactions between a prepared proactive practice teamand an informed activated patient. A

c When feasible, care systems should support team-based care, communityinvolvement, patient registries, and decision support tools to meet patientneeds. B

DIABETES CARE CONCEPTS

In the following sections, different components of the clinical management ofpatients with (or at risk for) diabetes are reviewed. We highlight the following threethemes that are woven throughout these sections that clinicians, policymakers, andadvocates should keep in mind:

1. Patient-Centeredness: Practice recommendations, whether based on evidence orexpert opinion, are intended to guide an overall approach to care. The science and artof medicine come together when the clinician is faced with making treatment recom-mendations for a patient whowould not havemet eligibility criteria for the studies onwhichguidelineswerebased.Recognizing thatone sizedoesnotfit all, theseStandardsprovide guidance for when and how to adapt recommendations (e.g., see Section 10.Older Adults and Fig. 6.1. Approach to the Management of Hyperglycemia). Becausepatients with diabetes are also at greatly increased risk of cardiovascular disease, apatient-centered approach should include a comprehensive plan to reduce cardiovas-cular risk by addressing blood pressure and lipid control, smoking cessation, weightmanagement, and healthy lifestyle changes that include adequate physical activity.

2. Diabetes Across the Life Span: An increasing proportion of patients with type 1diabetes are adults. Conversely, and for less salutary reasons, the incidence of type2 diabetes is increasing in children and young adults. Finally, patients bothwith type1 diabetes and with type 2 diabetes are living well into older age, a stage of life forwhich there is little evidence from clinical trials to guide therapy. All these de-mographic changes highlight another challenge to high-quality diabetes care, whichis theneed to improve coordinationbetween clinical teams aspatients pass throughdifferent stages of the life span or the stages of pregnancy (preconception, preg-nancy, and postpartum).

3. Advocacy for Patients With Diabetes: Advocacy can be defined as active supportand engagement to advance a cause or policy. Advocacy in the cause of improving thelives ofpatientswith (or at risk for) diabetes is anongoingneed.Given the tremendoustoll that lifestyle factors such as obesity, physical inactivity, and smoking have on thehealth of patients with diabetes, ongoing and energetic efforts are needed to addressand change the societal determinants at the root of these problems.Within themorenarrowdomain of clinical practice guidelines, the application of evidence level gradingto practice recommendations can help identify areas that require more researchinvestment (1). This topic is explored inmore depth in Section 14. Diabetes Advocacy.

Suggested citation: American Diabetes Associa-tion. Strategies for improving care. Sec. 1. InStandards of Medical Care in Diabetesd2015.Diabetes Care 2015;38(Suppl. 1):S5–S7

© 2015 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered.

American Diabetes Association


POSITIO

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CARE DELIVERY SYSTEMS

Therehasbeen steady improvement in theproportion of diabetic patients achievingrecommended levels of A1C, blood pres-sure, and LDL cholesterol in the last 10years (2). The mean A1C nationally hasdeclined from 7.6% in 1999–2002 to7.2% in 2007–2010 based on the NationalHealth and Nutrition Examination Survey(NHANES) data (E.W. Gregg, Centers forDisease Control and Prevention, personalcommunication). This has been accompa-nied by improvements in lipids and bloodpressure control and has led to substantialreductions in end-stage microvascularcomplications in patients with diabetes.Nevertheless, between 33 and 49% of pa-tients still do not meet targets for glyce-mic, bloodpressure, or cholesterol control,and only 14% meet targets for all threemeasures and nonsmoking status (2). Evi-dence also suggests that progress in car-diovascular risk factor control (particularlytobacco use) may be slowing (2,3). Certainpatient groups, such as young adults andpatients with complex comorbidities, fi-nancial or other social hardships, and/orlimited English proficiency, may presentparticular challenges to goal-based care(4–6). Persistent variation in quality of di-abetes care across providers and acrosspractice settings even after adjusting forpatient factors indicates that there re-mains potential for substantial system-level improvements in diabetes care.

Chronic Care ModelAlthough numerous interventions to im-prove adherence to the recommendedstandards have been implemented, ama-jor barrier to optimal care is a deliverysystem that too often is fragmented, lacksclinical information capabilities, dupli-cates services, and is poorly designedfor the coordinated delivery of chroniccare. The CCM has been shown to be aneffective framework for improving thequality of diabetes care (7). The CCM in-cludes six core elements for the provisionof optimal care of patients with chronicdisease: 1) delivery system design (mov-ing from a reactive to a proactive caredelivery system where planned visitsare coordinated through a team-basedapproach, 2) self-management support,3) decision support (basing care onevidence-based, effective care guide-lines), 4) clinical information systems(using registries that can provide patient-specific and population-based support

to the care team), 5) community resourcesand policies (identifying or developingresources to support healthy lifestyles),and 6) health systems (to create a quality-oriented culture). Redefining the rolesof the clinic staff and promoting self-management on the part of the patientare fundamental to the successful imple-mentation of the CCM (8). Collaborative,multidisciplinary teams are best suited toprovide care for people with chronic con-ditions such as diabetes and to facilitatepatients’ self-management (9–12).

Key ObjectivesThe National Diabetes Education Pro-gram (NDEP) maintains an online resource(www.betterdiabetescare.nih.gov) to helphealth care professionals design and im-plement more effective health care de-livery systems for those with diabetes.Three specific objectives, with refer-ences to literature that outlines practicalstrategies to achieve each, are delin-eated below.

Objective 1: Optimize Provider and Team

Behavior

The care team should prioritize timely andappropriate intensification of lifestyle and/orpharmaceutical therapy for patientswhohave not achievedbeneficial levels of bloodpressure, lipid, or glucose control (13).Strategies such as explicit goal settingwith patients (14); identifying and address-ing language, numeracy, or cultural barriersto care (15–18); integrating evidence-basedguidelines and clinical information toolsinto the process of care (19–21); and incor-poratingcaremanagement teams includingnurses, pharmacists, and other providers(22–24) have each been shown to optimizeprovider and team behavior and therebycatalyze reductions in A1C, blood pressure,and LDL cholesterol.

Objective 2: Support Patient Behavior

Change

Successful diabetes care requires a sys-tematic approach to supporting patients’behavior change efforts, including 1)healthy lifestyle changes (physical activity,healthy eating, tobacco cessation, weightmanagement, and effective coping), 2)disease self-management (taking andmanaging medication and, when clinicallyappropriate, self-monitoring of glucoseand blood pressure), and 3) preventionof diabetes complications (self-monitoringof foot health; active participation inscreening for eye, foot, and renal compli-cations; and immunizations). High-quality

diabetes self-management education(DSME) has been shown to improve pa-tient self-management, satisfaction, andglucose control (25,26), as has delivery ofongoing diabetes self-management sup-port (DSMS), so that gains achieved duringDSME are sustained (27–29). NationalDSME standards call for an integrated ap-proach that includes clinical content andskills, behavioral strategies (goal setting,problem solving), and engagement withemotional concerns in each needed curric-ulum content area.

Objective 3: Change the Care System

An institutional priority inmost successfulcare systems is providing a high quality ofcare (30). Changes that have been shownto increase quality of diabetes care in-clude basing care on evidence-basedguidelines (19); expanding the role ofteams and staff and implementing moreintensive disease management strategies(6,22,31); redesigning the care process(32); implementing electronic health re-cord tools (33,34); activating and educat-ing patients (35,36); removing financialbarriers and reducing patient out-of-pocket costs for diabetes education, eyeexams, self-monitoring of blood glucose,and necessary medications (6); and iden-tifying/developing/engaging communityresources and public policy that supporthealthy lifestyles (37). Recent initiativessuch as the Patient-Centered MedicalHome show promise for improving out-comes through coordinated primary careand offer new opportunities for team-based chronic disease care (38). Addi-tional strategies to improve diabetescare include reimbursement structuresthat, in contrast to visit-based billing, re-ward the provision of appropriate andhigh-quality care (39), and incentivesthat accommodate personalized caregoals (6,40).

It is clear that optimal diabetes man-agement requires an organized, system-atic approach and the involvement of acoordinated team of dedicated healthcare professionals working in an envi-ronment where patient-centered high-quality care is a priority (6).

WHEN TREATMENT GOALS ARENOT MET

Some patients and their health care pro-viders may not achieve the desiredtreatment goals. Reassessing the treat-ment regimenmay require evaluation of

S6 Position Statement Diabetes Care Volume 38, Supplement 1, January 2015

barriers such as income, health literacy,diabetes-related distress, depression,poverty, and competing demands, in-cluding those related to family respon-sibilities and dynamics. Other strategiesmay include culturally appropriate andenhanced DSME and DSMS, comanage-ment with a diabetes team, referral to amedical social worker for assistancewith insurance coverage, medication-taking behavior assessment, or changein pharmacological therapy. Initiation ofor increase in self-monitoring of bloodglucose, continuous glucosemonitoring,frequent patient contact, or referral to amental health professional or physicianwith special expertise in diabetes maybe useful.

References1. Grant RW, Kirkman MS. Trends in the evi-dence level for the American Diabetes Associ-ation’s “Standards of Medical Care inDiabetes” from 2005 to 2014. Diabetes Care2015;38:6–82. Ali MK, Bullard KM, Saaddine JB, Cowie CC,Imperatore G, Gregg EW. Achievement of goalsin U.S. diabetes care, 1999-2010. N Engl J Med2013;368:1613–16243. Wang J, Geiss LS, Cheng YJ, et al. Long-termand recent progress in blood pressure levelsamong U.S. adults with diagnosed diabetes,1988-2008. Diabetes Care 2011;34:1579–15814. Kerr EA, Heisler M, Krein SL, et al. Beyondcomorbidity counts: how do comorbidity typeand severity influence diabetes patients’ treat-ment priorities and self-management? J Gen In-tern Med 2007;22:1635–16405. Fernandez A, Schillinger D, Warton EM, et al.Language barriers, physician-patient languageconcordance, and glycemic control among in-sured Latinos with diabetes: the Diabetes Studyof Northern California (DISTANCE). J Gen InternMed 2011;26:170–1766. TRIAD Study Group. Health systems, pa-tients factors, and quality of care for diabetes:a synthesis of findings from the TRIAD study.Diabetes Care 2010;33:940–9477. Stellefson M, Dipnarine K, Stopka C. Thechronic care model and diabetes managementin US primary care settings: a systematic review.Prev Chronic Dis 2013;10:E268. Coleman K, Austin BT, Brach C, Wagner EH.Evidence on the Chronic Care Model in the newmillennium. Health Aff (Millwood) 2009;28:75–859. Piatt GA, Anderson RM, Brooks MM, et al. 3-year follow-up of clinical and behavioral im-provements following a multifaceted diabetescare intervention: results of a randomized con-trolled trial. Diabetes Educ 2010;36:301–30910. Renders CM, Valk GD, Griffin SJ,Wagner EH,Eijk Van JT, Assendelft WJ. Interventions to im-prove the management of diabetes in primarycare, outpatient, and community settings:

a systematic review. Diabetes Care 2001;24:1821–183311. Katon WJ, Lin EHB, Von Korff M, et al. Col-laborative care for patients with depression andchronic illnesses. N Engl J Med 2010;363:2611–262012. Parchman ML, Zeber JE, Romero RR, PughJA. Risk of coronary artery disease in type 2 di-abetes and the delivery of care consistent withthe chronic care model in primary care settings:a STARNet study. Med Care 2007;45:1129–113413. Davidson MB. How our current medicalcare system fails people with diabetes: lack oftimely, appropriate clinical decisions. DiabetesCare 2009;32:370–37214. Grant RW, Pabon-Nau L, Ross KM, Youatt EJ,Pandiscio JC, Park ER. Diabetes oral medicationinitiation and intensification: patient viewscompared with current treatment guidelines.Diabetes Educ 2011;37:78–8415. Schillinger D, Piette J, Grumbach K, et al.Closing the loop: physician communicationwith diabetic patients who have low health lit-eracy. Arch Intern Med 2003;163:83–9016. Rosal MC, Ockene IS, Restrepo A, et al. Ran-domized trial of a literacy-sensitive, culturallytailored diabetes self-management interven-tion for low-income Latinos: Latinos en Control.Diabetes Care 2011;34:838–84417. Osborn CY, Cavanaugh K,Wallston KA, et al.Health literacy explains racial disparities in di-abetes medication adherence. J Health Com-mun 2011;16(Suppl. 3):268–27818. Rothman R, Malone R, Bryant B, Horlen C,DeWalt D, PignoneM. The relationship betweenliteracy and glycemic control in a diabetesdisease-management program. Diabetes Educ2004;30:263–27319. O’Connor PJ, Bodkin NL, Fradkin J, et al. Di-abetes performance measures: current statusand future directions. Diabetes Care 2011;34:1651–165920. Garg AX, Adhikari NK, McDonald H, et al.Effects of computerized clinical decision sup-port systems on practitioner performance andpatient outcomes: a systematic review. JAMA2005;293:1223–123821. Smith SA, Shah ND, Bryant SC, et al.; Evi-dens Research Group. Chronic care model andshared care in diabetes: randomized trial of anelectronic decision support system. Mayo ClinProc 2008;83:747–75722. Jaffe MG, Lee GA, Young JD, Sidney S, GoAS. Improved blood pressure control associatedwith a large-scale hypertension program. JAMA2013;310:699–70523. DavidsonMB, Ansari A, Karlan VJ. Effect of anurse-directed diabetes disease managementprogram on urgent care/emergency room visitsand hospitalizations in a minority population.Diabetes Care 2007;30:224–22724. Stone RA, Rao RH, Sevick MA, et al. Activecare management supported by home telemon-itoring in veterans with type 2 diabetes: theDiaTel randomized controlled trial. DiabetesCare 2010;33:478–48425. Duncan I, Birkmeyer C, Coughlin S, Li QE,Sherr D, Boren S. Assessing the value of diabeteseducation. Diabetes Educ 2009;35:752–760

26. Berikai P, Meyer PM, Kazlauskaite R, SavoyB, Kozik K, Fogelfeld L. Gain in patients’ knowl-edge of diabetes management targets is associ-ated with better glycemic control. DiabetesCare 2007;30:1587–158927. Funnell MM, Brown TL, Childs BP, et al. Na-tional standards for diabetes self-managementeducation. Diabetes Care 2007;30:1630–163728. Klein S, Sheard NF, Pi-Sunyer X, et al.Weightmanagement through lifestylemodifica-tion for the prevention and management oftype 2diabetes: rationale and strategies: a state-ment of the American Diabetes Association, theNorth American Association for the Study ofObesity, and the American Society for ClinicalNutrition. Diabetes Care 2004;27:2067–207329. Norris SL, Zhang X, Avenell A, et al. Efficacyof pharmacotherapy for weight loss in adultswith type 2 diabetes mellitus: a meta-analysis.Arch Intern Med 2004;164:1395–140430. Tricco AC, Ivers NM, Grimshaw JM, et al.Effectiveness of quality improvement strategieson the management of diabetes: a systematicreview and meta-analysis. Lancet 2012;379:2252–226131. Peikes D, Chen A, Schore J, Brown R. Effectsof care coordination on hospitalization, qualityof care, and health care expenditures amongMedicare beneficiaries: 15 randomized trials.JAMA 2009;301:603–61832. Feifer C, Nemeth L, Nietert PJ, et al. Differ-ent paths to high-quality care: three archetypesof top-performing practice sites. Ann Fam Med2007;5:233–24133. Reed M, Huang J, Graetz I, et al. Outpatientelectronic health records and the clinical careand outcomes of patients with diabetes melli-tus. Ann Intern Med 2012;157:482–48934. Cebul RD, Love TE, Jain AK, Hebert CJ. Elec-tronic health records and quality of diabetescare. N Engl J Med 2011;365:825–83335. Battersby M, Von Korff M, Schaefer J, et al.Twelve evidence-based principles for implement-ing self-management support in primary care. JtComm J Qual Patient Saf 2010;36:561–57036. Grant RW, Wald JS, Schnipper JL, et al.Practice-linked online personal health recordsfor type 2 diabetes mellitus: a randomized con-trolled trial. Arch Intern Med 2008;168:1776–178237. Pullen-Smith B, Carter-Edwards L, LeathersKH. Community health ambassadors: a mod-el for engaging community leaders to pro-mote better health in North Carolina. JPublic Health Manag Pract 2008;14(Suppl.):S73–S8138. Bojadzievski T, Gabbay RA. Patient-centeredmedical home and diabetes. Diabetes Care 2011;34:1047–105339. Rosenthal MB, Cutler DM, Feder J. The ACOrulesdstriking the balance between participa-tion and transformative potential. N Engl J Med2011;365:e640. Washington AE, Lipstein SH. The Patient-Centered Outcomes Research Institutedpromoting better information, decisions, andhealth. N Engl J Med 2011;365:e31

care.diabetesjournals.org Position Statement S7

2. Classification and Diagnosis ofDiabetesDiabetes Care 2015;38(Suppl. 1):S8–S16 | DOI: 10.2337/dc15-S005

CLASSIFICATION

Diabetes can be classified into the following general categories:

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulindeficiency)

2. Type 2 diabetes (due to a progressive insulin secretory defect on the backgroundof insulin resistance)

3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or thirdtrimester of pregnancy that is not clearly overt diabetes)

4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes(such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), dis-eases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induceddiabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

This section reviews most common forms of diabetes but is not comprehensive.For additional information, see the American Diabetes Association (ADA) positionstatement “Diagnosis and Classification of Diabetes Mellitus” (1).Assigning a type of diabetes to an individual often depends on the circumstances

present at the time of diagnosis, with individuals not necessarily fitting clearly into asingle category. For example, some patients cannot be clearly classified as havingtype 1 or type 2 diabetes. Clinical presentation and disease progression may varyconsiderably in both types of diabetes.The traditional paradigms of type 2 diabetes occurring only in adults and type 1

diabetes only in children are no longer accurate, as both diseases occur in both cohorts.Occasionally, patients with type 2 diabetes may present with diabetic ketoacidosis(DKA). Children with type 1 diabetes typically present with the hallmark symptomsof polyuria/polydipsia and occasionally with DKA. The onset of type 1 diabetes may bevariable in adults and may not present with the classic symptoms seen in children.However, difficulties in diagnosis may occur in children, adolescents, and adults, withthe true diagnosis becoming more obvious over time.

DIAGNOSTIC TESTS FOR DIABETES

Diabetes may be diagnosed based on A1C criteria or plasma glucose criteria, either thefasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oralglucose tolerance test (OGTT) (1,2) (Table 2.1).The same tests are used to both screen for and diagnose diabetes. Diabetes may

be identified anywhere along the spectrum of clinical scenarios: in seemingly low-risk individuals who happen to have glucose testing, in symptomatic patients, and inhigher-risk individuals whom the provider tests because of a suspicion of diabetes.The same tests will also detect individuals with prediabetes.

A1CThe A1C test should be performed using a method that is certified by the NGSP andstandardized or traceable to the Diabetes Control and Complications Trial (DCCT)reference assay. Although point-of-care (POC) A1C assays may be NGSP certified,proficiency testing is not mandated for performing the test, so use of POC assays fordiagnostic purposes may be problematic and is not recommended.The A1C has several advantages to the FPG and OGTT, including greater conve-

nience (fasting not required), greater preanalytical stability, and less day-to-dayperturbations during stress and illness. These advantages must be balanced by

Suggested citation: American Diabetes Association.Classification and diagnosis of diabetes. Sec. 2.In Standards of Medical Care in Diabetesd2015.Diabetes Care 2015;38(Suppl. 1):S8–S16




POSITION

STATEMEN

T

greater cost, the limited availability ofA1C testing in certain regions of thedeveloping world, and the incompletecorrelation between A1C and averageglucose in certain individuals.It is important to take age, race/

ethnicity, and anemia/hemoglobinopathiesinto consideration when using the A1C todiagnose diabetes.

Age

The epidemiological studies that formedthe framework for recommending A1Cto diagnose diabetes only included adultpopulations. Therefore, it remains un-clear if A1C and the same A1C cut pointshould be used to diagnose diabetes inchildren and adolescents (3–5).

Race/Ethnicity

A1C levels may vary with patients’ race/ethnicity (6,7). For example, AfricanAmericans may have higher A1C levelsthan non-Hispanic whites despite simi-lar fasting and postglucose load glucoselevels. A recent epidemiological studyfound that, when matched for FPG,African Americans (with and without di-abetes) had higher A1C levels than non-Hispanicwhites, but also had higher levelsof fructosamine and glycated albuminand lower levels of 1,5-anhydroglucitol,suggesting that their glycemic burden(particularly postprandially) may behigher (8).

Hemoglobinopathies/Anemias

Interpreting A1C levels in the presence ofcertain hemoglobinopathies and anemiamay be problematic. For patients with anabnormal hemoglobin but normal red cellturnover, such as thosewith the sickle celltrait, an A1C assay without interferencefrom abnormal hemoglobins should beused. An updated list of interferences isavailable at www.ngsp.org/interf.asp. Inconditions associated with increased redcell turnover, such as pregnancy (secondand third trimesters), recent blood lossor transfusion, erythropoietin therapy,or hemolysis, only blood glucose criteriashould be used to diagnose diabetes.

Fasting and 2-Hour Plasma GlucoseIn addition to the A1C test, the FPG and2-h PGmay also be used to diagnose diabe-tes (Table 2.1). The concordance betweenthe FPG and 2-h PG tests is imperfect, asis the concordance between A1C and ei-ther glucose-based test. National Healthand Nutrition Examination Survey(NHANES) data indicate that an A1C cutpoint of $6.5% identifies one-thirdfewer cases of undiagnosed diabetesthan a fasting glucose cut point of$126 mg/dL (7.0 mmol/L) (9). Numer-ous studies have confirmed that, com-pared with these A1C and FPG cutpoints, the 2-h PG value diagnosesmore people with diabetes. Of note,the lower sensitivity of A1C at the desig-nated cut point may be offset by thetest’s ease of use and facilitation ofmore widespread testing.

Unless there is a clear clinical diagno-sis (e.g., a patient in a hyperglycemiccrisis or with classic symptoms of hyper-glycemia and a random plasma glucose$200 mg/dL), it is recommended thatthe same test be repeated immediatelyusing a new blood sample for confirma-tion because there will be a greater like-lihood of concurrence. For example, ifthe A1C is 7.0% and a repeat result is6.8%, the diagnosis of diabetes is con-firmed. If two different tests (such asA1Cand FPG) areboth above the diagnos-tic threshold, this also confirms the diag-nosis. On the other hand, if a patient hasdiscordant results from two differenttests, then the test result that is abovethe diagnostic cut point should be re-peated. The diagnosis is made on the ba-sis of the confirmed test. For example, if apatient meets the diabetes criterion ofthe A1C (two results $6.5%), but not

FPG (,126 mg/dL [7.0 mmol/L]), thatperson should nevertheless be consid-ered to have diabetes.

Since all the tests have preanalytic andanalytic variability, it is possible that an ab-normal result (i.e., above the diagnosticthreshold), when repeated, will producea value below the diagnostic cut point.This scenario is least likely for A1C,morelikely for FPG, andmost likely for the 2-hPG, especially if the glucose samples arecollected at room temperature and notcentrifuged promptly. Barring labora-tory error, such patients will likelyhave test results near the margins ofthe diagnostic threshold. The healthcare professional should follow thepatient closely and repeat the test in3–6 months.

CATEGORIES OF INCREASED RISKFOR DIABETES (PREDIABETES)

Recommendations

c Testing to assess risk for future di-abetes in asymptomatic peopleshould be considered in adults ofany age who are overweight orobese (BMI $25 kg/m2 or $23kg/m2 in Asian Americans) andwho have one or more additionalrisk factors for diabetes. For allpatients, particularly those whoare overweight or obese, testingshould begin at age 45 years. B

c If tests are normal, repeat testingcarried out at a minimum of 3-year intervals is reasonable. C

c To test for prediabetes, the A1C,FPG, and 2-h PG after 75-g OGTTare appropriate. B

c In patients with prediabetes, iden-tify and, if appropriate, treat othercardiovascular disease (CVD) riskfactors. B

c Testing to detect prediabetesshould be considered in childrenand adolescents who are over-weight or obese and who havetwo or more additional risk factorsfor diabetes. E

DescriptionIn 1997 and 2003, the Expert Commit-tee on Diagnosis and Classification ofDiabetes Mellitus (10,11) recognized agroup of individuals whose glucose lev-els did not meet the criteria for diabetesbut were too high to be considered

Table 2.1—Criteria for the diagnosisof diabetesA1C$6.5%. The test should be performed

in a laboratory using a method that isNGSP certified and standardized to theDCCT assay.*

OR

FPG $126 mg/dL (7.0 mmol/L). Fasting isdefined as no caloric intake for at least8 h.*

OR

2-h PG$200 mg/dL (11.1 mmol/L) duringan OGTT. The test should be performedas described by the WHO, usinga glucose load containing theequivalent of 75 g anhydrous glucosedissolved in water.*

OR

In a patient with classic symptoms ofhyperglycemia or hyperglycemic crisis,a random plasma glucose $200 mg/dL(11.1 mmol/L).

*In the absence of unequivocalhyperglycemia, results should be confirmedby repeat testing.


normal. “Prediabetes” is the term usedfor individuals with impaired fastingglucose (IFG) and/or impaired glucosetolerance (IGT) and indicates an in-creased risk for the future develop-ment of diabetes. IFG and IGT shouldnot be viewed as clinical entities intheir own right but rather risk factorsfor diabetes (Table 2.2) and CVD. IFGand IGT are associated with obesity(especially abdominal or visceral obe-sity), dyslipidemia with high triglycer-ides and/or low HDL cholesterol, andhypertension.

DiagnosisIn 1997 and 2003, the Expert Commit-tee on Diagnosis and Classification ofDiabetes Mellitus (10,11) defined IFGas FPG levels 100–125 mg/dL (5.6–6.9mmol/L) and IGT as 2-h PG after 75-gOGTT levels 140–199 mg/dL (7.8–11.0mmol/L). It should be noted that theWorld Health Organization (WHO) andnumerous diabetes organizations de-fine the IFG cutoff at 110 mg/dL (6.1mmol/L).As with the glucose measures, sev-

eral prospective studies that used A1Cto predict the progression to diabetesdemonstrated a strong, continuousassociation between A1C and sub-sequent diabetes. In a systematic re-view of 44,203 individuals from 16cohort studies with a follow-up intervalaveraging 5.6 years (range 2.8–12years), those with an A1C between5.5–6.0% had a substantially increasedrisk of diabetes (5-year incidence from

9 to 25%). An A1C range of 6.0–6.5%had a 5-year risk of developing diabe-tes between 25–50% and a relative risk20 times higher compared with an A1Cof 5.0% (12). In a community-basedstudy of African American and non-Hispanic white adults without diabetes,baseline A1C was a stronger predictorof subsequent diabetes and cardiovas-cular events than fasting glucose (13).Other analyses suggest that an A1C of5.7% is associated with a diabetes risksimilar to that of the high-risk partici-pants in the Diabetes Prevention Pro-gram (DPP) (14).

Hence, it is reasonable to consider anA1C range of 5.7–6.4% as identifying in-dividuals with prediabetes. As with thosewith IFG and/or IGT, individuals with anA1C of 5.7–6.4% should be informed oftheir increased risk for diabetes and CVDand counseled about effective strategiesto lower their risks (see Section 5. Preven-tion or Delay of Type 2 Diabetes). Similarto glucosemeasurements, the continuumof risk is curvilinear, so as A1C rises, thediabetes risk rises disproportionately(12). Aggressive interventions and vigilantfollow-up should be pursued for thoseconsidered at very high risk (e.g., thosewith A1C.6.0%).

Table 2.3 summarizes the categoriesof prediabetes. For recommendationsregarding risk factors and screening forprediabetes, see p. S12 (“Testing forType 2 Diabetes and Prediabetes inAsymptomatic Adults” and “Testing forType 2 Diabetes and Prediabetes in Chil-dren and Adolescents”).

TYPE 1 DIABETES

Recommendationc Inform the relatives of patients with

type 1 diabetes of the opportunityto be tested for type 1 diabetes risk,but only in the setting of a clinicalresearch study. E

Immune-Mediated DiabetesThis form, previously called “insulin-dependent diabetes” or “juvenile-onsetdiabetes,” accounts for 5–10% of diabetesand isduetocellular-mediatedautoimmunedestruction of the pancreatic b-cells.Autoimmune markers include islet cellautoantibodies, autoantibodies to insu-lin, autoantibodies to GAD (GAD65),autoantibodies to the tyrosine phospha-tases IA-2 and IA-2b, and autoantibodiesto zinc transporter 8 (ZnT8). Type 1 di-abetes is defined by the presence of oneor more of these autoimmune markers.The disease has strong HLA associations,with linkage to the DQA and DQB genes.These HLA-DR/DQ alleles can be eitherpredisposing or protective.

The rate of b-cell destruction is quitevariable, being rapid in some individuals(mainly infants and children) and slow inothers (mainly adults). Children andadolescents may present with ketoaci-dosis as the first manifestation of thedisease. Others have modest fasting hy-perglycemia that can rapidly change tosevere hyperglycemia and/or ketoacido-sis with infection or other stress. Adultsmay retain sufficient b-cell function toprevent ketoacidosis for many years;such individuals eventually become de-pendent on insulin for survival and areat risk for ketoacidosis. At this latterstage of the disease, there is little orno insulin secretion, as manifested bylow or undetectable levels of plasmaC-peptide. Immune-mediated diabetes

Table 2.2—Criteria for testing for diabetes or prediabetes in asymptomatic adults1. Testing should be considered in all adults who are overweight (BMI$25 kg/m2 or$23 kg/m2 in

Asian Americans) and have additional risk factors:c physical inactivityc first-degree relative with diabetesc high-risk race/ethnicity (e.g., African American, Latino, Native American, AsianAmerican, Pacific Islander)

c women who delivered a baby weighing .9 lb or were diagnosed with GDMc hypertension ($140/90 mmHg or on therapy for hypertension)c HDL cholesterol level,35 mg/dL (0.90 mmol/L) and/or a triglyceride level.250 mg/dL(2.82 mmol/L)

c women with polycystic ovary syndromec A1C $5.7%, IGT, or IFG on previous testingc other clinical conditions associated with insulin resistance (e.g., severe obesity,acanthosis nigricans)

c history of CVD

2. For all patients, particularly those who are overweight or obese, testing shouldbegin at age 45 years.

3. If results are normal, testing should be repeated at a minimum of 3-year intervals, withconsideration of more frequent testing depending on initial results (e.g., those withprediabetes should be tested yearly) and risk status.

Table 2.3—Categories of increased riskfor diabetes (prediabetes)*FPG 100mg/dL (5.6 mmol/L) to 125 mg/dL

(6.9 mmol/L) (IFG)

OR

2-h PG in the 75-g OGTT 140 mg/dL (7.8mmol/L) to 199mg/dL (11.0mmol/L) (IGT)

OR

A1C 5.7–6.4%

*For all three tests, risk is continuous,extending below the lower limit of the rangeand becoming disproportionately greater athigher ends of the range.


commonly occurs in childhood and ado-lescence, but it can occur at any age,even in the 8th and 9th decades of life.Autoimmune destruction ofb-cells has

multiple genetic predispositions and isalso related to environmental factorsthat are still poorly defined. Although pa-tients are not typically obese when theypresent with type 1 diabetes, obesityshould not preclude the diagnosis. Thesepatients are also prone to other autoim-mune disorders such as Graves’ disease,Hashimoto’s thyroiditis, Addison’s dis-ease, vitiligo, celiac disease, autoimmunehepatitis, myasthenia gravis, and perni-cious anemia.

Idiopathic DiabetesSome forms of type 1 diabetes have noknownetiologies. These patients haveper-manent insulinopenia and are prone toketoacidosis, but have no evidence of au-toimmunity. Although only a minority ofpatients with type 1 diabetes fall into thiscategory, of those who do, most are ofAfrican or Asian ancestry. Individualswith this form of diabetes suffer from ep-isodic ketoacidosis and exhibit varyingdegrees of insulin deficiency between epi-sodes. This form of diabetes is stronglyinherited, lacks immunological evidencefor b-cell autoimmunity, and is not HLAassociated. An absolute requirement forinsulin replacement therapy in affectedpatients may come and go.

Testing for Type 1 Diabetes

The incidence and prevalence of type 1diabetes is increasing (15). Type 1 dia-betic patients often present with acutesymptoms of diabetes and markedly ele-vated blood glucose levels, and some arediagnosed with life-threatening keto-acidosis. Several studies suggest thatmea-suring islet autoantibodies in relatives ofthose with type 1 diabetes may identifyindividuals who are at risk for developingtype 1 diabetes. Such testing, coupledwith education about diabetes symptomsand close follow-up in an observationalclinical study, may enable earlier identifi-cation of type 1 diabetes onset. There isevidence to suggest that early diagnosismay limit acute complications (16) andextend long-term endogenous insulinproduction (17).A recent study reported the risk of pro-

gression to type 1 diabetes from the timeof seroconversion to autoantibody posi-tivity in three pediatric cohorts from Fin-land, Germany, and the U.S. Of the 585

children who developed more than twoautoantibodies, nearly 70% developedtype 1 diabetes within 10 years and 84%within 15 years (16,18). Thesefindings arehighly significant because, while the Ger-man group was recruited from offspringof parents with type 1 diabetes, the Finn-ish and American groups were recruitedfrom the general population. Remark-ably, the findings in all three groupswere the same, suggesting that thesame sequence of events led to clinicaldisease in both “sporadic” and geneticcases of type 1 diabetes.

While there is currently a lack ofaccepted screening programs, oneshould consider referring relatives ofthose with type 1 diabetes for antibodytesting for risk assessment in thesetting of a clinical research study(http://www2.diabetestrialnet.org).Widespread clinical testing of asymptom-atic low-risk individuals is not currentlyrecommended due to lack of approvedtherapeutic interventions. Higher-risk in-dividuals may be tested, but only in thecontext of a clinical research setting. In-dividuals who test positive will be coun-seled about the risk of developingdiabetes, diabetes symptoms, and DKAprevention. Numerous clinical studiesare being conducted to test variousmeth-ods of preventing type 1 diabetes inthose with evidence of autoimmunity(www.clinicaltrials.gov).

TYPE 2 DIABETES

Recommendations

c Testing to detect type 2 diabetesin asymptomatic people shouldbe considered in adults of anyage who are overweight orobese (BMI $25 kg/m2 or $23kg/m2 in Asian Americans) andwho have one or more addi-tional risk factors for diabetes.For all patients, particularlythose who are overweight orobese, testing should begin atage 45 years. B

c If tests are normal, repeat testingcarried out at a minimum of 3-yearintervals is reasonable. C

c To test for diabetes, the A1C, FPG,and 2-h PG after 75-g OGTT areappropriate. B

c In patients with diabetes, identifyand, if appropriate, treat otherCVD risk factors. B

c Testing to detect type 2 diabetesshould be considered in childrenand adolescents who are over-weight or obese and who havetwo ormore additional risk factorsfor diabetes. E

DescriptionThis form, previously referred to as “non-insulin-dependent diabetes” or “adult-onset diabetes,” accounts for ;90–95%of all diabetes. Type 2 diabetes encom-passes individuals who have insulin resis-tance and usually relative (rather thanabsolute) insulin deficiency. At least ini-tially, and often throughout their lifetime,these individuals may not need insulintreatment to survive.

There are various causes of type 2 di-abetes. Although the specific etiologiesare not known, autoimmune destruc-tion of b-cells does not occur, and pa-tients do not have any of the otherknown causes of diabetes. Most, butnot all, patients with type 2 diabetesare obese. Obesity itself causes somedegree of insulin resistance. Patientswho are not obese by traditional weightcriteria may have an increased percent-age of body fat distributed predomi-nantly in the abdominal region.

Ketoacidosis seldom occurs sponta-neously in type 2 diabetes; when seen,it usually arises in association withthe stress of another illness such as in-fection. Type 2 diabetes frequently goesundiagnosed for many years because hy-perglycemia develops gradually and atearlier stages is often not severe enoughfor the patient to notice the classic di-abetes symptoms. Nevertheless, suchpatients are at an increased risk ofdeveloping macrovascular and micro-vascular complications.

Whereas patients with type 2 diabetesmay have insulin levels that appear nor-mal or elevated, the higher blood glucoselevels in these patientswould be expectedto result in even higher insulin values hadtheir b-cell function been normal. Thus,insulin secretion is defective in these pa-tients and insufficient to compensate forinsulin resistance. Insulin resistance mayimprove with weight reduction and/orpharmacological treatment of hyper-glycemia but is seldom restored to normal.

The risk of developing type 2 diabetesincreases with age, obesity, and lack ofphysical activity. It occurs more frequently


in women with prior GDM, in those withhypertension or dyslipidemia, and in cer-tain racial/ethnic subgroups (AfricanAmerican, American Indian, Hispanic/Latino, and Asian American). It is oftenassociated with a strong genetic predis-position, more so than type 1 diabetes.However, the genetics of type 2 diabetesis poorly understood.

Testing for Type 2 Diabetes andPrediabetes in Asymptomatic AdultsPrediabetes and diabetes meet criteria forconditions in which early detection is ap-propriate. Both conditions are commonand impose significant clinical and publichealth burdens. There is often a long pre-symptomatic phase before the diagnosisof type 2 diabetes. Simple tests to detectpreclinical disease are readily available.Thedurationof glycemic burden is a strongpredictor of adverse outcomes. There areeffective interventions that prevent pro-gression from prediabetes to diabetes(see Section 5. Prevention or Delay ofType 2 Diabetes) and reduce the riskof diabetes complications (see Section8. Cardiovascular Disease and RiskManagement and Section 9. Microvas-cular Complications and Foot Care).Approximately one-quarter of people

with diabetes in the U.S. are undiag-nosed. Although screening of asymptom-atic individuals to identify those withprediabetes or diabetes might seem rea-sonable, rigorous clinical trials to provethe effectiveness of such screening havenot been conducted and are unlikely tooccur. A large European randomized con-trolled trial compared the impact ofscreening for diabetes and intensivemultifactorial intervention with that ofscreening and routine care (19). Generalpractice patients between the ages of40–69 years were screened for diabetesand randomized by practice to intensivetreatment of multiple risk factors or rou-tine diabetes care. After 5.3 years offollow-up, CVD risk factorsweremodestlybut significantly improved with intensivetreatment compared with routine care,but the incidence of first CVD events ormortality was not significantly differentbetween the groups (19). The excellentcare provided to patients in the routinecare group and the lack of an unscreenedcontrol arm limit our ability to provethat screening and early intensive treat-ment impact outcomes. Mathematicalmodeling studies suggest that screening,

beginning at age 30 or 45 years andindependent of risk factors, may becost-effective (,$11,000 per quality-adjusted life-year gained) (20).

Additional considerations regardingtesting for type 2 diabetes and predia-betes in asymptomatic patients includethe following:

Age

Testing recommendations for diabetes inasymptomatic adults are listed in Table2.2. Age is amajor risk factor for diabetes.Testing should begin at age 45 years for allpatients, particularly those who are over-weight or obese.

BMI and Ethnicity

Testing should be considered in adultsof any age with BMI$25 kg/m2 and oneor more additional risk factors for dia-betes. However, recent data (21) andevidence from the ADA position state-ment “BMI Cut Points to Identify At-RiskAsian Americans for Type 2 DiabetesScreening” (22) suggest that the BMIcut point should be lower for the AsianAmerican population. For diabetesscreening purposes, the BMI cut pointsfall consistently between 23–24 kg/m2

(sensitivity of 80%) for nearly all AsianAmerican subgroups (with levels slightlylower for Japanese Americans). Thismakes a rounded cut point of 23 kg/m2

practical. In determining a single BMIcut point, it is important to balance sen-sitivity and specificity so as to provide avaluable screening tool without numer-ous false positives. An argument can bemade to push the BMI cut point to lowerthan 23 kg/m2 in favor of increasedsensitivity; however, this would leadto an unacceptably low specificity(13.1%). Data from the WHO also sug-gest that a BMI $23 kg/m2 should beused to define increased risk in AsianAmericans (23).

Evidence also suggests that otherpopulations may benefit from lowerBMI cut points. For example, in a largemultiethnic cohort study, for an equiv-alent incidence rate of diabetes, a BMIof 30 kg/m2 in non-Hispanic whites wasequivalent to a BMI of 26 kg/m2 in Afri-can Americans (24).

Medications

Certain medications, such as glucocorti-coids, thiazide diuretics, and atypical anti-psychotics (25), are known to increase therisk of diabetes and should be consideredwhen ascertaining a diagnosis.

Diagnostic Tests

The A1C, FPG, and 2-h PG after 75-gOGTTare appropriate for testing. It should benoted that the tests do not necessarilydetect diabetes in the same individuals.The efficacy of interventions for primaryprevention of type 2 diabetes (26–32) hasprimarily been demonstrated among in-dividualswith IGT, not for individualswithisolated IFG or for those with prediabetesdefined by A1C criteria.

Testing Interval

The appropriate interval between tests isnot known (33). The rationale for the3-year interval is that with this interval,the number of false-positive tests that re-quire confirmatory testing will be reducedand individuals with false-negative testswill be retested before substantial timeelapses and complications develop (33).

Community Screening

Ideally, testing should be carried outwithin a health care setting because ofthe need for follow-up and treatment.Community testing outside a health caresetting is not recommended because peo-ple with positive tests may not seek, orhave access to, appropriate follow-up test-ing and care. Community testing may alsobe poorly targeted; i.e., it may fail to reachthe groups most at risk and inappropri-ately test those at very low risk or eventhose who have already been diagnosed.

Testing for Type 2 Diabetes andPrediabetes in Children andAdolescentsIn the last decade, the incidence and prev-alence of type2diabetes in adolescents hasincreased dramatically, especially in ethnicpopulations (15). Recent studies questionthe validity of A1C in the pediatric popula-tion, especially among certain ethnicities,and suggest OGTT or FPG as more suitablediagnostic tests (34). However, many ofthese studies do not recognize that diabe-tes diagnostic criteria are based on long-term health outcomes, and validations arenot currently available in the pediatric pop-ulation (35). The ADA acknowledges thelimited data supporting A1C for diagnosingdiabetes in children and adolescents. How-ever, aside from rare instances, such as cys-tic fibrosis and hemoglobinopathies, theADA continues to recommend A1C in thiscohort (36,37). Themodified recommenda-tions of the ADA consensus report “Type 2Diabetes in Children and Adolescents” aresummarized in Table 2.4.


GESTATIONAL DIABETES MELLITUS

Recommendations

c Test for undiagnosed type 2 diabe-tes at the first prenatal visit inthose with risk factors, using stan-dard diagnostic criteria. B

c Test for GDMat 24–28weeks of ges-tation in pregnant women not pre-viously known to have diabetes. A

c Screen women with GDM for per-sistent diabetes at 6–12 weekspostpartum, using the OGTT andclinically appropriate nonpreg-nancy diagnostic criteria. E

c Women with a history of GDMshould have lifelong screening forthe development of diabetes orprediabetes at least every 3 years. B

c Women with a history of GDMfound to have prediabetes shouldreceive lifestyle interventions ormetformin to prevent diabetes. A

DefinitionFor many years, GDM was defined asany degree of glucose intolerance thatwas first recognized during pregnancy(10), regardless of whether the condi-tion may have predated the pregnancyor persisted after the pregnancy. Thisdefinition facilitated a uniform strategyfor detection and classification of GDM,but it was limited by imprecision.

The ongoing epidemic of obesity anddiabetes has led to more type 2 diabetesinwomenof childbearing age, resulting inan increase in the number of pregnantwomenwith undiagnosed type2 diabetes(38). Because of the number of pregnantwomen with undiagnosed type 2 diabe-tes, it is reasonable to test women withrisk factors for type 2 diabetes (Table 2.2)at their initial prenatal visit, using stan-dard diagnostic criteria (Table 2.1).Women with diabetes in the first trimes-ter would be classified as having type 2diabetes. GDM is diabetes diagnosed inthe second or third trimester of preg-nancy that is not clearly overt diabetes.

DiagnosisGDM carries risks for the mother andneonate. Not all adverse outcomes areof equal clinical importance. The Hyper-glycemia and Adverse Pregnancy Out-come (HAPO) study (39), a large-scale(;25,000 pregnant women) multina-tional cohort study, demonstrated thatrisk of adverse maternal, fetal, and neo-natal outcomes continuously increasedas a function of maternal glycemia at24–28 weeks, even within ranges previ-ously considered normal for pregnancy.For most complications, there was nothreshold for risk. These results haveled to careful reconsideration of the di-agnostic criteria for GDM. GDM diagno-sis (Table 2.5) can be accomplished witheither of two strategies:

1. “One-step” 75-g OGTT or2. “Two-step” approach with a 50-g

(nonfasting) screen followed by a100-g OGTT for those who screenpositive

Different diagnostic criteria will identifydifferent degrees of maternal hypergly-cemia and maternal/fetal risk, leadingsome experts to debate, and disagreeon, optimal strategies for the diagnosisof GDM.

One-Step Strategy

In the 2011 Standards of Care (40), theADA for the first time recommendedthat all pregnant women not known tohave prior diabetes undergo a 75-gOGTT at 24–28 weeks of gestation,based on a recommendation of the In-ternational Association of the Diabetesand Pregnancy Study Groups (IADPSG)(41). The IADPSG defined diagnostic cut

points for GDM as the average glucosevalues (fasting, 1-h, and 2-h PG) in theHAPO study at which odds for adverseoutcomes reached 1.75 times the esti-mated odds of these outcomes at themean glucose levels of the study popu-lation. This one-step strategy was an-ticipated to significantly increase theincidence of GDM (from 5–6% to ;15–20%), primarily becauseonly oneabnormalvalue, not two, became sufficient to makethe diagnosis. The ADA recognized that theanticipated increase in the incidence ofGDM would have significant impact onthe costs, medical infrastructure capacity,and potential for increased “medicaliza-tion” of pregnancies previously catego-rized as normal, but recommended thesediagnostic criteria changes in the contextof worrisomeworldwide increases in obe-sity and diabetes rates with the intent ofoptimizing gestational outcomes forwomen and their offspring.

The expected benefits to these preg-nancies and offspring are inferred fromintervention trials that focused onwomen with lower levels of hyperglyce-mia than identified using older GDM di-agnostic criteria and that found modestbenefits including reduced rates of large-for-gestational-age births and preeclamp-sia (42,43). It is important to note that80–90% of women being treated formild GDM in two randomized controlledtrials (whose glucose values overlappedwith the thresholds recommended bythe IADPSG) could be managed with life-style therapy alone. Data are lacking onhow the treatment of lower levels of hy-perglycemia affects a mother’s risk forthe development of type 2 diabetes inthe future and her offspring’s risk forobesity, diabetes, and other metabolicdysfunction. Additional well-designedclinical studies are needed to determinethe optimal intensity of monitoring andtreatment of women with GDM diag-nosed by the one-step strategy.

Two-Step Strategy

In 2013, the National Institutes of Health(NIH) convened a consensus develop-ment conference on diagnosing GDM.The15-memberpanel had representativesfrom obstetrics/gynecology, maternal-fetal medicine, pediatrics, diabetes re-search, biostatistics, and other relatedfields to consider diagnostic criteria (44).The panel recommended the two-stepapproach of screening with a 1-h 50-g

Table 2.4—Testing for type 2 diabetes orprediabetes in asymptomatic children*Criteria

c Overweight (BMI .85th percentilefor age and sex, weight for height.85th percentile, or weight .120%of ideal for height)

Plus any two of the following risk factors:c Family history of type 2 diabetes in

first- or second-degree relativec Race/ethnicity (Native American,

African American, Latino, AsianAmerican, Pacific Islander)

c Signs of insulin resistance orconditions associated with insulinresistance (acanthosis nigricans,hypertension, dyslipidemia,polycystic ovary syndrome, or small-for-gestational-age birth weight)

c Maternal history of diabetes or GDMduring the child’s gestation

Age of initiation: age 10 years or at onsetof puberty, if puberty occurs at ayounger age

Frequency: every 3 years

*Persons aged #18 years.


glucose load test (GLT) followed by a 3-h100-g OGTT for those who screenpositive, a strategy commonly used inthe U.S.Key factors reported in the NIH panel’s

decision-making process were the lack ofclinical trial interventions demonstratingthe benefits of the one-step strategyand the potential negative consequencesof identifying a large new group ofwomen with GDM, including medicaliza-tion of pregnancy with increased inter-ventions and costs. Moreover, screeningwith a 50-g GLT does not require fast-ing and is therefore easier to accomplishfor many women. Treatment of higherthreshold maternal hyperglycemia, asidentified by the two-step approach, re-duces rates of neonatal macrosomia,large-for-gestational-age births, andshoulder dystocia, without increasingsmall-for-gestational-age births (45).The American College of Obstetriciansand Gynecologists (ACOG) updated itsguidelines in 2013 and supported thetwo-step approach (46).

Future Considerations

The conflicting recommendations fromexpert groups underscore the fact thatthere are data to support each strategy.The decision of which strategy to

implementmust therefore bemade basedon the relative values placed on factorsthat have yet to be measured (e.g., cost-benefit estimation, willingness to changepractice based on correlation studiesrather than clinical intervention trialresults, relative role of cost consid-erations, and available infrastructure lo-cally, nationally, and internationally).

As the IADPSG criteria have beenadopted internationally, further evi-dence has emerged to support im-proved pregnancy outcomes with costsavings (47) and may be the preferredapproach. In addition, pregnanciescomplicated by GDM per IADPSG crite-ria, but not recognized as such, havecomparable outcomes to pregnancies di-agnosed as GDM by the more stringenttwo-step criteria (48). There remainsstrong consensus that establishing a uni-form approach to diagnosing GDM willbenefit patients, caregivers, and policy-makers. Longer-term outcome studies arecurrently underway.

MONOGENIC DIABETESSYNDROMES

Monogenic defects that cause b-cell dys-function, such as neonatal diabetes andMODY, represent a small fraction of pa-tients with diabetes (,5%). These forms

of diabetes are frequently characterizedby onset of hyperglycemia at an early age(generally before age 25 years).

Neonatal DiabetesDiabetes diagnosed in thefirst 6months oflife has been shown not to be typical au-toimmune type 1 diabetes. This so-calledneonatal diabetes can either be transientor permanent. The most common geneticdefect causing transient disease is a defecton ZAC/HYAMI imprinting, whereaspermanent neonatal diabetes is mostcommonly a defect in the gene encodingthe Kir6.2 subunit of the b-cell KATP chan-nel. Diagnosing the latter has implications,since such children can be well managedwith sulfonylureas.

Maturity-Onset Diabetes of the YoungMODY is characterized by impaired insulinsecretion with minimal or no defects in in-sulin action. It is inherited in an autosomaldominant pattern. Abnormalities at six ge-netic loci on different chromosomes havebeen identified to date. Themost commonform is associated with mutations on chro-mosome12 in ahepatic transcription factorreferred to as hepatocyte nuclear factor(HNF)-1a. A second form is associatedwith mutations in the glucokinase geneon chromosome 7p and results in a defec-tive glucokinase molecule. Glucokinaseconverts glucose to glucose-6-phosphate,the metabolism of which, in turn, stimu-lates insulin secretion by the b-cell. Theless common forms of MODY result frommutations in other transcription factors, in-cluding HNF-4a, HNF-1b, insulin promoterfactor (IPF)-1, and NeuroD1.

DiagnosisReadily available commercial genetictesting now enables a true genetic diag-nosis. It is important to correctly diag-nose one of the monogenic forms ofdiabetes because these children maybe incorrectly diagnosed with type 1 ortype 2 diabetes, leading to suboptimaltreatment regimens and delays in diag-nosing other family members (49).

The diagnosis of monogenic diabetesshould be considered in children withthe following findings:

○ Diabetes diagnosed within the first 6months of life

○ Strong family history of diabetes butwithout typical features of type 2 di-abetes (nonobese, low-risk ethnicgroup)

Table 2.5—Screening for and diagnosis of GDMOne-step strategy

Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and2 h, at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes.

The OGTT should be performed in the morning after an overnight fast of at least 8 h.

The diagnosis of GDM is made when any of the following plasma glucose values are met orexceeded:

c Fasting: 92 mg/dL (5.1 mmol/L)

c 1 h: 180 mg/dL (10.0 mmol/L)

c 2 h: 153 mg/dL (8.5 mmol/L)

Two-step strategy

Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24–28weeks of gestation in women not previously diagnosed with overt diabetes.

If the plasma glucose level measured 1 h after the load is$140 mg/dL* (7.8 mmol/L), proceedto a 100-g OGTT.

Step 2: The 100-g OGTT should be performed when the patient is fasting.

The diagnosis of GDM is made if at least two of the following four plasma glucose levels(measured fasting and 1 h, 2 h, 3 h after the OGTT) are met or exceeded:

Carpenter/Coustan (56) or NDDG (57)

c Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L)

c 1 h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L)



NDDG, National Diabetes Data Group.*The ACOG recommends a lower threshold of 135 mg/dL (7.5 mmol/L) in high-risk ethnicpopulations with higher prevalence of GDM; some experts also recommend 130 mg/dL(7.2 mmol/L).


○ Mild fasting hyperglycemia (100–150mg/dL [5.5–8.5mmol/L]), especially ifyoung and nonobese

○ Diabetes with negative autoantibod-ies and without signs of obesity or in-sulin resistance

CYSTIC FIBROSIS–RELATEDDIABETES

Recommendations

c Annual screening for cystic fibrosis–related diabetes (CFRD) with OGTTshould begin by age 10 years in allpatients with cystic fibrosis whodo not have CFRD. B A1C as ascreening test for CFRD is not rec-ommended. B

c Patients with CFRD should betreated with insulin to attain in-dividualized glycemic goals. A

c In patients with cystic fibrosis andIGT without confirmed diabetes,prandial insulin therapy should beconsidered to maintain weight. B

c Annual monitoring for complica-tions of diabetes is recommended,beginning 5 years after the diagno-sis of CFRD. E

CFRD is themost common comorbidityin people with cystic fibrosis, occurring inabout 20% of adolescents and 40–50% ofadults. Diabetes in this population is as-sociated with worse nutritional status,more severe inflammatory lung disease,and greater mortality from respiratoryfailure. Insulin insufficiency related topartial fibrotic destruction of the isletmass is the primary defect in CFRD. Ge-netically determined function of the re-maining b-cells and insulin resistanceassociated with infection and inflamma-tion may also play a role. While screeningfor diabetes before the age of 10 yearscan identify risk for progression to CFRDin thosewith abnormal glucose tolerance,there appears to be no benefit with re-spect toweight, height, BMI, or lung func-tion compared with those with normalglucose tolerance ,10 years of age. Theuse of continuous glucose monitoringmay be more sensitive than OGTT to de-tect risk for progression to CFRD, but thislikely needs more evidence.Encouraging data suggest that im-

proved screening (50,51) and aggressiveinsulin therapy have narrowed the gap inmortality between cystic fibrosis patients

with and without diabetes and have elim-inated the sex difference in mortality (52).Recent trials comparing insulin with oralrepaglinide showed no significant differ-ence between the groups. However, an-other study compared three differentgroups: premeal insulin aspart, repagli-nide, or oral placebo in cystic fibrosis pa-tients with abnormal glucose tolerance.Patients all had weight loss; however, inthe insulin-treated group, this pattern wasreversed, and they gained 0.39 (6 0.21)BMI units (P 5 0.02). Patients in therepaglinide-treated group had initial weightgain, but this was not sustained by 6months. The placebo group continued tolose weight (53). Insulin remains the mostwidely used therapy for CFRD (54).

Recommendations for the clinicalman-agement of CFRD can be found in theADAposition statement “Clinical Care Guide-lines for Cystic Fibrosis–Related Diabetes:A Position Statement of the AmericanDiabetes Association and a Clinical Prac-tice Guideline of the Cystic FibrosisFoundation, Endorsed by the PediatricEndocrine Society” (55).

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3. Initial Evaluation and DiabetesManagement PlanningDiabetes Care 2015;38(Suppl. 1):S17–S19 | DOI: 10.2337/dc15-S006

MEDICAL EVALUATION

Recommendation

c Consider screening those with type 1 diabetes for autoimmune diseases (e.g.,thyroid dysfunction, celiac disease) as appropriate. E

A complete medical evaluation should be performed at the initial visit to

1. Classify diabetes2. Detect diabetes complications3. Review previous treatment and risk factor control in patients with established

diabetes4. Assist in formulating a management plan5. Provide a basis for continuing care

Laboratory tests appropriate to the evaluation of each patient’s medical conditionshould be completed. A focus on the components of comprehensive care (Table 3.1)will enable the health care team to optimallymanage the patient with diabetes. Adultswho develop type 1 diabetes can develop additional autoimmune disorders, althoughtheir risk is lower than that in children and adolescents with type 1 diabetes. For ad-ditional details on autoimmune conditions, see Section 11. Children and Adolescents.

MANAGEMENT PLAN

Peoplewith diabetes should receivemedical care froma collaborative, integrated teamwith expertise in diabetes. This team may include physicians, nurse practitioners,physician’s assistants, nurses, dietitians, pharmacists, andmental health professionals.Individuals with diabetes must also assume an active role in their care.Themanagement plan should bewrittenwith input from the patient and family, the

physician, and other members of the health care team. Diabetes self-managementeducation (DSME) and ongoing diabetes support should be integral components ofthe management plan. Various strategies and techniques should be used to enablepatients to self-manage diabetes, including providing education on problem-solvingskills for all aspects of diabetes management. Treatment goals and plans should beindividualized and take patient preferences into account. In developing the plan,consideration should be given to the patient’s age, school/work schedule and con-ditions, physical activity, eating patterns, social situation, cultural factors, presenceof diabetes complications, health priorities, and other medical conditions.

COMMON COMORBID CONDITIONS

Recommendation

c Consider assessing for and addressing common comorbid conditions(e.g., depression, obstructive sleep apnea) that may complicate diabetesmanagement. B

Improved disease prevention and treatment efficacy means that patients withdiabetes are living longer, often with multiple comorbidities requiring complicatedmedical regimens (1). Obesity, hypertension, and dyslipidemia are the most com-monly appreciated comorbidities. However, concurrent conditions, such as heart

Suggested citation: American Diabetes Associa-tion. Initial evaluation and diabetes manage-ment planning. Sec. 3. In Standards of MedicalCare in Diabetesd2015. Diabetes Care 2015;38(Suppl. 1):S17–S19




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failure, depression, anxiety, and arthri-tis, are found at higher rates in peoplewith diabetes than in age-matchedpeoplewithout diabetes and often complicatediabetes management. These concurrentconditions present clinical challengesrelated to polypharmacy, prevalentsymptoms, and complexity of care (2–5).

DepressionAs discussed in Section 4. Foundationsof Care, depression, anxiety, and othermental health symptoms are highlyprevalent in people with diabetes andare associated with worse outcomes.

Obstructive Sleep ApneaAge-adjusted rates of obstructive sleepapnea, a risk factor for cardiovasculardisease, are significantly higher (4- to10-fold) with obesity, especially with cen-tral obesity, in men and women (6). Theprevalence in general populations withtype 2 diabetes may be up to 23% (7)and in obese participants enrolled inthe Look AHEAD trial exceeded 80%(8). Treatment of sleep apnea signif-icantly improves quality of life andblood pressure control. The evidencefor a treatment effect on glycemic controlis mixed (9).

Fatty Liver DiseaseUnexplained elevations of hepatic trans-aminase concentrations are signifi-cantly associated with higher BMI,waist circumference, triglycerides, andfasting insulin and with lower HDL cho-lesterol. In a prospective analysis, diabe-tes was significantly associated withincident nonalcoholic chronic liver dis-ease and with hepatocellular carcinoma(10). Interventions that improve meta-bolic abnormalities in patients with di-abetes (weight loss, glycemic control,and treatment with specific drugs for hy-perglycemia or dyslipidemia) are alsobeneficial for fatty liver disease (11).

CancerDiabetes (possibly only type 2 diabetes)is associated with increased risk ofcancers of the liver, pancreas, endome-trium, colon/rectum, breast, and blad-der (12). The association may resultfrom shared risk factors between type2 diabetes and cancer (obesity, olderage, and physical inactivity), but mayalso be due to hyperinsulinemia orhyperglycemia (13). Patients with diabe-tes should be encouraged to undergorecommended age- and sex-appropriatecancer screenings and to reduce theirmodifiable cancer risk factors (obesity,smoking, and physical inactivity).

FracturesAge-matched hip fracture risk is signifi-cantly increased in both type 1 (sum-mary relative risk [RR] 6.3) and type 2diabetes (summary RR 1.7) in both sexes(14). Type 1 diabetes is associated withosteoporosis, but in type 2 diabetes anincreased risk of hip fracture is seen de-spite higher bonemineral density (BMD)(15). In three large observational studiesof older adults, femoral neck BMD Tscore and the WHO Fracture Risk Algo-rithm (FRAX) score were associated withhip and nonspine fracture, althoughfracture risk was higher in participantswith diabetes compared with thosewithout diabetes for a given T score andage or for a given FRAX score (16). It isappropriate to assess fracture historyand risk factors in older patients withdiabetes and recommend BMD testingif appropriate for the patient’s age and sex.Prevention strategies are the same as forthe general population. For type2diabeticpatients with fracture risk factors, avoid-ing thiazolidinediones is warranted.

Table 3.1—Components of the comprehensive diabetes evaluationMedical history

c Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding)c Eating patterns, physical activity habits, nutritional status, and weight history; growth anddevelopment in children and adolescents

c Presence of common comorbidities, psychosocial problems, and dental diseasec Diabetes education historyc Review of previous treatment regimens and response to therapy (A1C records)c Current treatment of diabetes, including medications, medication adherence and barriersthereto, meal plan, physical activity patterns, and readiness for behavior change

c Results of glucose monitoring and patient’s use of datac DKA frequency, severity, and causec Hypoglycemic episodesc Hypoglycemia awarenessc Any severe hypoglycemia: frequency and cause

c History of diabetes-related complicationscMicrovascular: retinopathy, nephropathy, neuropathy (sensory, including history of footlesions; autonomic, including sexual dysfunction and gastroparesis)

cMacrovascular: coronary heart disease, cerebrovascular disease, and peripheral arterialdisease

Physical examinationc Height, weight, BMIc Blood pressure determination, including orthostatic measurements when indicatedc Fundoscopic examinationc Thyroid palpationc Skin examination (for acanthosis nigricans and insulin injection sites)c Comprehensive foot examinationc Inspectionc Palpation of dorsalis pedis and posterior tibial pulsesc Presence/absence of patellar and Achilles reflexesc Determination of proprioception, vibration, and monofilament sensation

Laboratory evaluationc A1C, if results not available within past 3 monthsc If not performed/available within past yearc Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides, as neededc Liver function testsc Test for urine albumin excretion with spot urine albumin-to-creatinine ratioc Serum creatinine and calculated glomerular filtration ratec TSH in type 1 diabetes, dyslipidemia, or women over age 50 years

Referralsc Eye care professional for annual dilated eye examc Family planning for women of reproductive agec Registered dietitian for medical nutrition therapyc DSME/DSMSc Dentist for comprehensive periodontal examinationc Mental health professional, if needed

DKA, diabetic ketoacidosis; DSMS, diabetes self-management support; TSH, thyroid-stimulatinghormone.


Cognitive ImpairmentDiabetes is associated with a signifi-cantly increased risk, and rate, of cogni-tive decline and with increased risk ofdementia (17,18). In a 15-year prospec-tive study of community-dwelling peo-ple over the age of 60 years, thepresence of diabetes at baseline sig-nificantly increased the age- and sex-adjusted incidence of all-cause dementia,Alzheimer disease, and vascular demen-tia compared with rates in those withnormal glucose tolerance (19). In a sub-study of the Action to Control Cardiovas-cular Risk in Diabetes (ACCORD) clinicaltrial, there were no differences in cogni-tive outcomes between intensive andstandard glycemic control, althoughthere was significantly less of a decre-ment in total brain volume, as measuredby MRI, in participants in the intensivearm (20). The effects of hyperglycemiaand insulin on the brain are areas of in-tense research interest.

Low Testosterone in MenMean levels of testosterone are lower inmen with diabetes compared with age-matched men without diabetes, butobesity is a major confounder (21).Treatment in asymptomatic men is con-troversial. The evidence that testoster-one replacement affects outcomes ismixed, and recent guidelines suggestthat testing and treating men withoutsymptoms are not recommended (22).

Periodontal DiseasePeriodontal disease is more severe, butnot necessarilymore prevalent, in patientswith diabetes than in those without (23).Current evidence suggests that periodon-tal disease adversely affects diabetes out-comes, although evidence for treatmentbenefits remains controversial (5).

Hearing ImpairmentHearing impairment, both in high fre-quency and low/mid frequency ranges,is more common in people with dia-betes than in those without, perhapsdue to neuropathy and/or vascular

disease. In a National Health and Nutri-tion Examination Survey (NHANES) anal-ysis, hearing impairment was abouttwice as prevalent in people with diabe-tes compared with those without, afteradjusting for age and other risk factorsfor hearing impairment (24).

References1. Selvin E, Coresh J, Brancati FL. The burdenand treatment of diabetes in elderly individualsin the U.S. Diabetes Care 2006;29:2415–24192. Grant RW, Ashburner JM, Hong CS, ChangY, Barry MJ, Atlas SJ. Defining patient complex-ity from the primary care physician’s perspec-tive: a cohort study. Ann Intern Med 2011;155:797–8043. Tinetti ME, Fried TR, Boyd CM. Designinghealth care for the most common chronicconditiondmultimorbidity. JAMA 2012;307:2493–24944. Sudore RL, Karter AJ, Huang ES, et al.Symptom burden of adults with type 2 diabetesacross the disease course: Diabetes & AgingStudy. J Gen Intern Med 2012;27:1674–16815. Borgnakke WS, Ylostalo PV, Taylor GW,Genco RJ. Effect of periodontal disease on di-abetes: systematic review of epidemiologicobservational evidence. J Periodontol 2013;84(Suppl.):S135–S1526. Li C, Ford ES, Zhao G, Croft JB, Balluz LS,Mokdad AH. Prevalence of self-reported clini-cally diagnosed sleep apnea according to obe-sity status in men and women: National Healthand Nutrition Examination Survey, 2005-2006.Prev Med 2010;51:18–237. West SD, Nicoll DJ, Stradling JR. Prevalenceof obstructive sleep apnoea in men with type 2diabetes. Thorax 2006;61:945–9508. Foster GD, Sanders MH, Millman R, et al.;Sleep AHEAD Research Group. Obstructivesleep apnea among obese patients with type 2diabetes. Diabetes Care 2009;32:1017–10199. Shaw JE, Punjabi NM, Wilding JP, AlbertiKGMM, Zimmet PZ; International Diabetes Fed-eration Taskforce on Epidemiology and Preven-tion. Sleep-disordered breathing and type 2diabetes: a report from the International DiabetesFederation Taskforce on Epidemiology and Pre-vention. Diabetes Res Clin Pract 2008;81:2–1210. El-Serag HB, Tran T, Everhart JE. Diabetesincreases the risk of chronic liver disease andhepatocellular carcinoma. Gastroenterology2004;126:460–46811. American Gastroenterological Association.American Gastroenterological Association med-ical position statement: nonalcoholic fatty liverdisease. Gastroenterology 2002;123:1702–1704

12. Suh S, Kim KW. Diabetes and cancer: isdiabetes causally related to cancer? DiabetesMetab J 2011;35:193–19813. Giovannucci E, Harlan DM, Archer MC,et al. Diabetes and cancer: a consensus report.Diabetes Care 2010;33:1674–168514. Janghorbani M, Van Dam RM, Willett WC,Hu FB. Systematic review of type 1 and type 2diabetes mellitus and risk of fracture. Am J Epi-demiol 2007;166:495–50515. Vestergaard P. Discrepancies in bone min-eral density and fracture risk in patients withtype 1 and type 2 diabetesda meta-analysis.Osteoporos Int 2007;18:427–44416. Schwartz AV, Vittinghoff E, Bauer DC,et al.; Study of Osteoporotic Fractures (SOF) Re-search Group; Osteoporotic Fractures in Men(MrOS) Research Group; Health, Aging, andBody Composition (Health ABC) ResearchGroup. Association of BMD and FRAX scorewith risk of fracture in older adults with type 2diabetes. JAMA 2011;305:2184–219217. Cukierman T, Gerstein HC, Williamson JD.Cognitive decline and dementia in diabetesdsystematic overview of prospective observationalstudies. Diabetologia 2005;48:2460–246918. Biessels GJ, Staekenborg S, Brunner E,Brayne C, Scheltens P. Risk of dementia in di-abetes mellitus: a systematic review. LancetNeurol 2006;5:64–7419. Ohara T, Doi Y, Ninomiya T, et al. Glucosetolerance status and risk of dementia in thecommunity: the Hisayama study. Neurology2011;77:1126–113420. Launer LJ, Miller ME, Williamson JD, et al.;ACCORD MIND investigators. Effects of inten-sive glucose lowering on brain structureand function in people with type 2 diabetes(ACCORD MIND): a randomised open-label sub-study. Lancet Neurol 2011;10:969–97721. Dhindsa S, Miller MG,McWhirter CL, et al.Testosterone concentrations in diabetic andnondiabetic obese men. Diabetes Care 2010;33:1186–119222. Bhasin S, Cunningham GR, Hayes FJ, et al.Testosterone therapy in men with androgen de-ficiency syndromes: an Endocrine Society clini-cal practice guideline. J Clin Endocrinol Metab2010;95:2536–255923. Khader YS, Dauod AS, El-Qaderi SS,Alkafajei A, Batayha WQ. Periodontal statusof diabetics comparedwith nondiabetics: a meta-analysis. J Diabetes Complications 2006;20:59–6824. Bainbridge KE, Hoffman HJ, Cowie CC.Diabetes and hearing impairment in the UnitedStates: audiometric evidence from the NationalHealth and Nutrition Examination Survey, 1999to 2004. Ann Intern Med 2008;149:1–10


4. Foundations of Care: Education,Nutrition, Physical Activity,Smoking Cessation, PsychosocialCare, and ImmunizationDiabetes Care 2015;38(Suppl. 1):S20–S30 | DOI: 10.2337/dc15-S007

DIABETES SELF-MANAGEMENT EDUCATION AND SUPPORT

Recommendations

c People with diabetes should receive diabetes self-management education(DSME) and diabetes self-management support (DSMS) according to the na-tional standards for DSME and DSMS when their diabetes is diagnosed and asneeded thereafter. B

c Effective self-management and quality of life are the key outcomes of DSMEand DSMS and should be measured and monitored as part of care. C

c DSME and DSMS should address psychosocial issues, as emotional well-beingis associated with positive diabetes outcomes. C

c DSME and DSMS programs are appropriate venues for people with prediabe-tes to receive education and support to develop and maintain behaviors thatcan prevent or delay the onset of diabetes. C

c Because DSME and DSMS can result in cost-savings and improved outcomes B,DSME and DSMS should be adequately reimbursed by third-party payers. E

DSME and DSMS are the ongoing processes of facilitating the knowledge, skill, andability necessary for diabetes self-care. This process incorporates the needs, goals,and life experiences of the person with diabetes. The overall objectives of DSME andDSMS are to support informed decision making, self-care behaviors, problem solv-ing, and active collaborationwith the health care team to improve clinical outcomes,health status, and quality of life in a cost-effective manner (1).DSME and DSMS are essential elements of diabetes care (2,3), and the current

national standards for DSME and DSMS (1) are based on evidence of their benefits.Education helps people with diabetes initiate effective self-management and copewith diabetes when they are first diagnosed. Ongoing DSME and DSMS also helppeople with diabetes maintain effective self-management throughout a lifetimeof diabetes as they face new challenges and as treatment advances become avail-able. DSME enables patients (including youth) to optimize metabolic control, pre-vent and manage complications, and maximize quality of life in a cost-effectivemanner (2,4).Current best practice of DSME is a skill-based approach that focuses on helping

those with diabetes make informed self-management choices (1,2). DSME haschanged from a didactic approach focusing on providing information to empow-erment models that focus on helping those with diabetes make informed self-management decisions (2). Diabetes care has shifted to an approach that is morepatient centered and places the person with diabetes and his or her family at thecenter of the care model, working in collaboration with health care professionals.Patient-centered care is respectful of and responsive to individual patient pref-erences, needs, and values and ensures that patient values guide all decisionmaking (5).

Evidence for the BenefitsMultiple studies have found that DSME is associated with improved diabetes knowl-edge, improved self-care behavior (1), improved clinical outcomes, such as lower

Suggested citation: American Diabetes Associa-tion. Foundations of care: education, nutrition,physical activity, smoking cessation, psychoso-cial care, and immunization. Sec. 4. In Standardsof Medical Care in Diabetesd2015. DiabetesCare 2015;38(Suppl. 1):S20–S30




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A1C (3,6–8), lower self-reported weight(9,10), improved quality of life (8,11),healthy coping (12,13), and lower costs(14,15). Better outcomes were reportedfor DSME interventions that were longerand included follow-up support (DSMS)(16–18), that were culturally (19,20) andage appropriate (21,22), that were tai-lored to individual needs and prefer-ences, and that addressed psychosocialissues and incorporated behavioralstrategies (2,12,23,24). Both individualand group approaches have been foundeffective (10,25). There is growing evi-dence for the role of community healthworkers (26), as well as peer (27–30) andlay leaders (31), in delivering DSME andDSMS (32).Diabetes education is associated with

increased use of primary and preventiveservices (14,33,34) and lower use ofacute, inpatient hospital services (14).Patients who participate in diabetes ed-ucation are more likely to follow bestpractice treatment recommendations,particularly among the Medicare popu-lation, and have lower Medicare and in-surance claim costs (15,33).

National StandardsThe national standards for DSME andDSMS are designed to define qualityand to assist diabetes educators in a va-riety of settings to provide evidence-based education and self-managementsupport (1). The standards are reviewedand updated every 5 years by a taskforce representing key organizations in-volved in diabetes education and care.

ReimbursementDSME, when provided by a program thatmeets national standards for DSME andis recognized by the American DiabetesAssociation (ADA) or other approvalbodies, is reimbursed as part of theMedicare program as overseen by theCenters for Medicare & Medicaid Ser-vices. DSME is also covered by mosthealth insurance plans. Although DSMShas been shown to be instrumentalfor improving outcomes and can be pro-vided via phone calls and telehealth, itcurrently has limited reimbursement asin-person follow-up to DSME.

MEDICAL NUTRITION THERAPY

For many individuals with diabetes, themost challenging part of the treatment

plan is determining what to eat. It is theposition of the ADA that there is not aone-size-fits-all eating pattern for indi-viduals with diabetes. The ADA also rec-ognizes the integral role of nutritiontherapy in overall diabetes manage-ment and recommends that each per-son with diabetes be actively engagedin self-management, education, andtreatment planning with his or herhealth care provider, which includesthe collaborative development of anindividualized eating plan (35,36).Therefore, it is important that all mem-bers of the health care team be knowl-edgeable about diabetes nutritiontherapy and support its implementa-tion. See Table 4.1 for specific nutritionrecommendations.

Goals of Nutrition Therapy for AdultsWith Diabetes1. To promote and support healthful

eating patterns, emphasizing a varietyof nutrient-dense foods in appropriateportion sizes, in order to improveoverall health and specifically to○ Attain individualized glycemic,

blood pressure, and lipid goals○ Achieve andmaintain bodyweight

goals○ Delay or prevent complications of

diabetes2. To address individual nutrition needs

based on personal and cultural pref-erences, health literacy and numer-acy, access to healthful food choices,willingness and ability to make be-havioral changes, and barriers tochange.

3. Tomaintain the pleasure of eating byproviding positive messages aboutfood choices while limiting foodchoices only when indicated by sci-entific evidence.

4. To provide the individual with diabe-teswith practical tools for day-to-daymeal planning rather than focusingon individual macronutrients, micro-nutrients, or single foods.

Nutrition therapy is an integral compo-nent of diabetes prevention, manage-ment, and self-management education.All individuals with diabetes should re-ceive individualized medical nutritiontherapy (MNT), preferably provided by aregistered dietitian who is knowledgeableand skilled in providing diabetes MNT.Comprehensive group diabetes education

programs including nutrition therapy orindividualized education sessions have re-ported A1C decreases of 0.3–1% for type1 diabetes (37–41) and 0.5–2% for type 2diabetes (42–49).

Carbohydrate ManagementIndividuals with type 1 diabetes shouldbe offered intensive insulin therapyeducation using the carbohydrate-counting meal planning approach(37,39,40,43,50), which has been shownto improve glycemic control (50,51).Consistent carbohydrate intake with re-spect to time and amount can result inimproved glycemic control for individu-als using fixed daily insulin doses (36). Asimple diabetesmeal planning approach,such as portion control or healthful foodchoices, may be better suited for individ-uals with health literacy and numeracyconcerns (36–40,42).

Weight LossIntensive lifestyle programs with fre-quent follow-up are required to achievesignificant reductions in excess bodyweight and improve clinical indicators(52,53). Weight loss of 2–8 kg may pro-vide clinical benefits in those with type 2diabetes, especially early in the diseaseprocess (52,53). Although several studiesresulted in improvements in A1C at 1 year(52,54–56), not all weight-loss interven-tions led to 1-year A1C improvements(45,57–60). The most consistently identi-fied changes in cardiovascular risk factorswere an increase in HDL cholesterol(52,54,56,59,61), decrease in triglycerides(52,61–63), and decrease in blood pres-sure (52,54,57,59,61).

Weight-loss studies have used a vari-ety of energy-restricted eating patterns,with no clear evidence that one eatingpattern or optimal macronutrient dis-tribution was ideal, suggesting thatmacronutrient proportions should beindividualized (64). Studies show thatpeople with diabetes eat on averageabout 45% of their calories from carbo-hydrates,;36–40% of calories from fat,and ;16–18% from protein (57–59). Avariety of eating patterns have beenshown to be effective in managing di-abetes, including Mediterranean-style(53,65), Dietary Approaches to StopHypertension (DASH)-style (66), andplant-based (vegan or vegetarian) (67),lower-fat (68), and lower-carbohydratepatterns (68).


Table 4.1—Nutrition therapy recommendations

Topic Recommendations Evidence rating

Effectiveness of nutrition therapy c Nutrition therapy is recommended for all people with type 1 and type 2diabetes as an effective component of the overall treatment plan.

A

c Individuals who have diabetes should receive individualized MNT toachieve treatment goals, preferably provided by a registered dietitianfamiliar with the components of diabetes MNT.

A

c For individuals with type 1 diabetes, participation in an intensive, flexibleinsulin therapy education program using the carbohydrate-countingmealplanning approach can result in improved glycemic control.

A

c For individuals using fixed daily insulin doses, consistent carbohydrateintake with respect to time and amount can result in improved glycemiccontrol and reduce hypoglycemia risk.

B

c A simple diabetes meal planning approach, such as portion control orhealthful food choices, may be better suited to individuals with type 2diabetes with health and numeracy literacy concerns. This strategy alsomay be effective for older adults.

C

c Because diabetes nutrition therapy can result in cost savings B andimproved outcomes (e.g., A1C reduction) A, MNT should be adequatelyreimbursed by insurance and other payers. E

B, A, E

Energy balance c For overweight or obese adults with type 2 diabetes or at risk fordiabetes, reducing energy intake while maintaining a healthful eatingpattern is recommended to promote weight loss.

A

cModest weight loss may provide clinical benefits in some individuals withdiabetes, especially those early in the disease process. To achievemodestweight loss, intensive lifestyle interventions with ongoing support arerecommended.

A

Eating patterns and macronutrientdistribution

c Evidence suggests that there is not an ideal percentage of calories fromcarbohydrate, protein, and fat for all people with diabetes B; therefore,macronutrient distribution should be based on individualized assessmentof current eating patterns, preferences, and metabolic goals. E

B, E

c Carbohydrate amount and available insulin may be the most importantfactors influencing glycemic response after eating and should beconsidered when developing the eating plan.

A

c Monitoring carbohydrate intake, whether by carbohydrate counting orexperience-based estimation, remains critical in achieving glycemiccontrol.

B

c Carbohydrate intake from vegetables, fruits, whole grains, legumes, anddairy products should be advised over intake from other carbohydratesources, especially those that contain added fats, sugars, or sodium.

B

c Substituting low glycemic2load foods for higher glycemic2load foodsmay modestly improve glycemic control.

C

c Individuals at high risk for type 2 diabetes should be encouraged toachieve the U.S. Department of Agriculture recommendation for dietaryfiber (14 g fiber/1,000 kcal) and to consume foods containing wholegrains (one-half of grain intake).

B

c While substituting sucrose-containing foods for isocaloric amounts ofother carbohydrates may have similar blood glucose effects,consumption should be minimized to avoid displacing nutrient-densefood choices.

A

c People with diabetes and those at risk should limit or avoid intake ofsugar-sweetened beverages to reduce risk for weight gain and worseningof cardiometabolic risk profile.

B

Protein c In individuals with type 2 diabetes, ingested protein appears to increaseinsulin response without increasing plasma glucose concentrations.Therefore, carbohydrate sources high in protein should not be used totreat or prevent hypoglycemia.

B

c Evidence is inconclusive regarding an ideal amount of total fat for peoplewith diabetes; therefore, goals should be individualized. C Fat qualityappears to be far more important than quantity. B

C, B

c A Mediterranean-style eating pattern, rich in monounsaturated fattyacids, may benefit glycemic control and CVD risk factors and cantherefore be recommended as an effective alternative to a lower-fat,higher-carbohydrate eating pattern.

B

Continued on p. S23


Macronutrients

Carbohydrates

Studies examining the ideal amountof carbohydrate intake for people withdiabetes are inconclusive, althoughmonitoring carbohydrate intake andconsidering the available insulin arekey strategies for improving postpran-dial glucose control (37,69). The litera-ture concerning glycemic index andglycemic load in individuals with diabe-tes is complex, although reductions inA1C of20.2% to20.5% have been dem-onstrated in some studies (64,70). A sys-tematic review (64) found consumptionof whole grains was not associated withimprovements in glycemic control inpeople with type 2 diabetes, althoughit may reduce systemic inflammation.One study did find a potential benefit ofwhole-grain intake in reducing mortalityand cardiovascular disease (CVD) (71).

Proteins

For people with diabetes and no evi-dence of diabetic kidney disease, theevidence is inconclusive about recom-mending an ideal amount of proteinfor optimizing glycemic control or forimproving one or more CVD risk mea-sures (64). Therefore, these goals shouldbe individualized. For people with dia-betes and diabetic kidney disease (withalbuminuria), reducing the amount ofdietary protein below usual intake isnot recommended because it does notalter glycemic measures, cardiovascularrisk measures, or the course of glomer-ular filtration rate decline (72,73). In in-dividuals with type 2 diabetes, ingestedprotein appears to increase insulin re-sponsewithout increasing plasma glucoseconcentrations (74). Therefore, carbohy-drate sources high in protein should notbe used to treat or prevent hypoglycemia.

Protein’s effect on blood glucose levels intype 1 diabetes is less clear.

Fats

Limited research exists concerning theideal amount of fat for individuals withdiabetes. The Institute of Medicine hasdefined an acceptable macronutrientdistribution range for all adults for totalfat of 20–35% of energy with no tolera-ble upper intake level defined (75). Thetype of fatty acids consumed is moreimportant than total amount of fatwhen looking at metabolic goals andrisk of CVD (53,76,77). Multiple random-ized controlled trials including patientswith type 2 diabetes have reported im-proved glycemic control and/or blood lip-ids when a Mediterranean-style eatingpattern, rich in monounsaturated fattyacid, was consumed (53,57,78,79). A sys-tematic review (64) concluded that

Table 4.1—Continued

Topic Recommendations Evidence rating

Dietary fat c Increased consumption of foods containing long-chain omega-3 fatty acids(EPA and DHA), such as fatty fish, and omega-3 linolenic acid (ALA) isrecommended.

B

c The consumption of fish (particularly fatty fish) at least two times (twoservings) per week is recommended.

B

c The amount of dietary saturated fat, cholesterol, and trans fat recommendedfor people with diabetes is the same as that recommendedfor the general population.

C

c Evidencedoes not support recommending omega-3 supplements for peoplewith diabetes for the prevention or treatment of cardiovascular events.

A

Micronutrientsandherbal supplements c There is no clear evidence of benefit from vitamin or mineralsupplementation in people with diabetes who do not have underlyingdeficiencies.

C

c Routine supplementation with antioxidants, such as vitamins E and C andcarotene, is not advised due to insufficient evidence of efficacy andconcerns related to long-term safety.

C

c There is insufficient evidence to support the routine use ofmicronutrients such as chromium, magnesium, and vitamin D to improveglycemic control in people with diabetes.

C

c There is insufficient evidence to support the use of cinnamon or otherherbs/supplements for the treatment of diabetes.

E

c It is recommended that individualizedmeal planning include optimizationof food choices to meet recommended dietary allowance/dietaryreference intake for all micronutrients.

E

Alcohol c If adultswithdiabetes choose todrink alcohol, they should be advised to do soin moderation (no more than one drink per day for adult women and nomore than two drinks per day for adult men).

C

cAlcohol consumptionmayplace peoplewithdiabetes at an increased risk fordelayed hypoglycemia, especially if taking insulin or insulin secretagogues.Education and awareness regarding the recognition and managementof delayed hypoglycemia are warranted.

B

Sodium c The recommendation for the general population to reduce sodium to less than2,300 mg/day is also appropriate for people with diabetes.

B

c For individualswithbothdiabetes andhypertension, further reduction in sodiumintake should be individualized.

B


supplementation with omega-3 fattyacids did not improve glycemic controlbut that higher dose supplementationdecreased triglycerides in individualswith type 2 diabetes. Randomized con-trolled trials also do not support recom-mending omega-3 supplements forprimary or secondary prevention of CVD(80–85). People with diabetes should beadvised to follow the guidelines for thegeneral population for the recommendedintakes of saturated fat, dietary choles-terol, and trans fat (86).

SodiumA review found that decreasing sodiumintake reduces blood pressure in thosewith diabetes (87). Incrementally lower-ing sodium intake (i.e., to 1,500mg/day)has shown beneficial effects on bloodpressure (87–89). The American HeartAssociation recommends 1,500 mg/dayfor African Americans, people diag-nosed with hypertension, diabetes, orchronic kidney disease, and those over51 years of age (90). However, otherstudies (88,89) have warranted cautionfor universal sodium restriction to1,500 mg in this population. For indi-viduals with diabetes and hyperten-sion, setting a sodium intake goal of,2,300 mg/day should be consideredon an individual basis. Sodium intakerecommendations should take into ac-count palatability, availability, additionalcost of specialty low-sodium products,and the difficulty of achieving both low-sodium recommendations and a nutri-tionally adequate diet (86).For complete discussion and refer-

ences of all recommendations, see theADA position statement “Nutrition Ther-apy Recommendations for the Manage-ment of Adults With Diabetes” (36).

PHYSICAL ACTIVITY

Recommendations

c Children with diabetes or predia-betes should be encouraged to en-gage in at least 60 min of physicalactivity each day. B

c Adults with diabetes should be ad-vised to perform at least 150 min/week of moderate-intensity aero-bic physical activity (50–70% ofmaximum heart rate), spreadover at least 3 days/week with nomore than 2 consecutive dayswithout exercise. A

c Evidence supports that all individ-uals, including those with diabe-tes, should be encouraged toreduce sedentary time, particu-larly by breaking up extendedamounts of time (.90 min) spentsitting. B

c In the absence of contraindica-tions, adults with type 2 diabetesshould be encouraged to performresistance training at least twiceper week. A

Exercise is an important part of the di-abetes management plan. Regular exer-cise has been shown to improve bloodglucose control, reduce cardiovascularrisk factors, contribute to weight loss,and improve well-being. Furthermore,regular exercise may prevent type 2 di-abetes in high-risk individuals (91–93).Structured exercise interventions of atleast 8 weeks’ duration have beenshown to lower A1C by an average of0.66% in people with type 2 diabetes,even with no significant change in BMI(94). There are considerable data for thehealth benefits (e.g., increased cardiovas-cular fitness, muscle strength, improvedinsulin sensitivity, etc.) of regular physicalactivity for those with type 1 diabetes(95). Higher levels of exercise intensityare associated with greater improve-ments in A1C and in fitness (96). Otherbenefits include slowing the decline inmobility among overweight patientswith diabetes (97). “Exercise and Type 2Diabetes: The American College of SportsMedicine and the American Diabetes As-sociation: Joint Position Statement Exec-utive Summary” reviews the evidence forthe benefits of exercise in people withtype 2 diabetes (98).

Exercise and ChildrenAs is recommended for all children, chil-dren with diabetes or prediabetes shouldbe encouraged to engage in at least 60min of physical activity each day. Includedin the 60 min each day, children shouldengage in vigorous-intensity aerobicactivity, muscle-strengthening activities,and bone-strengthening activities at least3 of those days (99).

Frequency and Type of ExerciseThe U.S. Department of Health andHuman Services’ physical activityguidelines for Americans (100) suggestthat adults over age 18 years do 150min/week of moderate-intensity or 75

min/week of vigorous-intensity aerobicphysical activity, or an equivalent com-bination of the two. In addition, theguidelines suggest that adults also domuscle-strengthening activities that in-volve all major muscle groups 2 or moredays/week. The guidelines suggest thatadults over age 65 years, or those withdisabilities, follow the adult guidelines ifpossible or, if this is not possible, be asphysically active as they are able.

Recent evidence supports that all in-dividuals, including those with diabetes,should be encouraged to reduce theamount of time spent being sedentary(e.g., working at a computer, watchingTV) particularly by breaking up ex-tended amounts of time (.90 min)spent sitting (101).

Exercise and Glycemic ControlBased on physical activity studies that in-clude people with diabetes, it seems rea-sonable to recommend that people withdiabetes follow the physical activity guide-lines as for the general population. Forexample, studies included in the meta-analysis of effects of exercise interventionson glycemic control (94) had amean of 3.4sessions/week, with a mean of 49 min/session. Also, theDiabetes PreventionPro-gram (DPP) lifestyle intervention included150min/weekofmoderate-intensity exer-cise and showed beneficial effect on gly-cemia in those with prediabetes (91).

Clinical trials have provided strong evi-dence for the A1C-lowering value of re-sistance training in older adults with type2 diabetes (98) and for an additive benefitof combined aerobic and resistance exer-cise in adults with type 2 diabetes(102,103). If not contraindicated, patientswith type 2 diabetes should be encour-aged to do at least two weekly sessionsof resistance exercise (exercise with freeweights or weight machines), with eachsession consisting of at least one set offive or more different resistance exercisesinvolving the large muscle groups (98).

Pre-exercise EvaluationAs discussed more fully in Section 8. Car-diovascular Disease and Risk Manage-ment, the best protocol for screeningasymptomatic diabetic patients for coro-nary artery disease (CAD) remains unclear.The ADA consensus report “Screening forCoronary Artery Disease in Patients WithDiabetes” (104) on this issue concludedthat routine screening is not recommended.Providers should use clinical judgment in


this area. Certainly, high-risk patientsshould be encouraged to start with shortperiods of low-intensity exercise andslowly increase the intensity and dura-tion. Providers should assess patientsfor conditions that might contraindicatecertain types of exercise or predispose toinjury, such as uncontrolled hyperten-sion, severe autonomic neuropathy, se-vere peripheral neuropathy, a history offoot lesions, and unstable proliferativeretinopathy. The patient’s age and pre-vious physical activity level should beconsidered. For type 1 diabetic patients,the provider should customize the exer-cise regimen to the individual’s needs.Those with complications may require amore thorough evaluation (95).

Exercise in the Presence ofNonoptimal Glycemic Control

Hyperglycemia

When individuals with type 1 diabetesare deprived of insulin for 12–48 h andare ketotic, exercise can worsen hyper-glycemia and ketosis (105); therefore,vigorous activity should be avoidedwith ketosis. However, it is not neces-sary to postpone exercise based simplyon hyperglycemia, provided the patientfeels well and urine and/or blood ke-tones are negative.

Hypoglycemia

In individuals taking insulin and/or insu-lin secretagogues, physical activity cancause hypoglycemia if medication doseor carbohydrate consumption is not al-tered. For individuals on these thera-pies, added carbohydrate should beingested if pre-exercise glucose levelsare,100 mg/dL (5.6 mmol/L). Hypogly-cemia is less common in diabetic pa-tients who are not treated with insulinor insulin secretagogues, and no preven-tive measures for hypoglycemia are usu-ally advised in these cases.

Exercise in the Presence of SpecificLong-Term Complications of Diabetes

Retinopathy

If proliferative diabetic retinopathy orsevere nonproliferative diabetic reti-nopathy is present, then vigorous aero-bic or resistance exercise may becontraindicated because of the risk oftriggering vitreous hemorrhage or reti-nal detachment (106).

Peripheral Neuropathy

Decreased pain sensation and a higherpain threshold in the extremities result

in an increased risk of skin breakdownand infection and of Charcot joint de-struction with some forms of exercise.However, studies have shown thatmoderate-intensity walking may notlead to an increased risk of foot ulcersor reulceration in those with peripheralneuropathy (107). In addition, 150 min/week of moderate exercise was re-ported to improve outcomes in patientswith milder forms of neuropathy (106).All individuals with peripheral neuropa-thy should wear proper footwear andexamine their feet daily to detect le-sions early. Anyone with a foot injuryor open sore should be restricted tonon–weight-bearing activities.

Autonomic Neuropathy

Autonomic neuropathy can increase therisk of exercise-induced injury or ad-verse event through decreased cardiacresponsiveness to exercise, postural hy-potension, impaired thermoregulation,impaired night vision due to impairedpapillary reaction, and higher suscepti-bility to hypoglycemia (108). Cardiovas-cular autonomic neuropathy is also anindependent risk factor for cardiovascu-lar death and silent myocardial ischemia(109). Therefore, individuals with dia-betic autonomic neuropathy shouldundergo cardiac investigation beforebeginning physical activity more intensethan that to which they are accustomed.

Albuminuria and Nephropathy

Physical activity can acutely increase uri-nary protein excretion. However, thereis no evidence that vigorous exerciseincreases the rate of progression ofdiabetic kidney disease, and thereappears to be no need for specific exer-cise restrictions for people with diabetickidney disease (106).

SMOKING CESSATION

Recommendations

c Advise all patients not to smoke oruse tobacco products. A

c Include smoking cessation coun-seling andother forms of treatmentas a routine component of diabetescare. B

Results from epidemiological, case-control, and cohort studies provide con-vincing evidence to support the causallink between cigarette smoking andhealth risks.Much of thework document-ing the effect of smoking on health does

not separately discuss results on subsetsof individuals with diabetes, but it doessuggest that the identified risks are atleast equivalent to those found in thegeneral population. Other studies of in-dividuals with diabetes consistentlydemonstrate that smokers (and peopleexposed to secondhand smoke) have aheightened risk of CVD, prematuredeath, and the microvascular complica-tions of diabetes. Smoking may have arole in the development of type 2 diabe-tes (110). One study in smokers withnewly diagnosed type 2 diabetes foundthat smoking cessation was associatedwith amelioration of metabolic parame-ters and reduced blood pressure and al-buminuria at 1 year (111).

The routine and thorough assessmentof tobacco use is essential to preventsmoking or encourage cessation. Nu-merous large randomized clinical trialshave demonstrated the efficacy andcost-effectiveness of brief counseling insmoking cessation, including the use ofquit lines, in reducing tobacco use. Forthe patient motivated to quit, the addi-tion of pharmacological therapy to coun-seling is more effective than eithertreatment alone. Special considerationsshould include assessment of level ofnicotine dependence, which is associ-ated with difficulty in quitting and re-lapse (112). Although some patientsmay gainweight in the period shortly aftersmoking cessation, recent research hasdemonstrated that this weight gain doesnot diminish the substantial CVD risk ben-efit realized from smoking cessation (113).

There is no evidence that e-cigarettesare a healthier alternative to smoking orthat e-cigarettes can facilitate smokingcessation. Rigorous study of their short-and long-term effects is needed in de-termining their safety and efficacy andtheir cardiopulmonary effects in com-parison with smoking and standard ap-proaches to smoking cessation (114).

PSYCHOSOCIAL ASSESSMENT ANDCARE

Recommendations

c Include assessment of the pa-tient’s psychological and socialsituation as an ongoing partof the medical management ofdiabetes. B

c Psychosocial screening and follow-upmay include, but are not limited


to, attitudes about the illness,expectations for medical man-agement and outcomes, affect/mood, general and diabetes-related quality of life, resources(financial, social, and emotional),and psychiatric history. E

c Routinely screen for psychosocialproblems such as depression,diabetes-related distress, anxi-ety, eating disorders, and cogni-tive impairment. B

c Older adults (aged $65 years)with diabetes should be consid-ered a high-priority populationfor depression screening andtreatment. B

c Patients with comorbid diabetesand depression should receive astepwise collaborative care ap-proach for the management ofdepression. A

Emotional well-being is an important partof diabetes care and self-management.Psychological and social problems canimpair the individual’s (115–117) orfamily’s (118) ability to carry outdiabetes care tasks and thereforecompromise health status. There areopportunities for the clinician to rou-tinely assess psychosocial status in atimely and efficient manner so that re-ferral for appropriate services can be ac-complished. A systematic review andmeta-analysis showed that psychosocialinterventions modestly but significantlyimproved A1C (standardized mean dif-ference20.29%) and mental health out-comes. However, there was a limitedassociation between the effects on A1Cand mental health, and no interventioncharacteristics predicted benefit on bothoutcomes (119).

ScreeningKey opportunities for routine screeningof psychosocial status occur at diagno-sis, during regularly scheduled manage-ment visits, during hospitalizations, withnew-onset complications, or when prob-lems with glucose control, quality of life,or self-management are identified. Pa-tients are likely to exhibit psychologicalvulnerability at diagnosis, when theirmedical status changes (e.g., end of thehoneymoon period), when the need forintensified treatment is evident, andwhen complications are discovered. De-pression affects about 20–25% of people

with diabetes (120) and increases the riskfor myocardial infarction and postmyo-cardial infarction (121) and all-causemortality (122). There appears to be abidirectional relationship between de-pression and both diabetes (123) andmetabolic syndrome (124).

Diabetes-related distress is distinctfrom clinical depression and is very com-mon (125–127) among people with di-abetes and their family members (118).Prevalence is reported as 18–45%, withan incidence of 38–48% over 18months.High levels of distress are significantlylinked to A1C, self-efficacy, dietary andexercise behaviors (13,126), and medi-cation adherence (128). Other issuesknown to impact self-management andhealth outcomes include, but are not lim-ited to, attitudes about the illness, ex-pectations for medical management andoutcomes, anxiety, general and diabetes-related quality of life, resources (finan-cial, social, and emotional) (129), andpsychiatric history (130). Screening toolsare available for a number of these areas(23,131,132).

Referral to Mental Health SpecialistIndications for referral to a mentalhealth specialist familiar with diabetesmanagement may include gross disre-gard for the medical regimen (by selfor others) (133), depression, overallstress related to work-life balance, pos-sibility of self-harm, debilitating anxiety(alone or with depression), indicationsof an eating disorder (134), or cognitivefunctioning that significantly impairsjudgment. It is preferable to incorporatepsychological assessment and treatmentinto routine care rather than waiting for aspecific problem or deterioration in met-abolic or psychological status (23,125). Inthe Second Diabetes Attitudes, Wishesand Needs (DAWN2) study, significantdiabetes-related distress was reportedby 44.6% of the participants, but only23.7% reported that their health careteam asked them how diabetes impactedtheir life (125).

Although the clinician may not feelqualified to treat psychological prob-lems (135), optimizing the patient-provider relationship as a foundationcan increase the likelihood that the pa-tient will accept referral for other ser-vices. Collaborative care interventionsand use of a team approach have dem-onstrated efficacy in diabetes and

depression (136,137). Interventions toenhance self-management and addresssevere distress have demonstrated effi-cacy in diabetes-related distress (13).

IMMUNIZATION

Recommendations

c Provide routine vaccinations forchildren and adults with diabetesas for the general population. C

c Annually provide an influenza vac-cine to all patients with diabetes$6 months of age. C

c Administer pneumococcal poly-saccharide vaccine 23 (PPSV23)to all patients with diabetes $2years of age. C

c Adults $65 years of age, if notpreviously vaccinated, should re-ceive pneumococcal conjugatevaccine 13 (PCV13), followed byPPSV23 6–12 months after initialvaccination. C

c Adults $65 years of age, if previ-ously vaccinated with PPSV23,should receive a follow-up $12months with PCV13. C

c Administer hepatitis B vaccinationto unvaccinated adults with diabe-tes who are aged 19–59 years. C

c Consider administering hepatitis Bvaccination to unvaccinated adultswith diabetes who are aged $60years. C

As for the general population, all chil-dren and adults with diabetes should re-ceive routine vaccinations (138,139).Influenza and pneumonia are common,preventable infectious diseases associ-ated with high mortality and morbidityin vulnerable populations, such as theyoung and the elderly, and in peoplewith chronic diseases. Although thereare limited studies reporting the mor-bidity and mortality of influenza andpneumococcal pneumonia specificallyin people with diabetes, observationalstudies of patients with a variety ofchronic illnesses, including diabetes,show that these conditions are associ-ated with an increase in hospitalizationsfor influenza and its complications. Peo-ple with diabetesmay be at an increasedrisk of the bacteremic form of pneumo-coccal infection and have been reportedto have a high risk of nosocomial bacter-emia, with a mortality rate as high as50% (140). In a case-control series,


influenza vaccine was shown to reducediabetes-related hospital admission byas much as 79% during flu epidemics(141). There is sufficient evidence tosupport that people with diabeteshave appropriate serologic and clinicalresponses to these vaccinations. TheCenters for Disease Control and Preven-tion (CDC) Advisory Committee onImmunization Practices recommends in-fluenza and pneumococcal vaccines forall individuals with diabetes (http://www.cdc.gov/vaccines/recs).

Pneumococcal Vaccines in OlderAdultsThe ADA endorses a recent CDC advisorypanel that recommends that bothPCV13 and PPSV23 should be adminis-tered routinely in series to all adults 65years of age or older (142).

Pneumococcal Vaccine-Naïve People

Adults 65 years of age or older who havenot previously received pneumococcalvaccine or whose previous vaccinationhistory is unknown should receive adose of PCV13 first, followed by PPSV23.A dose of PPSV23 should be given 6–12months following a dose of PCV13. IfPPSV23 cannot be given within this timeperiod, a dose of PPSV23 should be givenduring the next visit. The two vaccinesshould not be coadministered, and theminimum interval between vaccine dos-ing should be 8 weeks.

Previous Vaccination With PPSV23

Adults 65 years of age or older who pre-viously have received one or more dosesof PPSV23 should also receive PCV13 ifthey have not yet received it. PCV13should be given no sooner than 12monthsafter receipt of the most recent PPSV23dose. For those for whom an additionaldose of PPSV23 is indicated, this subse-quent PPSV23 dose should be given 6–12months after PCV13 and at least 5 yearssince the most recent dose of PPSV23.

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5. Prevention or Delay of Type 2DiabetesDiabetes Care 2015;38(Suppl. 1):S31–S32 | DOI: 10.2337/dc15-S008

Recommendations

c Patients with impaired glucose tolerance (IGT) A, impaired fasting glucose(IFG) E, or an A1C 5.7–6.4% E should be referred to an intensive diet andphysical activity behavioral counseling program targeting loss of 7% of bodyweight and increasing moderate-intensity physical activity (such as brisk walk-ing) to at least 150 min/week.

c Follow-up counseling may be important for success. Bc Based on the cost-effectiveness of diabetes prevention, such programs should

be covered by third-party payers. Bc Metformin therapy for prevention of type 2 diabetes may be considered in

those with IGT A, IFG E, or an A1C 5.7–6.4% E, especially for those with BMI.35 kg/m2, aged ,60 years, and women with prior gestational diabetesmellitus (GDM). A

c At least annual monitoring for the development of diabetes in those withprediabetes is suggested. E

c Screening for and treatment of modifiable risk factors for cardiovascular dis-ease is suggested. B

c Diabetes self-management education (DSME) and support (DSMS) programsare appropriate venues for people with prediabetes to receive educationand support to develop and maintain behaviors that can prevent or delaythe onset of diabetes. C

LIFESTYLE MODIFICATIONS

Randomized controlled trials have shown that individuals at high risk for developingtype 2 diabetes (IFG, IGT, or both) can significantly decrease the rate of diabetesonset with particular interventions (1–5). These include intensive lifestyle modifi-cation programs that have been shown to be very effective (;58% reduction after 3years). Follow-up of all three large studies of lifestyle intervention has shown sus-tained reduction in the rate of conversion to type 2 diabetes: 43% reduction at 20years in the Da Qing study (6), 43% reduction at 7 years in the Finnish DiabetesPrevention Study (DPS) (7), and 34% reduction at 10 years in the U.S. Diabetes Pre-vention Program Outcomes Study (DPPOS) (8). A cost-effectiveness model suggestedthat lifestyle interventions in the Diabetes Prevention Program (DPP) are cost-effective(9). Actual cost data from the DPP and DPPOS confirm that the lifestyle interventionsare highly cost-effective (10). Group delivery of the DPP intervention in communitysettings has the potential to be significantly less expensive while still achieving similarweight loss (11). The Centers forDiseaseControl and Prevention (CDC) helps coordinatethe National Diabetes Prevention Program, a resource designed to bring evidence-based lifestyle change programs for preventing type 2 diabetes to communities(http://www.cdc.gov/diabetes/prevention/index.htm).Given the clinical trial results and the known risks of progression of prediabetes to

diabetes, people with an A1C 5.7–6.4%, IGT, or IFG should be counseled on lifestylechanges with goals similar to those of the DPP (7% weight loss and moderate-intensity physical activity of at least 150 min/week).

PHARMACOLOGICAL INTERVENTIONS

Pharmacological agents, such as metformin, a-glucosidase inhibitors, orlistat, andthiazolidinediones, have each been shown to decrease incident diabetes to various

Suggested citation: American Diabetes Associa-tion. Prevention or delay of type 2 diabetes. Sec.5. In StandardsofMedical Care inDiabetesd2015.Diabetes Care 2015;38(Suppl. 1):S31–S32




POSITIO

NSTA

TEMEN

T

degrees. Metformin has the strongestevidence base and demonstrated long-term safety as pharmacological therapyfor diabetes prevention (12). For otherdrugs, cost, side effects, and lack of apersistent effect require consideration.Metformin was less effective than

lifestyle modification in the DPP andDPPOS but may be cost-saving over a10-year period (10). It was as effectiveas lifestyle modification in participantswith BMI $35 kg/m2 but not signifi-cantly better than placebo in thoseover 60 years of age (1). In the DPP, forwomen with a history of GDM, metfor-min and intensive lifestyle modificationled to an equivalent 50% reduction indiabetes risk (13). Metformin may berecommended for very high-risk individu-als (e.g., with history of GDM,who are veryobese, and/or those with more severe orprogressive hyperglycemia).People with prediabetes often have

other cardiovascular risk factors, such asobesity, hypertension, and dyslipidemia,and are at an increased risk for cardiovas-cular disease events. While treatmentgoals are the same as for other patientswithout diabetes, increased vigilance iswarranted to identify and treat theseand other risk factors (e.g., smoking).

DIABETES SELF-MANAGEMENTEDUCATION AND SUPPORT

The standards for DSME and DSMS (seeSection 4. Foundations of Care) can alsoapply to the education and support ofpeoplewith prediabetes. Currently, thereare significant barriers to the provision ofeducation and support to those with pre-diabetes. However, the strategies for

supporting successful behavior changeand the healthy behaviors recommendedfor people with prediabetes are largelyidentical to those for people with diabe-tes. Given their training and experience,providers of DSME and DSMS are partic-ularly well equipped to assist people withprediabetes in developing and maintain-ing behaviors that can prevent or delaythe onset of diabetes (14–16).

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diabetes by lifestyle intervention: follow-up ofthe Finnish Diabetes Prevention Study. Lancet2006;368:1673–16798. Knowler WC, Fowler SE, Hamman RF, et al.;Diabetes Prevention Program Research Group.10-year follow-up of diabetes incidence andweight loss in the Diabetes Prevention ProgramOutcomes Study. Lancet 2009;374:1677–16869. Herman WH, Hoerger TJ, Brandle M, et al.;Diabetes Prevention Program Research Group.The cost-effectiveness of lifestyle modificationor metformin in preventing type 2 diabetes inadults with impaired glucose tolerance. Ann In-tern Med 2005;142:323–33210. Diabetes Prevention Program ResearchGroup. The 10-year cost-effectiveness of life-style intervention or metformin for diabetesprevention: an intent-to-treat analysis of theDPP/DPPOS. Diabetes Care 2012;35:723–73011. Ackermann RT, Finch EA, Brizendine E, ZhouH, Marrero DG. Translating the Diabetes Pre-vention Program into the community. TheDEPLOY Pilot Study. Am J Prev Med 2008;35:357–36312. Diabetes Prevention Program ResearchGroup. Long-term safety, tolerability, andweight loss associated with metformin in theDiabetes Prevention Program Outcomes Study.Diabetes Care 2012;35:731–73713. Ratner RE, Christophi CA, Metzger BE, et al.;Diabetes Prevention Program Research Group.Prevention of diabetes in women with a historyof gestational diabetes: effects of metforminand lifestyle interventions. J Clin EndocrinolMetab 2008;93:4774–477914. Parekh D, Sarathi V, Shivane VK, BandgarTR, Menon PS, Shah NS. Pilot study to evaluatethe effect of short-term improvement in vita-min D status on glucose tolerance in patientswith type 2 diabetes mellitus. Endocr Pract2010;16:600–60815. Shah M, Kaselitz E, Heisler M. The role ofcommunity health workers in diabetes: updateon current literature. Curr Diab Rep 2013;13:163–17116. Heisler M. Overview of peer support mod-els to improve diabetes self-management andclinical outcomes. Diabetes Spectrum 2007;20:214–221


6. Glycemic TargetsDiabetes Care 2015;38(Suppl. 1):S33–S40 | DOI: 10.2337/dc15-S009

ASSESSMENT OF GLYCEMIC CONTROL

Two primary techniques are available for health providers and patients to assess theeffectiveness of the management plan on glycemic control: patient self-monitoringof blood glucose (SMBG) or interstitial glucose and A1C. Continuous glucose mon-itoring (CGM) may be a useful adjunct to SMBG in selected patients.

Recommendations

c When prescribed as part of a broader educational context, SMBG results mayhelp guide treatment decisions and/or self-management for patients using lessfrequent insulin injections B or noninsulin therapies. E

c When prescribing SMBG, ensure that patients receive ongoing instruction andregular evaluation of SMBG technique, SMBG results, and their ability to useSMBG data to adjust therapy. E

c Patients onmultiple-dose insulin or insulin pump therapy should perform SMBGprior to meals and snacks, occasionally postprandially, at bedtime, prior to ex-ercise, when they suspect low blood glucose, after treating low blood glucoseuntil they are normoglycemic, and prior to critical tasks such as driving. B

c Whenusedproperly, CGM in conjunctionwith intensive insulin regimens is a usefultool to lower A1C in selected adults (aged$25 years) with type 1 diabetes. A

c Although the evidence for A1C lowering is less strong in children, teens, andyounger adults, CGM may be helpful in these groups. Success correlates withadherence to ongoing use of the device. B

c CGM may be a supplemental tool to SMBG in those with hypoglycemia un-awareness and/or frequent hypoglycemic episodes. C

c Given variable adherence to CGM, assess individual readiness for continuinguse of CGM prior to prescribing. E

c When prescribing CGM, robust diabetes education, training, and support arerequired for optimal CGM implementation and ongoing use. E

Self-monitoring of Blood GlucoseMajor clinical trials of insulin-treated patients have included SMBG as part of themultifactorial interventions to demonstrate the benefit of intensive glycemic con-trol on diabetes complications. SMBG is thus an integral component of effectivetherapy (1). SMBG allows patients to evaluate their individual response to therapyand assess whether glycemic targets are being achieved. Integrating SMBG resultsinto diabetesmanagement can be a useful tool for guidingmedical nutrition therapyand physical activity, preventing hypoglycemia, and adjusting medications (partic-ularly prandial insulin doses). Evidence supports a correlation between greaterSMBG frequency and lower A1C (2). The patient’s specific needs and goals shoulddictate SMBG frequency and timing.

Optimization

SMBG accuracy is dependent on the instrument and user (3), so it is important toevaluate each patient’s monitoring technique, both initially and at regular intervalsthereafter. Optimal use of SMBG requires proper review and interpretation of thedata, both by the patient and provider. Among patients who check their bloodglucose at least once daily, many report taking no action when results are high orlow (4). In a yearlong study of insulin-naıve patients with suboptimal initial glycemiccontrol, a group trained in structured SMBG (a paper tool was used at least quarterlyto collect and interpret 7-point SMBG profiles taken on 3 consecutive days) reducedtheir A1C by 0.3 percentage points more than the control group (5). Patients should

Suggested citation: American Diabetes Associa-tion. Glycemic targets. Sec. 6. In Standards ofMedical Care in Diabetesd2015. Diabetes Care2015;38(Suppl. 1):S33–S40




POSITIO

NSTA

TEMEN

T

be taught how to use SMBG data toadjust food intake, exercise, or phar-macological therapy to achieve specificgoals. The ongoing need for and fre-quency of SMBG should be reevaluatedat each routine visit. SMBG is especiallyimportant for insulin-treated patientsto monitor for and prevent asymptom-atic hypoglycemia and hyperglycemia.

For Patients on Intensive Insulin Regimens

Most patients on intensive insulin regi-mens (multiple-dose insulin or insulinpump therapy, including patients withtype 1 diabetes) should consider SMBGprior to meals and snacks, occasionallypostprandially, at bedtime, prior to exer-cise, when they suspect low blood glu-cose, after treating low blood glucoseuntil they are normoglycemic, and priorto critical tasks such as driving. For manypatients, this will require testing 6–10 (ormore) times daily, although individualneeds may vary. A database study ofalmost 27,000 children and adolescentswith type 1 diabetes showed that, afteradjustment for multiple confounders, in-creased daily frequency of SMBG wassignificantly associated with lower A1C(20.2% per additional test per day)and with fewer acute complications (6).

For Patients Using Basal Insulin or

Oral Agents

The evidence is insufficient regardingwhen to prescribe SMBG and how oftentesting is needed for patients who donot use an intensive insulin regimen,such as those with type 2 diabetes usingbasal insulin or oral agents.Several randomized trials have called

into question the clinical utility and cost-effectiveness of routineSMBG innoninsulin-treated patients (7–9). A meta-analysissuggested that SMBG reduced A1C by0.25% at 6 months (10), but the reductionsubsides after 12 months (11). A key con-sideration is that performing SMBG alonedoes not lower blood glucose levels. To beuseful, the informationmust be integratedinto clinical and self-management plans.

Continuous Glucose MonitoringReal-time CGMmeasures interstitial glu-cose (which correlates well with plasmaglucose) and includes sophisticatedalarms for hypo- and hyperglycemic ex-cursions, but the devices are still notapproved by the U.S. Food and Drug Ad-ministration as a sole agent to monitorglucose. CGMs require calibration with

SMBG, with the latter still required formaking acute treatment decisions.

A 26-week randomized trial of 322type 1 diabetic patients showed thatadults aged $25 years using intensiveinsulin therapy and CGM experienced a0.5% reduction in A1C (from ;7.6% to7.1%), compared with those using inten-sive insulin therapy with SMBG (12). Sen-sor use in those aged,25 years (children,teens, and adults) did not result in signif-icant A1C lowering, and there was nosignificant difference in hypoglycemiain any group. The greatest predictor ofA1C lowering for all age-groups was fre-quency of sensor use, whichwas highestin those aged $25 years and lower inyounger age-groups.

A recent registry study of 17,317 partic-ipants confirmed thatmore frequent CGMuse is associated with lower A1C (13),while another study showed that childrenwith .70% sensor use missed fewerschool days (14). Small randomized con-trolled trials in adults and children withbaseline A1C 7.0–7.5% have confirmed fa-vorable outcomes (A1C and hypoglycemiaoccurrence) in groups using CGM, suggest-ing that CGMmay provide further benefitfor individuals with type 1 diabetes whoalready have tight control (15,16).

A meta-analysis suggests that, com-pared with SMBG, CGM is associ-ated with short-term A1C lowering of;0.26% (17). The long-term effective-ness of CGM needs to be determined.This technology may be particularlyuseful in those with hypoglycemiaunawareness and/or frequent hypogly-cemic episodes, although studies havenot shown significant reductions in se-vere hypoglycemia (17,18). A CGM de-vice equipped with an automatic lowglucose suspend feature has been ap-proved by the U.S. Food and Drug Admin-istration. The Automation to SimulatePancreatic Insulin Response (ASPIRE) trialof 247 patients showed that sensor-augmented insulin pump therapy with alowglucose suspend significantly reducednocturnal hypoglycemia, without increas-ing A1C levels for those over 16 years ofage (19). These devices may offer the op-portunity to reduce severe hypoglycemiafor those with a history of nocturnalhypoglycemia. Due to variable adher-ence, optimal CGM use requires an as-sessment of individual readiness for thetechnology as well as initial and ongoingeducation and support (13,20,21).

A1C Testing

Recommendations

c Perform the A1C test at least twotimes a year in patients who aremeeting treatment goals (and whohave stable glycemic control). E

c Perform the A1C test quarterly in pa-tients whose therapy has changed orwhoarenotmeetingglycemicgoals.E

c Use of point-of-care testing forA1C provides the opportunity formore timely treatment changes. E

A1C reflects average glycemia over sev-eral months (3) and has strong predictivevalue for diabetes complications (22,23).Thus, A1C testing should be performedroutinely in all patients with diabetesdatinitial assessment and as part of continu-ing care. Measurement approximatelyevery 3 months determines whether pa-tients’ glycemic targets have beenreached and maintained. The frequencyof A1C testing should depend on the clin-ical situation, the treatment regimen, andthe clinician’s judgment. Some patientswith stable glycemia well within targetmay do well with testing only twice peryear. Unstable or highly intensively man-aged patients (e.g., pregnantwomenwithtype1 diabetes)may require testingmorefrequently than every 3 months (24).

A1C Limitations

The A1C test is subject to certain limita-tions. Conditions that affect red blood cellturnover (hemolysis, blood loss) and he-moglobin variants must be considered,particularly when the A1C result doesnot correlate with the patient’s blood glu-cose levels (3). For patients in whomA1C/estimated average glucose (eAG) andmeasured blood glucose appear discrep-ant, clinicians should consider the possi-bilities of hemoglobinopathy or alteredred blood cell turnover and the optionsof more frequent and/or different timingof SMBG or CGM use. Other measures ofchronic glycemia such as fructosamineare available, but their linkage to averageglucose and their prognostic significanceare not as clear as for A1C.

The A1C does not provide a measureof glycemic variability or hypoglycemia.For patients prone to glycemic variabil-ity, especially type 1 diabetic patients ortype 2 diabetic patients with severe in-sulin deficiency, glycemic control is bestevaluated by the combination of results


from self-monitoring and the A1C. TheA1C may also confirm the accuracy ofthe patient’s meter (or the patient’s re-ported SMBG results) and the adequacyof the SMBG testing schedule.

A1C and Mean Glucose

Table 6.1 shows the correlation betweenA1C levels and mean glucose levels basedon two studies: the international A1C-Derived Average Glucose (ADAG) trial,which based the correlation with A1Con frequent SMBG and CGM in 507 adults(83% non-Hispanic whites) with type 1,type 2, and no diabetes (25), and an em-pirical study of the average blood glucoselevels at premeal, postmeal, and bedtimeassociated with specified A1C levels usingdata from the ADAG trial (21). The Amer-ican Diabetes Association (ADA) and theAmerican Association for Clinical Chemis-try have determined that the correlation(r 5 0.92) in the ADAG trial is strongenough to justify reporting both the A1Cresult and the eAG result when a clinicianorders the A1C test. Clinicians shouldnote that the mean plasma glucose num-bers in the table are based on ;2,800readings per A1C in the ADAG trial.

A1C Differences in Ethnic Populations and

Children

In the ADAG study, there were no signif-icant differences among racial and ethnicgroups in the regression lines betweenA1C and mean glucose, although therewas a trend toward a difference betweenthe African/African American and non-Hispanic white cohorts. A small study

comparing A1C to CGM data in childrenwith type 1 diabetes found a highly sta-tistically significant correlation betweenA1C and mean blood glucose, althoughthe correlation (r5 0.7) was significantlylower than in the ADAG trial (26).Whether there are significant differencesin how A1C relates to average glucose inchildren or in different ethnicities is anarea for further study (27,28). For thetime being, the question has not led todifferent recommendations about testingA1C or to different interpretations of theclinical meaning of given levels of A1C inthose populations.

A1C GOALS

For glycemic goals in children, please referto Section11. ChildrenandAdolescents. Forglycemic goals in pregnant women, pleaserefer to Section 12. Management of Diabe-tes in Pregnancy.

Recommendations

c Lowering A1C to approximately 7%or less has been shown to reducemicrovascular complications of dia-betes, and, if implemented soon af-ter the diagnosis of diabetes, it isassociated with long-term reduc-tion in macrovascular disease.Therefore, a reasonable A1C goalfor many nonpregnant adults is,7%. B

c Providers might reasonably sug-gest more stringent A1C goals(such as ,6.5%) for selected in-dividual patients if this canbe achieved without significant

hypoglycemia or other adverse ef-fects of treatment. Appropriatepatients might include those withshort duration of diabetes, type 2diabetes treated with lifestyle ormetformin only, long life expec-tancy, or no significant cardiovas-cular disease (CVD). C

c Less stringent A1C goals (such as,8%) may be appropriate for pa-tients with a history of severe hypo-glycemia, limited life expectancy,advanced microvascular or macro-vascular complications, extensive co-morbid conditions, or long-standingdiabetes in whom the general goalis difficult to attain despite diabetesself-management education, ap-propriate glucose monitoring,and effective doses of multipleglucose-lowering agents includinginsulin. B

A1C and Microvascular ComplicationsHyperglycemia defines diabetes, andglycemic control is fundamental todiabetes management. The DiabetesControl and Complications Trial (DCCT)(1), a prospective randomized controlledtrial of intensive versus standard glyce-mic control in patients with relativelyrecently diagnosed type 1 diabetesshowed definitively that improved glyce-mic control is associated with signifi-cantly decreased rates of microvascular(retinopathy and diabetic kidney dis-ease) and neuropathic complications.Follow-up of the DCCT cohorts in the

Table 6.1—Mean glucose levels for specified A1C levels (21,25)

A1C (%)

Mean plasma glucose*Mean fasting glucose Mean premeal glucose Mean postmeal glucose Mean bedtime glucose

mg/dL mmol/L mg/dL mg/dL mg/dL mg/dL

6 126 7.0

,6.5 122 118 144 136

6.5–6.99 142 139 164 153

7 154 8.6

7.0–7.49 152 152 176 177

7.5–7.99 167 155 189 175

8 183 10.2

8–8.5 178 179 206 222

9 212 11.8

10 240 13.4

11 269 14.9

12 298 16.5

A calculator for converting A1C results into eAG, in either mg/dL or mmol/L, is available at http://professional.diabetes.org/eAG.*These estimates are based on ADAG data of;2,700 glucose measurements over 3 months per A1Cmeasurement in 507 adults with type 1, type 2,and no diabetes. The correlation between A1C and average glucose was 0.92 (25).


Epidemiology of Diabetes Interventionsand Complications (EDIC) study (29,30)demonstrated persistence of thesemicrovascular benefits in previouslyintensively treated subjects, eventhough their glycemic control approxi-mated that of previous standard armsubjects during follow-up.The Kumamoto Study (31) and UK

Prospective Diabetes Study (UKPDS)(32,33) confirmed that intensiveglycemic control was associated with sig-nificantly decreased rates of microvascu-lar and neuropathic complications intype 2 diabetic patients. Long-termfollow-up of the UKPDS cohorts showedenduring effects of early glycemic con-trol on most microvascular complica-tions (34).Three landmark trials (Action to Con-

trol Cardiovascular Risk in Diabetes[ACCORD], Action in Diabetes and Vas-cular Disease: Preterax and DiamicronMR Controlled Evaluation [ADVANCE],and Veterans Affairs Diabetes Trial[VADT]) showed that lower A1C levelswere associated with reduced onset orprogression of microvascular complica-tions (35–37).Epidemiological analyses of the DCCT

(1) and UKPDS (38) demonstrate acurvilinear relationship between A1Cand microvascular complications.Such analyses suggest that, on a popu-lation level, the greatest number ofcomplications will be averted by takingpatients from very poor control to fair/good control. These analyses also sug-gest that further lowering of A1C from7% to 6% is associated with further re-duction in the risk of microvascularcomplications, though the absoluterisk reductions become much smaller.Given the substantially increased riskof hypoglycemia in type 1 diabetes tri-als and in recent type 2 diabetes trials,the risks of lower glycemic targets may,on a population level, outweigh thepotential benefits on microvascularcomplications.The concerning mortality findings in

the ACCORD trial, discussed below(39), and the relatively intense effortsrequired to achieve near-euglycemiashould also be considered when settingglycemic targets. However, based onphysician judgment and patient prefer-ences, select patients, especially thosewith little comorbidity and long life ex-pectancy, may benefit from adopting

more intensive glycemic targets (e.g.,A1C target ,6.5%) as long as signifi-cant hypoglycemia does not become abarrier.

A1C and Cardiovascular DiseaseOutcomesCVD is a more common cause of deaththan microvascular complications inpopulations with diabetes. There is evi-dence for a cardiovascular benefit of in-tensive glycemic control after long-termfollow-up of study cohorts treated earlyin the course of type 1 and type 2 di-abetes. In the DCCT, there was a trendtoward lower risk of CVD events withintensive control. In the 9-year post-DCCT follow-up of the EDIC cohort, par-ticipants previously randomized to theintensive arm had a significant 57% re-duction in the risk of nonfatal myocar-dial infarction (MI), stroke, or CVDdeath compared with those previouslyin the standard arm (40). The benefit ofintensive glycemic control in this type 1diabetic cohort has recently beenshown to persist for several decades(41).

In type 2 diabetes, there is evidencethat more intensive treatment ofglycemia in newly diagnosed patientsmay reduce long-term CVD rates. Dur-ing the UKPDS trial, there was a 16%reduction in CVD events (combinedfatal or nonfatal MI and sudden death)in the intensive glycemic controlarm that did not reach statistical sig-nificance (P 5 0.052), and there wasno suggestion of benefit on otherCVD outcomes (e.g., stroke). However,after 10 years of follow-up, those orig-inally randomized to intensive glyce-mic control had significant long-termreductions in MI (15% with sulfo-nylurea or insulin as initial pharmaco-therapy, 33% with metformin as initialpharmacotherapy) and in all-causemortality (13% and 27%, respectively)(34).

The ACCORD, ADVANCE, and VADTsuggested no significant reduction inCVD outcomes with intensive glycemiccontrol in participants followed for3.525.6 years who had more advancedtype 2 diabetes than UKPDS partici-pants. All three trials were conductedin participants with more long-standingdiabetes (mean duration 8–11 years)and either known CVD or multiple car-diovascular risk factors. The target A1C

among intensive control subjects was,6% in ACCORD, ,6.5% in ADVANCE,and a 1.5% reduction in A1C comparedwith control subjects in VADT. Details ofthese studies are reviewed extensivelyin the ADA position statement “IntensiveGlycemic Control and the Preventionof Cardiovascular Events: Implicationsof the ACCORD, ADVANCE, and VADiabetes Trials: A Position Statementof the American Diabetes Associationand a Scientific Statement of theAmerican College of Cardiology Foun-dation and the American HeartAssociation” (42).

The glycemic control comparison inACCORD was halted early due to anincreased mortality rate in the inten-sive compared with the standardarm (1.41% vs. 1.14% per year; hazardratio 1.22 [95% CI 1.01–1.46]), with asimilar increase in cardiovasculardeaths.

Key Points1. Analysis of the ACCORD data did not

identify a clear explanation for theexcess mortality in the intensivearm (39).

2. A group-level meta-analysis ofACCORD, ADVANCE, and VADTsuggested that glucose loweringhad a modest (9%) but statisti-cally significant reduction in majorCVD outcomes, primarily nonfatalMI, with no significant effect onmortality.

3. Heterogeneity of the mortality ef-fects across studies was noted.

4. A prespecified subgroup analy-sis suggested that major CVDoutcome reduction occurred in pa-tients without known CVD at base-line (hazard ratio 0.84 [95% CI0.74–0.94]) (43).

5. Mortality findings in ACCORD (39)and subgroup analyses of the VADT(44) suggested that the potentialrisks of intensive glycemic controlmay outweigh its benefits in somepatients.

6. Those with long duration of diabetes,known history of severe hypoglyce-mia, advanced atherosclerosis, or ad-vanced age/frailty may benefit fromless aggressive targets.

7. Severe hypoglycemia was signifi-cantly more likely in participants inall three trials randomized to the in-tensive glycemic control arm.


Providers should be vig i lant inpreventing severe hypoglycemia inpatients with advanced disease andshould not aggressively attempt toachieve near-normal A1C levels in pa-tients in whom such targets cannot besafely and reasonably achieved. Severeor frequent hypoglycemia is an abso-lute indication for the modification oftreatment regimens, including settinghigher glycemic goals. Many factors,including patient preferences, shouldbe taken into account when develop-ing a patient’s individualized goals(Table 6.2).

A1C and Glycemic TargetsNumerous aspects must be consideredwhen setting glycemic targets. TheADA proposes optimal targets, buteach target must be individualized tothe needs of each patient and theirdisease factors. When possible, suchdecisions should be made with thepatient, reflecting his or her preferences,needs, and values. Figure 6.1 is notdesigned to be applied rigidly but usedas a broad construct to guide clinicaldecision making (45), both in type 1and type 2 diabetes.Recommended glycemic targets for

many nonpregnant adults are shownin Table 6.2. The recommendationsinclude blood glucose levels that ap-pear to correlate with achievement ofan A1C of ,7%. The issue of prepran-dial versus postprandial SMBG targetsis complex (46). Elevated postchal-lenge (2-h oral glucose tolerancetest) glucose values have been associ-ated with increased cardiovascularrisk independent of fasting plasma glu-cose in some epidemiological studies.In subjects with diabetes, surrogatemeasures of vascular pathology, suchas endothelial dysfunction, are

negatively affected by postprandialhyperglycemia (47). It is clear that post-prandial hyperglycemia, like prepran-dial hyperglycemia, contributes toelevated A1C levels, with its relativecontribution being greater at A1C levelsthat are closer to 7%. However, outcomestudies have clearly shown A1C to bethe primary predictor of complications,and landmark glycemic control trialssuch as the DCCT and UKPDS reliedoverwhelmingly on preprandial SMBG.Additionally, a randomized controlledtrial in patients with known CVD foundno CVD benefit of insulin regimens

targeting postprandial glucose com-pared with those targeting prepran-dial glucose (48). Therefore, it isreasonable for postprandial testingto be recommended for individualswho have premeal glucose valueswithin target but have A1C valuesabove target. Taking postprandialplasma glucose measurements 1–2 hafter the start of a meal and usingtreatments aimed at reducing post-prandial plasma glucose values to,180 mg/dL (10 mmol/L) may helplower A1C.

An analysis of data from 470 par-ticipants of the ADAG study (237with type 1 diabetes and 147 withtype 2 diabetes) found that actualaverage glucose levels associatedwith conventional A1C targets werehigher than older DCCT and ADAtargets (Table 6.1) (21,25). These find-ings support that premeal glucosetargets may be relaxed without un-dermining overall glycemic control asmeasured by A1C. These data haveprompted a revision in the ADA-recommended premeal target to 80–130 mg/dL (4.4–7.2 mmol/L).

Table 6.2—Summary of glycemic recommendations for nonpregnant adults withdiabetesA1C ,7.0%*

Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L)

Peak postprandial capillary plasma glucose† ,180 mg/dL* (,10.0 mmol/L)

*More or less stringent glycemic goals may be appropriate for individual patients. Goals shouldbe individualized based on duration of diabetes, age/life expectancy, comorbid conditions,known CVD or advanced microvascular complications, hypoglycemia unawareness, andindividual patient considerations.†Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandialglucose goals. Postprandial glucose measurements should be made 1–2 h after the beginning ofthe meal, generally peak levels in patients with diabetes.

Figure 6.1—Depicted are patient and disease factors used to determine optimal A1C targets.Characteristics and predicaments toward the left justify more stringent efforts to lower A1C;those toward the right suggest less stringent efforts. Adapted with permission from Inzucchiet al. (45).


HYPOGLYCEMIA

Recommendations

c Individuals at risk for hypoglycemiashould be asked about symptom-atic and asymptomatic hypoglyce-mia at each encounter. C

c Glucose (15–20 g) is the preferredtreatment for the conscious individ-ual with hypoglycemia, although anyform of carbohydrate that containsglucosemaybeused. Fifteenminutesafter treatment, if SMBG shows con-tinued hypoglycemia, the treatmentshould be repeated. Once SMBG re-turns tonormal, the individual shouldconsume a meal or snack to preventrecurrence of hypoglycemia. E

c Glucagon should be prescribed forall individuals at an increased risk ofsevere hypoglycemia, and care-givers or family members of theseindividuals should be instructed onits administration. Glucagon admin-istration is not limited to healthcare professionals. E

c Hypoglycemia unawareness or oneor more episodes of severe hypo-glycemia should trigger reevalua-tion of the treatment regimen. E

c Insulin-treated patients with hypo-glycemia unawareness or an episodeof severe hypoglycemia should beadvised to raise their glycemic tar-gets to strictly avoid further hypogly-cemia for at least several weeks inorder to partially reverse hypoglyce-mia unawareness and reduce risk offuture episodes. A

c Ongoing assessment of cognitivefunction is suggested with increasedvigilance for hypoglycemia by the cli-nician, patient, and caregivers if lowcognition and/or declining cognitionis found. B

Hypoglycemia is the leading limiting fac-tor in the glycemic management of type1 and insulin-treated type 2 diabetes(49). Mild hypoglycemia may be incon-venient or frightening to patients withdiabetes. Severe hypoglycemia cancause acute harm to the person with di-abetes or others, especially if it causesfalls, motor vehicle accidents, or otherinjury. A large cohort study suggestedthat among older adults with type 2diabetes, a history of severe hypoglycemiawas associated with greater risk of

dementia (50). Conversely, in a substudyof the ACCORD trial, cognitive impair-ment at baseline or decline in cognitivefunction during the trial was significantlyassociated with subsequent episodes ofsevere hypoglycemia (51). Evidence fromthe DCCT/EDIC, which involved youngeradults and adolescents with type 1 diabe-tes, found no association between fre-quency of severe hypoglycemia andcognitive decline (52), as discussed inSection 11. Children and Adolescents.

Severe hypoglycemia was associatedwith mortality in participants in both thestandard and intensive glycemia armsof the ACCORD trial, but the relation-ships between hypoglycemia, achievedA1C, and treatment intensity were notstraightforward. An association of severehypoglycemia with mortality was alsofound in the ADVANCE trial (53). An asso-ciation between self-reported severe hy-poglycemia and 5-year mortality has alsobeen reported in clinical practice (54).

In 2013, the ADA and the EndocrineSociety published the consensus report“Hypoglycemia and Diabetes: A Reportof a Workgroup of the American Diabe-tes Association and the Endocrine Soci-ety” (55) on the effect and treatment ofhypoglycemia in patients with diabetes.Severe hypoglycemia was defined as anevent requiring the assistance of an-other person. Young children with type1 diabetes and the elderly were notedas particularly vulnerable due to theirlimited ability to recognize hypogly-cemic symptoms and effectively com-municate their needs. Individualizedpatient education, dietary interven-tion (e.g., bedtime snack to preventovernight hypoglycemia), exercisemanagement, medication adjustment,glucose monitoring, and routine clini-cal surveillance may improve patientoutcomes.

Hypoglycemia TreatmentHypoglycemia treatment requires inges-tion of glucose- or carbohydrate-containing foods. The acute glycemicresponse correlates better with the glu-cose content of food than with the car-bohydrate content of food. Pure glucoseis the preferred treatment, but any formof carbohydrate that contains glucosewill raise blood glucose. Added fat mayretard and then prolong the acute gly-cemic response. Ongoing insulin activityor insulin secretagogues may lead to

recurrent hypoglycemia unless furtherfood is ingested after recovery.

Glucagon

Those in close contact with, or having cus-todial care of, people with hypoglycemia-prone diabetes (family members,roommates, school personnel, child careproviders, correctional institution staff, orcoworkers) should be instructed on theuse of glucagon kits. An individual doesnot need to be a health care professionalto safely administer glucagon. A glucagonkit requires a prescription. Care should betaken to ensure that glucagon kits are notexpired.

Hypoglycemia PreventionHypoglycemia prevention is a criticalcomponent of diabetes management.SMBG and, for some patients, CGM areessential tools to assess therapy and de-tect incipient hypoglycemia. Patientsshould understand situations thatincrease their risk of hypoglycemia,such as fasting for tests or procedures,during or after intense exercise, andduring sleep. Hypoglycemia may in-crease the risk of harm to self or others,such as with driving. Teaching peoplewith diabetes to balance insulin useand carbohydrate intake and exerciseare necessary, but these strategies arenot always sufficient for prevention.

In type 1 diabetes and severelyinsulin-deficient type 2 diabetes, hypo-glycemia unawareness (or hypoglycemia-associated autonomic failure) canseverely compromise stringent diabe-tes control and quality of life. This syn-drome is characterized by deficientcounterregulatory hormone release, es-pecially in older adults, and a dimin-ished autonomic response, which bothare risk factors for, and caused by, hy-poglycemia. A corollary to this “viciouscycle” is that several weeks of avoid-ance of hypoglycemia has been demon-strated to improve counterregulationand awareness to some extent inmany patients (56). Hence, patientswith one or more episodes of severehypoglycemia may benefit from at leastshort-term relaxation of glycemictargets.

INTERCURRENT ILLNESS

For further information on managementof patients with hyperglycemia in thehospital, please refer to Section 13. Di-abetes Care in the Hospital, Nursing


Home, and Skilled Nursing Facility.Stressful events (e.g., illness, trauma,surgery, etc.) frequently aggravateglycemic control and may precipitatediabetic ketoacidosis or nonketotic hy-perosmolar state, life-threatening con-ditions that require immediate medicalcare to prevent complications and death.Any condition leading to deterioration inglycemic control necessitates more fre-quent monitoring of blood glucose;ketosis-prone patients also require urineor blood ketone monitoring. If accompa-nied by ketosis, vomiting, or alteration inlevel of consciousness, marked hypergly-cemia requires temporary adjustment ofthe treatment regimen and immediateinteraction with the diabetes careteam. The patient treated with noninsu-lin therapies or medical nutrition ther-apy alone may temporarily requireinsulin. Adequate fluid and caloric intakemust be assured. Infection or dehydra-tion is more likely to necessitate hospi-talization of the person with diabetesthan the person without diabetes.A physician with expertise in diabetes

management should treat the hospital-ized patient. For further information ondiabetic ketoacidosis management or hy-perglycemic nonketotic hyperosmolarstate, please refer to the ADA statement“Hyperglycemic Crises in Adult PatientsWith Diabetes” (57).

References1. The Diabetes Control and Complications TrialResearch Group. The effect of intensive treatmentof diabetes on the development and progressionof long-term complications in insulin-dependentdiabetesmellitus. N Engl JMed 1993;329:977–9862. Miller KM, Beck RW, Bergenstal RM, et al.;T1D Exchange Clinic Network. Evidence of astrong association between frequency of self-monitoring of blood glucose and hemoglobinA1c levels in T1D Exchange clinic registry partic-ipants. Diabetes Care 2013;36:2009–20143. Sacks DB, ArnoldM, Bakris GL, et al.; NationalAcademy of Clinical Biochemistry. Positionstatement executive summary: guidelines andrecommendations for laboratory analysis inthe diagnosis andmanagement of diabetes mel-litus. Diabetes Care 2011;34:1419–14234. Wang J, Zgibor J, Matthews JT, Charron-Prochownik D, Sereika SM, Siminerio L. Self-monitoring of blood glucose is associated withproblem-solving skills in hyperglycemia and hy-poglycemia. Diabetes Educ 2012;38:207–2185. Polonsky WH, Fisher L, Schikman CH, et al.Structured self-monitoring of blood glucose sig-nificantly reduces A1C levels in poorly con-trolled, noninsulin-treated type 2 diabetes:results from the Structured Testing Programstudy. Diabetes Care 2011;34:262–267

6. Ziegler R, Heidtmann B, Hilgard D, Hofer S,Rosenbauer J, Holl R; DPV-Wiss-Initiative. Fre-quency of SMBG correlates with HbA1c andacute complications in children and adolescentswith type 1 diabetes. Pediatr Diabetes 2011;12:11–177. Farmer A, Wade A, Goyder E, et al. Impact ofself monitoring of blood glucose in the manage-ment of patients with non-insulin treated dia-betes: open parallel group randomised trial.BMJ 2007;335:1328. O’Kane MJ, Bunting B, Copeland M, CoatesVE; ESMON Study Group. Efficacy of self moni-toring of blood glucose in patients with newlydiagnosed type 2 diabetes (ESMON study):randomised controlled trial. BMJ 2008;336:1174–11779. Simon J, Gray A, Clarke P, Wade A, Neil A,Farmer A; Diabetes Glycaemic Education andMonitoring Trial Group. Cost effectiveness ofself monitoring of blood glucose in patientswith non-insulin treated type 2 diabetes: eco-nomic evaluation of data from the DiGEM trial.BMJ 2008;336:1177–118010. Willett LR. ACP Journal Club. Meta-analysis:self-monitoring in non-insulin-treated type 2 di-abetes improved HbA1c by 0.25%. Ann InternMed 2012;156:JC6–JC1211. Malanda UL, Welschen LM, Riphagen II,Dekker JM, Nijpels G, Bot SD. Self-monitoringof blood glucose in patients with type 2 diabetesmellitus who are not using insulin. CochraneDatabase Syst Rev 2012;1:CD00506012. Tamborlane WV, Beck RW, Bode BW, et al.;Juvenile Diabetes Research Foundation Contin-uous Glucose Monitoring Study Group. Con-tinuous glucose monitoring and intensivetreatment of type 1 diabetes. N Engl J Med2008;359:1464–147613. Wong JC, Foster NC, Maahs DM, et al.; T1DExchange Clinic Network. Real-time continuousglucose monitoring among participants in theT1D Exchange clinic registry. Diabetes Care2014;37:2702–270914. Hommel E, Olsen B, Battelino T, et al.;SWITCH Study Group. Impact of continuous glu-cose monitoring on quality of life, treatmentsatisfaction, and use of medical care resources:analyses from the SWITCH study. Acta Diabetol2014;51:845–85115. Battelino T, Phillip M, Bratina N, Nimri R,Oskarsson P, Bolinder J. Effect of continuousglucose monitoring on hypoglycemia in type 1diabetes. Diabetes Care 2011;34:795–80016. Beck RW, Hirsch IB, Laffel L, et al.; JuvenileDiabetes Research Foundation Continuous Glu-coseMonitoring Study Group. The effect of con-tinuous glucose monitoring in well-controlledtype 1 diabetes. Diabetes Care 2009;32:1378–138317. Yeh H-C, Brown TT, Maruthur N, et al. Com-parative effectiveness and safety of methods ofinsulin delivery and glucose monitoring for di-abetes mellitus: a systematic review and meta-analysis. Ann Intern Med 2012;157:336–34718. Choudhary P, Ramasamy S, Green L, et al.Real-time continuous glucose monitoringsignificantly reduces severe hypoglycemia inhypoglycemia-unaware patients with type 1 di-abetes. Diabetes Care 2013;36:4160–416219. Bergenstal RM, Klonoff DC, Garg SK, et al.;ASPIRE In-Home Study Group. Threshold-based

insulin-pump interruption for reduction of hy-poglycemia. N Engl J Med 2013;369:224–23220. McQueen RB, Ellis SL, Maahs DM, AndersonHD, Nair KV, Campbell JD. Frequency of contin-uous glucose monitoring use and change in he-moglobin A1c for adults with type 1 diabetes ina clinical practice setting. Endocr Pract 2014;20:1007–101521. Wei N, Zheng H, Nathan DM. Empiricallyestablishing blood glucose targets to achieveHbA1c goals. Diabetes Care 2014;37:1048–105122. Albers JW, Herman WH, Pop-Busui R,et al.; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions andComplications Research Group. Effect of priorintensive insulin treatment during the DiabetesControl and Complications Trial (DCCT) on pe-ripheral neuropathy in type 1 diabetes duringthe Epidemiology of Diabetes Interventionsand Complications (EDIC) study. Diabetes Care2010;33:1090–109623. Stratton IM, Adler AI, Neil HAW, et al. As-sociation of glycaemia with macrovascular andmicrovascular complications of type 2 diabetes(UKPDS 35): prospective observational study.BMJ 2000;321:405–41224. Jovanovic L, Savas H, Mehta M, Trujillo A,Pettitt DJ. Frequent monitoring of A1C duringpregnancy as a treatment tool to guide therapy.Diabetes Care 2011;34:53–5425. Nathan DM, Kuenen J, Borg R, Zheng H,Schoenfeld D, Heine RJ; A1c-Derived AverageGlucose Study Group. Translating the A1C assayinto estimated average glucose values. DiabetesCare 2008;31:1473–147826. Wilson DM, Kollman; Diabetes Researchin Children Network (DirecNet) Study Group.Relationship of A1C to glucose concentrationsin children with type 1 diabetes: assessments byhigh-frequency glucose determinations by sen-sors. Diabetes Care 2008;31:381–38527. Buse JB, Kaufman FR, Linder B, Hirst K, ElGhormli L, Willi S; HEALTHY Study Group. Dia-betes screening with hemoglobin A(1c) versusfasting plasma glucose in a multiethnic middle-school cohort. Diabetes Care 2013;36:429–43528. Kamps JL, Hempe JM, Chalew SA. Racial dis-parity in A1C independent of mean blood glu-cose in children with type 1 diabetes. DiabetesCare 2010;33:1025–102729. The Diabetes Control and ComplicationsTrial/Epidemiology of Diabetes Interventionsand Complications Research Group. Retinopa-thy and nephropathy in patients with type 1 di-abetes four years after a trial of intensivetherapy. N Engl J Med 2000;342:381–38930. Martin CL, Albers J, Herman WH, et al.;DCCT/EDIC Research Group. Neuropathy amongthe Diabetes Control and Complications Trialcohort 8 years after trial completion. DiabetesCare 2006;29:340–34431. Ohkubo Y, Kishikawa H, Araki E, et al. Inten-sive insulin therapy prevents the progression ofdiabetic microvascular complications in Japa-nese patients with non-insulin-dependent dia-betesmellitus: a randomized prospective 6-yearstudy. Diabetes Res Clin Pract 1995;28:103–11732. UK Prospective Diabetes Study (UKPDS)Group. Effect of intensive blood-glucose controlwith metformin on complications in overweightpatients with type 2 diabetes (UKPDS 34). Lan-cet 1998;352:854–865


33. UK Prospective Diabetes Study (UKPDS)Group. Intensive blood-glucose control with sul-phonylureas or insulin compared with conven-tional treatment and risk of complications inpatients with type 2 diabetes (UKPDS 33). Lan-cet 1998;352:837–85334. Holman RR, Paul SK, Bethel MA, MatthewsDR, Neil HAW. 10-year follow-up of intensiveglucose control in type 2 diabetes. N EnglJ Med 2008;359:1577–158935. Duckworth W, Abraira C, Moritz T, et al.;VADT Investigators. Glucose control and vascu-lar complications in veterans with type 2 diabe-tes. N Engl J Med 2009;360:129–13936. Patel A, MacMahon S, Chalmers J, et al.;ADVANCE Collaborative Group. Intensive bloodglucose control and vascular outcomes in pa-tients with type 2 diabetes. N Engl J Med2008;358:2560–257237. Ismail-Beigi F, Craven T, Banerji MA, et al.;ACCORD trial group. Effect of intensive treat-ment of hyperglycaemia on microvascular out-comes in type 2 diabetes: an analysis of theACCORD randomised trial. Lancet 2010;376:419–43038. Adler AI, Stratton IM, Neil HAW, et al. As-sociation of systolic blood pressure with macro-vascular and microvascular complications oftype 2 diabetes (UKPDS 36): prospective obser-vational study. BMJ 2000;321:412–41939. Gerstein HC, Miller ME, Byington RP, et al.;Action to Control Cardiovascular Risk in Diabe-tes Study Group. Effects of intensive glucoselowering in type 2 diabetes. N Engl J Med2008;358:2545–255940. Nathan DM, Cleary PA, Backlund J-YC,et al.; Diabetes Control and ComplicationsTrial/Epidemiology of Diabetes Interventionsand Complications (DCCT/EDIC) Study ResearchGroup. Intensive diabetes treatment and cardio-vascular disease in patients with type 1 diabetes.N Engl J Med 2005;353:2643–265341. Nathan DM, Zinman B, Cleary PA, et al.;Diabetes Control and Complications Trial/

Epidemiology of Diabetes Interventions andComplications (DCCT/EDIC) Research Group.Modern-day clinical course of type 1 diabetesmellitus after 30 years’ duration: the DiabetesControl and Complications Trial/Epidemiologyof Diabetes Interventions and Complicationsand Pittsburgh Epidemiology of Diabetes Com-plications Experience (1983-2005). Arch InternMed 2009;169:1307–131642. Skyler JS, Bergenstal R, Bonow RO, et al.Intensive glycemic control and the preventionof cardiovascular events: implications of theACCORD, ADVANCE, and VA Diabetes Trials:a position statement of the American DiabetesAssociation and a scientific statement of theAmerican College of Cardiology Foundationand the American Heart Association. DiabetesCare 2009;32:187–19243. Turnbull FM, Abraira C, Anderson RJ, et al.Intensive glucose control and macrovascularoutcomes in type 2 diabetes. Diabetologia2009;52:2288–229844. Duckworth WC, Abraira C, Moritz TE, et al.;Investigators of the VADT. The duration of di-abetes affects the response to intensive glucosecontrol in type 2 subjects: the VA Diabetes Trial.J Diabetes Complications 2011;25:355–36145. Inzucchi SE, Bergenstal RM, Buse JB, et al.Management of hyperglycemia in type 2 diabe-tes, 2015: a patient-centered approach. Updateto a position statement of the American Diabe-tes Association and the European Associationfor the Study of Diabetes. Diabetes Care 2015;38:140–14946. American Diabetes Association. Postpran-dial blood glucose. Diabetes Care 2001;24:775–77847. Ceriello A, Taboga C, Tonutti L, et al. Evi-dence for an independent and cumulative effectof postprandial hypertriglyceridemia and hyper-glycemia on endothelial dysfunction and oxida-tive stress generation: effects of short- andlong-term simvastatin treatment. Circulation2002;106:1211–1218

48. Raz I, Wilson PWF, Strojek K, et al. Effects ofprandial versus fasting glycemia on cardiovas-cular outcomes in type 2 diabetes: the HEART2Dtrial. Diabetes Care 2009;32:381–38649. Cryer PE. Hypoglycaemia: the limiting factorin the glycaemicmanagement of type I and type IIdiabetes. Diabetologia 2002;45:937–94850. Whitmer RA, Karter AJ, Yaffe K, QuesenberryCP Jr, Selby JV. Hypoglycemic episodes and riskof dementia in older patients with type 2 diabe-tes mellitus. JAMA 2009;301:1565–157251. Punthakee Z, Miller ME, Launer LJ, et al.;ACCORD Group of Investigators; ACCORD-MIND Investigators. Poor cognitive functionand risk of severe hypoglycemia in type 2 dia-betes: post hoc epidemiologic analysis of theACCORD trial. Diabetes Care 2012;35:787–79352. Jacobson AM, Musen G, Ryan CM, et al.;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Com-plications Study Research Group. Long-term ef-fect of diabetes and its treatment on cognitivefunction. N Engl J Med 2007;356:1842–185253. Zoungas S, Patel A, Chalmers J, et al.;ADVANCE Collaborative Group. Severe hypo-glycemia and risks of vascular events and death.N Engl J Med 2010;363:1410–141854. McCoy RG, Van Houten HK, Ziegenfuss JY,Shah ND, Wermers RA, Smith SA. Increasedmortality of patients with diabetes reportingsevere hypoglycemia. Diabetes Care 2012;35:1897–190155. Seaquist ER, Anderson J, Childs B, et al. Hy-poglycemia and diabetes: a report of a work-group of the American Diabetes Associationand the Endocrine Society. Diabetes Care2013;36:1384–139556. Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N EnglJ Med 2004;350:2272–227957. Kitabchi AE, Umpierrez GE, Miles JM,Fisher JN. Hyperglycemic crises in adult pa-tients with diabetes. Diabetes Care 2009;32:1335–1343


7. Approaches to GlycemicTreatmentDiabetes Care 2015;38(Suppl. 1):S41–S48 | DOI: 10.2337/dc15-S010

PHARMACOLOGICAL THERAPY FOR TYPE 1 DIABETES

Recommendations

c Most people with type 1 diabetes should be treated with multiple-dose insulin(MDI) injections (three to four injections per day of basal and prandial insulin)or continuous subcutaneous insulin infusion (CSII). A

c Most people with type 1 diabetes should be educated in how to match pran-dial insulin dose to carbohydrate intake, premeal blood glucose, and antici-pated activity. E

c Most people with type 1 diabetes should use insulin analogs to reduce hypo-glycemia risk. A

Insulin TherapyThere are excellent reviews to guide the initiation and management of insulintherapy to achieve desired glycemic goals (1,2,3). Although most studies of MDIversus pump therapy have been small and of short duration, a systematic review andmeta-analysis concluded that there were no systematic differences in A1C or severehypoglycemia rates in children and adults between the two forms of intensive in-sulin therapy (4). A large randomized trial in type 1 diabetic patients with nocturnalhypoglycemia reported that sensor-augmented insulin pump therapy with thethreshold suspend feature reduced nocturnal hypoglycemia, without increasingglycated hemoglobin values (5). Overall, intensive management through pumptherapy/continuous glucose monitoring and active patient/family participationshould be strongly encouraged (6–8). For selected individuals who have masteredcarbohydrate counting, education on the impact of protein and fat on glycemicexcursions can be incorporated into diabetes management (9).The Diabetes Control and Complications Trial (DCCT) clearly showed that intensive

insulin therapy (three ormore injections per day of insulin) or CSII (insulin pump therapy)was a key part of improved glycemia and better outcomes (10,11). The studywas carriedout with short- and intermediate-acting human insulins. Despite better microvascularoutcomes, intensive insulin therapy was associated with a high rate of severe hypogly-cemia (62 episodes per 100 patient-years of therapy). Since the DCCT, a number of rapid-acting and long-acting insulin analogs havebeendeveloped. These analogs are associatedwith less hypoglycemia in type 1 diabetes, while matching the A1C lowering of humaninsulins (1,12).

Recommended therapy for type 1 diabetes consists of the following:1. Use MDI injections (three to four injections per day of basal and prandial insulin)

or CSII therapy.2. Match prandial insulin to carbohydrate intake, premeal blood glucose, and an-

ticipated physical activity.3. For most patients (especially those at an elevated risk of hypoglycemia), use

insulin analogs.4. For patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness,

a sensor-augmented low glucose threshold suspend pump may be considered.

PramlintidePramlintide, an amylin analog, is an agent that delays gastric emptying, bluntspancreatic secretion of glucagon, and enhances satiety. It is a U.S. Food and Drug

Suggested citation: American Diabetes Associa-tion. Approaches to glycemic treatment. Sec. 7.In Standards ofMedical Care in Diabetesd2015.Diabetes Care 2015;38(Suppl. 1):S41–S48




POSITIO

NSTA

TEMEN

T

Administration (FDA)-approved therapyfor use in type 1 diabetes. It has beenshown to induce weight loss and lowerinsulin dose; however, it is only indi-cated in adults. Concurrent reductionof prandial insulin dosing is required toreduce the risk of severe hypoglycemia.

Investigational AgentsMetformin

Adding metformin to insulin therapy mayreduce insulin requirements and improvemetabolic control in overweight/obesepatients with poorly controlled type 1diabetes. In a meta-analysis, metforminin type 1 diabetes was found to reduceinsulin requirements (6.6 U/day, P ,0.001) and led to small reductions inweight and total and LDL cholesterol butnot to improved glycemic control (abso-lute A1C reduction 0.11%, P5 0.42) (13).

Incretin-Based Therapies

Therapies approved for the treatment oftype 2 diabetes are currently being eval-uated in type 1 diabetes. Glucagon-likepeptide 1 (GLP-1) agonists and dipep-tidyl peptidase 4 (DPP-4) inhibitors arenot currently FDA approved for thosewith type 1 diabetes, but are being stud-ied in this population.

Sodium–Glucose Cotransporter 2 Inhibitors

Sodium–glucose cotransporter 2 (SGLT2)inhibitors provide insulin-independentglucose lowering by blocking glucosereabsorption in the proximal renal tubuleby inhibiting SGLT2. These agents providemodest weight loss and blood pressurereduction. Although there are two FDA-approved agents for use in patients withtype 2 diabetes, there are insufficientdata to recommend clinical use in type 1diabetes at this time (14).

PHARMACOLOGICAL THERAPY FORTYPE 2 DIABETES

Recommendations

c Metformin, if not contraindicatedand if tolerated, is the preferredinitial pharmacological agent fortype 2 diabetes. A

c In patients with newly diagnosedtype2 diabetes andmarkedly symp-tomatic and/or elevated blood glu-cose levels or A1C, consider initiatinginsulin therapy (with or withoutadditional agents). E

c If noninsulin monotherapy at max-imum tolerated dose does not

achieve or maintain the A1C targetover 3 months, add a second oralagent, a GLP-1 receptor agonist, orbasal insulin. A

c A patient-centered approachshould be used to guide choiceof pharmacological agents. Con-siderations inc lude efficacy,cost, potential side effects, weight,comorbidities, hypoglycemia risk,and patient preferences. E

c Due to the progressive nature oftype 2 diabetes, insulin therapy iseventually indicated for many pa-tients with type 2 diabetes. B

An updated American Diabetes Asso-ciation/European Association for theStudy of Diabetes position statement(15) evaluated the data and developedrecommendations, including advan-tages and disadvantages, for antihyper-glycemic agents for type 2 diabeticpatients. A patient-centered approachis stressed, including patient prefer-ences, cost and potential side effectsof each class, effects on body weight,and hypoglycemia risk. Lifestyle modifi-cations that improve health (see Section4. Foundations of Care) should be em-phasized along with any pharmacologi-cal therapy.

Initial TherapyMost patients should begin with life-style changes (lifestyle counseling,weight-loss education, exercise, etc.).When lifestyle efforts alone have notachieved or maintained glycemic goals,metformin monotherapy should beadded at, or soon after, diagnosis, un-less there are contraindications or intol-erance. Metformin has a long-standingevidence base for efficacy and safety, isinexpensive, and may reduce risk of car-diovascular events (16). In patients withmetformin intolerance or contraindica-tions, consider an initial drug from otherclasses depicted in Fig. 7.1 under “Dualtherapy” and proceed accordingly.

Combination TherapyAlthough there are numerous trialscomparing dual therapy with metforminalone, few directly compare drugs asadd-on therapy. A comparative effec-tiveness meta-analysis (17) suggeststhat overall each new class of noninsulinagents added to initial therapy lowers

A1C around 0.9–1.1%. A comprehensivelisting, including the cost, is available inTable 7.1.

If the A1C target is not achieved afterapproximately 3 months, consider acombination of metformin and one ofthese six treatment options: sulfonyl-urea, thiazolidinedione, DPP-4 inhibi-tors, SGLT2 inhibitors, GLP-1 receptoragonists, or basal insulin (Fig. 7.1).Drug choice is based on patient prefer-ences as well as various patient, disease,and drug characteristics, with the goal ofreducing blood glucose levels whileminimizing side effects, especially hypo-glycemia. Figure 7.1 emphasizes drugscommonly used in theU.S. and/or Europe.

Rapid-acting secretagogues (megliti-nides) may be used instead of sulfonyl-ureas in patients with irregular mealschedules or who develop late post-prandial hypoglycemia on a sulfonyl-urea. Other drugs not shown in thefigure (e.g., a-glucosidase inhibitors, co-lesevelam, bromocriptine, pramlintide)may be tried in specific situations, butare generally not favored due to modestefficacy, the frequency of administra-tion, and/or side effects.

For all patients, consider initiatingtherapy with a dual combination whenA1C is $9% to more expeditiouslyachieve the target A1C level. Insulinhas the advantage of being effectivewhere other agents may not be andshould be considered as part of anycombination regimen when hyperglyce-mia is severe, especially if symptoms arepresent or any catabolic features(weight loss, ketosis) are in evidence.Consider initiating combination insulininjectable therapy when blood glucoseis$300–350 mg/dL (16.7–19.4 mmol/L)and/or A1C is $10–12%. As the pa-tient’s glucose toxicity resolves, theregimen can, potentially, be subse-quently simplified.

Insulin TherapyMany patients with type 2 diabetes even-tually require and benefit from insulintherapy. Providers may wish to considerregimen flexibility when devising a planfor the initiation and adjustment of insu-lin therapy in people with type 2 diabetes(Fig. 7.2). The progressive nature of type2 diabetes and its therapies should beregularly and objectively explained to pa-tients. Providers should avoid using insu-lin as a threat or describing it as a failure


or punishment. Equipping patients withan algorithm for self-titration of insulindoses based on self-monitoring of bloodglucose (SMBG) improves glycemic con-trol in type 2 diabetic patients initiatinginsulin (18).Basal insulin alone is the most conve-

nient initial insulin regimen, beginningat 10 U or 0.1–0.2 U/kg, depending onthe degree of hyperglycemia. Basal in-sulin is usually prescribed in conjunctionwith metformin and possibly one addi-tional noninsulin agent. If basal insulinhas been titrated to an acceptable fast-ing blood glucose level, but A1C remainsabove target, consider advancing to

combination injectable therapy (Fig. 7.2)to cover postprandial glucose excur-sions. Options include adding a GLP-1receptor agonist or mealtime insulin,consisting of one to three injections ofrapid-acting insulin analog (lispro, as-part, or glulisine) administered just be-fore eating. A less studied alternative,transitioning from basal insulin totwice-daily premixed (or biphasic) insu-lin analog (70/30 aspart mix, 75/25or 50/50 lispro mix), could also be con-sidered. Regular human insulin andhuman NPH-Regular premixed formula-tions (70/30) are less costly alternativesto rapid-acting insulin analogs and

premixed insulin analogs, respectively,but their pharmacodynamic profilesmake them suboptimal for the coverageof postprandial glucose excursions. Aless commonly used and more costlyalternative to “basal–bolus” therapywith multiple daily injections is CSII(insulin pump). In addition to the sug-gestions provided for determiningthe starting dose of mealtime insulinunder a basal–bolus regimen, anothermethod consists of adding up the totalcurrent insulin dose and then providingone-half of this amount as basal andone-half as mealtime insulin, the lattersplit evenly between three meals.

Figure 7.1—Antihyperglycemic therapy in type 2 diabetes: general recommendations (15). The order in the chart was determined by historicalavailability and the route of administration, with injectables to the right; it is not meant to denote any specific preference. Potential sequences ofantihyperglycemic therapy for patients with type 2 diabetes are displayed, with the usual transition moving vertically from top to bottom (althoughhorizontal movement within therapy stages is also possible, depending on the circumstances). DPP-4-i, DPP-4 inhibitor; fxs, fractures; GI, gastro-intestinal; GLP-1-RA, GLP-1 receptor agonist; GU, genitourinary; HF, heart failure; Hypo, hypoglycemia; SGLT2-i, SGLT2 inhibitor; SU, sulfonylurea;TZD, thiazolidinedione. *See ref. 15 for description of efficacy categorization. †Consider starting at this stage when A1C is$9%. ‡Consider starting atthis stage when blood glucose is$300–350 mg/dL (16.7–19.4 mmol/L) and/or A1C is$10–12%, especially if symptomatic or catabolic features arepresent, in which case basal insulin 1 mealtime insulin is the preferred initial regimen. §Usually a basal insulin (NPH, glargine, detemir, degludec).Adapted with permission from Inzucchi et al. (15).


Table

7.1—

Pro

pertiesofava

ilable

gluco

se-loweringagen

tsin

theU.S.andEuro

pethat

mayguideindividualize

dtreatm

entch

oicesin

patients

withtype2diabetes(15)

Class

Compound(s)

Cellularmechanism(s)

Primaryph

ysiologicalaction(s)

Advantages

Disadvantages

Cost*

Biguanides

cMetform

inActivates

AMP-kinase

(?other)

c↓Hep

aticglucose

production

cExtensive

experience

cGastrointestinalsideeffects(diarrhea,

abdominalcram

ping)

Low

cNohypoglycem

iacLacticacidosisrisk

(rare)

c↓CVDeven

ts(UKP

DS)

cVitam

inB12defi

cien

cycMultiple

contraindications:CKD

,acidosis,hypoxia,deh

ydration,etc.

Sulfonylureas

2ndGen

eration

ClosesKATPchan

nelson

b-cellp

lasm

amem

branes

c↑Insulin

secretion

cExtensive

experience

cHypoglycem

iaLow

cGlyburide/gliben

clam

ide

c↓Microvascularrisk

(UKP

DS)

c↑Weight

cGlipizide

c?Bluntsmyocardialischem

icpreconditioning

cGliclazide†

cLowdurability

cGlim

epiride

Meglitinides

(glinides)

cRep

aglinide

ClosesKATPchan

nelson

b-cellp

lasm

amem

branes

c↑Insulin

secretion

c↓P

ostprandialglucose

excursions

cHypoglycem

iaModerate

cNateglinide

cDosingflexibility

c↑Weight

c?Bluntsmyocardialischem

icpreconditioning

cFreq

uen

tdosingsched

ule

TZDs

cPioglitazone‡

Activates

thenuclear

transcriptionfactor

PPAR-g

c↑Insulin

sensitivity

cNohypoglycem

iac↑Weight

Low

cRosiglitazone§

cDurability

cEdem

a/heartfailure

c↑HDL-C

cBonefractures

c↓Triglycerides

(pioglitazone)

c↑LD

L-C(rosiglitazone)

c?↓CVDeven

ts(PROactive,

pioglitazone)

c?↑MI(m

eta-an

alyses,rosiglitazone)

a-Glucosidase

inhibitors

cAcarbose

Inhibitsintestinal

a-glucosidase

cSlow

sintestinalcarboh

ydrate

digestion/absorption

cNohypoglycem

iacGen

erallymodestA1C

efficacy

Moderate

cMiglitol

c↓P

ostprandialglucose

excursions

c?↓CVDeven

ts(STO

P-NIDDM)

cGastrointestinalsideeffects

(flatulence,d

iarrhea)

cNonsystem

ic

cFreq

uen

tdosingsched

ule

DPP

-4inhibitors

cSitagliptin

InhibitsDPP

-4activity,

increasingpostprandial

active

incretin

(GLP-1,GIP)

concentrations

c↑Insulin

secretion

(glucose-dep

enden

t)cNohypoglycem

iacAngioedem

a/urticariaandother

immune-mediatedderm

atological

effects

High

cVildagliptin†

c↓Glucago

nsecretion

(glucose-dep

enden

t)

cWelltolerated

c?Acute

pancreatitis

cSaxagliptin

cLinagliptin

c?↑Heartfailure

hospitalizations

cAlogliptin

Bile

acid

sequestrants

cColesevelam

Bindsbile

acidsin

intestinaltract,increasing

hep

aticbile

acid

production

c?↓Hep

aticglucose

production

cNohypoglycem

iacGen

erallymodestA1C

efficacy

High

c?↑Incretin

levels

c↓LD

L-C

cConstipation

c↑Triglycerides

cMay

↓absorptionofother

med

ications

Con

tinu

edon

p.S45


Table

7.1—

Continued

Class

Compound(s)

Cellularmechanism(s)

Primaryph

ysiologicalaction(s)

Advantages

Disad

vantages

Cost*

Dopam

ine-2

agonists

cBromocriptine(quickrelease)§

Activates

dopam

inergic

receptors

cModulateshypothalam

icregu

lationofmetabolism

cNohypoglycem

iacGen

erallymodestA1C

efficacy

High

cDizziness/syncope

c↑Insulin

sensitivity

c?↓CVDeven

ts(CyclosetSafety

Trial)

cNausea

cFatigue

cRhinitis

SGLT2inhibitors

cCan

aglifl

ozin

InhibitsSG

LT2in

the

proximalnep

hron

cBlocksglucose

reab

sorption

bythekidney,increasing

glucosuria

cNohypoglycem

iacGen

itourinaryinfections

High

cDapagliflozin‡

c↓Weigh

tcPo

lyuria

cEm

paglifl

ozin

cVolumedep

letion/hypotension/

dizziness

c↓Bloodpressure

c↑LD

L-C

cEffectiveat

allstages

ofT2DM

c↑Creatinine(transien

t)

GLP-1

receptor

agonists

cExen

atide

Activates

GLP-1

receptors

c↑Insulin

secretion(glucose-

dep

enden

t)cNohypoglycem

iacGastrointestinalsideeffects(nausea/

vomiting/diarrhea)

High

cExen

atideextended

release

c↓Glucagonsecretion

(glucose-dep

enden

t)c↑Heartrate

cLiraglutide

c↓Weigh

t

c?Acute

pancreatitis

cAlbiglutide

cSlowsgastricem

ptying

c↓Po

stprandialglucose

excursions

cC-cellh

yperplasia/med

ullary

thyroid

tumorsin

anim

als

cLixisenatide†

c↑Satiety

c↓Somecardiovascular

risk

factors

cInjectab

lecDulaglutide

cTrainingrequirem

ents

Amylin

mim

etics

cPram

lintide§

Activates

amylin

receptors

c↓Glucagonsecretion

c↓Postprandialglucose

excursions

cGen

erallymodestA1C

efficacy

High

c↑Satiety

c↓Weigh

tcGastrointestinalsideeffects(nausea/

vomiting)

cHypoglycem

iaunless

insulin

dose

issimultan

eouslyreduced

cSlowsgastricem

ptying

cInjectab

lecFreq

uen

tdosingsched

ule

cTrainingrequirem

ents

Insulins

cRapid-actinganalogs

Activates

insulin

receptors

c↑Glucose

disposal

cNearlyuniversal

response

cHypoglycem

iaVariable#

-Lispro

-Aspart

-Glulisine

cShort-acting

-Human

Regular

cInterm

ediate-acting

cWeigh

tgain

-Human

NPH

cBasalinsulin

analogs

c↓Hep

aticglucose

production

c↓Microvascularrisk

(UKPD

S)

c?Mitogeniceffects

-Glargine

cInjectab

le

-Detem

ir

cTrainingrequirem

ents

-Degludec†

cOther

cTheo

retically

unlim

ited

efficacy

cPatien

treluctan

ce

cPrem

ixed

(severaltypes)

CKD

,chronickidney

disease;CVD,cardiovasculardisease;GIP,glucose-dep

enden

tinsulinotropicpep

tide;

HDL-C,H

DLcholesterol;LD

L-C,LDLcholesterol;MI,myocardialinfarction;PP

AR-g,p

eroxisome

proliferator–activatedreceptorg;PR

Oactive,P

rospective

PioglitazoneClinicalTrialinMacrovascularEven

ts(30);STOP-NIDDM,Studyto

Preven

tNon-Insulin-Dep

enden

tDiabetes

Mellitus(31);TZD,

thiazolidined

ione;T2DM,type2diabetes

mellitus;UKP

DS,UKProspective

Diabetes

Study(32,33

).Cyclosettrialofq

uick-releasebromocriptine(34).*Costisbased

onlowest-pricedmem

ber

oftheclass(see

ref.

15).†Notlicen

sedintheU.S.‡Initialconcernsregardingbladder

cancerrisk

aredecreasingaftersubsequen

tstudy.§N

otlicen

sedinEuropefortype2diabetes.#Costishighlydep

enden

tontype/brand(analogs

.human

insulins)anddosage.Adap

tedwithpermissionfrom

Inzucchietal.(15).


Figure 7.2 focuses solely on sequen-tial insulin strategies, describing thenumber of injections and the relativecomplexity and flexibility of each stage.Once an insulin regimen is initiated,dose titration is important, with adjust-ments made in both mealtime and basalinsulins based on the prevailing bloodglucose levels and an understanding ofthe pharmacodynamic profile of eachformulation (pattern control).Noninsulin agents may be continued,

although sulfonylureas, DPP-4 inhibitors,and GLP-1 receptor agonists are typicallystopped once more complex insulin regi-mens beyond basal are used. In patientswith suboptimal blood glucose control,especially those requiring increasing insu-lin doses, adjunctive use of thiazolidine-diones (usually pioglitazone) or SGLT2

inhibitors may be helpful in improvingcontrol and reducing the amount of in-sulin needed. Comprehensive educa-tion regarding SMBG, diet, exercise,and the avoidance of and response tohypoglycemia are critically important inany patient using insulin.

BARIATRIC SURGERY

Recommendations

c Bariatric surgery may be con-sidered for adults with BMI .35kg/m2 and type 2 diabetes, espe-cially if diabetes or associated co-morbidities are difficult to controlwith lifestyle and pharmacologicaltherapy. B

c Patients with type 2 diabetes whohave undergone bariatric surgery

need lifelong lifestyle supportand medical monitoring. B

c Although small trials have shownglycemic benefit of bariatric surgeryin patients with type 2 diabetes andBMI 30–35 kg/m2, there is currentlyinsufficient evidence to generallyrecommend surgery in patientswith BMI,35 kg/m2. E

Bariatric and metabolic surgeries,either gastric banding or proceduresthat involve resecting, bypassing, ortransposing sections of the stomachand small intestine, can be effectiveweight-loss treatments for severeobesity when performed as part of acomprehensive weight-managementprogram with lifelong lifestyle support

Figure 7.2—Approach to starting and adjusting insulin in type 2 diabetes (15). FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; hypo,hypoglycemia; mod., moderate; PPG, postprandial glucose; #, number. Adapted with permission from Inzucchi et al. (15).


andmedical monitoring. National guide-lines support consideration for bariatricsurgery for people with type 2 diabeteswith BMI .35 kg/m2.

AdvantagesTreatment with bariatric surgery hasbeen shown to achieve near- or com-plete normalization of glycemia 2 yearsfollowing surgery in 72% of patients(compared with 16% in a matched con-trol group treated with lifestyle andpharmacological interventions) (19). Astudy evaluated the long-term (3-year)outcomes of surgical intervention(Roux-en-Y gastric bypass or sleeve gas-trectomy) and intensive medical ther-apy (quarterly visits, pharmacologicaltherapy, SMBG, diabetes education, life-style counseling, and encouragement toparticipate in Weight Watchers) com-pared with just intensive medical ther-apy on achieving a target A1C #6%among obese patients with uncon-trolled type 2 diabetes (mean A1C9.3%). This A1C target was achieved by38% (P , 0.001) in the gastric bypassgroup, 24% (P5 0.01) in the sleeve gas-trectomy group, and 5% in those receiv-ing medical therapy (20). Diabetesremission rates tend to be higher withprocedures that bypass portions of thesmall intestine and lower with proce-dures that only restrict the stomach.Younger age, shorter duration of type

2 diabetes, lower A1C, higher serum in-sulin levels, and nonuse of insulin haveall been associated with higher remis-sion rates after bariatric surgery (21).Although bariatric surgery has been

shown to improve themetabolic profilesof morbidly obese patients with type 1diabetes, the role of bariatric surgery insuch patients will require larger and lon-ger studies (22).

DisadvantagesBariatric surgery is costly and has asso-ciated risks. Morbidity and mortalityrates directly related to the surgeryhave decreased considerably in recentyears, with 30-day mortality rates now0.28%, similar to those for laparoscopiccholecystectomy (23). Outcomes varydepending on the procedure and theexperience of the surgeon and center.Longer-term concerns include vitaminand mineral deficiencies, osteoporosis,and rare but often severe hypoglycemiafrom insulin hypersecretion. Cohort

studies attempting to match surgicaland nonsurgical subjects suggest thatthe procedure may reduce longer-termmortality rates (19). In contrast, a pro-pensity score-adjusted analysis of older,severely obese patients in Veterans Af-fairs Medical Centers found that bariatricsurgery was not associated with de-creased mortality compared with usualcare (mean follow-up 6.7 years) (24). Ret-rospective analyses and modeling studiessuggest that bariatric surgery may becost-effective for patients with type 2diabetes, but the results are largely de-pendent on assumptions about thelong-term effectiveness and safety ofthe procedures (25–27). Understandingthe long-term benefits and risks of bariat-ric surgery in individuals with type 2 diabe-tes, especially those who are not severelyobese, will require well-designed clinicaltrials, with optimal medical therapy asthe comparator (28). Unfortunately, suchstudies may not be feasible (29).

References1. DeWitt DE, Hirsch IB. Outpatient insulin ther-apy in type 1 and type 2 diabetes mellitus: sci-entific review. JAMA 2003;289:2254–22642. American Diabetes Association. IntensiveDiabetes Management. 4th ed. Wolfsdorf JI, Ed.Alexandria, VA, American Diabetes Association,20093. Mooradian AD, Bernbaum M, Albert SG. Nar-rative review: a rational approach to starting in-sulin therapy. Ann Intern Med 2006;145:125–1344. Yeh H-C, Brown TT, Maruthur N, et al. Com-parative effectiveness and safety of methods ofinsulin delivery and glucose monitoring for di-abetes mellitus: a systematic review and meta-analysis. Ann Intern Med 2012;157:336–3475. Bergenstal RM, Klonoff DC, Garg SK, et al.;ASPIRE In-Home Study Group. Threshold-basedinsulin-pump interruption for reduction of hy-poglycemia. N Engl J Med 2013;369:224–2326. Wood JR, Miller KM, Maahs DM, et al.; T1DExchange Clinic Network. Most youth with type 1diabetes in the T1D Exchange clinic registry donot meet American Diabetes Association or In-ternational Society for Pediatric and AdolescentDiabetes clinical guidelines. Diabetes Care 2013;36:2035–20377. Kmietowicz Z. Insulin pumps improve controland reduce complications in children with type1 diabetes. BMJ 2013;347:f51548. PhillipM, Battelino T, Atlas E, et al. Nocturnalglucose control with an artificial pancreas at adiabetes camp. N Engl J Med 2013;368:824–8339. Wolpert HA, Atakov-Castillo A, Smith SA,Steil GM. Dietary fat acutely increases glucoseconcentrations and insulin requirements inpatients with type 1 diabetes: implications forcarbohydrate-based bolus dose calculation andintensive diabetes management. Diabetes Care2013;36:810–816

10. The Diabetes Control and ComplicationsTrial Research Group. The effect of intensivetreatment of diabetes on the developmentand progression of long-term complications ininsulin-dependent diabetes mellitus. N Engl JMed 1993;329:977–98611. Nathan DM, Cleary PA, Backlund J-YC, et al.;Diabetes Control and Complications Trial/Epi-demiology of Diabetes Interventions and Com-plications (DCCT/EDIC) Study Research Group.Intensive diabetes treatment and cardiovascu-lar disease in patients with type 1 diabetes.N Engl J Med 2005;353:2643–265312. Rosenstock J, Dailey G, Massi-Benedetti M,Fritsche A, Lin Z, Salzman A. Reduced hypoglyce-mia risk with insulin glargine: a meta-analysiscomparing insulin glargine with human NPHinsulin in type 2 diabetes. Diabetes Care 2005;28:950–95513. Vella S, Buetow L, Royle P, Livingstone S,Colhoun HM, Petrie JR. The use of metforminin type 1 diabetes: a systematic review of effi-cacy. Diabetologia 2010;53:809–82014. Chiang JL, KirkmanMS, Laffel LM, Peters AL;Type 1 Diabetes Sourcebook Authors. Type 1diabetes through the life span: a position state-ment of the American Diabetes Association. Di-abetes Care 2014;37:2034–205415. Inzucchi SE, Bergenstal RM, Buse JB, et al.Management of hyperglycemia in type 2 diabe-tes, 2015: a patient-centered approach. Updateto a position statement of the American Diabe-tes Association and the European Associationfor the Study of Diabetes. Diabetes Care 2015;38:140–14916. Holman RR, Paul SK, Bethel MA, MatthewsDR, Neil HA. 10-year follow-up of intensive glu-cose control in type 2 diabetes. N Engl J Med2008;359:1577–158917. Bennett WL, Maruthur NM, Singh S, et al.Comparative effectiveness and safety of medi-cations for type 2 diabetes: an update includingnew drugs and 2-drug combinations. Ann InternMed 2011;154:602–61318. Blonde L, Merilainen M, Karwe V, Raskin P;TITRATE Study Group. Patient-directed titrationfor achieving glycaemic goals using a once-dailybasal insulin analogue: an assessment of two dif-ferent fasting plasma glucose targets - the TITRATEstudy. Diabetes Obes Metab 2009;11:623–63119. Sjostrom L, Peltonen M, Jacobson P, et al.Association of bariatric surgery with long-termremission of type 2 diabetes and with microvas-cular and macrovascular complications. JAMA2014;311:2297–230420. Schauer PR, Bhatt DL, Kirwan JP, et al.;STAMPEDE Investigators. Bariatric surgeryversus intensive medical therapy for diabetesd3-year outcomes. N Engl J Med 2014;370:2002–201321. Still CD, Wood GC, Benotti P, et al. Preop-erative prediction of type 2 diabetes remissionafter Roux-en-Y gastric bypass surgery: a retro-spective cohort study. Lancet Diabetes Endocri-nol 2014;2:38–4522. Brethauer SA, Aminian A, Rosenthal RJ,Kirwan JP, Kashyap SR, Schauer PR. Bariatricsurgery improves the metabolic profile of mor-bidly obese patients with type 1 diabetes. Di-abetes Care 2014;37:e51–e5223. Buchwald H, Estok R, Fahrbach K, Banel D,Sledge I. Trends in mortality in bariatric surgery:


a systematic review and meta-analysis. Surgery2007;142:621–63224. Maciejewski ML, Livingston EH, Smith VA,et al. Survival among high-risk patients afterbariatric surgery. JAMA 2011;305:2419–242625. Hoerger TJ, Zhang P, Segel JE, Kahn HS,Barker LE, Couper S. Cost-effectiveness of bari-atric surgery for severely obese adults with di-abetes. Diabetes Care 2010;33:1933–193926. Makary MA, Clark JM, Shore AD, et al. Med-ication utilization and annual health care costsin patients with type 2 diabetes mellitus beforeand after bariatric surgery. Arch Surg 2010;145:726–73127. Keating CL, Dixon JB,MoodieML, Peeters A,Playfair J, O’Brien PE. Cost-efficacy of surgicallyinduced weight loss for the management oftype 2 diabetes: a randomized controlled trial.Diabetes Care 2009;32:580–584

28. Wolfe BM, Belle SH. Long-term risks andbenefits of bariatric surgery: a research chal-lenge. JAMA 2014;312:1792–179329. Courcoulas AP, Goodpaster BH, Eagleton JK,et al. Surgical vs medical treatments for type 2diabetes mellitus: a randomized clinical trial.JAMA Surg 2014;149:707–71530. Dormandy JA, Charbonnel B, Eckland DJ,et al.; PROactive Investigators. Secondary pre-vention of macrovascular events in patientswith type 2 diabetes in the PROactive Study(PROspective pioglitAzone Clinical Trial In mac-rovascular Events): a randomised controlled tri-al. Lancet 2005;366:1279–128931. Chiasson JL, Gomis R, HanefeldM, Josse RG,Karasik A, Laakso M; STOP-NIDDM TrialResearch Group. The STOP-NIDDM Trial: an in-ternational study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes

in a populationwith impaired glucose tolerance:rationale, design, and preliminary screeningdata. Diabetes Care 1998;21:1720–172532. UK Prospective Diabetes Study (UKPDS)Group. Intensive blood-glucose control with sul-phonylureas or insulin compared with conven-tional treatment and risk of complications inpatients with type 2 diabetes (UKPDS 33). Lan-cet 1998;352:837–85333. UK Prospective Diabetes Study (UKPDS)Group. Effect of intensive blood-glucose controlwith metformin on complications in overweightpatients with type 2 diabetes (UKPDS 34). Lan-cet 1998;352:854–86534. Gaziano JM, Cincotta AH, O’Connor CM,et al. Randomized clinical trial of quick-releasebromocriptine among patients with type 2 di-abetes on overall safety and cardiovascular out-comes. Diabetes Care 2010;33:1503–1508


8. Cardiovascular Disease and RiskManagementDiabetes Care 2015;38(Suppl. 1):S49–S57 | DOI: 10.2337/dc15-S011

For prevention and management of diabetes complications in children and adoles-cents, please refer to Section 11. Children and Adolescents.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality forindividuals with diabetes and is the largest contributor to the direct and indirectcosts of diabetes. The common conditions coexisting with type 2 diabetes (e.g.,hypertension and dyslipidemia) are clear risk factors for CVD, and diabetesitself confers independent risk. Numerous studies have shown the efficacy of con-trolling individual cardiovascular risk factors in preventing or slowing CVD in peoplewith diabetes. Large benefits are seen when multiple risk factors are addressedglobally (1,2). There is evidence that measures of 10-year coronary heart disease (CHD)risk among U.S. adults with diabetes have improved significantly over the past decade (3).

HYPERTENSION/BLOOD PRESSURE CONTROL

Recommendations

Screening and Diagnosisc Blood pressure should be measured at every routine visit. Patients found to

have elevated blood pressure should have blood pressure confirmed on aseparate day. B

Goalsc People with diabetes and hypertension should be treated to a systolic blood

pressure (SBP) goal of ,140 mmHg. Ac Lower systolic targets, such as ,130 mmHg, may be appropriate for certain

individuals, such as younger patients, if they can be achieved without unduetreatment burden. C

c Individuals with diabetes should be treated to a diastolic blood pressure (DBP),90 mmHg. A

c Lower diastolic targets, such as ,80 mmHg, may be appropriate for certainindividuals, such as younger patients, if they can be achieved without unduetreatment burden. B

Treatmentc Patients with blood pressure .120/80 mmHg should be advised on lifestyle

changes to reduce blood pressure. Bc Patients with confirmed office-based blood pressure higher than 140/90

mmHg should, in addition to lifestyle therapy, have prompt initiation andtimely subsequent titration of pharmacological therapy to achieve blood pres-sure goals. A

c Lifestyle therapy for elevated blood pressure consists of weight loss, if over-weight or obese; a Dietary Approaches to Stop Hypertension (DASH)-styledietary pattern including reducing sodium and increasing potassium intake;moderation of alcohol intake; and increased physical activity. B

c Pharmacological therapy for patients with diabetes and hypertension shouldcomprise a regimen that includes either an ACE inhibitor or an angiotensinreceptor blocker (ARB). B If one class is not tolerated, the other should besubstituted. C

c Multiple-drug therapy (including a thiazide diuretic and ACE inhibitor/ARB, atmaximal doses) is generally required to achieve blood pressure targets. B

Suggested citation: American Diabetes Associa-tion. Cardiovascular disease and risk manage-ment. Sec. 8. In Standards of Medical Care inDiabetesd2015. Diabetes Care 2015;38(Suppl. 1):S49–S57




POSITIO

NSTA

TEMEN

T

c If ACE inhibitors, ARBs, or diureticsareused, serumcreatinine/estimatedglomerular filtration rate (eGFR) andserum potassium levels should bemonitored. E

c In pregnant patients with diabetesand chronic hypertension, bloodpressure targets of 110–129/65–79 mmHg are suggested in theinterest of optimizing long-termmaternal health and minimizingimpaired fetal growth. ACE inhibi-tors and ARBs are contraindicatedduring pregnancy. E

Hypertension is a common diabetescomorbidity that affects the majorityof patients, with the prevalence de-pending on type of diabetes, age, obe-sity, and ethnicity. Hypertension is amajor risk factor for both CVD and mi-crovascular complications. In type 1 di-abetes, hypertension is often the resultof underlying nephropathy, while intype 2 diabetes it usually coexists withother cardiometabolic risk factors.

Screening and DiagnosisBlood pressure measurement should bedone by a trained individual and followthe guidelines established for the gen-eral population: measurement in theseated position, with feet on the floorand arm supported at heart level, after 5min of rest. Cuff size should be appro-priate for the upper arm circumference.Elevated values should be confirmedon a separate day.Home blood pressure self-monitoring

and 24-h ambulatory blood pressuremonitoring may provide evidence ofwhite coat hypertension, masked hyper-tension, or other discrepancies betweenoffice and “true” blood pressure. Stud-ies in individuals without diabetes foundthat home measurements may bettercorrelate with CVD risk than officemeasurements (4,5). However, most ofthe evidence of benefits of hypertensiontreatment in people with diabetes isbased on office measurements.

Treatment GoalsEpidemiological analyses show thatblood pressure.115/75 mmHg is asso-ciated with increased cardiovascularevent rates and mortality in individualswith diabetes and that SBP.120 mmHgpredicts long-term end-stage renal dis-ease. Randomized clinical trials have

demonstrated the benefit (reduction ofCHD events, stroke, and diabetic kidneydisease) of lowering blood pressure to,140 mmHg systolic and ,90 mmHgdiastolic in individuals with diabetes(6). There is limited prespecified clinicaltrial evidence for the benefits of lowerSBP or DBP targets (7). A meta-analysisof randomized trials of adults with type2 diabetes comparing intensive bloodpressure targets (upper limit of 130mmHg systolic and 80 mmHg diastolic)to standard targets (upper limit of 140–160 mmHg systolic and 85–100 mmHgdiastolic) found no significant reductionin mortality or nonfatal myocardial in-farction (MI). There was a statisticallysignificant 35% relative risk (RR) reduc-tion in stroke with intensive targets, butthe absolute risk reduction was only 1%,and intensive targets were associatedwith an increased risk for adverse eventssuch as hypotension and syncope (8).

Given the epidemiological relation-ship between lower blood pressureand better long-term clinical outcomes,two landmark trials, Action to ControlCardiovascular Risk in Diabetes (ACCORD)and Action in Diabetes and VascularDisease: Preterax and Diamicron MRControlled Evaluation–Blood Pressure(ADVANCE-BP), were conducted in thepast decade to examine the benefit oftighter blood pressure control in pa-tients with type 2 diabetes.

The ACCORD trial examined whether alower SBP of ,120 mmHg, in type 2 di-abetic patients at high risk for CVD, pro-vided greater cardiovascular protectionthan an SBP level of 130–140 mmHg (9).The study did not find a benefit in primaryend point (nonfatal MI, nonfatal stroke,and cardiovascular death) comparing in-tensive blood pressure treatment (goal,120 mmHg, average blood pressureachieved5 119/64 mmHg on 3.4 medica-tions) with standard treatment (averageblood pressure achieved5 143/70 mmHgon 2.1medications). In ACCORD, there wasno benefit of aggressive blood pressurelowering, despite the extra cost and efforts.

In ADVANCE, the active blood pres-sure intervention arm (a single-pill,fixed-dose combination of perindopriland indapamide) showed a significantreduction in the risk of the primary com-posite end point (major macrovascularor microvascular event), as well as sig-nificant reductions in the risk of deathfrom any cause and of death from

cardiovascular causes (10). The baselineblood pressure among the study sub-jects was 145/81 mmHg. Comparedwith the placebo group, the patientstreated with a single-pill, fixed-dosecombination of perindopril and indapa-mide experienced an average reductionof 5.6 mmHg in SBP and 2.2 mmHg inDBP. The final blood pressure in thetreated group was 136/73 mmHg, notquite the intensive or tight controlachieved in ACCORD. Recently published6-year follow-up of the ADVANCE-BPstudy reported that the reductions inthe risk of death from any cause and ofdeath from cardiovascular causes in theintervention group were attenuated, butremained significant (11).

These results underscore the impor-tant clinical difference between patientswho are able to easily achieve lowerblood pressure levels (e.g., as seen inobservational epidemiology studies)and patients who require intensivemedical management to achieve thesegoals (e.g., the clinical trials).

Systolic Blood Pressure

The clear body of evidence that SBP.140mmHg is harmful suggests that cliniciansshould promptly initiate and titrate ther-apy in an ongoing fashion to achieve andmaintain SBP ,140 mmHg in virtually allpatients. Patientswith long life expectancymay have renal benefits from long-termintensive blood pressure control. Addi-tionally, individuals in whom stroke riskis a concern may, as part of shared deci-sionmaking, have appropriately lower sys-tolic targets such as ,130 mmHg. This isespecially true if lower blood pressure canbe achieved with few drugs and withoutside effects of therapy.

Diastolic Blood Pressure

Similarly, the clearest evidence from ran-domized clinical trials supports DBPtargets of ,90 mmHg. Prior recommen-dations for lower DBP targets (,80mmHg) were based primarily on a posthoc analysis of the Hypertension OptimalTreatment (HOT) trial (12). This level maystill be appropriate for patients with longlife expectancy and those with chronickidney disease and elevated urine albu-min excretion (12). The 2015 AmericanDiabetes Association (ADA) Standards ofCare have been revised to reflect thehigher-quality evidence that exists tosupport a goal of DBP ,90 mmHg, al-though lower targets may be appropriate


for certain individuals. This is in harmoni-zation with a recent publication by theEighth Joint National Committee that rec-ommended, for individuals over 18 yearsof age with diabetes, a DBP threshold of,90 mmHg and SBP,140 mmHg (7).

Treatment Strategies

Lifestyle Modifications

Although there are no well-controlledstudies of diet and exercise in the treat-ment of elevated blood pressure or hy-pertension in individuals with diabetes,the DASH study evaluated the impact ofhealthy dietary patterns in individualswithout diabetes and has shown antihy-pertensiveeffects similar to thoseofphar-macological monotherapy.Lifestyle therapy consists of restrict-

ing sodium intake (,2,300 mg/day); re-ducing excess body weight; increasingconsumption of fruits, vegetables (8–10 servings per day), and low-fat dairyproducts (2–3 servings per day); avoid-ing excessive alcohol consumption (nomore than 2 servings per day in menand no more than 1 serving per day inwomen) (13); and increasing activity lev-els (14). For individuals with diabetesand hypertension, setting a sodium in-take goal of ,1,500 mg/day should beconsidered on an individual basis.These lifestyle (nonpharmacological)

strategies may also positively affect gly-cemia and lipid control and should beencouraged in those with even mildlyelevated blood pressure. The effects oflifestyle therapy on cardiovascularevents have not been established. Non-pharmacological therapy is reasonablein individuals with diabetes and mildlyelevated blood pressure (SBP .120mmHg or DBP.80 mmHg). If the bloodpressure is confirmed to be$140mmHgsystolic and/or $90 mmHg diastolic,pharmacological therapy should be ini-tiated along with nonpharmacologicaltherapy (14). To enable long-termadherence, lifestyle therapy shouldbe adapted to suit the needs of the pa-tient and discussed as part of diabetesmanagement.

Pharmacological Interventions

Lowering of blood pressure with regi-mens based on a variety of antihyper-tensive agents, including ACE inhibitors,ARBs, b-blockers, diuretics, and calciumchannel blockers, has been shown to beeffective in reducing cardiovascularevents. Several studies have suggested

that ACE inhibitors may be superior todihydropyridine calcium channel blockersin reducing cardiovascular events (15–17).However, several studies have alsoshown no specific advantage to ACE inhib-itors as initial treatment of hypertensionin the general hypertensive population,while showing an advantage of initialtherapy with low-dose thiazide diureticson cardiovascular outcomes (14,18,19).

In people with diabetes, inhibitors ofthe renin-angiotensin system (RAS) mayhave unique advantages for initial orearly treatment of hypertension. In a tri-al of individuals at high risk for CVD,including a large subset with diabetes,an ACE inhibitor reduced CVD outcomes(20). In patients with congestive heartfailure (CHF), including subgroups withdiabetes, ARBs have been shown to re-duce major CVD outcomes (21–24). Intype 2 diabetic patients with significantdiabetic kidney disease, ARBs were su-perior to calcium channel blockers forreducing heart failure (25). Although ev-idence for distinct advantages of RASinhibitors on CVD outcomes in diabetesremains conflicting (10,19), the highCVD risks associated with diabetes, andthe high prevalence of undiagnosedCVD, may still favor recommendationsfor their use as first-line hypertensiontherapy in people with diabetes (14).

The blood pressure arm of theADVANCE trial demonstrated that rou-tine administration of a fixed combina-tion of the ACE inhibitor perindopril andthe diuretic indapamide significantly re-duced combined microvascular andmacrovascular outcomes, as well as deathfrom cardiovascular causes and totalmortality. The improved outcomes couldalso have been due to lower achievedblood pressure in the perindopril-indapamide arm (10). Another trialshowed a decrease in morbidity andmor-tality in those receiving benazepril andamlodipine versus benazepril and hydro-chlorothiazide (HCTZ). The compellingbenefits of RAS inhibitors in diabetic pa-tients with albuminuria or renal insuffi-ciency provide additional rationale forthese agents (see Section 9. Microvascu-lar Complications and Foot Care). Ifneeded to achieve blood pressure targets,amlodipine, HCTZ, or chlorthalidone canbe added. If eGFR is ,30 mL/min/m2, aloop diuretic, rather than HCTZ or chlor-thalidone, should be prescribed. Titrationof and/or addition of further blood

pressure medications should be made intimely fashion to overcome clinical inertiain achieving blood pressure targets.

Growing evidence suggests that there isan association between increase in sleep-time blood pressure and incidence of CVDevents. A randomized controlled trial of448 participants with type 2 diabetes andhypertension demonstrated reducedcardiovascular events and mortality withmedian follow-up of 5.4 years if at leastone antihypertensive medication wasgiven at bedtime (26). Consider adminis-tering one or more antihypertensive med-ications at bedtime (27).

An important caveat is that most pa-tients with hypertension require multiple-drug therapy to reach treatment goals (13).Identifying and addressing barriers tomedication adherence (such as cost andside effects) should routinely be done. Ifblood pressure remains uncontrolled de-spite confirmed adherence to optimaldoses of at least three antihypertensiveagents of different classifications, one ofwhich shouldbeadiuretic, clinicians shouldconsider an evaluation for secondary formsof hypertension.

Pregnancy and Antihypertensive

Medications

In a pregnancy complicated by diabetesand chronic hypertension, target bloodpressure goals of SBP 110–129 mmHgand DBP 65–79 mmHg are reasonable, asthey contribute to improved long-termmaternal health. Lower blood pressurelevels may be associated with im-paired fetal growth. During pregnancy,treatment with ACE inhibitors and ARBsis contraindicated, since they may causefetal damage. Antihypertensive drugsknown to be effective and safe in preg-nancy include methyldopa, labetalol, dil-tiazem, clonidine, and prazosin. Chronicdiuretic use during pregnancy has beenassociated with restricted maternalplasma volume, which may reduceuteroplacental perfusion (28).

DYSLIPIDEMIA/LIPIDMANAGEMENT

Recommendations

Screeningc In adults, a screening lipid profile is

reasonable at the time of first diag-nosis, at the initial medical evalua-tion, and/or at age 40 years andperiodically (e.g., every 1–2 years)thereafter. E


Treatment Recommendations andGoalsc Lifestyle modification focusing on

the reduction of saturated fat, transfat, and cholesterol intake; increaseof omega-3 fatty acids, viscous fiber,and plant stanols/sterols; weightloss (if indicated); and increasedphysical activity should be recom-mended to improve the lipid profilein patients with diabetes. A

c Intensify lifestyle therapy and opti-mize glycemic control for patientswith elevated triglyceride levels($150 mg/dL [1.7 mmol/L]) and/orlow HDL cholesterol (,40 mg/dL[1.0 mmol/L] for men, ,50 mg/dL[1.3 mmol/L] for women). C Forpatients with fasting triglyceridelevels $500 mg/dL (5.7 mmol/L),evaluate for secondary causesand consider medical therapy toreduce risk of pancreatitis. C

c For patients of all ages with diabe-tes and overt CVD, high-intensitystatin therapy should be added tolifestyle therapy. A

c For patients with diabetes aged,40 years with additional CVD riskfactors, consider using moderate-or high-intensity statin and lifestyletherapy. C

c For patients with diabetes aged40–75 years without additionalCVD risk factors, consider usingmoderate-intensity statin and life-style therapy. A

c For patients with diabetes aged 40–75 yearswith additional CVD risk fac-tors, consider using high-intensitystatin and lifestyle therapy. B

c For patients with diabetes aged.75 years without additionalCVD risk factors, consider usingmoderate-intensity statin therapyand lifestyle therapy. B

c For patients with diabetes aged.75years with additional CVD risk fac-tors, consider using moderate- orhigh-intensity statin therapy and life-style therapy. B

c In clinical practice, providers mayneed to adjust intensity of statintherapy based on individual patientresponse to medication (e.g., sideeffects, tolerability, LDL cholesterollevels). E

c Cholesterol laboratory testingmay be helpful in monitoring

adherence to therapy, but maynot be needed once the patientis stable on therapy. E

c Combination therapy (statin/fibrate and statin/niacin) has notbeen shown to provide additionalcardiovascular benefit above statintherapy alone and is not generallyrecommended. A

c Statin therapy is contraindicatedin pregnancy. B

Lifestyle InterventionLifestyle intervention, including MNT, in-creased physical activity, weight loss, andsmoking cessation, may allow some pa-tients to reduce CVD risk factors, such asby lowering LDL cholesterol. Nutrition in-tervention should be tailored according toeach patient’s age, diabetes type, pharma-cological treatment, lipid levels, and medi-cal conditions. Recommendations shouldfocus on reducing saturated fat, choles-terol, and trans unsaturated fat intakeand increasing omega-3 fatty acids and vis-cous fiber (such as in oats, legumes, andcitrus). Glycemic control can also benefi-ciallymodifyplasma lipid levels, particularlyin patients with very high triglycerides andpoor glycemic control.

Statin Treatment

Initiating Statin Therapy Based on Risk

Patients with type 2 diabetes have anincreased prevalence of lipid abnormal-ities, contributing to their high risk ofCVD.Multiple clinical trials have demon-strated significant effects of pharmaco-logical (primarily statin) therapy on CVDoutcomes in individual subjects withCHD and for primary CVD prevention(29,30). Subgroup analyses of diabetic

patients in larger trials (31–35) and trialsin patients with diabetes (36,37)showed significant primary and second-ary prevention of CVD events1/2 CHDdeaths in patients with diabetes. Meta-analyses, including data from over18,000 patients with diabetes from 14randomized trials of statin therapy(mean follow-up 4.3 years), demonstratea 9% proportional reduction in all-causemortality and 13% reduction in vascularmortality, for each mmol/L reduction inLDL cholesterol (38). As in those withoutdiabetes, absolute reductions in objectiveCVD outcomes (CHD death and nonfatalMI) are greatest in people with high base-line CVD risk (known CVD and/or very highLDL cholesterol levels), but the overall ben-efits of statin therapy in people with diabe-tes at moderate or high risk for CVD areconvincing (39,40). Statins are the drugs ofchoice for LDL cholesterol lowering and car-dioprotection.

Most trials of statins and CVD out-comes tested specific doses of statinsagainst placebo or other statins, ratherthan aiming for specific LDL cholesterolgoals (41). In light of this fact, the 2015ADA Standards of Care have been revisedto recommendwhen to initiate and inten-sify statin therapy (high versus moderate)based on risk profile (Table 8.1).

The American College of Cardiology/American Heart Association new PooledCohort Equation, the “Risk Calculator,”may be a useful tool to estimate 10-year atherosclerotic CVD (http://my.americanheart.org). Since diabetes it-self confers increased risk for CVD, theRisk Calculator has limited use for as-sessing risk in individuals with diabetes.The following recommendations are

Table 8.1—Recommendations for statin treatment in people with diabetes

Age Risk factorsRecommendedstatin dose* Monitoring with lipid panel

,40 years None None Annually or as needed to monitorfor adherenceCVD risk factor(s)** Moderate or high

Overt CVD*** High

40–75 years None Moderate As needed to monitor adherenceCVD risk factors HighOvert CVD High

.75 years None Moderate As needed to monitor adherenceCVD risk factors Moderate or highOvert CVD High

*In addition to lifestyle therapy.**CVD risk factors include LDL cholesterol $100 mg/dL (2.6 mmol/L), high blood pressure,smoking, and overweight and obesity.***Overt CVD includes those with previous cardiovascular events or acute coronary syndromes.


supported by evidence from trials focus-ing specifically on patients with diabetes.

Age ‡40 Years

In all patients with diabetes aged $40years, and if clinically indicated,moderate-intensity statin treatment should beconsidered, in addition to lifestyle ther-apy. Clinical trials in high-risk patients,such as those with acute coronary syn-dromes or previous cardiovascularevents (42–44), have demonstratedthat more aggressive therapy with highdoses of statins led to a significant re-duction in further events. Therefore, inpatients with increased cardiovascularrisk (e.g., LDL cholesterol $100 mg/dL[2.6 mmol/L], high blood pressure, smok-ing, and overweight/obesity) or with overtCVD, high-dose statins are recommended.For adultswith diabetes over 75 years of

age, there are limited data regarding statintherapy. Statin therapy should be individ-ualized based on risk profile. High-dosestatins, if well tolerated,may still be appro-priate and are recommended for olderadults with overt CVD. However, the risk-benefit profile should be routinely evalu-ated in this population, with downwardtitration (e.g., high to moderate intensity)performed as needed. See Section 10.Older Adults for more details on clinicalconsiderations for this unique population.

Age <40 Years and/or Type 1 Diabetes

Very little clinical trial evidence existsfor type 2 diabetic patients under theage of 40 years or for type 1 diabeticpatients of any age. In the Heart Protec-tion Study (lower age limit 40 years), thesubgroup of ;600 patients with type 1diabetes had a proportionately similar,although not statistically significant, re-duction in risk to patients with type 2diabetes (32). Even though the dataare not definitive, similar statin treat-ment approaches should be consideredfor both type 1 and type 2 diabetic pa-tients, particularly in the presence ofcardiovascular risk factors. Please referto “Type 1 DiabetesMellitus and Cardio-vascular Disease: A Scientific StatementFrom the American Heart Associationand American Diabetes Association”(45) for additional discussion.Treatment with a moderate dose of sta-

tin should be considered if the patient hasincreased cardiovascular risk (e.g., cardio-vascular risk factors such as LDL cholesterol$100mg/dL) andwith a high dose of statinif the patient has overt CVD.

Ongoing Therapy and MonitoringWith Lipid PanelIn adults with diabetes, a screening lipidprofile (total cholesterol, LDL cholesterol,HDL cholesterol, and triglycerides) is rea-sonable at the time of first diagnosis, atthe initial medical evaluation, and/or atage 40 and periodically (e.g., every 1–2years) thereafter. Once a patient is on astatin, testing for LDL cholesterol may beconsidered on an individual basis to, forexample, monitor adherence and efficacy.In cases where patients are adherent, butLDL cholesterol level is not responding, clin-ical judgment is recommended to deter-mine theneed forand timingof lipidpanels.

In individual patients, the highly variableLDL cholesterol–lowering response seenwith statins is poorly understood (46). Re-duction of CVD events with statins corre-lates very closely with LDL cholesterollowering (29). Clinicians should attempt tofind a dose or alternative statin that is tol-erable, if side effects occur. There is evi-dence for significant LDL cholesterollowering from even extremely low, lessthan daily, statin doses (47).

Whenmaximally tolerated doses of sta-tins fail to significantly lower LDL choles-terol (,30% reduction from the patient’sbaseline), there is no strong evidence thatcombination therapy should be used toachieve additional LDL cholesterol lower-ing. Although niacin, fenofibrate, ezeti-mibe, and bile acid sequestrants all offeradditional LDL cholesterol lowering to sta-tins alone, there is insufficient evidencethat such combination therapy provides asignificant increment in CVD risk reductionover statin therapy alone.

Treatment of Other LipoproteinFractions or TargetsHypertriglyceridemia should be addressedwith dietary and lifestyle changes. Severehypertriglyceridemia (.1,000mg/dL) maywarrant immediate pharmacological ther-apy (fibric acid derivatives or fish oil) toreduce the risk of acute pancreatitis. If se-vere hypertriglyceridemia is absent, thentherapy targeting HDL cholesterol or triglyc-erides lacks the strong evidence base ofstatin therapy. If HDL cholesterol is,40mg/dL and LDL cholesterol is between100 and 129 mg/dL, a fibrate or niacinmight be used, especially if a patient isintolerant to statins.

Low levels of HDL cholesterol, often as-sociated with elevated triglyceride levels,are the most prevalent pattern of dyslipi-demia in persons with type 2 diabetes.

However, the evidence base for drugsthat target these lipid fractions is signifi-cantly less robust than that for statin ther-apy (48). In a large trial specific to diabeticpatients, fenofibrate failed to reduce over-all cardiovascular outcomes (49).

Combination Therapy

Statin and Fibrate

Combination therapy (statin and fibrate)may be efficacious for treatment for LDLcholesterol, HDL cholesterol, and triglycer-ides, but this combination is associatedwith an increased risk for abnormal trans-aminase levels, myositis, or rhabdomyoly-sis. The risk of rhabdomyolysis is morecommon with higher doses of statins andwith renal insufficiency and seems to belower when statins are combined with fe-nofibrate than gemfibrozil (50).

In the ACCORD study, in patients withtype 2 diabetes who were at high risk forCVD, the combination of fenofibrate andsimvastatin did not reduce the rate of fatalcardiovascular events, nonfatalMI, or non-fatal stroke, as compared with simvastatinalone. Prespecified subgroup analyses sug-gested heterogeneity in treatment effectsaccording to sex, with a benefit of combi-nation therapy for men and possible harmfor women, and a possible benefit for pa-tients with both triglyceride level $204mg/dL (2.3 mmol/L) and HDL cholesterollevel#34 mg/dL (0.9 mmol/L) (51).

Statin and Niacin

The Atherothrombosis Intervention in Met-abolic SyndromeWith LowHDL/High Triglyc-erides: Impact on Global Health Outcomes(AIM-HIGH) trial randomized over 3,000 pa-tients (about one-third with diabetes) withestablished CVD, low LDL cholesterol levels(,180 mg/dL [4.7 mmol/L]), low HDL cho-lesterol levels (men,40mg/dL [1.0mmol/L]and women ,50 mg/dL [1.3 mmol/L]),and triglyceride levels of 150–400 mg/dL(1.7–4.5 mmol/L) to statin therapy plusextended-release niacin ormatching pla-cebo. The trial was halted early due tolack of efficacy on the primary CVD out-come (first event of the composite of deathfrom CHD, nonfatal MI, ischemic stroke,hospitalization for an acute coronary syn-drome, or symptom-driven coronary or ce-rebral revascularization) and a possibleincrease in ischemic stroke in those oncombination therapy (52). Hence, combi-nation therapy with niacin is not recom-mended given the lack of efficacy onmajor CVD outcomes, possible increase inrisk of ischemic stroke, and side effects.


Diabetes With Statin UseThere is an increased risk of incident dia-betes with statin use (53,54), which maybe limited to those with diabetes risk fac-tors. These patients may benefit from di-abetes screening when on statin therapy.An analysis of one of the initial studiessuggested that statins were linked to di-abetes risk, the cardiovascular event ratereduction with statins far outweighed therisk of incident diabetes even for patientsat highest risk for diabetes (55). The abso-lute risk increasewas small (over 5 years offollow-up, 1.2% of participants on placebodeveloped diabetes and 1.5% on rosuvas-tatin) (56). A meta-analysis of 13 random-ized statin trials with 91,140 participantsshowed an odds ratio of 1.09 for a newdiagnosis of diabetes, so that (on average)treatment of 255 patients with statins for4 years resulted in one additional case ofdiabetes, while simultaneously prevent-ing 5.4 vascular events among those 255patients (54). The RR-benefit ratio favor-ing statins is further supported by meta-analysis of individual data of over 170,000persons from 27 randomized trials. Thisdemonstrated that individuals at low riskof vascular disease, including those un-dergoing primary prevention, receivedbenefits from statins that included reduc-tions in major vascular events and vascu-lar death without increase in incidence ofcancer or deaths from other causes (30).

ANTIPLATELET AGENTS

Recommendations

c Consider aspirin therapy (75–162mg/day) as a primary preventionstrategy in those with type 1 ortype 2 diabetes at increased car-diovascular risk (10-year risk.10%). This includes most menaged .50 years or women aged.60 years who have at least oneadditional major risk factor (familyhistory of CVD, hypertension,smoking, dyslipidemia, or albu-minuria). C

c Aspirin should not be recom-mended for CVD prevention foradults with diabetes at low CVDrisk (10-year CVD risk ,5%, suchas in men aged ,50 years andwomen aged ,60 years with nomajor additional CVD risk factors),since the potential adverse effectsfrom bleeding likely offset thepotential benefits. C

c In patients in these age-groupswith multiple other risk factors(e.g., 10-year risk 5–10%), clinicaljudgment is required. E

c Use aspirin therapy (75–162mg/day)as a secondary prevention strategyin those with diabetes and a his-tory of CVD. A

c For patients with CVD and docu-mented aspirin allergy, clopidogrel(75 mg/day) should be used. B

c Dual antiplatelet therapy is rea-sonable for up to a year after anacute coronary syndrome. B

Risk ReductionAspirin has been shown to be effective inreducing cardiovascular morbidity andmortality in high-risk patients with previ-ous MI or stroke (secondary prevention).Its net benefit in primary preventionamong patients with no previous cardio-vascular events is more controversial,both for patients with and without a his-tory of diabetes (57,58). Two randomizedcontrolled trials of aspirin specifically inpatients with diabetes failed to show asignificant reduction in CVD end points,raising questions about the efficacy of as-pirin for primary prevention in peoplewith diabetes (59,60).

The Antithrombotic Trialists’ (ATT) col-laborators published an individual patient-level meta-analysis of the six large trials ofaspirin for primary prevention in the gen-eral population. These trials collectivelyenrolled over 95,000 participants, includ-ing almost 4,000 with diabetes. Overall,they found that aspirin reduced the riskof vascular events by 12% (RR 0.88 [95%CI 0.82–0.94]). The largest reduction wasfor nonfatal MI with little effect on CHDdeath (RR 0.95 [95%CI 0.78–1.15]) or totalstroke. There was some evidence of a dif-ference in aspirin effect by sex: aspirinsignificantly reduced CVD events in men,but not inwomen. Conversely, aspirin hadnoeffect on stroke inmenbut significantlyreduced stroke in women. Sex differencesin aspirin’s effects havenot beenobservedin studies of secondary prevention (57). Inthe six trials examined by the ATT collab-orators, the effects of aspirin on majorvascular events were similar for patientswith or without diabetes: RR 0.88 (95% CI0.67–1.15) and RR 0.87 (95% CI 0.79–0.96), respectively. The confidence inter-val was wider for those with diabetesbecause of smaller numbers.

Aspirin appears to have a modest ef-fect on ischemic vascular events withthe absolute decrease in events depend-ing on the underlying CVD risk. Themainadverse effects appear to be an in-creased risk of gastrointestinal bleeding.The excess risk may be as high as 1–5 per1,000 per year in real-world settings. Inadults with CVD risk greater than 1% peryear, the number of CVD events pre-vented will be similar to or greaterthan the number of episodes of bleedinginduced, although these complicationsdo not have equal effects on long-termhealth (61).

Treatment ConsiderationsIn 2010, a position statement of the ADA,the American Heart Association, and theAmerican College of Cardiology Founda-tion recommended that low-dose (75–162mg/day) aspirin for primary prevention isreasonable for adults with diabetes andno previous history of vascular diseasewho are at increased CVD risk (10-yearrisk of CVD events over 10%) and whoare not at increased risk for bleeding.This generally includes most men overage 50 years and women over age 60years who also have one or more of thefollowing major risk factors: smoking, hy-pertension, dyslipidemia, family history ofpremature CVD, and albuminuria (62).

However, aspirin is no longer recom-mended for those at low CVD risk(women under age 60 years and menunder age 50 years with no major CVDrisk factors; 10-year CVD risk under 5%)as the low benefit is likely to be out-weighed by the risks of significant bleed-ing. Clinical judgment should be used forthose at intermediate risk (younger pa-tients with one or more risk factors orolder patients with no risk factors; thosewith 10-year CVD risk of 5–10%) untilfurther research is available. Aspirinuse in patients under the age of 21 yearsis contraindicated due to the associatedrisk of Reye syndrome.

Average daily dosages used in mostclinical trials involving patients with di-abetes ranged from 50 to 650 mg butwere mostly in the range of 100 to325 mg/day. There is little evidence tosupport any specific dose, but using thelowest possible dose may help reduceside effects (63). In the U.S., the mostcommon low dose tablet is 81 mg.Although platelets from patients withdiabetes have altered function, it is


unclear what, if any, impact that findinghas on the required dose of aspirin forcardioprotective effects in the patientwith diabetes. Many alternate pathwaysfor platelet activation exist that are in-dependent of thromboxane A2 and thusnot sensitive to the effects of aspirin(64). Therefore, while “aspirin resis-tance” appears higher in patients withdiabetes when measured by a variety ofex vivo and in vitro methods (plateletaggregometry, measurement of throm-boxane B2), these observations aloneare insufficient to empirically recom-mend that higher doses of aspirin beused in this group at this time.A P2Y12 receptor antagonist in com-

bination with aspirin should be used forat least 1 year in patients following anacute coronary syndrome. Evidencesupports use of either ticagrelor or clo-pidogrel if no percutaneous coronaryintervention (PCI) was performed andthe use of clopidogrel, ticagrelor, orprasugrel if PCI was performed (65).

CORONARY HEART DISEASE

Recommendations

Screeningc In asymptomatic patients, routine

screening for coronary artery dis-ease (CAD) is not recommendedbecause it does not improve out-comes as long as CVD risk factorsare treated. A

Treatmentc In patients with known CVD, use

aspirin and statin therapy (if notcontraindicated) A and considerACE inhibitor therapy C to reducethe risk of cardiovascular events.

c InpatientswithapriorMI,b-blockersshould be continued for at least 2years after the event. B

c In patients with symptomaticheart failure, thiazolidinedionetreatment should not be used. A

c In patients with stable CHF, met-formin may be used if renal func-tion is normal but should beavoided in unstable or hospital-ized patients with CHF. B

In all patients with diabetes, cardio-vascular risk factors should be assessedat least annually. These risk factorsinclude dyslipidemia, hypertension,smoking, a family history of prematurecoronary disease, and the presence of

albuminuria. Abnormal risk factorsshould be treated as described else-where in these guidelines.

ScreeningCandidates for advanced or invasive car-diac testing include those with 1) typicalor atypical cardiac symptoms and 2) anabnormal resting ECG. The screening ofasymptomatic patients with high CVDrisk is not recommended (39), in partbecause these high-risk patients shouldalready be receiving intensive medicaltherapy, an approach that provides sim-ilar benefit as invasive revascularization(66,67). There is also some evidencethat silent MI may reverse over time,adding to the controversy concerningaggressive screening strategies (68). Arandomized observational trial demon-strated no clinical benefit to routinescreening of asymptomatic patientswith type 2 diabetes and normal ECGs(69). Despite abnormal myocardial per-fusion imaging in more than one in fivepatients, cardiac outcomes were essen-tially equal (and very low) in screenedversus unscreened patients. Accord-ingly, indiscriminate screening is notconsidered cost-effective. Studies havefound that a risk factor–based approachto the initial diagnostic evaluation andsubsequent follow-up for CAD fails toidentify which patients with type 2 di-abetes will have silent ischemia onscreening tests (70,71). Any benefit ofnewer noninvasive CAD screeningmeth-ods, such as computed tomography andcomputed tomography angiography, toidentify patient subgroups for differenttreatment strategies, remain unproven.Although asymptomatic diabetic pa-tients with higher coronary disease bur-den have more future cardiac events(72–74), the role of these tests beyondrisk stratification is not clear. Their rou-tine use leads to radiation exposure andmay result in unnecessary invasive test-ing such as coronary angiography andrevascularization procedures. The ulti-mate balance of benefit, cost, and risksof such an approach in asymptomaticpatients remains controversial, particu-larly in the modern setting of aggressiveCVD risk factor control.

Lifestyle and PharmacologicalInterventionsIntensive lifestyle intervention focusingon weight loss through decreased

caloric intake and increased physical ac-tivity as performed in the Action forHealth in Diabetes (Look AHEAD) trialmay be considered for improving glu-cose control, fitness, and some CVDrisk factors. Patients at increased CVDrisk should receive aspirin and a statin,and ACE inhibitor or ARB therapy if hy-pertensive, unless there are contraindi-cations to a particular drug class. Whileclear benefit exists for ACE inhibitor andARB therapy in patients with nephropa-thy or hypertension, the benefits in pa-tients with CVD in the absence of theseconditions are less clear, especiallywhen LDL cholesterol is concomitantlycontrolled (75,76). In patients with aprior MI, b-blockers should be contin-ued for at least 2 years after the event(77). A systematic review of 34,000 pa-tients showed that metformin is as safeas other glucose-lowering treatments inpatients with diabetes and CHF, even inthose with reduced left ventricular ejec-tion fraction or concomitant chronickidney disease; however, metforminshould be avoided in hospitalizedpatients (78).

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45. de Ferranti SD, de Boer IH, Fonseca V, et al.Type 1 diabetes mellitus and cardiovascular dis-ease: a scientific statement from the AmericanHeart Association and American Diabetes Asso-ciation. Circulation 2014;130:1110–113046. Chasman DI, Posada D, Subrahmanyan L,Cook NR, Stanton VP Jr, Ridker PM. Pharmaco-genetic study of statin therapy and cholesterolreduction. JAMA 2004;291:2821–282747. Meek C,Wierzbicki AS, Jewkes C, et al. Dailyand intermittent rosuvastatin 5 mg therapy instatin intolerant patients: an observationalstudy. Curr Med Res Opin 2012;28:371–37848. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a sys-tematic review. JAMA 2007;298:786–79849. Keech A, Simes RJ, Barter P, et al.; FIELDstudy investigators. Effects of long-term fenofi-brate therapy on cardiovascular events in 9795people with type 2 diabetes mellitus (the FIELDstudy): randomised controlled trial. Lancet2005;366:1849–186150. Jones PH, Davidson MH. Reporting rate ofrhabdomyolysis with fenofibrate 1 statin ver-sus gemfibrozil1 any statin. Am J Cardiol 2005;95:120–12251. Ginsberg HN, Elam MB, Lovato LC, et al.;ACCORD Study Group. Effects of combinationlipid therapy in type 2 diabetes mellitus. NEngl J Med 2010;362:1563–157452. BodenWE, Probstfield JL, Anderson T, et al.;AIM-HIGH Investigators. Niacin in patients withlow HDL cholesterol levels receiving intensivestatin therapy. N Engl J Med 2011;365:2255–226753. Rajpathak SN, Kumbhani DJ, Crandall J,Barzilai N, AldermanM, Ridker PM. Statin therapyand risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 2009;32:1924–192954. Sattar N, Preiss D, Murray HM, et al. Statinsand risk of incident diabetes: a collaborativemeta-analysis of randomised statin trials. Lan-cet 2010;375:735–74255. Ridker PM, Danielson E, Fonseca FAH, et al.;JUPITER Study Group. Rosuvastatin to preventvascular events in men and women with ele-vated C-reactive protein. N Engl J Med 2008;359:2195–220756. Ridker PM, Pradhan A,MacFadyen JG, LibbyP, Glynn RJ. Cardiovascular benefits and diabe-tes risks of statin therapy in primary prevention:an analysis from the JUPITER trial. Lancet 2012;380:565–57157. Baigent C, Blackwell L, Collins R, et al.; An-tithrombotic Trialists’ (ATT) Collaboration. Aspi-rin in the primary and secondary prevention ofvascular disease: collaborative meta-analysis ofindividual participant data from randomised tri-als. Lancet 2009;373:1849–186058. Perk J, De Backer G, Gohlke H, et al.; Euro-pean Association for Cardiovascular Prevention& Rehabilitation (EACPR); ESC Committee forPractice Guidelines (CPG). European Guidelines

on cardiovascular disease prevention in clinicalpractice (version 2012). The Fifth Joint TaskForce of the European Society of Cardiologyand Other Societies on Cardiovascular DiseasePrevention in Clinical Practice (constituted byrepresentatives of nine societies and by invitedexperts). Eur Heart J 2012;33:1635–170159. Ogawa H, Nakayama M, Morimoto T, et al.;Japanese Primary Prevention of AtherosclerosisWith Aspirin for Diabetes (JPAD) Trial Investiga-tors. Low-dose aspirin for primary prevention ofatherosclerotic events in patients with type 2diabetes: a randomized controlled trial. JAMA2008;300:2134–214160. Belch J, MacCuish A, Campbell I, et al. Theprevention of progression of arterial diseaseand diabetes (POPADAD) trial: factorial rando-mised placebo controlled trial of aspirin andantioxidants in patients with diabetes andasymptomatic peripheral arterial disease. BMJ2008;337:a184061. Pignone M, Earnshaw S, Tice JA, PletcherMJ. Aspirin, statins, or both drugs for the pri-mary prevention of coronary heart diseaseevents in men: a cost-utility analysis. Ann InternMed 2006;144:326–33662. Pignone M, Alberts MJ, Colwell JA, et al.;American Diabetes Association; American HeartAssociation; American College of CardiologyFoundation. Aspirin for primary prevention ofcardiovascular events in people with diabetes:a position statement of the American DiabetesAssociation, a scientific statement of the Amer-ican Heart Association, and an expert consensusdocument of the American College of Cardiol-ogy Foundation. Diabetes Care 2010;33:1395–140263. Campbell CL, Smyth S, Montalescot G,Steinhubl SR. Aspirin dose for the preventionof cardiovascular disease: a systematic review.JAMA 2007;297:2018–202464. Davı G, Patrono C. Platelet activation andatherothrombosis. N Engl J Med 2007;357:2482–249465. Vandvik PO, Lincoff AM, Gore JM, et al.;American College of Chest Physicians. Primaryand secondary prevention of cardiovascular dis-ease: antithrombotic therapy and prevention ofthrombosis, 9th ed: American College of ChestPhysicians Evidence-Based Clinical PracticeGuidelines. Chest 2012;141(Suppl.):e637S–e668S66. Boden WE, O’Rourke RA, Teo KK, et al.;COURAGE Trial Research Group. Optimal medi-cal therapy with or without PCI for stable coro-nary disease. N Engl J Med 2007;356:1503–151667. BARI 2D Study Group; Frye RL, August P,et al. A randomized trial of therapies for type2 diabetes and coronary artery disease. N Engl JMed 2009;360:2503–251568. Wackers FJT, Chyun DA, Young LH, et al.;Detection of Ischemia in Asymptomatic Dia-betics (DIAD) Investigators. Resolution of

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9. Microvascular Complicationsand Foot CareDiabetes Care 2015;38(Suppl. 1):S58–S66 | DOI: 10.2337/dc15-S012

NEPHROPATHY

Recommendations

c Optimize glucose control to reduce the risk or slow the progression of diabetickidney disease. A

c Optimize blood pressure control to reduce the risk or slow the progression ofdiabetic kidney disease. A

Screeningc At least once a year, quantitatively assess urinary albumin (e.g., urine albumin-

to-creatinine ratio [UACR]) and estimated glomerular filtration rate (eGFR) inpatients with type 1 diabetes duration of$5 years and in all patients with type2 diabetes. B

Treatmentc An ACE inhibitor or angiotensin receptor blocker (ARB) is not recommended

for the primary prevention of diabetic kidney disease in patients with diabeteswho have normal blood pressure and normal UACR (,30 mg/g). B

c Either an ACE inhibitor or ARB is suggested for the treatment of the non-pregnant patient with modestly elevated urinary albumin excretion (30–299mg/day) C and is recommended for those with urinary albumin excretion.300 mg/day. A

c When ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinineand potassium levels for the development of increased creatinine or changesin potassium. E

c Continued monitoring of UACR in patients with albuminuria is reasonable toassess progression of diabetic kidney disease. E

c When eGFR is ,60 mL/min/1.73 m2, evaluate and manage potential compli-cations of chronic kidney disease (CKD). E

c Consider referral to a physician experienced in the care of kidney diseasewhenthere is uncertainty about the etiology of kidney disease, difficult manage-ment issues, or advanced kidney disease. B

Nutritionc For people with diabetic kidney disease, reducing the amount of dietary pro-

tein below the recommended daily allowance of 0.8 g/kg/day (based on idealbody weight) is not recommended because it does not alter glycemic mea-sures, cardiovascular risk measures, or the course of GFR decline. A

The terms “microalbuminuria” (30–299 mg/24 h) and “macroalbuminuria”(.300 mg/24 h) will no longer be used, since albuminuria occurs on a continuum.Albuminuria is defined as UACR $30 mg/g.Diabetic kidney disease occurs in 20–40% of patients with diabetes and is the

leading cause of end-stage renal disease (ESRD). Persistent increased albumin-uria in the range of UACR 30–299 mg/g is an early indicator of diabetic kidneydisease in type 1 diabetes and a marker for development of diabetic kidneydisease in type 2 diabetes. It is a well-established marker of increased cardiovas-cular disease (CVD) risk (1–3). However, there is increasing evidence of sponta-neous remission of UACR levels 30–299 mg/g in up to 40% of patients with type 1diabetes. About 30–40% remain with UACR levels of 30–299 mg/g and do not

Suggested citation: American Diabetes Association.Microvascular complications and foot care. Sec. 9.In Standards ofMedical Care in Diabetesd2015.Diabetes Care 2015;38(Suppl. 1):S58–S66




POSITION

STATEMEN

T

progress to higher levels ($300 mg/g)over 5–10 years of follow-up (4–7). Pa-tients with persistent albuminuria arelikely to develop ESRD (8,9).

Interventions

Glycemia

A number of interventions have beendemonstrated to reduce the risk andslow the progression of diabetic kid-ney disease. Intensive diabetes man-agement with the goal of achievingnear-normoglycemia has been shownin large prospective randomized stud-ies to delay the onset and progressionof increased urinary albumin excre-tion and reduced eGFR in patientswith type 1 (9) and type 2 diabetes(10–14).Despite prior concerns and published

case reports, current data indicate thatthe overall risk of metformin-associatedlactic acidosis is low (14). GFR may be amore appropriate measure to assesscontinued metformin use than serumcreatinine considering that the serumcreatinine level can translate intowidely varying eGFR levels dependingon age, ethnicity, and muscle mass(15). A recent review (16) proposesthat metformin use should be reeval-uated at an eGFR ,45 mL/min/1.73 m2

with a reduction in maximum dose to1,000 mg/day and discontinued wheneGFR ,30 mL/min/1.73 m2 or in clini-cal situations in which there is an in-creased risk of lactic acidosis, such assepsis, hypotension, and hypoxia, or inwhich there is a high risk of acute kid-ney injury resulting in a worseningof GFR, such as administration ofradiocontrast dye in those with eGFR,60 mL/min/1.73 m2.

Blood Pressure

The UK Prospective Diabetes Study(UKPDS) provided strong evidence thatblood pressure control can reduce thedevelopment of diabetic kidney disease(17). In addition, large prospective ran-domized studies in patients with type 1diabetes have shown that ACE inhibitorshave achieved lower systolic blood pres-sure levels (,140 mmHg) and haveprovided a selective benefit over otherantihypertensive drug classes in delay-ing the progression of increased urinaryalbumin excretion and can slow the de-cline in GFR in patients with higher lev-els of albuminuria (18,19). In patientswith type 2 diabetes, hypertension,

and normoalbuminuria, renin-angiotensinsystem inhibition has been demon-strated to delay onset of elevated al-buminuria (20,21). Of note, in thelatter study, there was an unexpectedhigher rate of fatal cardiovascularevents with olmesartan comparedwith placebo among patients with pre-existing CVD.

ACE inhibitors have been shown toreduce major CVD outcomes (i.e.,myocardial infarction, stroke, death)in patients with diabetes (22), thusfurther supporting the use of theseagents in patients with elevatedalbuminuria, a CVD risk factor. ARBsdo not have the same beneficial effecton cardiovascular outcomes or pre-vent the onset of elevated albuminuriain normotensive patients with type 1or type 2 diabetes (23). However, ARBshave been shown to reduce the pro-gression of albuminuria, as well asESRD, in patients with type 2 diabetes(24–26). In those with diabetic kidneydisease, some evidence suggests thatARBs are associated with a smaller in-crease in serum potassium levels com-pared with ACE inhibitors (27).

Combination Therapy

Drug combinations that block the renin-angiotensin system (e.g., an ACE inhibi-tor plus an ARB, a mineralocorticoidantagonist, or a direct renin inhibitor)provide additional lowering of albumin-uria (28). However, compared withsingle-agent use, such combinationshave been found to provide no addi-tional benefit on CVD or diabetic kid-ney disease and have higher adverseevent rates (hyperkalemia or acute kid-ney injury) (29). Therefore, the com-bined use of different inhibitors of therenin-angiotensin system should beavoided.

Diuretics, calcium channel blockers,andb-blockers can be used as additionaltherapy to further lower blood pressurein patients already treated with maxi-mum doses of ACE inhibitors or ARBs(30) or as alternate therapy in the rareindividual unable to tolerate ACE inhib-itors and ARBs.

Studies in patients with varyingstages of diabetic kidney diseasehave shown that the limitation of di-etary protein to avoid excess intakeslows the progression of albuminuria,GFR decline, and occurrence of ESRD

(31–34), although more recent studieshave provided conflicting results (35).Dietary protein limitation, if proteinintake is high, is a consideration par-ticularly in patients whose diabetickidney disease is progressing despiteoptimal glucose and blood pressurecontrol and use of an ACE inhibitor orARB (34).

Assessment of Albuminuria Status andRenal FunctionScreening for increased urinary albu-min excretion can be performed byUACR in a random spot urine collec-tion; 24-h or timed collections aremore burdensome and add little toprediction or accuracy (36,37). Mea-surement of a spot urine sample foralbumin alone (whether by immunoas-say or by using a sensitive dipstick testspecific for albuminuria) without si-multaneously measuring urine creati-nine is less expensive but susceptible tofalse-negative and false-positive deter-minations as a result of variation inurine concentration due to hydrationand other factors.

Abnormalities of albumin excretionand the linkage between UACR and24-h albumin excretion are defined inTable 9.1. Because of variability in urinaryalbumin excretion, two of three speci-mens collected within a 3- to 6-monthperiod should be abnormal beforeconsidering a patient to have developedalbuminuria. Exercise within 24 h, infec-tion, fever, congestive heart failure,marked hyperglycemia, and marked hy-pertension may elevate urinary albuminexcretion over baseline values.

Abnormal urine albumin excretionand GFR level may be used to stageCKD. The National Kidney Foundationclassification (Table 9.2) is primarilybased on GFR levels and may be super-seded by other systems in which staging

Table 9.1—Definitions of abnormalitiesin albumin excretion

CategorySpot collection

(mg/g creatinine)

Normal ,30

Increased urinaryalbumin excretion* $30

*Historically, ratios between 30 and 299mg/g have been called “microalbuminuria”and those .300 mg/g have been called“macroalbuminuria” (or clinicalalbuminuria).


includes other variables such as urinaryalbumin excretion (38). Studies havefound decreased GFR without increasedurine albumin excretion in a substantialpercentage of adults with type 2 diabe-tes (39). Substantial evidence showsthat in patients with type 1 diabetesand persistent UACR 30–299 mg/g,screening with albumin excretion ratealone would miss .20% of progressivedisease (7). Serum creatinine with eGFRshould therefore be assessed at leastannually in all adults with diabetes, re-gardless of the degree of urine albuminexcretion.Serum creatinine should be used to

estimate GFR and to stage the levelof CKD, if present. eGFR is commonlycoreported by laboratories or can beestimated using formulae such as theModification of Diet in Renal Disease(MDRD) study equation (40) or theChronic Kidney Disease EpidemiologyCollaboration (CKD-EPI) equation. Thelatter is the current preferred GFR es-timating equation. GFR calculators areavailable at http://www.nkdep.nih.gov.The need for annual quantitative as-

sessment of albumin excretion afterdiagnosis of albuminuria and institu-tion of ACE inhibitor or ARB therapyand blood pressure control is a subjectof debate. Continued surveillance canassess both response to therapy anddisease progression and may aid in as-sessing adherence to ACE inhibitor orARB therapy. Some suggest that reduc-ing UACR to normal (,30 mg/g) ornear normal may improve CKD andCVD prognosis, but this approach hasnot been formally evaluated in pro-spective trials, and evidence demon-strates spontaneous remission ofalbuminuria in up to 40% of type 1 di-abetic patients.Conversely, patients with increasing

albumin levels, declining GFR, increas-ing blood pressure, retinopathy, macro-vascular disease, elevated lipids and/oruric acid concentrations, or a family his-tory of CKD are more likely to ex-perience a progression of diabetickidney disease (7).Complications of kidney disease cor-

relate with level of kidney function.When the eGFR is ,60 mL/min/1.73 m2,screening for complications of CKDis indicated (Table 9.3). Early vacci-nation against hepatitis B virus is

indicated in patients likely to progressto ESRD.

Referral to NephrologistConsider referral to a physician experi-enced in the care of kidney diseasewhen there is uncertainty about theetiology of kidney disease (heavy pro-teinuria, active urine sediment, absenceof retinopathy, rapid decline in GFR).Other triggers for referral may includedifficult management issues (anemia,secondary hyperparathyroidism, meta-bolic bone disease, resistant hyperten-sion, or electrolyte disturbance) oradvanced kidney disease. The thresholdfor referral may vary depending onthe frequency with which a providerencounters diabetic patients with sig-nificant kidney disease. Consultationwith a nephrologist when stage 4 CKDdevelops has been found to reduce cost,improve quality of care, and delay dial-ysis (41). However, other specialists andproviders should not delay educatingtheir patients about the progressive na-ture of diabetic kidney disease, the kid-ney preservation benefits of proactive

treatment of blood pressure and bloodglucose, and the potential need for renaltransplant.

RETINOPATHY

Recommendations

c Optimize glycemic control to re-duce the risk or slow the progres-sion of retinopathy. A

c Optimize blood pressure controlto reduce the risk or slow the pro-gression of retinopathy. A

Screeningc Adults with type 1 diabetes

should have an initial dilated andcomprehensive eye examinationby an ophthalmologist or optom-etrist within 5 years after the on-set of diabetes. B

c Patients with type 2 diabetesshould have an initial dilated andcomprehensive eye examinationby an ophthalmologist or optom-etrist shortly after the diagnosis ofdiabetes. B

Table 9.2—Stages of CKD

Stage Description GFR (mL/min/1.73 m2)

1 Kidney damage* with normal or increased GFR $90

2 Kidney damage* with mildly decreased GFR 60–89

3 Moderately decreased GFR 30–59

4 Severely decreased GFR 15–29

5 Kidney failure ,15 or dialysis

*Kidney damage is defined as abnormalities on pathological, urine, blood, or imaging tests.Adapted from Levey et al. (37).

Table 9.3—Management of CKD in diabetes (7)

GFR (mL/min/1.73 m2) Recommended management

All patients Yearlymeasurement of creatinine, urinary albumin excretion, potassium

45–60 Referral to a nephrologist if possibility for nondiabetic kidneydisease exists (duration of type 1 diabetes,10 years, persistentalbuminuria, abnormal findings on renal ultrasound, resistanthypertension, rapid fall in GFR, or active urinary sediment onultrasound)

Consider the need for dose adjustment of medicationsMonitor eGFR every 6 monthsMonitor electrolytes, bicarbonate, hemoglobin, calcium,

phosphorus, parathyroid hormone at least yearlyAssure vitamin D sufficiencyConsider bone density testingReferral for dietary counseling

30–44 Monitor eGFR every 3 monthsMonitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid

hormone, hemoglobin, albumin, weight every 3–6 monthsConsider the need for dose adjustment of medications

,30 Referral to a nephrologist


c If there is no evidence of retinopathyfor one or more eye exams, then ex-ams every 2 years may be consid-ered. If diabetic retinopathy ispresent, subsequent examinationsfor patients with type 1 and type 2diabetes shouldbe repeatedannuallyby an ophthalmologist or optome-trist. If retinopathy is progressing orsight-threatening, then examinationswill be required more frequently. B

c High-quality fundus photographscan detect most clinically signifi-cant diabetic retinopathy. Inter-pretation of the images shouldbe performed by a trained eyecare provider. While retinal pho-tography may serve as a screeningtool for retinopathy, it is not a sub-stitute for a comprehensive eyeexam, which should be performedat least initially and at intervalsthereafter as recommended byan eye care professional. E

c Women with preexisting diabeteswho are planning pregnancy orwho have become pregnantshould have a comprehensive eyeexamination and be counseled onthe risk of development and/orprogression of diabetic retinopa-thy. Eye examination should occurin the first trimester with closefollow-up throughout pregnancyand for 1 year postpartum. B

Treatmentc Promptly refer patients with any

level of macular edema, severenonproliferative diabetic retinop-athy (NPDR), or any proliferativediabetic retinopathy (PDR) to anophthalmologist who is knowl-edgeable and experienced in themanagement and treatment of di-abetic retinopathy. A

c Laser photocoagulation therapy isindicated to reduce the risk of visionloss in patients with high-risk PDR,clinically significantmacular edema,and, in some cases, severe NPDR. A

c Antivascular endothelial growthfactor (VEGF) therapy is indicatedfor diabetic macular edema. A

c The presence of retinopathy isnot a contraindication to aspirintherapy for cardioprotection, asaspirin does not increase the riskof retinal hemorrhage. A

Diabetic retinopathy is a highly specificvascular complication of both type 1and type 2 diabetes, with prevalencestrongly related to the duration of dia-betes. Diabetic retinopathy is the mostfrequent cause of new cases of blind-ness among adults aged 20–74 years.Glaucoma, cataracts, and other disor-ders of the eye occur earlier and morefrequently in people with diabetes.

In addition to diabetes duration, fac-tors that increase the risk of, or are as-sociated with, retinopathy includechronic hyperglycemia (42), nephropa-thy (43), and hypertension (44). Inten-sive diabetes management with thegoal of achieving near-normoglycemiahas been shown in large prospectiverandomized studies to prevent and/ordelay the onset and progression of di-abetic retinopathy (11,45). Loweringblood pressure has been shown to de-crease retinopathy progression, al-though tight targets (systolic ,120mmHg) do not impart additional benefit(45). Several case series and a con-trolled prospective study suggest thatpregnancy in type 1 diabetic patientsmay aggravate retinopathy (46,47). La-ser photocoagulation surgery can mini-mize this risk (47).

ScreeningThe preventive effects of therapy andthe fact that patients with PDR or mac-ular edema may be asymptomatic pro-vide strong support for a screeningprogram to detect diabetic retinopathy.Because retinopathy is estimated totake at least 5 years to develop afterthe onset of hyperglycemia, patientswith type 1 diabetes should have an ini-tial dilated and comprehensive eye ex-amination within 5 years after thediabetes diagnosis (48). Patients withtype 2 diabetes whomay have had yearsof undiagnosed diabetes and have a sig-nificant risk of prevalent diabetic ret-inopathy at the time of diagnosisshould have an initial dilated and com-prehensive eye examination shortly af-ter diagnosis. Examinations should beperformed by an ophthalmologist or op-tometrist who is knowledgeable andexperienced in diagnosing diabetic reti-nopathy. Subsequent examinations fortype 1 and type 2 diabetic patients aregenerally repeated annually. Exams ev-ery 2 years may be cost-effective afterone or more normal eye exams, and

in a population with well-controlledtype 2 diabetes, there was essentiallyno risk of development of significant ret-inopathy with a 3-year interval after anormal examination (49). Examinationswill be required more frequently if reti-nopathy is progressing.

Retinal photography, with remotereading by experts, has great potentialin areas where qualified eye care profes-sionals are not readily available (50). Italso may enhance efficiency and reducecosts when the expertise of ophthalmol-ogists can be used for more complexexaminations and for therapy (51). In-person exams are still necessary whenthe photos are unacceptable and forfollow-up if abnormalities are detected.Photos are not a substitute for a com-prehensive eye exam, which should beperformed at least initially and at inter-vals thereafter as recommended by aneye care professional. Results of eye ex-aminations should be documented andtransmitted to the referring health careprofessional.

TreatmentOne of themainmotivations for screeningfor diabetic retinopathy is the long-established efficacy of laser photocoag-ulation surgery in preventing visual loss.Two large trials, the Diabetic Retinopa-thy Study (DRS) in patients with PDR andthe Early Treatment Diabetic RetinopathyStudy (ETDRS) in patients with macularedema, provide the strongest supportfor the therapeutic benefits of photoco-agulation surgery. The DRS (52) showedthat panretinal photocoagulation surgeryreduced the risk of severe vision loss fromPDR from 15.9% in untreated eyes to6.4% in treated eyes, with the greatestrisk-benefit ratio in those with baselinedisease (disc neovascularization or vitre-ous hemorrhage).

The ETDRS (53) established the ben-efit of focal laser photocoagulation sur-gery in eyes with macular edema,particularly those with clinically signif-icant macular edema, with reduction ofdoubling of the visual angle (e.g., 20/50to 20/100) from 20% in untreated eyesto 8% in treated eyes. The ETDRS alsoverified the benefits of panretinal pho-tocoagulation for high-risk PDR and inolder-onset patients with severe NPDRor less-than-high-risk PDR.

Laser photocoagulation surgery inboth trials was beneficial in reducing


the risk of further visual loss, but gener-ally not beneficial in reversing alreadydiminished acuity. Recombinant mono-clonal neutralizing antibody to VEGF im-proves vision and reduces the need forlaser photocoagulation in patients withmacular edema (54). Other emergingtherapies for retinopathy include sus-tained intravitreal delivery of fluocin-olone (55) and the possibility ofprevention with fenofibrate (56,57).

NEUROPATHY

Recommendations

c All patients should be screened fordiabetic peripheral neuropathy(DPN) starting at diagnosis oftype 2 diabetes and 5 years afterthe diagnosis of type 1 diabetesand at least annually thereafter,using simple clinical tests, suchas a 10-g monofilament. B

c Screening for signs and symptoms(e.g., orthostasis, resting tachycar-dia) of cardiovascular autonomicneuropathy (CAN) shouldbe consid-eredwithmore advanced disease. E

c Tight glycemic control is the onlystrategy convincingly shown toprevent or delay the developmentof DPN and CAN in patients withtype 1 diabetes A and to slow theprogression of neuropathy in somepatients with type 2 diabetes. B

c Assess and treat patients to re-duce pain related to DPN B andsymptoms of autonomic neuropa-thy and to improve quality of life. E

The diabetic neuropathies are heteroge-neous with diverse clinical manifestations.They may be focal or diffuse. The mostprevalent neuropathies are DPN and auto-nomic neuropathy. Although DPN is a diag-nosis of exclusion, complex investigationsor referral for neurology consultation to ex-clude other conditions is rarely needed.The early recognition and appropriate

management of neuropathy in the pa-tient with diabetes is important for anumber of reasons:

1. Nondiabetic neuropathies may bepresent in patients with diabetesand may be treatable.

2. A number of treatment options existfor symptomatic diabetic neuropathy.

3. Up to 50% of DPNmay be asymptom-atic, and patients are at risk for in-sensate injury to their feet.

4. Autonomic neuropathy, particularlyCAN, is an independent risk factorfor cardiovascular mortality (58,59).

Specific treatment for the underlyingnerve damage, other than improved gly-cemic control, is currently not available.Glycemic control was shown to effec-tively prevent DPN and CAN in type 1diabetes (60,61) and may modestlyslow progression in type 2 diabetes(13) but does not reverse neuronalloss. Therapeutic strategies (pharmaco-logical and nonpharmacological) for therelief of specific symptoms related topainful DPN or autonomic neuropathyare recommended because they can po-tentially reduce pain (62) and improvequality of life.

Diagnosis

Diabetic Peripheral Neuropathy

Patients with diabetes should bescreened annually for DPN symptomsusing simple clinical tests. Symptomsvary according to the class of sensoryfibers involved. The most commonsymptoms are induced by the involve-ment of small fibers and include pain,dysesthesias (unpleasant abnormal sen-sations of burning and tingling), andnumbness. Clinical tests include assess-ment of pinprick sensation, vibrationthreshold using a 128-Hz tuning fork,light touch perception using a 10-gmonofilament, and ankle reflexes. As-sessment should follow the typicalDPN pattern, starting distally (the dorsalaspect of the hallux) on both sides andmove proximally until threshold is de-tected. Several clinical instrumentsthat combine more than one test have.87% sensitivity in detecting DPN(63–65). Electrophysiological testing orreferral to a neurologist is rarely needed,except in situations where the clinicalfeatures are atypical or the diagnosis isunclear.

In patients with severe or atypical neu-ropathy, causes other than diabetesshould always be considered, such as neu-rotoxic medications, heavy metal poison-ing, alcohol abuse, vitamin B12 deficiency(66), renal disease, chronic inflammatorydemyelinatingneuropathy, inheritedneu-ropathies, and vasculitis (67).

Diabetic Autonomic Neuropathy

The symptoms and signs of autonomicdysfunction should be elicited care-fully during the history and physical

examination. Major clinical manifesta-tions of diabetic autonomic neuropathyinclude resting tachycardia, exerciseintolerance, orthostatic hypotension,gastroparesis, constipation, erectile dys-function, sudomotor dysfunction, im-paired neurovascular function, and,potentially, autonomic failure in responseto hypoglycemia.

Cardiovascular Autonomic Neuropathy

CAN is the most studied and clinicallyimportant form of diabetic autonomicneuropathy because of its associationwith mortality independent of othercardiovascular risk factors (58,68). Inearly stages, CAN may be completelyasymptomatic and detected by changesin heart rate variability with deepbreathing and abnormal cardiovascularreflex tests (R-R interval response todeep breathing, standing, and Valsalvamaneuver tests). Advanced disease maybe indicated by resting tachycardia(.100 bpm) and orthostasis (a fall insystolic blood pressure .20 mmHg ordiastolic blood pressure of at least 10mmHg upon standing without an appro-priate heart rate response). The stan-dard cardiovascular reflex tests (deepbreathing, standing, and Valsalvamaneuver) are noninvasive, easy toperform, reliable, and reproducible, es-pecially the deep breathing test, andhave prognostic value (69). Althoughsome societies have developed guide-lines for screening for CAN, the benefitsof sophisticated testing beyond riskstratification are not clear (69).

Gastrointestinal Neuropathies

Gastrointestinal neuropathies (e.g.,esophageal enteropathy, gastroparesis,constipation, diarrhea, fecal inconti-nence) may involve any section of thegastrointestinal tract. Gastroparesisshould be suspected in individuals witherratic glucose control or with upper gas-trointestinal symptoms without anotheridentified cause. Evaluation of solid-phase gastric emptying using double-isotope scintigraphy may be done ifsymptoms are suggestive, but test re-sults often correlate poorly with symp-toms. Constipation is the most commonlower-gastrointestinal symptom but canalternate with episodes of diarrhea.

Genitourinary Tract Disturbances

Diabetic autonomic neuropathy is alsoassociated with genitourinary tract dis-turbances. In men, diabetic autonomic


neuropathy may cause erectile dysfunc-tion and/or retrograde ejaculation. Eval-uation of bladder dysfunction should beperformed for individuals with diabeteswho have recurrent urinary tract infec-tions, pyelonephritis, incontinence, or apalpable bladder.

Treatment

Glycemic Control

Tight glycemic control, implementedearly in the course of diabetes, hasbeen shown to effectively prevent or de-lay the development of DPN and CAN inpatients with type 1 diabetes (70–73).While the evidence is not as strong fortype 2 diabetes, some studies havedemonstrated a modest slowing of pro-gression (74,75) without reversal ofneuronal loss. Several observationalstudies further suggest that neuropathicsymptoms improve not only with opti-mization of glycemic control but alsowith the avoidance of extreme bloodglucose fluctuations.

Diabetic Peripheral Neuropathy

DPN symptoms, and especially neuro-pathic pain, can be severe, have suddenonset, and are associated with lowerquality of life, limited mobility, depres-sion, and social dysfunction (76). Thereis limited clinical evidence regarding themost effective treatments for individualpatients given the wide range of avail-able medications (77,78). Several drugshave been approved specifically for re-lief of DPN pain in the U.S. (pregabalin,duloxetine, and tapentadol), but noneaffords complete relief, even whenused in combination. Venlafaxine, ami-triptyline, gabapentin, valproate, andother opioids (morphine sulfate, trama-dol, oxycodone controlled release) maybe effective and may be considered fortreatment of painful DPN. Head-to-head treatment comparisons and stud-ies that include quality-of-life outcomesare rare, so treatment decisions mustconsider each patient’s presentationand comorbidities and often follow atrial-and-error approach. Given therange of partially effective treatmentoptions, a tailored and stepwise phar-macological strategy with careful atten-tion to relative symptom improvement,medication adherence, and medicationside effects is recommended to achievepain reduction and improve quality oflife (62).

Autonomic Neuropathy

An intensive multifactorial cardiovascu-lar risk intervention targeting glucose,blood pressure, lipids, smoking, andother lifestyle factors has been shownto reduce the progression and develop-ment of CAN among patients with type 2diabetes (79). For those with significantCAN, referral to a cardiologist may beindicated.

Orthostatic Hypotension

Treatment of orthostatic hypotension ischallenging. The therapeutic goal is tominimize postural symptoms ratherthan to restore normotension. Most pa-tients require the use of both pharma-cological and nonpharmacologicalmeasures (e.g., avoiding medicationsthat aggravate hypotension, using com-pressive garments over the legs and ab-domen). Midodrine is the only drugapproved by the U.S. Food and DrugAdministration for the treatment oforthostatic hypotension.

Gastroparesis Symptoms

Gastroparesis symptoms may improvewith dietary changes andprokinetic agentssuch as erythromycin. Recently, the Euro-pean Medicines Agency (www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/07/WC500146614.pdf)decided that risks of extrapyramidal symp-tomswithmetoclopramide outweigh ben-efits. In Europe, metoclopramide use isnow restricted to a maximum of 5 daysand is no longer indicated for the long-term treatment of gastroparesis. Althoughthe U.S. Food and Drug Administration’sdecision is pending, it is suggested thatmetoclopramide be reserved for only themost severe cases that are unresponsiveto other therapies. Side effects should beclosely monitored.

Erectile Dysfunction

Treatments for erectile dysfunction mayinclude phosphodiesterase type 5 inhibi-tors, intracorporeal or intraurethral prosta-glandins, vacuum devices, or penileprostheses. Interventions for other mani-festations of autonomic neuropathy aredescribed in the American Diabetes Asso-ciation (ADA) statement on neuropathy(78). As with DPN treatments, these inter-ventions do not change the underlyingpathology and natural history of the dis-ease process but may have a positive im-pact on the quality of life of the patient.

FOOT CARE

Recommendations

c For all patients with diabetes, per-form an annual comprehensivefoot examination to identify riskfactors predictive of ulcers andamputations. The foot examina-tion should include inspectionand assessment of foot pulses. B

c Patients with insensate feet, footdeformities, and ulcers shouldhave their feet examined at everyvisit. E

c Provide general foot self-careeducation to all patients with di-abetes. B

c A multidisciplinary approach isrecommended for individualswith foot ulcers and high-risk feet(e.g., dialysis patients and thosewith Charcot foot, prior ulcers, oramputation). B

c Refer patients who smoke or whohave a loss of protective sensation(LOPS), structural abnormalities,or a history of prior lower-extremity complications to footcare specialists for ongoing pre-ventive care and lifelong surveil-lance. C

c Initial screening for peripheralarterial disease (PAD) shouldinclude a history for claudicationand an assessment of the pedalpulses. C

c Refer patients with significantclaudication or a positive ankle-brachial index (ABI) for furthervascular assessment and considerexercise, medications, and surgicaloptions. C

Amputation and foot ulceration, whichare consequences of diabetic neuropa-thy and/or PAD, are common and repre-sent major causes of morbidity anddisability in people with diabetes. Lossof 10-g monofilament perception andreduced vibration perception predictfoot ulcers (78). Early recognition andmanagement of risk factors can preventor delay adverse outcomes.

The risk of ulcers or amputations isincreased in people who have the fol-lowing risk factors:

○ Previous amputation○ Past foot ulcer history○ Peripheral neuropathy○ Foot deformities


○ Peripheral vascular disease○ Visual impairment○ Diabetic nephropathy (especially pa-

tients on dialysis)○ Poor glycemic control○ Cigarette smoking

Clinicians are encouraged to reviewADA screening recommendations forfurther details and practical descriptionsof how to perform components of thecomprehensive foot examination (80).

ExaminationAll adults with diabetes shouldundergo a comprehensive foot exami-nation at least annually to identifyhigh-risk conditions. Clinicians shouldask about history of previous foot ulcer-ation or amputation, neuropathic or pe-ripheral vascular symptoms, impairedvision, tobacco use, and foot care prac-tices. A general inspection of skin integ-rity and musculoskeletal deformitiesshould be done in a well-lit room. Vas-cular assessment would include inspec-tion and assessment of pedal pulses.The neurological exam recommended

is designed to identify LOPS rather thanearly neuropathy. The clinical examinationto identify LOPS is simple and requires noexpensive equipment. Five simple clinicaltests (use of a 10-g monofilament, vibra-tion testing using a 128-Hz tuning fork,tests of pinprick sensation, ankle reflex as-sessment, and testing vibration percep-tion threshold with a biothesiometer),each with evidence from well-conductedprospective clinical cohort studies, areconsidered useful in the diagnosis ofLOPS in the diabetic foot. Any of the fivetests listed above could be used by clini-cians to identify LOPS, although ideallytwo of these should be regularly per-formed during the screening examdnormally the 10-g monofilament and oneother test. One or more abnormal testswould suggest LOPS, while at least twonormal tests (andnoabnormal test)wouldrule out LOPS. The last test listed, vibrationassessment using a biothesiometer or sim-ilar instrument, is widely used in the U.S.;however, identification of the patientwithLOPS can easily be carried out without thisor other expensive equipment.

ScreeningInitial screening for PAD shouldinclude a history for claudication andan assessment of the pedal pulses.

A diagnostic ABI should be consideredin patients with PAD. Due to the highestimated prevalence of PAD in patientswith diabetes and the fact that manypatients with PAD are asymptomatic,an ADA consensus report on PAD (81)suggested that a screening ABI be per-formed in patients over 50 years of ageand be considered in patients under 50years of age who have other PAD riskfactors (e.g., smoking, hypertension, hy-perlipidemia, or duration of diabetes.10 years). Refer patients with signifi-cant symptoms or a positive ABI for fur-ther vascular assessment and considerexercise, medications, and surgicaloptions (81).

Patient EducationPatients with diabetes and high-risk footconditions should be educated abouttheir risk factors and appropriate man-agement. Patients at risk should under-stand the implications of LOPS; theimportance of footmonitoring on a dailybasis; the proper care of the foot, includ-ing nail and skin care; and the selectionof appropriate footwear. Patients withLOPS should be educated on ways tosubstitute other sensory modalities(hand palpation, visual inspection) forsurveillance of early foot problems. Pa-tients’ understanding of these issuesand their physical ability to conductproper foot surveillance and care shouldbe assessed. Patients with visual difficul-ties, physical constraints preventingmovement, or cognitive problems thatimpair their ability to assess the condi-tion of the foot and to institute appro-priate responses will need other people,such as family members, to assist intheir care.

TreatmentPeople with neuropathy or evidence ofincreased plantar pressure (e.g., ery-thema, warmth, callus, or measuredpressure) may be adequately managedwithwell-fittedwalking shoes or athleticshoes that cushion the feet and redis-tribute pressure. Calluses can be de-brided with a scalpel by a foot carespecialist or other health professionalwith experience and training in footcare. People with bony deformities (e.g.,hammertoes, prominent metatarsalheads, bunions) may need extra wideor deep shoes. People with extremebony deformities (e.g., Charcot foot)who cannot be accommodated with

commercial therapeutic footwear mayneed custom-molded shoes.

Most diabetic foot infections are poly-microbial, with aerobic gram-positivecocci (GPC). Staphylococci are the mostcommon causative organisms. Woundswithout evidence of soft-tissue or boneinfection do not require antibiotic ther-apy. Empiric antibiotic therapy can benarrowly targeted at GPC in manyacutely infected patients, but those atrisk for infection with antibiotic-resistantorganisms or with chronic, previouslytreated, or severe infections requirebroader-spectrum regimens and shouldbe referred to specialized care centers(82). Foot ulcers and wound care mayrequire care by a podiatrist, orthopedicor vascular surgeon, or rehabilitationspecialist experienced in the manage-ment of individuals with diabetes.Guidelines for treatment of diabeticfoot ulcers have recently been updated(82).

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36. Eknoyan G, Hostetter T, Bakris GL, et al. Pro-teinuria and other markers of chronic kidneydisease: a position statement of the NationalKidney Foundation (NKF) and the National In-stitute of Diabetes and Digestive and KidneyDiseases (NIDDK). Am J Kidney Dis 2003;42:617–62237. Levey AS, Coresh J, Balk E, et al.; NationalKidney Foundation. National Kidney Foundationpractice guidelines for chronic kidney disease:evaluation, classification, and stratification. AnnIntern Med 2003;139:137–14738. Kramer H, MolitchME. Screening for kidneydisease in adults with diabetes. Diabetes Care2005;28:1813–181639. Kramer HJ, Nguyen QD, Curhan G, Hsu C-Y.Renal insufficiency in the absence of albumin-uria and retinopathy among adults with type 2diabetes mellitus. JAMA 2003;289:3273–327740. Levey AS, Bosch JP, Lewis JB, Greene T,Rogers N, Roth D; Modification of Diet in RenalDisease Study Group. A more accurate methodto estimate glomerular filtration rate from se-rum creatinine: a new prediction equation. AnnIntern Med 1999;130:461–47041. Smart NA, Dieberg G, Ladhani M, Titus T.Early referral to specialist nephrology servicesfor preventing the progression to end-stage kid-ney disease. Cochrane Database Syst Rev 2014;6:CD00733342. Klein R. Hyperglycemia and microvascularand macrovascular disease in diabetes. Diabe-tes Care 1995;18:258–26843. Estacio RO, McFarling E, Biggerstaff S,Jeffers BW, Johnson D, Schrier RW. Overt albu-minuria predicts diabetic retinopathy in His-panics with NIDDM. Am J Kidney Dis 1998;31:947–95344. Leske MC, Wu S-Y, Hennis A, et al.; Barba-dos Eye Study Group. Hyperglycemia, bloodpressure, and the 9-year incidence of diabeticretinopathy: the Barbados Eye Studies. Oph-thalmology 2005;112:799–80545. Chew EY, Ambrosius WT, Davis MD, et al.;ACCORD Study Group; ACCORD Eye StudyGroup. Effects of medical therapies on retinop-athy progression in type 2 diabetes. N Engl JMed 2010;363:233–24446. Fong DS, Aiello LP, Ferris FL 3rd, Klein R.Diabetic retinopathy. Diabetes Care 2004;27:2540–255347. Diabetes Control and Complications TrialResearch Group. Effect of pregnancy on micro-vascular complications in the diabetes controland complications trial. Diabetes Care 2000;23:1084–109148. Hooper P, Boucher MC, Cruess A, et al.Canadian Ophthalmological Society evidence-based clinical practice guidelines for themanagement of diabetic retinopathy. Can JOphthalmol 2012;47(Suppl. 2):S12S3049. Agardh E, Tababat-Khani P. Adopting 3-yearscreening intervals for sight-threatening retinalvascular lesions in type 2 diabetic subjects with-out retinopathy. Diabetes Care 2011;34:1318–131950. Bragge P, Gruen RL, Chau M, Forbes A,Taylor HR. Screening for presence or absenceof diabetic retinopathy: a meta-analysis. ArchOphthalmol 2011;129:435–44451. Ahmed J, Ward TP, Bursell S-E, Aiello LM,Cavallerano JD, Vigersky RA. The sensitivity and


specificity of nonmydriatic digital stereoscopicretinal imaging in detecting diabetic retinopa-thy. Diabetes Care 2006;29:2205–220952. The Diabetic Retinopathy Study ResearchGroup. Preliminary report on effects of photo-coagulation therapy. Am J Ophthalmol 1976;81:383–39653. Early Treatment Diabetic RetinopathyStudy Research Group. Photocoagulation for di-abetic macular edema. Early Treatment DiabeticRetinopathy Study report number 1. Arch Oph-thalmol 1985;103:1796–180654. Nguyen QD, Brown DM, Marcus DM, et al.;RISE and RIDE Research Group. Ranibizumab fordiabetic macular edema: results from 2 phase IIIrandomized trials: RISE and RIDE. Ophthalmol-ogy 2012;119:789–80155. Pearson PA, Comstock TL, Ip M, et al. Fluo-cinolone acetonide intravitreal implant for dia-betic macular edema: a 3-year multicenter,randomized, controlled clinical trial. Ophthal-mology 2011;118:1580–158756. Chew EY, Ambrosius WT. Update of theACCORD Eye Study. N Engl J Med 2011;364:188–18957. Keech AC, Mitchell P, Summanen PA, et al.;FIELD study investigators. Effect of fenofibrateon the need for laser treatment for diabeticretinopathy (FIELD study): a randomised con-trolled trial. Lancet 2007;370:1687–169758. Pop-Busui R, Evans GW, Gerstein HC, et al.;Action to Control Cardiovascular Risk in DiabetesStudy Group. Effects of cardiac autonomic dys-function onmortality risk in the Action to ControlCardiovascular Risk in Diabetes (ACCORD) trial.Diabetes Care 2010;33:1578–158459. Spallone V, Ziegler D, Freeman R, et al.;Toronto Consensus Panel on Diabetic Neuropa-thy. Cardiovascular autonomic neuropathy indiabetes: clinical impact, assessment, diagnosis,and management. Diabetes Metab Res Rev2011;27:639265360. Ang L, Jaiswal M, Martin C, Pop-Busui R.Glucose control and diabetic neuropathy: les-sons from recent large clinical trials. Curr DiabRep 2014;14:52861. Martin CL, Albers JW, Pop-Busui R; DCCT/EDIC Research Group. Neuropathy and relatedfindings in the Diabetes Control and Complica-tions Trial/Epidemiology of Diabetes Interven-tions and Complications study. Diabetes Care2014;37:31–3862. Bril V, England J, Franklin GM, et al.; Amer-ican Academy of Neurology; American Associa-tion of Neuromuscular and ElectrodiagnosticMedicine; American Academy of Physical Med-icine and Rehabilitation. Evidence-based guide-line: treatment of painful diabetic neuropathy:report of the American Academy of Neurology,the American Association of Neuromuscularand Electrodiagnostic Medicine, and the

American Academy of Physical Medicine andRehabilitation [published correction appears inNeurology 2011;77:603]. Neurology 2011;76:1758–176563. Pop-Busui R, Lu J, Brooks MM, et al.; BARI2D Study Group. Impact of glycemic controlstrategies on the progression of diabetic periph-eral neuropathy in the Bypass Angioplasty Re-vascularization Investigation 2 Diabetes (BARI2D) cohort. Diabetes Care 2013;36:3208–321564. Martin CL, Albers J, Herman WH, et al.;DCCT/EDIC Research Group. Neuropathy amongthe diabetes control and complications trial co-hort 8 years after trial completion. DiabetesCare 2006;29:340–34465. Herman WH, Pop-Busui R, Braffett BH,et al.; DCCT/EDIC Research Group. Use of theMichigan Neuropathy Screening Instrument as ameasure of distal symmetrical peripheral neu-ropathy in type 1 diabetes: results from the Di-abetes Control and Complications Trial/Epidemiology of Diabetes Interventions andComplications. Diabet Med 2012;29:937–94466. Wile DJ, Toth C. Association of metformin,elevated homocysteine, and methylmalonicacid levels and clinically worsened diabetic pe-ripheral neuropathy. Diabetes Care 2010;33:156–16167. Freeman R. Not all neuropathy in diabetesis of diabetic etiology: differential diagnosis ofdiabetic neuropathy. Curr Diab Rep 2009;9:423–43168. Young LH, Wackers FJT, Chyun DA, et al.;DIAD Investigators. Cardiac outcomes afterscreening for asymptomatic coronary artery dis-ease in patients with type 2 diabetes: the DIADstudy: a randomized controlled trial. JAMA2009;301:1547–155569. Spallone V, Bellavere F, Scionti L, et al.; Di-abetic Neuropathy Study Group of the ItalianSociety of Diabetology. Recommendations forthe use of cardiovascular tests in diagnosing di-abetic autonomic neuropathy. Nutr Metab Car-diovasc Dis 2011;21:69–7870. Diabetes Control and Complications Trial(DCCT) Research Group. Effect of intensive di-abetes treatment on nerve conduction in theDiabetes Control and Complications Trial. AnnNeurol 1995;38:869–88071. CDC Study Group. The effect of intensivediabetes therapy on measures of autonomicnervous system function in the Diabetes Controland Complications Trial (DCCT). Diabetologia1998;41:416–42372. Albers JW, Herman WH, Pop-Busui R, et al.;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions andComplications Research Group. Effect of priorintensive insulin treatment during the DiabetesControl and Complications Trial (DCCT) on pe-ripheral neuropathy in type 1 diabetes during

the Epidemiology of Diabetes Interventions andComplications (EDIC) study. Diabetes Care2010;33:1090–109673. Pop-Busui R, Low PA, Waberski BH, et al.;DCCT/EDIC Research Group. Effects of prior in-tensive insulin therapy on cardiac autonomicnervous system function in type 1 diabetes mel-litus: the Diabetes Control and ComplicationsTrial/Epidemiology of Diabetes Interventionsand Complications study (DCCT/EDIC). Circula-tion 2009;119:2886–289374. Callaghan BC, Little AA, Feldman EL, HughesRAC. Enhanced glucose control for preventingand treating diabetic neuropathy. Cochrane Da-tabase Syst Rev 2012;6:CD00754375. Riddle MC, Ambrosius WT, Brillon DJ, et al.;Action to Control Cardiovascular Risk in Diabe-tes Investigators. Epidemiologic relationshipsbetween A1C and all-cause mortality during amedian 3.4-year follow-up of glycemic treat-ment in the ACCORD trial. Diabetes Care 2010;33:983–99076. Sadosky A, Schaefer C, Mann R, et al. Bur-den of illness associated with painful diabeticperipheral neuropathy among adults seekingtreatment in the US: results from a retrospec-tive chart review and cross-sectional survey. Di-abetes Metab Syndr Obes 2013;6:79–9277. Snedecor SJ, Sudharshan L, Cappelleri JC,Sadosky A, Mehta S, Botteman M. Systematicreview and meta-analysis of pharmacologicaltherapies for painful diabetic peripheral neu-ropathy. Pain Pract 2014;14:167–18478. Boulton AJM, Vinik AI, Arezzo JC, et al.;American Diabetes Association. Diabeticneuropathies: a statement by the AmericanDiabetes Association. Diabetes Care 2005;28:956–96279. Gaede P, Vedel P, Larsen N, Jensen GVH,Parving H-H, Pedersen O. Multifactorial inter-vention and cardiovascular disease in patientswith type 2 diabetes. N Engl J Med 2003;348:383–39380. Boulton AJM, Armstrong DG, Albert SF,et al.; American Diabetes Association; AmericanAssociation of Clinical Endocrinologists. Com-prehensive foot examination and risk assess-ment: a report of the task force of the footcare interest group of the American DiabetesAssociation, with endorsement by the AmericanAssociation of Clinical Endocrinologists. Diabe-tes Care 2008;31:1679–168581. American Diabetes Association. Peripheralarterial disease in people with diabetes. Diabe-tes Care 2003;26:3333–334182. Lipsky BA, Berendt AR, Cornia PB, et al.; In-fectious Diseases Society of America. 2012 In-fectious Diseases Society of America clinicalpractice guideline for the diagnosis and treat-ment of diabetic foot infections. Clin Infect Dis2012;54:e132–e173


10. Older AdultsDiabetes Care 2015;38(Suppl. 1):S67–S69 | DOI: 10.2337/dc15-S013

Recommendations

c Older adults who are functional and cognitively intact and have significant lifeexpectancy should receive diabetes care with goals similar to those developedfor younger adults. E

c Glycemic goals for some older adults might reasonably be relaxed, using in-dividual criteria, but hyperglycemia leading to symptoms or risk of acutehyperglycemic complications should be avoided in all patients. E

c Other cardiovascular risk factors should be treated in older adults with con-sideration of the time frame of benefit and the individual patient. Treatmentof hypertension is indicated in virtually all older adults, and lipid-lowering andaspirin therapy may benefit those with life expectancy at least equal to thetime frame of primary or secondary prevention trials. E

c Screening for diabetes complications should be individualized in older adults,but particular attention should be paid to complications that would lead tofunctional impairment. E

c Older adults ($65 years of age) with diabetes should be considered a high-priority population for depression screening and treatment. B

Diabetes is an important health condition for the aging population; at least 20% ofpatients over the age of 65 years have diabetes, and this number is expected to growrapidly in the coming decades. Older individuals with diabetes have higher rates ofpremature death, functional disability, and coexisting illnesses, such as hyperten-sion, coronary heart disease, and stroke, than those without diabetes. Older adultswith diabetes are also at a greater risk than other older adults for several commongeriatric syndromes, such as polypharmacy, cognitive impairment, urinary inconti-nence, injurious falls, and persistent pain. Screening for diabetes complications inolder adults also should be individualized. Older adults are at an increased risk fordepression and should therefore be screened and treated accordingly (1). Particularattention should be paid to complications that can develop over short periods oftime and/or that would significantly impair functional status, such as visual andlower-extremity complications. Please refer to the American Diabetes Associationconsensus report “Diabetes in Older Adults” for details (2).The care of older adults with diabetes is complicated by their clinical and func-

tional heterogeneity. Some older individuals developed diabetes years earlier andmay have significant complications; others are newly diagnosed and may have hadyears of undiagnosed diabetes with resultant complications; and still other olderadults may have truly recent-onset disease with few or no complications. Someolder adults with diabetes are frail and have other underlying chronic conditions,substantial diabetes-related comorbidity, or limited physical or cognitive functioning.Other older individuals with diabetes have little comorbidity and are active.Life expectancies are highly variable for this population but are often longer thanclinicians realize. Providers caring for older adults with diabetes must take this hetero-geneity into consideration when setting and prioritizing treatment goals (Table 10.1).

TREATMENT GOALS

There are few long-term studies in older adults demonstrating the benefits of in-tensive glycemic, blood pressure, and lipid control. Patients who can be expected tolive long enough to reap the benefits of long-term intensive diabetes management,who have good cognitive and physical function, and who choose to do so via shareddecision making may be treated using therapeutic interventions and goals similar to

Suggested citation: American Diabetes Associa-tion. Older adults. Sec. 10. In Standards of Med-ical Care in Diabetesd2015. Diabetes Care2015;38(Suppl. 1):S67–S69




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those for younger adults with diabetes.As with all diabetic patients, diabetesself-management education and ongo-ing diabetes self-management supportare vital components of diabetes carefor older adults and their caregivers.For patients with advanced diabetes

complications, life-limiting comorbid ill-ness, or substantial cognitive or func-tional impairment, it is reasonable toset less intensive glycemic target goals.These patients are less likely to benefitfrom reducing the risk of microvascularcomplications and more likely to sufferserious adverse effects from hypoglyce-mia. However, patients with poorly con-trolled diabetes may be subject to acutecomplications of diabetes, includingdehydration, poor wound healing, andhyperglycemic hyperosmolar coma.Glycemic goals at a minimum shouldavoid these consequences.Although hyperglycemia control may

be important in older individuals withdiabetes, greater reductions in morbid-ity andmortality are likely to result fromcontrol of other cardiovascular risk

factors rather than from tight glycemiccontrol alone. There is strong evidencefrom clinical trials of the value of treat-ing hypertension in the elderly (3,4).There is less evidence for lipid-loweringand aspirin therapy, although the bene-fits of these interventions for primaryand secondary prevention are likely toapply to older adults whose life expec-tancies equal or exceed the time framesseen in clinical trials.

HYPOGLYCEMIA

Older adults are at a higher risk of hypo-glycemia for many reasons, including in-sulin deficiency and progressive renalinsufficiency. In addition, older adultstend to have higher rates of unidentifiedcognitive deficits, causing difficulty incomplex self-care activities (e.g., glucosemonitoring, adjusting insulin doses, etc.).These deficits have been associated withincreased risk of hypoglycemia and withsevere hypoglycemia linked to increaseddementia. Therefore, it is important toroutinely screen older adults for cognitivedysfunction and discuss findings with the

caregivers. Hypoglycemic events shouldbe diligentlymonitored, and glycemic tar-gets may need to be adjusted to accom-modate for the changing needs of theolder adult (2).

PHARMACOLOGICAL THERAPY

Special care is required in prescribing andmonitoring pharmacological therapy inolder adults. Cost may be a significantfactor, especially as older adults tend tobe onmany medications. Metforminmaybe contraindicatedbecause of renal insuf-ficiency or significant heart failure. Thia-zolidinediones, if used at all, should beused very cautiously in those with, or atrisk for, congestive heart failure and havebeen associated with fractures. Sulfonyl-ureas, other insulin secretagogues, andinsulin can cause hypoglycemia. Insulinuse requires that patients or caregivershave good visual andmotor skills and cog-nitive ability. GLP-1 agonists and dipep-tidyl peptidase-4 inhibitors have fewside effects, but their costs may be a bar-rier to some older patients. A clinical trial,Saxagliptin Assessment of Vascular

Table 10.1—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults withdiabetes

Patient characteristics/health status Rationale

ReasonableA1C goal‡

Fasting orpreprandial

glucose (mg/dL)

Bedtimeglucose(mg/dL)

Bloodpressure(mmHg) Lipids

Healthy (few coexistingchronic illnesses, intactcognitive and functionalstatus)

Longer remaining lifeexpectancy

,7.5% 90–130 90–150 ,140/90 Statin unlesscontraindicatedor not tolerated

Complex/intermediate(multiple coexistingchronic illnesses* or 21instrumental ADLimpairments or mild-to-moderate cognitiveimpairment)

Intermediate remaininglife expectancy, hightreatment burden,hypoglycemiavulnerability, fall risk

,8.0% 90–150 100–180 ,140/90 Statin unlesscontraindicatedor not tolerated

Very complex/poor health(long-term care or end-stage chronic illnesses**or moderate-to-severecognitive impairment or21 ADL dependencies)

Limited remaining lifeexpectancy makesbenefit uncertain

,8.5%† 100–180 110–200 ,150/90 Consider likelihood ofbenefit with statin(secondary preventionmore so than primary)

This represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes.The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category. Consideration of patient andcaregiver preferences is an important aspect of treatment individualization. Additionally, a patient’s health status and preferences may change overtime. ADL, activities of daily living.‡A lower A1C goal may be set for an individual if achievable without recurrent or severe hypoglycemia or undue treatment burden.*Coexisting chronic illnesses are conditions serious enough to require medications or lifestyle management and may include arthritis, cancer,congestive heart failure, depression, emphysema, falls, hypertension, incontinence, stage 3 or worse chronic kidney disease, myocardial infarction,and stroke. By “multiple,” we mean at least three, but many patients may have five or more (6).**The presence of a single end-stage chronic illness, such as stage 3–4 congestive heart failure or oxygen-dependent lung disease, chronic kidneydisease requiring dialysis, or uncontrolled metastatic cancer, may cause significant symptoms or impairment of functional status and significantlyreduce life expectancy.†A1C of 8.5% equates to an estimated average glucose of ;200 mg/dL. Looser glycemic targets than this may expose patients to acute risks fromglycosuria, dehydration, hyperglycemic hyperosmolar syndrome, and poor wound healing.


Outcomes Recorded in Patients withDiabetes Mellitus–Thrombolysis in Myo-cardial Infarction 53 (SAVOR-TIMI 53),evaluated saxagliptin (a dipeptidylpeptidase-4 inhibitor) and its impacton cardiovascular outcomes (5). Pa-tients treated with saxagliptin weremore likely to be hospitalized for heartfailure than were those given a placebo(3.5% vs. 2.8%, respectively, according to2-year Kaplan-Meier estimates; hazardratio 1.27 [95%CI 1.0721.51]; P5 0.007).

References1. Kimbro LB, Mangione CM, Steers WN, et al.Depression and all-cause mortality in personswith diabetes mellitus: are older adults at higherrisk? Results from the Translating Research IntoAction for Diabetes Study. J Am Geriatr Soc 2014;62:1017–10222. KirkmanMS, Briscoe VJ, Clark N, et al. Diabetesin older adults. Diabetes Care 2012;35:2650–26643. Beckett NS, Peters R, Fletcher AE, et al.;HYVET Study Group. Treatment of hypertensionin patients 80 years of age or older. N Engl J Med2008;358:1887–1898

4. James PA, Oparil S, Carter BL, et al. 2014evidence-based guideline for the management ofhigh blood pressure in adults: report from thepanel members appointed to the Eighth Joint Na-tional Committee (JNC8). JAMA2014;311:507–5205. Scirica BM, Bhatt DL, Braunwald E, et al.;SAVOR-TIMI 53 Steering Committee and Investi-gators. Saxagliptin and cardiovascular outcomesin patients with type 2 diabetes mellitus. N Engl JMed 2013;369:1317–13266. Laiteerapong N, Iveniuk J, John PM, LaumannEO, Huang ES. Classification of older adults whohave diabetes by comorbid conditions, UnitedStates, 2005-2006. Prev Chronic Dis 2012;9:E100


11. Children and AdolescentsDiabetes Care 2015;38(Suppl. 1):S70–S76 | DOI: 10.2337/dc15-S014

TYPE 1 DIABETES

Three-quarters of all cases of type 1 diabetes are diagnosed in individuals,18 years ofage.Theprovidermust consider theuniqueaspectsofcareandmanagementofchildrenand adolescents with type 1 diabetes, such as changes in insulin sensitivity related tosexualmaturityandphysical growth, ability toprovide self-care, supervision in child careand school, and unique neurological vulnerability to hypoglycemia and possibly hyper-glycemia as well as diabetic ketoacidosis. Attention to family dynamics, developmentalstages, and physiological differences related to sexual maturity are all essential in de-veloping and implementing an optimal diabetes regimen. Due to the paucity of clinicalresearch inchildren, the recommendations for childrenandadolescents are less likely tobe based on clinical trial evidence. However, expert opinion and a review of availableand relevant experimental data are summarized in the American Diabetes Association(ADA) position statement “Care of Children and Adolescents With Type 1 Diabetes” (1)and have been updated in the recently published ADA position statement “Type 1Diabetes Through the Life Span” (2).A multidisciplinary team of specialists trained in pediatric diabetes management

and sensitive to the challenges of children and adolescentswith type 1 diabetes shouldprovide care for this population. It is essential that diabetes self-management educa-tion (DSME) and support (DSMS), medical nutrition therapy (MNT), and psychosocialsupport be provided at diagnosis and regularly thereafter by individuals experiencedwith the educational, nutritional, behavioral, and emotional needs of the growingchild and family. The balance between adult supervision and self-care should be de-fined at the first interaction and reevaluated at each clinic visit. This relationship willevolve as the child reaches physical, psychological, and emotional maturity.

Glycemic Control

Recommendation

c An A1C goal of ,7.5% is recommended across all pediatric age-groups. E

Current standards for diabetes management reflect the need to lower glucose assafely as possible. This should be done with stepwise goals. Special considerationshould be given to the unique risks of hypoglycemia in young children (aged ,6years), as they are often unable to recognize, articulate, and/or manage their hy-poglycemic symptoms. This “hypoglycemia unawareness” should be consideredwhen establishing individualized glycemic targets.Although it was previously thought that young children were at risk for cognitive

impairment after episodes of severe hypoglycemia, current data have not confirmedthis (3–5). Furthermore, new therapeuticmodalities, such as rapid- and long-acting insulinanalogs, technological advances (e.g., continuous glucose monitors, low glucose suspendinsulinpumps), andeducation,maymitigate the incidenceof severehypoglycemia (6). TheDiabetes Control and Complications Trial (DCCT) demonstrated that near-normalizationof blood glucose levels was more difficult to achieve in adolescents than in adults.Nevertheless, the increaseduseof basal–bolus regimens and insulin pumps in youth frominfancy through adolescence has been associated withmore children reaching the bloodglucose targets set by the ADA (7–9) in those families in which both parents and the childwith diabetes participate jointly to perform the required diabetes-related tasks. Further-more, studies documenting neurocognitive imaging differences related to hyperglycemiain children provide another compelling motivation for lowering glycemic targets (10).In selecting glycemic goals, the long-term health benefits of achieving a lower A1C

should be balanced against the risks of hypoglycemia and the developmental burdens

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of intensive regimens in children andyouth. In addition, achieving lower A1Clevels is more likely to be related to set-ting lower A1C targets (11). A1C goals arepresented in Table 11.1.

Autoimmune Conditions

Recommendation

c Assess for the presence of addi-tional autoimmune conditions at di-agnosis and if symptoms develop. E

Because of the increased frequency ofother autoimmune diseases in type 1 di-abetes, screening for thyroid dysfunc-tion, vitamin B12 deficiency (due toautoimmune gastritis), and celiac dis-ease should be considered based onsigns and symptoms. Periodic screeningin asymptomatic individuals has beenrecommended, but the effectivenessand optimal frequency are unclear.Although less common than celiac

disease and thyroid dysfunction, thereare other autoimmune conditions thatoccur more commonly in type 1 diabe-tes, such as Addison’s disease (primaryadrenal insufficiency), autoimmunehepatitis, dermatomyositis, myastheniagravis, etc., which should be assessedand monitored as clinically indicated.

Celiac Disease

Recommendations

c Consider screening children withtype 1 diabetes for celiac diseaseby measuring tissue transglutami-nase or deamidated gliadin antibod-ies, with documentation of normaltotal serum IgA levels, soon after thediagnosis of diabetes. E

c Consider screening in children with apositive family history of celiac dis-ease, growth failure, failure to gainweight, weight loss, diarrhea, flatu-lence, abdominal pain, or signs ofmalabsorption or in children with

frequent unexplained hypoglycemiaor deterioration in glycemic control.E

c Children with biopsy-confirmedceliac disease should be placedon a gluten-free diet and haveconsultation with a dietitian expe-rienced in managing both diabetesand celiac disease. B

Celiac disease is an immune-mediateddisorder that occurs with increased fre-quency in patients with type 1 diabetes(1–16%of individuals comparedwith 0.3–1% in the general population) (12,13).

Testing for celiac disease includes mea-suring serum levels of IgA antitissuetransglutaminase antibodies or, with IgAdeficiency, screening can include measur-ing IgG tissue transglutaminase antibodiesor IgGdeamidatedgliadinpeptideantibod-ies. A small-bowel biopsy in antibody-positive children is recommended toconfirmthediagnosis (14).Europeanguide-lines on screening for celiac disease in chil-dren (not specific to children with type 1diabetes) suggested thatbiopsymaynotbenecessary in symptomatic children withhigh-positive antibody titers as long as fur-ther testing such as genetic or HLA testingwas supportive, but that asymptomatic at-risk children should have biopsies (15).

In symptomatic children with type 1 di-abetes and confirmed celiac disease,gluten-free diets reduce symptoms andrates of hypoglycemia (16). The challengingdietary restrictions associated with havingboth type 1 diabetes and celiac diseaseplace a significant burden on individuals.Therefore, we recommend a biopsy con-firming the diagnosis of celiac disease be-fore endorsing significant dietary changes,especially in asymptomatic children.

Thyroid Disease

Recommendations

c Consider testing children withtype 1 diabetes for antithyroid

peroxidase and antithyroglobulinantibodies soon after diagnosis. E

c Measuring thyroid-stimulating hor-mone concentrations soon afterdiagnosis of type 1 diabetes isreasonable. If normal, consider re-checking every 1–2 years or soonerif the patient develops symptomsof thyroid dysfunction, thyrome-galy, an abnormal growth rate, orunusual glycemic variation. E

Autoimmune thyroid disease is themostcommon autoimmune disorder associ-ated with diabetes, occurring in 17–30% of patients with type 1 diabetes(17). About one-quarter of childrenwith type 1 diabetes have thyroid auto-antibodies at the time of diagnosis (18),and the presence of thyroid autoantibod-ies is predictive of thyroid dysfunctiondmost commonly hypothyroidism, al-though hyperthyroidism may occur (19).Subclinical hypothyroidism may be asso-ciatedwith increased risk of symptomatichypoglycemia (20) and reduced lineargrowth. Hyperthyroidism alters glucosemetabolism, potentially resulting in dete-rioration of metabolic control.

Management of Cardiovascular RiskFactors

Hypertension

Recommendations

Screening

c Blood pressure should be mea-sured at each routine visit. Chil-dren found to have high-normalblood pressure (systolic bloodpressure [SBP] or diastolic bloodpressure [DBP] $90th percentilefor age, sex, and height) or hyper-tension (SBP or DBP $95th per-centile for age, sex, and height)should have blood pressure con-firmed on three separate days. B

Table 11.1—Plasma blood glucose and A1C goals for type 1 diabetes across all pediatric age-groups

Plasma blood glucose goal range

A1C RationaleBefore meals Bedtime/overnight

90–130 mg/dL 90–150 mg/dL ,7.5% A lower goal (,7.0%) is reasonable if it can beachieved without excessive hypoglycemia(5.0–7.2 mmol/L) (5.0–8.3 mmol/L)

Key concepts in setting glycemic goals:c Goals should be individualized, and lower goals may be reasonable based on benefit-risk assessment.c Blood glucose goals should be modified in children with frequent hypoglycemia or hypoglycemia unawareness.c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levelsand to help assess glycemia in those on basal–bolus regimens.


Treatmentc Initial treatment of high-normal

blood pressure (SBP or DBP consis-tently $90th percentile for age,sex, and height) includes dietaryintervention and exercise, aimedat weight control and increasedphysical activity, if appropriate. Iftarget blood pressure is notreached with 3–6 months oflifestyle intervention, pharmaco-logical treatment should be con-sidered. E

c Pharmacological treatment of hy-pertension (SBP or DBP consistently$95th percentile for age, sex, andheight) should be considered assoon as hypertension is confirmed. E

c ACE inhibitors or angiotensin recep-tor blockers (ARBs) should be consid-ered for the initial pharmacologicaltreatment of hypertension, followingappropriate reproductive counsel-ing due to its potential teratogeniceffects. E

c The goal of treatment is bloodpressure consistently ,90th per-centile for age, sex, and height. E

Blood pressure measurements shouldbe determined correctly, using the ap-propriate size cuff, and with the childseated and relaxed. Hypertensionshould be confirmed on at least threeseparate days. Evaluation should pro-ceed as clinically indicated. Treatmentis generally initiated with an ACE inhibi-tor, but an ARB can be used if the ACEinhibitor is not tolerated (e.g., due tocough). Normal blood pressure levels forage, sex, and height and appropriatemethods for measurement are availableonline at www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf.

Dyslipidemia

Recommendations

Testingc Obtain a fasting lipid profile on

children $2 years of age soon af-ter the diagnosis (after glucosecontrol has been established). E

c If lipids are abnormal, annualmonitoring is reasonable. If LDLcholesterol values are withinthe accepted risk levels (,100mg/dL [2.6 mmol/L]), a lipidprofile repeated every 5 years isreasonable. E

Treatmentc Initial therapy may consist of opti-

mization of glucose control andMNT using a Step 2 American HeartAssociation (AHA) diet aimed at adecrease in the amount of satu-rated fat in the diet. B

c After the age of 10 years, the addi-tion of a statin in patients who, afterMNT and lifestyle changes, haveLDL cholesterol .160 mg/dL (4.1mmol/L) or LDL cholesterol .130mg/dL (3.4 mmol/L) and one ormore cardiovascular disease (CVD)risk factors is reasonable. E

c The goal of therapy is an LDL cho-lesterol value ,100 mg/dL (2.6mmol/L). E

Children diagnosed with type 1 diabeteshave a high risk of early subclinical (21,22)andclinical (23)CVD.Although interventiondata are lacking, the AHA categorizes chil-drenwith type1diabetes in thehighest tierfor cardiovascular risk and recommendsboth lifestyle and pharmacological treat-ment for those with elevated LDL choles-terol levels (24,25). Initial therapyshouldbewith a Step 2 AHA diet, which restricts sat-urated fat to 7% of total calories and re-stricts dietary cholesterol to 200 mg/day.Data from randomized clinical trials in chil-dren as young as 7 months of age indicatethat this diet is safe and does not interferewithnormal growthanddevelopment (26).

For children with significant family his-tory of CVD, the National Heart, Lung, andBlood Institute recommends a fasting lipidpanel beginning at 2 years of age (27).Abnormal results from a random lipidpanel should be confirmed with a fastinglipid panel. Evidence has shown that im-proved glucose control correlates with amore favorable lipid profile. However, im-proved glycemic control alone will not re-verse significant dyslipidemia (28).

Neither long-term safety nor cardiovas-cular outcome efficacy of statin therapyhas been established for children. How-ever, studies have shown short-termsafety equivalent to that seen in adultsand efficacy in lowering LDL cholesterollevels, improving endothelial function,and causing regression of carotid intimalthickening (29,30). Statins are not ap-proved for use in patients under the ageof 10 years, and statin treatment shouldgenerally not be used in children withtype 1 diabetes prior to this age. For post-pubertal girls, issues of pregnancy

prevention are paramount, as statinsare category X in pregnancy (see Section12. Management of Diabetes in Preg-nancy for more information).

Smoking

Recommendation

c Elicit smoking history at initial andfollow-up diabetes visits and dis-courage smoking in nonsmokingyouth and encourage smoking ces-sation in those who smoke. B

The adverse health effects of smokingare well recognized with respect to fu-ture cancer and CVD risk. In youth withdiabetes, it remains important to avoidadditional CVD risk factors; thus, dis-couraging cigarette smoking, includinge-cigarettes, is important as part of rou-tine diabetes care. In younger children,it is important to assess exposure to cig-arette smoke in the home due to theadverse effects of secondhand smokeand to discourage youth from adoptingsmoking behaviors if exposed to them inchildhood. In addition, smoking hasbeen associated with onset of albumin-uria; therefore, avoiding smoking is im-portant to prevent both microvascularandmacrovascular complications (31,32).

Microvascular Complications

Nephropathy

Recommendations

Screeningc At least an annual screening for

albuminuria, with a random spoturine sample for albumin-to-creatinine ratio (UACR), shouldbe considered once the child hashad diabetes for 5 years. B

c Measure creatinine clearance/es-timated glomerular filtration rateat initial evaluation and thenbased on age, diabetes duration,and treatment. E

Treatmentc Treatment with an ACE inhibitor,

titrated to normalization of albuminexcretion, should be consideredwhen elevated UACR (.30 mg/g)is documented with at least twoof three urine samples. This shouldbe obtained over a 6-month inter-val following efforts to improveglycemic control and normalizeblood pressure for age. B


Recent research demonstrates the im-portance of tight glycemic and bloodpressure control, especially as diabetesduration increases (33). A creatinineclearance using an estimated glomeru-lar filtration rate can be obtained withthe serum creatinine, height, age, andsex of the patient (34) and should beobtained at baseline and repeated as in-dicated based on clinical status, age, di-abetes duration, and therapies. Thereare ongoing clinical trials assessing theefficacy of early treatment with ACE in-hibitors for persistent albuminuria (35).

Retinopathy

Recommendations

c An initial dilated and comprehen-sive eye examination should beconsidered for the child at thestart of puberty or at age $10years, whichever is earlier, oncethe youth has had diabetes for 3–5 years. B

c After the initial examination, an-nual routine follow-up is generallyrecommended. Less frequent ex-aminations, every 2 years, may beacceptable on the advice of an eyecare professional. E

Although retinopathy (like albuminuria)most commonly occurs after the onsetof puberty and after 5–10 years of diabe-tes duration (36), it has been reported inprepubertal children and with diabetesduration of only 1–2 years. Referralsshould be made to eye care professionalswith expertise in diabetic retinopathy, anunderstanding of retinopathy risk in thepediatric population, and experience incounseling the pediatric patient and fam-ily on the importance of early prevention/intervention.

Neuropathy

Recommendation

c Consider an annual comprehen-sive foot exam for the child atthe start of puberty or at age$10 years, whichever is earlier,once the youth has had type 1 di-abetes for 5 years. E

Neuropathy rarely occurs in prepubertalchildren or in youth with 1–2 years ofduration of diabetes (36). A comprehen-sive foot exam, including inspection,palpation of dorsalis pedis and posterior

tibial pulses, assessment of the pres-ence or absence of patellar and Achillesreflexes, and determination of proprio-ception, vibration, and monofilamentsensation, should be performed annu-ally along with assessment of symptomsof neuropathic pain. Foot inspection canbe performed at each visit as educationfor youth regarding the importance offoot care.

Diabetes Self-managementEducation and Support

Recommendation

c Youth with type 1 diabetes andparents/caregivers (for patientsaged ,18 years) should receiveculturally sensitive and develop-mentally appropriate individual-ized DSME and DSMS accordingto national standards when theirdiabetes is diagnosed and rou-tinely thereafter. B

No matter how sound the medicalregimen, it can only be as good asthe ability of the family and/or indi-vidual to implement it. Family in-volvement remains an importantcomponent of optimal diabetes man-agement throughout childhood andadolescence. Health care providerswho care for children and adoles-cents, therefore, must be capable ofevaluating the educational, behav-ioral, emotional, and psychosocial fac-tors that impact implementation of atreatment plan and must work withthe individual and family to overcomebarriers or redefine goals as appropri-ate. DSME and DSMS are activitiesthat require ongoing reassessment,especially as the youth grows, devel-ops, and acquires need for greaterself-care skills. In addition, it may benecessary to assess the educationalneeds and skills of day care providers,school nurses, or school personnel whomay participate in the care of the youngchild with diabetes (37).

School and Child CareAs a large portion of a child’s day is spentin school, close communicationwith andcooperation of school or day care per-sonnel is essential for optimal diabetesmanagement, safety, and maximal aca-demic opportunities. Please refer to theADA position statements “Diabetes Carein the School and Day Care Setting” (38)

and “Care of Young Children WithDiabetes in the Child Care Setting” (39)for additional details.

Transition From Pediatric to AdultCare

Recommendations

c As teens transition into emergingadulthood, health care providersand families must recognize theirmany vulnerabilities B and preparethe developing teen, beginning inearly to mid-adolescence and atleast 1 year prior to the transition. E

c Both pediatricians and adulthealth care providers should assistin providing support and links toresources for the teen and emerg-ing adult. B

Care and close supervision of diabetesmanagement are increasingly shiftedfrom parents and other adults to theyouth with diabetes throughout child-hood and adolescence. However, theshift from pediatrics to adult healthcare providers often occurs very abruptlyas the older teen enters the next devel-opmental stage referred to as emergingadulthood (40), which is a critical periodfor young people who have diabetes.During this period of major life transi-tions, youth begin to move out of theirparents’ home and must become fullyresponsible for their diabetes care. Theirnew responsibilities include themany as-pects of managing self-care, makingmedical appointments, and financinghealth care, once they are no longer cov-ered under their parents’ health insur-ance (although ongoing coverage untilage 26 years is possible with recentU.S. health care reform). In addition tolapses in health care, this is also a periodof deterioration in glycemic control; in-creased occurrence of acute complica-tions and psychosocial, emotional, andbehavioral issues; and emergence ofchronic complications (41–44).

Although scientific evidence contin-ues to be limited, it is clear that compre-hensive and coordinated planning,beginning early and with ongoing atten-tion, facilitates a seamless transitionfrom pediatric to adult health care(41,42). Transition planning should be-gin in early adolescence. Even after thetransition to adult care is made, supportand reinforcement are recommended.


A comprehensive discussion regardingthe challenges faced during this period,including specific recommendations, isfound in the ADA position statement “Di-abetes Care for Emerging Adults: Recom-mendations for Transition From Pediatricto Adult Diabetes Care Systems” (42).The National Diabetes Education

Program (NDEP) has materials avail-able to facilitate the transition process(http://ndep.nih.gov/transitions), andthe Endocrine Society in collaborationwith ADA and other organizations hasdeveloped transition tools for clini-cians and youth and families (http://www.endo-society.org/clinicalpractice/transition_of_care.cfm).

TYPE 2 DIABETES

For information on testing for type 2 di-abetes and prediabetes in children andadolescents, please refer to Section 2.Classification and Diagnosis of Diabetes.The Centers for Disease Control and

Prevention recently published projec-tions for type 2 diabetes prevalence us-ing the SEARCH database. Assuming a2.3% annual increase, the prevalenceof type 2 diabetes in those under 20years of age will quadruple in 40 years(45,46). Given the current obesity epi-demic, distinguishing between type 1and type 2 diabetes in children can bedifficult. For example, autoantibodiesand ketosis may be present in patientswith features of type 2 diabetes (includ-ing obesity and acanthosis nigricans).Nevertheless, accurate diagnosis is crit-ical as treatment regimens, educationalapproaches, dietary counsel, and out-comes will differ markedly betweenthe two diagnoses.Significant comorbidities may already

be present at the time of a type 2 diabe-tes diagnosis (47). It is recommended thatblood pressure measurement, a fastinglipid panel, assessment for albumin excre-tion, and dilated eye examination beperformed at diagnosis. Thereafter,screening guidelines and treatment rec-ommendations for hypertension, dyslipi-demia, albumin excretion, and retinopathyin youthwith type 2 diabetes are similar tothose for youth with type 1 diabetes. Ad-ditional problems that may need to be ad-dressed include polycystic ovary diseaseand the various comorbidities associatedwith pediatric obesity, such as sleepapnea, hepatic steatosis, orthopedic com-plications, and psychosocial concerns. The

ADA consensus report “Type 2 Diabetes inChildren and Adolescents” (48) providesguidance on the prevention, screening,and treatment of type 2 diabetes and itscomorbidities in young people.

PSYCHOSOCIAL ISSUES

Recommendations

c At diagnosis and during routinefollow-up care, assess psychoso-cial issues and family stressesthat could impact adherence withdiabetes management and pro-vide appropriate referrals totrainedmental health professionals,preferably experienced in child-hood diabetes. E

c Encourage developmentally ap-propriate family involvement in di-abetes management tasks forchildren and adolescents, recog-nizing that premature transfer ofdiabetes care to the child can re-sult in nonadherence and deterio-ration in glycemic control. B

Diabetes management throughoutchildhood and adolescence places sub-stantial burdens on the youth and fam-ily, necessitating ongoing assessment ofpsychosocial issues and distress duringroutine diabetes visits (49–51). Further,the complexities of diabetes manage-ment require ongoing parental involve-ment in care throughout childhood withdevelopmentally appropriate familyteamwork between the growing child/teen and parent in order to maintainadherence and prevent deteriorationin glycemic control (52,53). In addition,as diabetes-specific family conflict is re-lated to poorer adherence and glycemiccontrol, it is appropriate to inquireabout such conflict during visits and toeither help negotiate a plan for resolu-tion or refer to an appropriate mentalhealth specialist (54).

Screening for psychosocial distressandmental health problems is an impor-tant component of ongoing care. It isimportant to consider the impact of di-abetes on quality of life as well as thedevelopment ofmental health problemsrelated to diabetes distress, fear of hy-poglycemia (and hyperglycemia), symp-toms of anxiety, disordered eatingbehaviors as well as eating disorders,and symptoms of depression (55). Con-sider screening for depression and

disordered eating behaviors using avail-able screening tools, and, with respectto disordered eating, it is important torecognize the unique and dangerousdisordered eating behavior of insulinomission for weight control in type 1diabetes (49,56). The presence of amental health professional on pediatricmultidisciplinary teams highlights theimportance of attending to the psycho-social issues of diabetes. These psycho-social factors are significantly related tononadherence, suboptimal glycemiccontrol, reduced quality of life, and higherrates of acute and chronic diabetescomplications.

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12. Management of Diabetes inPregnancyDiabetes Care 2015;38(Suppl. 1):S77–S79 | DOI: 10.2337/dc15-S015

For guidelines related to the diagnosis of gestational diabetes mellitus (GDM),please refer to Section 2. Classification and Diagnosis of Diabetes.

Recommendations

c Provide preconception counseling that addresses the importance of tightcontrol in reducing the risk of congenital anomalies with an emphasis onachieving A1C ,7%, if this can be achieved without hypoglycemia. B

c Potentially teratogenic medications (ACE inhibitors, statins, etc.) should beavoided in sexually active women of childbearing age who are not using reli-able contraception. B

c GDM should be managed first with diet and exercise, and medications shouldbe added if needed. A

c Women with pregestational diabetes should have a baseline ophthalmologyexam in the first trimester and then be monitored every trimester as indicatedby degree of retinopathy. B

c Due to alterations in red blood cell turnover that lower the normal A1C level inpregnancy, the A1C target in pregnancy is,6% if this can be achieved withoutsignificant hypoglycemia. B

c Medications widely used in pregnancy include insulin, metformin, and glybur-ide; most oral agents cross the placenta or lack long-term safety data. B

DIABETES IN PREGNANCY

The prevalence of diabetes in pregnancy has been increasing in the U.S. Themajority isGDM with the remainder divided between pregestational type 1 diabetes and type 2diabetes. Both pregestational type 1 diabetes and type 2 diabetes confer significantlygreater risk than GDM, with differences according to type as outlined below.

PRECONCEPTION COUNSELING

All women of childbearing age with diabetes should be counseled about the impor-tance of strict glycemic control prior to conception. Observational studies show anincreased risk of diabetic embryopathy, especially anencephaly, microcephaly, andcongenital heart disease, that increases directly with elevations in A1C. Spontane-ous abortion is also increased in the setting of uncontrolled diabetes. While obser-vational studies are confounded by the relationship between elevatedpericonceptional A1C and other poor self-care behaviors, the quantity and consistencyof data are convincing, and the recommendation remains to aim for an A1C,7% priorto conception tominimize risk (1,2). There are opportunities to educate adolescents ofreproductive age with diabetes about the risks of unplanned pregnancies and theopportunities for healthy maternal and fetal outcomes with pregnancy planning (3).Targeted preconception counseling visits should include routine rubella, rapid plasma

reagin, hepatitis B virus, and HIV testing as well as Pap smear, cervical cultures, bloodtyping, andprescriptionof prenatal vitamins (with at least 400mg of folic acid). Diabetes-specific management should include A1C, thyroid-stimulating hormone, creatinine, andurine albumin-to-creatinine ratio testing; review of the medication list for potentiallyteratogenic drugs (i.e., ACE inhibitors, statins); and referral for an ophthalmologic exam.Specific risks of uncontrolled diabetes include fetal anomalies, preeclampsia,

macrosomia, intrauterine fetal demise, neonatal hypoglycemia, and neonatal hy-perbilirubinemia, among others. In addition, diabetes in pregnancy increases therisk of obesity and type 2 diabetes in offspring later in life (4,5).

Suggested citation: American Diabetes Asso-ciation. Management of diabetes in preg-nancy. Sec. 12. In Standards of Medical Carein Diabetesd2015. Diabetes Care 2015;38(Suppl. 1):S77–S79




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GLYCEMIC TARGETS INPREGNANCY

The goals for glycemic control for GDMare based on recommendations from theFifth International Workshop-Conferenceon Gestational Diabetes Mellitus (6) andhave the following targets for maternalcapillary glucose concentrations:

○ Preprandial#95mg/dL (5.3mmol/L)and either

○ One-hour postmeal #140 mg/dL(7.8 mmol/L) or

○ Two-hour postmeal #120 mg/dL(6.7 mmol/L)

For women with preexisting type 1diabetes or type 2 diabetes who be-come pregnant, the following are rec-ommended as optimal glycemic goalsif they can be achieved without exces-sive hypoglycemia (7):

○ Premeal, bedtime, and overnightglucose 60–99 mg/dL (3.3–5.4mmol/L)

○ Peak postprandial glucose 100–129mg/dL (5.4–7.1 mmol/L)

○ A1C ,6.0%

Metabolic physiology of pregnancy ischaracterized by fasting hypoglycemiadue to insulin-independent glucose up-take by the placenta, postprandial hyper-glycemia, and carbohydrate intoleranceas a result of diabetogenic placental hor-mones. In addition, insulin resistance in-creases exponentially during the secondtrimester and levels off toward the end ofthe third trimester.Reflecting this physiology, pre- and

postprandial monitoring of blood glucoseis recommended to achieve metaboliccontrol. The American College ofObstetricians and Gynecologists (ACOG)recommends the following targets: fast-ing,90mg/dL, preprandial,105mg/dL,1-h postprandial ,130–140 mg/dL, and2-h postprandial,120mg/dL. If womencannot achieve these targets withoutsignificant hypoglycemia, the AmericanDiabetes Association (ADA) suggestsconsideration of slightly higher targets:fasting ,105 mg/dL, 1-h postprandial,155 mg/dL, and 2-h postprandial,130 mg/dL. Until harmonization ofthese guidelines is achieved, the ADArecommends setting targets basedon clinical experience, individualizingcare, as needed.

Due to increases in red blood cellturnover associated with pregnancy,A1C levels fall during pregnancy. Addi-tionally, as A1C represents an average, itmay not fully capture physiologically rel-evant glycemic parameters in pregnancy.A1C should be used as a secondary mea-sure, next to self-monitoring of blood glu-cose. The recommended A1C target inpregnancy is,6% if this can be achievedwithout hypoglycemia. Given the alter-ation in red blood cell kinetics duringpregnancy, A1C levels may need to bemonitored more frequently than usual(e.g., monthly).

PREGNANCY ANDANTIHYPERTENSIVE DRUGS

In a pregnancy complicated by diabetesand chronic hypertension, target bloodpressure goals of systolic blood pres-sure 110–129mmHg and diastolic bloodpressure 65–79 mmHg are reasonable,as they contribute to improved long-term maternal health. Lower bloodpressure levels may be associated withimpaired fetal growth. During preg-nancy, treatment with ACE inhibitorsand angiotensin receptor blockers iscontraindicated because they maycause fetal damage. Antihypertensivedrugs known to be effective and safe inpregnancy include methyldopa, labetalol,diltiazem, clonidine, and prazosin.Chronic diuretic use during pregnancyhas been associated with restricted ma-ternal plasma volume, whichmay reduceuteroplacental perfusion (8).

MANAGEMENT OF GESTATIONALDIABETES MELLITUS

As highlighted in Section 2. Classificationand Diagnosis of Diabetes, GDM is char-acterized by increased risk ofmacrosomiaand birth complications, without a riskthreshold (9). Treatment starts withmed-ical nutrition therapy, exercise, and glu-cose monitoring aiming for the targetsdescribed previously. A total of 70 to85% of women diagnosed with GDM un-der older criteria can control GDM withlifestyle modification alone; it is antici-pated that this numberwill increase usingthe lower International Association of theDiabetes and Pregnancy Study Groups(IADPSG) thresholds. Treatment hasbeen demonstrated to improve perinataloutcomes in randomized studies and in aU.S. Preventive Services Task Force re-view (10). Historically, insulin has been

the recommended treatment for GDMin the U.S. Randomized controlled trialssupport the efficacy and short-termsafety of glyburide (11) (pregnancy cat-egory B) and metformin (12,13) (preg-nancy category B) for the treatmentof GDM. However, both agents crossthe placenta, and long-term safetydata are not available (14). Insulin alsomay be used and should follow theguidelines below.

MANAGEMENT OFPREGESTATIONAL TYPE 1DIABETES AND TYPE 2 DIABETESIN PREGNANCY

Insulin Use in PregnancyInsulin is the preferred agent for man-agement of diabetes in pregnancy be-cause of the lack of long-term safetydata for noninsulin agents. The physiol-ogy of pregnancy requires frequent ti-tration of insulin to match changingrequirements. In the first trimester,there is often a decrease in total dailydose of insulin. In the second trimester,rapidly increasing insulin resistance re-quires weekly or biweekly increase ininsulin dose to achieve glycemic targets.In general, a small proportion of the to-tal daily dose should be given as basalinsulin and a greater proportion as pran-dial insulin. Due to the complexity ofinsulin management in pregnancy, re-ferral to a specialized center is recom-mended if this resource is available. Allinsulins are pregnancy category B ex-cept for glargine and glulisine, whichare labeled C.

Concerns Related to Type 1 Diabetesin PregnancyWomen with type 1 diabetes have anincreased risk of hypoglycemia in thefirst trimester. Frequent hypoglycemiacan be associated with intrauterinegrowth restriction. In addition, rapid im-plementation of tight glycemic controlin the setting of retinopathy is associ-ated with worsening of retinopathy(15). Insulin resistance drops rapidlywith delivery of the placenta, andwomen become very insulin sensitive,requiring much less insulin than in theprepartum period.

Concerns Related to Type 2 Diabetesin PregnancyPregestational type 2 diabetes is oftenassociated with obesity. Recommendedweight gain during pregnancy for


overweight women is 15–25 lb and forobese women is 10–20 lb. Glycemic con-trol is often easier to achieve in type 2diabetes than in type 1 diabetes, buthypertension and other comorbiditiesoften render pregestational type 2 dia-betes as high or higher risk than preges-tational type 1 diabetes (16,17).

POSTPARTUM CARE

LactationAll women should be supported in at-tempts to nurse their babies, given im-mediate nutritional and immunologicalbenefits of breastfeeding for the baby;there may also be a longer-term meta-bolic benefit to both mother (18) andoffspring (19), though data are mixed.

Gestational Diabetes MellitusBecause GDM may represent preexistingundiagnosed type 2 diabetes, womenwith GDM should be screened for persis-tent diabetes or prediabetes at 6–12weeks postpartum using nonpregnancycriteria and every 1–3 years thereafterdepending on other risk factors. Womenwith a history of GDM have a greatly in-creased risk of conversion to type 2 dia-betes over time and not solely within the6–12 weeks’ postpartum time frame(20). In the prospective Nurses’ HealthStudy II (21), subsequent diabetesrisk after a history of GDM was signifi-cantly lower in women who followedhealthy eating patterns. Adjusting forBMI moderately, but not completely,attenuated this association. Interpreg-nancy or postpartum weight gain is as-sociated with increased risk of adversepregnancy outcomes in subsequentpregnancies (22) and earlier progressionto type 2 diabetes. Both metformin andintensive lifestyle intervention preventor delay progression to diabetes inwomenwith a history of GDM. Ofwomenwith a history of GDM and impaired glu-cose tolerance, only 5–6 individuals needto be treated with either interventionto prevent one case of diabetes over3 years (23).

Type 1 DiabetesInsulin sensitivity increases in the imme-diate postpartum period and then returnsto normal over the following 1–2 weeks,

and many women will require signifi-cantly less insulin at this time thanduring the prepartum period. Breast-feeding may cause hypoglycemia, whichmay be ameliorated by consuming a snack(such as milk) prior to nursing. Diabetesself-management often suffers in thepostpartum period.

Type 2 DiabetesIf the pregnancy has motivated the adop-tion of a healthier diet, building on thesegains to support weight loss is recom-mended in the postpartum period.

ContraceptionAll women of childbearing age, includingthose who are postpartum, should havecontraception options reviewed at reg-ular intervals.

References1. Guerin A, Nisenbaum R, Ray JG. Use of ma-ternal GHb concentration to estimate the risk ofcongenital anomalies in the offspring of womenwith prepregnancy diabetes. Diabetes Care2007;30:1920–19252. Jensen DM, Korsholm L, Ovesen P, et al.Peri-conceptional A1C and risk of serious ad-verse pregnancy outcome in 933 women withtype 1 diabetes. Diabetes Care 2009;32:1046–10483. Charron-Prochownik D, Sereika SM, BeckerD, et al. Long-term effects of the booster-enhanced READY-Girls preconception counsel-ing program on intentions and behaviors forfamily planning in teens with diabetes. DiabetesCare 2013;36:3870–38744. Holmes VA, Young IS, Patterson CC, et al.;Diabetes and Pre-eclampsia Intervention TrialStudy Group. Optimal glycemic control, pre-eclampsia, and gestational hypertension inwomen with type 1 diabetes in the diabetesand pre-eclampsia intervention trial. DiabetesCare 2011;34:1683–16885. Dabelea D, Hanson RL, Lindsay RS, et al. In-trauterine exposure to diabetes conveys risksfor type 2 diabetes and obesity: a study of dis-cordant sibships. Diabetes 2000;49:2208–22116. Metzger BE, Buchanan TA, Coustan DR, et al.Summary and recommendations of the Fifth In-ternational Workshop-Conference on Gesta-tional Diabetes Mellitus. Diabetes Care 2007;30(Suppl. 2):S251–S2607. Kitzmiller JL, Block JM, Brown FM, et al.Managing preexisting diabetes for pregnancy:summary of evidence and consensus recom-mendations for care. Diabetes Care 2008;31:1060–10798. Sibai BM. Treatment of hypertension in preg-nant women. N Engl J Med 1996;335:257–265

9. Metzger BE, Lowe LP, Dyer AR, et al.; HAPOStudy Cooperative Research Group. Hyperglyce-mia and adverse pregnancy outcomes. N Engl JMed 2008;358:1991–200210. Hartling L, Dryden DM, Guthrie A, Muise M,Vandermeer B, Donovan L. Benefits and harmsof treating gestational diabetes mellitus: a sys-tematic review and meta-analysis for the U.S.Preventive Services Task Force and the NationalInstitutes of Health Office of Medical Applica-tions of Research. Ann Intern Med 2013;159:123–12911. Langer O, Conway DL, Berkus MD, XenakisEM-J, Gonzales O. A comparison of glyburideand insulin in women with gestational diabetesmellitus. N Engl J Med 2000;343:1134–113812. Rowan JA, Hague WM, Gao W, Battin MR,Moore MP; MiG Trial Investigators. Metforminversus insulin for the treatment of gestationaldiabetes. N Engl J Med 2008;358:2003–201513. Gui J, Liu Q, Feng L. Metformin vs insulin inthe management of gestational diabetes:a meta-analysis. PLoS One 2013;8:e6458514. Coustan DR. Pharmacological managementof gestational diabetes: an overview. DiabetesCare 2007;30(Suppl. 2):S206–S20815. Chew EY, Mills JL, Metzger BE, et al.; Na-tional Institute of Child Health and Human De-velopment Diabetes in Early Pregnancy Study.Metabolic control and progression of retinopa-thy: the Diabetes in Early Pregnancy Study. Di-abetes Care 1995;18:631–63716. Clausen TD, Mathiesen E, Ekbom P, HellmuthE, Mandrup-Poulsen T, Damm P. Poor pregnancyoutcome in women with type 2 diabetes. Diabe-tes Care 2005;28:323–32817. Cundy T, Gamble G, Neale L, et al. Differingcauses of pregnancy loss in type 1 and type 2diabetes. Diabetes Care 2007;30:2603–260718. Stuebe AM, Rich-Edwards JW, Willett WC,Manson JE, Michels KB. Duration of lactationand incidence of type 2 diabetes. JAMA 2005;294:2601–261019. Pereira PF, Alfenas R de CG, Araujo RMA.Does breastfeeding influence the risk of develop-ing diabetes mellitus in children? A review of cur-rent evidence. J Pediatr (Rio J) 2014;90:7–1520. Kim C, Newton KM, Knopp RH. Gestationaldiabetes and the incidence of type 2 diabetes:a systematic review. Diabetes Care 2002;25:1862–186821. Tobias DK, Hu FB, Chavarro J, Rosner B,Mozaffarian D, Zhang C. Healthful dietary pat-terns and type 2 diabetes mellitus risk amongwomen with a history of gestational diabetesmellitus. Arch Intern Med 2012;172:1566–157222. Villamor E, Cnattingius S. Interpregnancyweight change and risk of adverse pregnancyoutcomes: a population-based study. Lancet2006;368:1164–117023. Ratner RE, Christophi CA, Metzger BE, et al.;Diabetes Prevention Program Research Group.Prevention of diabetes in women with a historyof gestational diabetes: effects of metforminand lifestyle interventions. J Clin EndocrinolMetab 2008;93:477424779


13. Diabetes Care in the Hospital,NursingHome, andSkilledNursingFacilityDiabetes Care 2015;38(Suppl. 1):S80–S85 | DOI: 10.2337/dc15-S016

Recommendations

c Diabetes discharge planning should start at hospital admission, and cleardiabetes management instructions should be provided at discharge. E

c The sole use of sliding scale insulin (SSI) in the inpatient hospital setting isstrongly discouraged. A

c All patients with diabetes admitted to the hospital should have their diabetestype clearly identified in the medical record. E

Critically Ill Patientsc Insulin therapy should be initiated for treatment of persistent hyperglycemiastarting at a threshold of no greater than 180 mg/dL (10 mmol/L). Once insulintherapy is started, a glucose range of 140–180 mg/dL (7.8–10 mmol/L) is recom-mended for the majority of critically ill patients. A

c More stringent goals, such as 110–140 mg/dL (6.1–7.8 mmol/L), may beappropriate for selected patients, as long as this can be achieved withoutsignificant hypoglycemia. C

c Critically ill patients require an intravenous insulin protocol that has demon-strated efficacy and safety in achieving the desired glucose range withoutincreasing risk for severe hypoglycemia. E

Noncritically Ill Patients

c If treated with insulin, generally premeal blood glucose targets of,140mg/dL(7.8 mmol/L) with random blood glucose ,180 mg/dL (10.0 mmol/L) arereasonable, provided these targets can be safely achieved. More stringenttargets may be appropriate in stable patients with previous tight glycemiccontrol. Less stringent targets may be appropriate in those with severe co-morbidities. C

c A basal plus correction insulin regimen is the preferred treatment for patientswith poor oral intake or who are taking nothing by mouth (NPO). An insulinregimen with basal, nutritional, and correction components is the preferredtreatment for patients with good nutritional intake. A

c A hypoglycemia management protocol should be adopted and implemented byeach hospital or hospital system. A plan for preventing and treating hypoglycemiashould be established for each patient. Episodes of hypoglycemia in the hospitalshould be documented in the medical record and tracked. E

c Consider obtaining an A1C in patients with diabetes admitted to the hospital ifthe result of testing in the previous 3 months is not available. E

c Consider obtaining an A1C in patients with risk factors for undiagnoseddiabetes who exhibit hyperglycemia in the hospital. E

c Patients with hyperglycemia in the hospital who do not have a prior diagnosisof diabetes should have appropriate follow-up testing and care documented atdischarge. E

Suggested citation: American Diabetes Associa-tion. Diabetes care in the hospital, nursing home,and skilled nursing facility. Sec. 13. In Standardsof Medical Care in Diabetesd2015. DiabetesCare 2015;38(Suppl. 1):S80–S85




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HYPERGLYCEMIA IN THE HOSPITAL

Hyperglycemia in the hospital can re-flect previously known or previously un-diagnosed diabetes or may be hospitalrelated. The difficulty distinguishing be-tween the second and third categoriesduring the hospitalization may be over-come by measuring A1C, as long as con-ditions interfering with A1C equilibrium(such as hemolysis, blood transfusion,blood loss, or erythropoietin therapy)have not occurred. A1C values $6.5%in undiagnosed patients suggest thatdiabetes preceded hospitalization (1).Hyperglycemia management in the hos-pital has often been considered second-ary in importance to the condition thatprompted admission. However, a bodyof literature now supports targeted glu-cose control in the hospital setting forimproved clinical outcomes (2). Hyper-glycemia in the hospital may resultfrom stress or decompensation oftype 1, type 2, or other forms of diabe-tes and/ormay be iatrogenic due towith-holding of antihyperglycemicmedicationsor administration of hyperglycemia-provoking agents, such as glucocorticoids,vasopressors, and enteral or parenteralnutrition.There is substantial observational

evidence linking hyperglycemia in hos-pitalized patients (with or without dia-betes) to poor outcomes. Cohort studiesas well as a few early randomized con-trolled trials (RCTs) suggested that in-tensive treatment of hyperglycemiaimproved hospital outcomes (3,4). Ingeneral, these studies were heteroge-neous in terms of patient population,blood glucose targets, insulin protocols,provision of nutritional support, and theproportion of patients receiving insulin,which limits the ability to make mean-ingful comparisons among them. Trialsin critically ill patients have failed toshow a significant improvement in mor-tality with intensive glycemic control orhave even shown increased mortalityrisk (5). Moreover, RCTs have high-lighted the risk of severe hypoglycemiaresulting from such efforts (6–9).The largest study to date, Normo-

glycemia in Intensive Care Evaluation-Survival Using Glucose AlgorithmRegulation (NICE-SUGAR), a multicen-ter, multinational RCT, compared theeffect of intensive glycemic control(target 81–108 mg/dL [4.5–6.0 mmol/L];

mean blood glucose attained 115 mg/dL[6.4 mmol/L]) to standard glycemic con-trol (target 144–180 mg/dL [8.0–10.0mmol/L]; mean blood glucose attained144 mg/dL [8.0 mmol/L]) on outcomesamong 6,104 critically ill participants,almost all of whom required mechanicalventilation (6).

Ninety-day mortality was signifi-cantly higher in the intensive versusthe conventional treatment group inboth surgical and medical patients, aswas mortality from cardiovascularcauses. Severe hypoglycemia was alsomore common in the intensively treatedgroup (6.8% vs. 0.5%; P , 0.001).

The study results lie in stark contrastto a 2001 single-center study that re-ported a 42% relative reduction in inten-sive care unit (ICU)mortality in critically illsurgical patients treated to a target bloodglucose of 80–110 mg/dL (3). The NICE-SUGAR findings do not disprove the no-tion that glycemic control in the ICU isimportant. However, they do stronglysuggest that it may not be necessary totarget blood glucose values ,140 mg/dL(7.8 mmol/L) and that a highly stringenttarget of ,110 mg/dL (6.1 mmol/L) mayactually be dangerous.

In a meta-analysis of 26 trials (n 513,567), which included the NICE-SUGAR data, the pooled relative risk[RR] of death with intensive insulin ther-apy was 0.93 as compared with conven-tional therapy (95% CI 0.83–1.04) (9).Approximately half of these trials re-ported hypoglycemia, with a pooledRR of intensive therapy of 6.0 (95% CI4.5–8.0). The specific ICU setting influ-enced the findings, with patients in sur-gical ICUs appearing to benefit fromintensive insulin therapy (RR 0.63 [95%CI 0.44–0.91]), while those in othermedical and mixed critical care settingsdid not. It was concluded that, overall,intensive insulin therapy increased therisk of hypoglycemia and provided nooverall benefit on mortality in the criti-cally ill, although a possible mortalitybenefit to patients admitted to the sur-gical ICU was suggested.

GLYCEMIC TARGETS INHOSPITALIZED PATIENTS

Definition of Glucose Abnormalities inthe Hospital SettingHyperglycemia in the hospital has been de-fined as any blood glucose .140 mg/dL(7.8 mmol/L). Levels that are significantly

and persistently above this may re-quire treatment in hospitalized pa-tients. A1C values $6.5% suggest, inundiagnosed patients, that diabetespreceded hospitalization (1). Hypoglyce-mia has been defined as any blood glu-cose ,70 mg/dL (3.9 mmol/L). This isthe standard definition in outpatientsand correlates with the initial thresholdfor the release of counterregulatoryhormones. Severe hypoglycemia in hos-pitalized patients has been defined bymany as ,40 mg/dL (2.2 mmol/L),although this is lower than the ;50mg/dL (2.8 mmol/L) level at which cog-nitive impairment begins in normal in-dividuals (10). Both hyperglycemia andhypoglycemia among inpatients are as-sociated with adverse short- and long-term outcomes. Early recognition andtreatment of mild to moderate hypogly-cemia (40–69 mg/dL [2.2–3.8 mmol/L])can prevent deterioration to a moresevere episode with potential adversesequelae (11).

Critically Ill PatientsBased on available evidence, for thema-jority of critically ill patients in the ICUsetting, intravenous insulin infusionshould be used to control hyperglyce-mia, with a starting threshold of nohigher than 180 mg/dL (10.0 mmol/L).Once intravenous insulin is started, theglucose level should be maintained be-tween 140–180mg/dL (7.8–10.0mmol/L).Greater benefit may be realized at thelower end of this range. Although strongevidence is lacking, lower glucose targetsmay be appropriate in select patients.One small study suggested that ICU pa-tients treated to targets of 120–140mg/dL (6.7–7.8 mmol/L) had less nega-tive nitrogen balance than those treatedto higher targets (12). However, targets,110 mg/dL (6.1 mmol/L) are not rec-ommended. Insulin infusion protocolswith demonstrated safety and efficacy,resulting in low rates of hypoglycemia,are highly recommended (11).

Noncritically Ill PatientsWith no prospective RCT data to informspecific glycemic targets in noncriticallyill patients, recommendations arebased on clinical experience and judg-ment (13). For the majority of noncriti-cally ill patients treated with insulin,premeal glucose targets should gener-ally be ,140 mg/dL (7.8 mmol/L) with


random blood glucose ,180 mg/dL(10.0 mmol/L), as long as these targetscan be safely achieved. To avoid hypo-glycemia, consideration should be givento reassessing the insulin regimen ifblood glucose levels fall below 100mg/dL (5.6 mmol/L). Modifying the reg-imen is required when blood glucosevalues are,70mg/dL (3.9 mmol/L), un-less the event is easily explained byother factors (such as a missed meal).There is some evidence that systematicattention to hyperglycemia in the emer-gency room leads to better glycemiccontrol in the hospital for those subse-quently admitted (14).Patients with a prior history of suc-

cessful tight glycemic control in the out-patient setting who are clinically stablemay be maintained with a glucose rangebelow the aforementioned cut points.Conversely, higher glucose ranges maybe acceptable in terminally ill patients orin patients with severe comorbidities, aswell as in those in patient-care settingswhere frequent glucose monitoring orclose nursing supervision is not feasible.Clinical judgment combined with on-

going assessment of the patient’s clini-cal status, including changes in thetrajectory of glucose measures, the se-verity of illness, nutritional status, orconcomitant medications that might af-fect glucose levels (e.g., glucocorticoids,octreotide), must be incorporated intothe day-to-day decisions regarding insu-lin dosing (11).

ANTIHYPERGLYCEMIC AGENTS INHOSPITALIZED PATIENTS

Inmost clinical situations in the hospital,insulin therapy is the preferred methodof glycemic control (11). In the ICU, in-travenous infusion is the preferredroute of insulin administration. Whenthe patient is transitioned off intrave-nous insulin to subcutaneous therapy,precautions should be taken to preventhyperglycemia (15,16). Outside of criti-cal care units, scheduled subcutaneousinsulin that delivers basal, nutritional,and correction components (basal–bolusregimen) is recommended for patientswith good nutritional intake. A basalplus correction insulin regimen is thepreferred treatment for patients withpoor oral intake or who are NPO. SSIis strongly discouraged in hospitalizedpatients as the sole method of insulintreatment.

For patients with type 1 diabetes,dosing insulin solely based on premealglucose levels does not account for basalinsulin requirements or caloric intake,increasing both hypoglycemia and hy-perglycemia risks and potentially lead-ing to diabetic ketoacidosis. It hasbeen shown in an RCT that basal–bolustreatment improved glycemic controland reduced hospital complicationscompared with SSI in general surgerypatients with type 2 diabetes (17). Typ-ical dosing schemes are based on bodyweight, with some evidence that pa-tients with renal insufficiency shouldbe treated with lower doses (18). Thereader is referred to publications andreviews that describe available insulinpreparations and protocols and provideguidance in the use of insulin therapyin specific clinical settings, includingparenteral nutrition (19), enteral tubefeedings, and high-dose glucocorticoidtherapy (11).

Recent studies have investigated thesafety and efficacy of oral agents and in-jectable noninsulin therapies, such as GLP-1 analogs, in the hospital. A small study ingeneral medicine and surgical wardsshowed that treatment with sitagliptin re-sulted in similar glycemic control as abasal–bolus regimen in patients with type2 diabetes who had an A1C,7.5% and, inaddition to a nutrition intervention, weretreated with oral agents or low doses ofinsulin prior to hospitalization (20). Use ofintravenous exenatide infusion resulted inimproved glycemic control in patients ad-mitted to a cardiac ICU (21). Further stud-ies are needed to define the role ofincretinmimetics in the inpatientmanage-ment of hyperglycemia.

PREVENTING HYPOGLYCEMIA

Patients with or without diabetes mayexperience hypoglycemia in the hospitalsetting in association with altered nutri-tional state, heart failure, renal or liverdisease, malignancy, infection, or sepsis.Additional triggering events leading toiatrogenic hypoglycemia include suddenreduction of corticosteroid dose, alteredability of the patient to report symp-toms, reduced oral intake, emesis, newNPO status, inappropriate timing ofshort- or rapid-acting insulin in relationto meals, reduced infusion rate of intra-venous dextrose, and unexpected inter-ruption of enteral feedings or parenteralnutrition.

Despite the preventable nature ofmany inpatient episodes of hypoglyce-mia, institutions are more likely to havenursing protocols for hypoglycemia treat-ment than for its prevention. Trackingsuch episodes and analyzing their causesare important quality-improvementactivities (22).

DIABETES CARE PROVIDERS IN THEHOSPITAL

Inpatient diabetes management may beeffectively championed and/or providedby primary care physicians, endocrinol-ogists, intensive care specialists, or hos-pitalists. Involvement of appropriatelytrained specialists or specialty teamsmay reduce length of stay, improve gly-cemic control, and improve outcomes(11). Standardized orders for scheduledand correction-dose insulin should beimplemented, while sole reliance on anSSI regimen is strongly discouraged. Ashospitals move to comply with “mean-ingful use” regulations for electronichealth records, as mandated by theHealth Information Technology for Eco-nomic and Clinical Health Act, effortsshould be made to ensure that all com-ponents of structured insulin order setsare incorporated into electronic insulinorder sets (23,24).

To achieve glycemic targets associ-ated with improved hospital outcomes,hospitals will need a multidisciplinaryapproach to develop insulin manage-ment protocols that effectively andsafely enable achievement of glycemictargets (25).

SELF-MANAGEMENT IN THEHOSPITAL

Diabetes self-management in the hospi-tal may be appropriate for competentyouth and adult patients who have a sta-ble level of consciousness and reason-ably stable daily insulin requirements,successfully conduct self-managementof diabetes at home, have physical skillsneeded to successfully self-administerinsulin and perform self-monitoring ofblood glucose, have adequate oral in-take, are proficient in carbohydratecounting, use multiple daily insulin in-jections or insulin pump therapy, andunderstand sick-day management. Thepatient and physician, in consultationwith nursing staff, must agree that pa-tient self-management is appropriatewhile hospitalized.


Patients who use continuous subcuta-neous insulin infusion (CSII) pump therapyin the outpatient setting can be candi-dates for diabetes self-management inthe hospital, provided that they havethe mental and physical capacity to doso (11). Hospital policy and proceduresdelineating inpatient guidelines for CSIItherapy are advisable, and availability ofhospital personnel with expertise in CSIItherapy is essential. It is important thatnursing personnel document basal ratesand bolus doses taken on a daily basis.

MEDICAL NUTRITION THERAPY INTHE HOSPITAL

The goals of medical nutrition therapyare to optimize glycemic control, pro-vide adequate calories to meet meta-bolic demands, and create a dischargeplan for follow-up care (2,26). TheAmerican Diabetes Association (ADA)does not endorse any single meal planor specified percentages of macronu-trients, and the term “ADA diet” shouldno longer be used. Current nutrition rec-ommendations advise individualizationbased on treatment goals, physiologicalparameters, and medication use. Con-sistent carbohydrate meal plans arepreferred by many hospitals as they fa-cilitate matching the prandial insulindose to the amount of carbohydrateconsumed (27). Because of the complex-ity of nutrition issues in the hospital, aregistered dietitian, knowledgeable andskilled in medical nutrition therapy,should serve as an inpatient teammember. The dietitian is responsiblefor integrating information about thepatient’s clinical condition, meal plan-ning, and lifestyle habits and for estab-lishing treatment goals to determine arealistic plan for nutrition therapy (28).

BEDSIDE BLOOD GLUCOSEMONITORING

Bedside point-of-care (POC) blood glu-cose monitoring is used to guide insulindosing. In the patient receiving nutri-tion, the timing of glucose monitoringshould match carbohydrate exposure.In the patient not receiving nutrition,glucose monitoring is performed every4–6 h (29,30). More frequent blood glu-cose testing ranging from every 30 minto every 2 h is required for patients onintravenous insulin infusions.Safety standards should be estab-

lished for blood glucose monitoring

that prohibit the sharing of finger-sticklancing devices, lancets, needles, andme-ters to reduce the risk of transmission ofblood-borne diseases. Shared lancing de-vices carry essentially the same risk assharing syringes and needles (31).

Accuracy of blood glucose measure-ments using POC meters has limitationsthat must be considered. Although theU.S. Food and Drug Administration cur-rently allows a 620% error for bloodglucose meters, questions about the ap-propriateness of these criteria havebeen raised, especially for lower bloodglucose readings (32). Glucose mea-sures differ significantly between plasmaand whole blood, terms that are oftenused interchangeably and can lead tomisinterpretation. Most commerciallyavailable capillary blood glucose metersintroduce a correction factor of ;1.12to report a “plasma-adjusted” value (33).

Significant discrepancies betweencapillary, venous, and arterial plasmasamples have been observed in patientswith low or high hemoglobin concentra-tions, hypoperfusion, and interferingsubstances such as maltose (containedin immunoglobulins) (34). Analytical var-iability has been described with severalmeters (35). Increasingly,newer-generationPOC blood glucose meters correct forvariation in hematocrit and for interfer-ing substances. Any glucose result thatdoes not correlate with the patient’sstatus should be confirmed throughconventional laboratory sampling ofplasma glucose. The U.S. Food and DrugAdministration has become increasinglyconcerned about POC blood glucosemeter use in the hospital and is presentlyreviewing matters related to their use.

DISCHARGE PLANNING

Transition from the acute care settingis a high-risk time for all patients, notjust those with diabetes or new hyper-glycemia. Although there is extensiveliterature concerning safe transitionwithin and from the hospital, little of itis specific to diabetes (36). Diabetes dis-charge planning is not a separate entitybut is an important part of an overalldischarge plan. As such, discharge plan-ning begins at admission to the hospitaland is updated as projected patientneeds change.

Inpatients may be discharged to var-ied settings, including home (with orwithout visiting nurse services), assisted

living, rehabilitation, or skilled nursingfacilities. For the patient who is dis-charged to assisted living or to home,the optimal program will need to con-sider the type and severity of diabetes,the effects of the patient’s illness onblood glucose levels, and the capacitiesand desires of the patient. Smooth tran-sition to outpatient care should beensured.

An outpatient follow-up visit with theprimary care provider, endocrinologist,or diabetes educator within 1 month ofdischarge is advised for all patients hav-ing hyperglycemia in the hospital. Clearcommunication with outpatient pro-viders either directly or via hospitaldischarge summaries facilitates safetransitions to outpatient care. Providinginformation regarding the cause of hy-perglycemia (or the plan for determin-ing the cause), related complicationsand comorbidities, and recommendedtreatments can assist outpatient pro-viders as they assume ongoing care.

The Agency for Healthcare Researchand Quality recommends that, at aminimum, discharge plans include thefollowing:

Medication Reconciliation○ The patient’s medications must be

cross-checked to ensure that nochronic medications were stoppedand to ensure the safety of newprescriptions.

○ Prescriptions for new or changedmedication should be filled and re-viewed with the patient and familyat or before discharge.

Structured Discharge Communication○ Information on medication changes,pending tests and studies, and follow-up needs must be accurately andpromptly communicated to outpatientphysicians.

○ Discharge summaries should be trans-mitted to the primary physician as soonas possible after discharge.

○ Appointment-keeping behavior isenhanced when the inpatient teamschedules outpatient medical follow-up prior to discharge. Ideally, the inpa-tient care providers or case managers/discharge planners will schedulefollow-up visit(s) with the appropriateprofessionals, including primary careprovider, endocrinologist, and diabeteseducator (37).


DIABETES SELF-MANAGEMENTEDUCATION

Teaching diabetes self-management topatients in hospitals is a challengingtask. Patients are ill, under increasedstress related to their hospitalizationand diagnosis, and in an environmentnot conducive to learning. Ideally, peoplewith diabetes should be taught at a timeand place conducive to learning: as anoutpatient in a recognized program of di-abetes education. For the hospitalizedpa-tient, diabetes “survival skills” educationis generally a feasible approach toprovidesufficient information and training to en-able safe care at home. Patients hospital-ized because of a crisis related to diabetesmanagement or poor care at home re-quire education to prevent subsequentepisodes of hospitalization. Assessingthe need for a home health referralor referral to an outpatient diabetes ed-ucation program should be part ofdischarge planning for all patients. Ex-panded diabetes education can be ar-ranged in the community.Diabetes self-management education

should start upon admission or as soonas feasible, especially in those new toinsulin therapy or in whom the diabetesregimen has been substantially alteredduring the hospitalization.It is recommended that the following

areas of knowledge be reviewed and ad-dressed prior to hospital discharge:

○ Identification of the health care pro-vider who will provide diabetes careafter discharge

○ Level of understanding related to thediagnosis of diabetes, self-monitoringof blood glucose, and explanation ofhome blood glucose goals

○ Definition, recognition, treatment,and prevention of hyperglycemiaand hypoglycemia

○ Information on consistent eating pat-terns

○ When and how to take bloodglucose–lowering medications, in-cluding insulin administration (if go-ing home on insulin)

○ Sick-day management○ Proper use and disposal of needlesand syringes

It is important that patients be pro-vided with appropriate durable medi-cal equipment, medication, supplies,and prescriptions at the time of

discharge in order to avoid a poten-tially dangerous hiatus in care. Thesesupplies/prescriptions should includethe following:

○ Insulin (vials or pens), if needed○ Syringes or pen needles, if needed○ Oral medications, if needed○ Blood glucose meter and strips○ Lancets and lancing devices○ Urine ketone strips (type 1 diabetes)○ Glucagon emergency kit (insulin-

treated patients)○ Medical alert application/charms

References1. Saudek CD, Herman WH, Sacks DB,Bergenstal RM, Edelman D, Davidson MB. Anew look at screening and diagnosing diabetesmellitus. J Clin Endocrinol Metab 2008;93:2447–24532. Clement S, Braithwaite SS, Magee MF, et al.;American Diabetes Association Diabetes inHospitals Writing Committee. Management ofdiabetes and hyperglycemia in hospitals [pub-lished correction in Diabetes Care 2004;27:856]. Diabetes Care 2004;27:553–5913. van den Berghe G, Wouters P, Weekers F,et al. Intensive insulin therapy in critically illpatients. N Engl J Med 2001;345:1359–13674. Malmberg K, Norhammar A, Wedel H,Ryden L. Glycometabolic state at admission:important risk marker of mortality in conven-tionally treated patients with diabetes melli-tus and acute myocardial infarction: long-termresults from the Diabetes and Insulin-GlucoseInfusion in Acute Myocardial Infarction(DIGAMI) study. Circulation 1999;99:2626–26325. Finar S, Liu B, Chittock DR, et al.; NICE-SUGARStudy Investigators. Hypoglycemia and risk ofdeath in critically ill patients. N Engl J Med2012;367:1108–11186. Finfer S, Chittock DR, Su SY, et al.;NICE-SUGAR Study Investigators. Intensiveversus conventional glucose control in criti-cally ill patients. N Engl J Med 2009;360:1283–12977. Krinsley JS, Grover A. Severe hypoglycemia incritically ill patients: risk factors and outcomes.Crit Care Med 2007;35:2262–22678. Van den Berghe G, Wilmer A, Hermans G,et al. Intensive insulin therapy in the medicalICU. N Engl J Med 2006;354:449–4619. Griesdale DE, de Souza RJ, van Dam RM, et al.Intensive insulin therapy andmortality among crit-ically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009;180:821–82710. Cryer PE, Davis SN, Shamoon H. Hypoglyce-mia in diabetes. Diabetes Care 2003;26:1902–191211. Moghissi ES, Korytkowski MT, DiNardo M,et al.; American Association of Clinical Endocri-nologists; American Diabetes Association.American Association of Clinical Endocrinolo-gists and American Diabetes Association con-sensus statement on inpatient glycemiccontrol. Diabetes Care 2009;32:1119–1131

12. Hsu C-W, Sun S-F, Lin S-L, Huang H-H, WongK-F. Moderate glucose control results in lessnegative nitrogen balances in medical intensivecare unit patients: a randomized, controlledstudy. Crit Care 2012;16:R5613. Umpierrez GE, Hellman R, Korytkowski MT,et al.; Endocrine Society.Management of hyper-glycemia in hospitalized patients in non-criticalcare setting: an endocrine society clinical prac-tice guideline. J Clin Endocrinol Metab 2012;97:16–3814. Bernard JB, Munoz C, Harper J, Muriello M,Rico E, Baldwin D. Treatment of inpatient hyper-glycemia beginning in the emergency depart-ment: a randomized trial using insulins aspartand detemir compared with usual care. J HospMed 2011;6:279–28415. Czosnowski QA, Swanson JM, Lobo BL,Broyles JE, Deaton PR, Finch CK. Evaluation ofglycemic control following discontinuation of anintensive insulin protocol. J Hosp Med 2009;4:28–3416. Shomali ME, Herr DL, Hill PC, PehlivanovaM, Sharretts JM, Magee MF. Conversion fromintravenous insulin to subcutaneous insulin af-ter cardiovascular surgery: Transition to TargetStudy. Diabetes Technol Ther 2011;13:121–12617. Umpierrez GE, Smiley D, Jacobs S, et al. Ran-domized Study of Basal-Bolus Insulin Therapy inthe InpatientManagement of PatientswithType 2Diabetes undergoing general surgery (RABBIT 2Surgery). Diabetes Care 2011;34:256–26118. Baldwin D, Zander J, Munoz C, et al. A ran-domized trial of two weight-based doses of in-sulin glargine and glulisine in hospitalizedsubjects with type 2 diabetes and renal insuffi-ciency. Diabetes Care 2012;35:1970–197419. Pasquel FJ, Spiegelman R, McCauley M,et al. Hyperglycemia during total parenteral nu-trition: an important marker of poor outcomeand mortality in hospitalized patients. DiabetesCare 2010;33:739–741

20. Umpierrez GE, Gianchandani R, Smiley D,et al. Safety and efficacy of sitagliptin therapyfor the inpatient management of general med-icine and surgery patients with type 2 diabetes:a pilot, randomized, controlled study. DiabetesCare 2013;36:3430–343521. Abuannadi M, Kosiborod M, Riggs L, et al.Management of hyperglycemia with the admin-istration of intravenous exenatide to patients inthe cardiac intensive care unit. Endocr Pract2013;19:81–90

22. Seaquist ER, Anderson J, Childs B, et al. Hy-poglycemia and diabetes: a report of a work-group of the American Diabetes Associationand the Endocrine Society. Diabetes Care2013;36:1384–139523. Schnipper JL, Liang CL, Ndumele CD,Pendergrass ML. Effects of a computerized or-der set on the inpatient management of hyper-glycemia: a cluster-randomized controlled trial.Endocr Pract 2010;16:209–218

24. Wexler DJ, Shrader P, Burns SM, Cagliero E.Effectiveness of a computerized insulin ordertemplate in general medical inpatients withtype 2 diabetes: a cluster randomized trial. Di-abetes Care 2010;33:2181–2183

25. Furnary AP, Braithwaite SS. Effects of out-come on in-hospital transition from intravenousinsulin infusion to subcutaneous therapy. Am JCardiol 2006;98:557–564


26. Schafer RG, Bohannon B, Franz MJ, et al.;American Diabetes Association. Diabetesnutrition recommendations for health care in-stitutions. Diabetes Care 2004;27(Suppl. 1):S55–S5727. Curll M, Dinardo M, Noschese M,Korytkowski MT. Menu selection, glycaemiccontrol and satisfaction with standard andpatient-controlled consistent carbohydratemeal plans in hospitalised patients with diabe-tes. Qual Saf Health Care 2010;19:355–35928. Evert AB, Boucher JL, Cypress M, et al. Nu-trition therapy recommendations for the man-agement of adults with diabetes. Diabetes Care2014;37(Suppl. 1):S120–S14329. Korytkowski MT, Salata RJ, Koerbel GL,et al. Insulin therapy and glycemic controlin hospitalized patients with diabetes duringenteral nutrition therapy: a randomized controlledclinical trial. Diabetes Care 2009;32:594–596

30. Umpierrez GE. Basal versus sliding-scaleregular insulin in hospitalized patients with hy-perglycemia during enteral nutrition therapy.Diabetes Care 2009;32:751–75331. Klonoff DC, Perz JF. Assisted monitoring ofblood glucose: special safety needs for a newparadigm in testing glucose. J Diabetes SciTech 2010;4:1027–103132. Vandvik PO, Lincoff AM, Gore JM, et al.;American College of Chest Physicians. Primaryand secondary prevention of cardiovascular dis-ease: Antithrombotic Therapy and Prevention ofThrombosis, 9th ed: American College of ChestPhysicians Evidence-Based Clinical Practice Guide-lines. Chest 2012;141(Suppl.):e637S–e668S33. D’Orazio P, Burnett RW, Fogh-Andersen N,et al.; International Federation of Clinical Chem-istry Scientific DivisionWorking Group on Selec-tive Electrodes and Point of Care Testing.Approved IFCC recommendation on reporting

results for blood glucose (abbreviated). ClinChem 2005;51:1573–157634. Dungan K, Chapman J, Braithwaite SS, BuseJ. Glucose measurement: confounding issues insetting targets for inpatient management. Dia-betes Care 2007;30:403–40935. Boyd JC, Bruns DE. Quality specifications forglucose meters: assessment by simulation mod-eling of errors in insulin dose. Clin Chem 2001;47:209–21436. Shepperd S, Lannin NA, Clemson LM,McCluskey A, Cameron ID, Barras SL. Dischargeplanning from hospital to home. Cochrane Da-tabase Syst Rev 2013;1:CD00031337. Agency for Healthcare Research and Qual-ity. AHRQ Patient Safety Networkdadverseevents after hospital discharge [Internet],2014. Available from http://psnet.ahrq.gov/primer.aspx?primerID511. Accessed 1 October2014


14. Diabetes AdvocacyDiabetes Care 2015;38(Suppl. 1):S86–S87 | DOI: 10.2337/dc15-S017

Managing the daily health demands of diabetes can be challenging. People livingwith diabetes should not have to face additional discrimination due to diabetes. Byadvocating for the rights of those with diabetes at all levels, the American DiabetesAssociation (ADA) can help ensure that they live a healthy and productive life. Astrategic goal of the ADA is that by the end of 2015, more children and adults withdiabetes will be living free from the burden of discrimination.One tactic for achieving this goal is to implement the ADA’s Standards of Medical

Care through advocacy-oriented position statements. The ADA publishes evidence-based, peer-reviewed statements on topics such as diabetes and employment, di-abetes and driving, and diabetes management in certain settings such as schools,child care programs, and correctional institutions. In addition to ADA’s clinicalposition statements, these advocacy position statements are important tools ineducating schools, employers, licensing agencies, policy makers, and others aboutthe intersection of diabetes medicine and the law.

ADVOCACY POSITION STATEMENTS

Partial list, with most recent publications appearing first

Care of Young Children With Diabetes in the Child Care Setting (1)

First publication: 2014Very young children (aged ,6 years) with diabetes have legal protections and canbe safely cared forby child care providerswithappropriate training, access to resources,and a system of communication with parents and the child’s diabetes provider. SeetheADAposition statement “CareofYoungChildrenWithDiabetes in theChildCareSet-ting” for further discussion: http://care.diabetesjournals.org/content/37/10/2834.

Diabetes and Driving (2)

First publication: 2012Peoplewith diabeteswhowish to operatemotor vehicles are subject to a great variety oflicensing requirements applied by both state and federal jurisdictions, whichmay lead toloss of employment or significant restrictions onaperson’s license. Presenceof amedicalcondition that can lead to significantly impaired consciousness or cognition may lead todrivers being evaluated for fitness to drive. People with diabetes should be individuallyassessed by a health care professional knowledgeable in diabetes if license restrictionsare being considered, and patients should be counseled about detecting and avoidinghypoglycemia while driving. See the ADA position statement “Diabetes and Driving” forfurther discussion: http://care.diabetesjournals.org/content/37/Supplement_1/S97.

Diabetes and Employment (3)

First publication: 1984 (revised 2009)Any person with diabetes, whether insulin-treated or noninsulin-treated, should beeligible for any employment for which he or she is otherwise qualified. Employmentdecisions should never be based on generalizations or stereotypes regarding theeffects of diabetes. When questions arise about the medical fitness of a person withdiabetes for a particular job, a health care professional with expertise in treatingdiabetes should performan individualized assessment. See theADAposition statement“Diabetes and Employment” for further discussion: http://care.diabetesjournals.org/content/37/Supplement_1/S112.

Diabetes Care in the School and Day Care Setting (4)*

First publication: 1998 (revised 2008)As a sizeable portion of a child’s day is spent in school, close communication with andcooperation of school personnel are essential for optimal diabetes management,safety, andmaximal academic opportunities. See theADAposition statement “Diabetes

Suggested citation: American Diabetes Associa-tion. Diabetes advocacy. Sec. 14. In Standards ofMedical Care in Diabetesd2015. Diabetes Care2015;38(Suppl. 1):S86–S87




POSITION

STATEMEN

T

Care in the School and Day Care Setting”for further discussion: http://care.diabetesjournals.org/content/37/Supplement_1/S91.*In October 2014, a separate statement

on the careof young childrenwithdiabetesin the child care setting was published.

Diabetes Management in CorrectionalInstitutions (5)

First publication: 1989 (revised 2008)Peoplewith diabetes in correctional facili-ties should receive care that meets na-tional standards. Because it is estimated

that nearly 80,000 inmates have diabetes,correctional institutions should havewrit-ten policies and procedures for the man-agement of diabetes and for training ofmedical and correctional staff in diabetescare practices. See the ADA positionstatement “Diabetes Management inCorrectional Institutions” for further dis-cussion: http://care.diabetesjournals.org/content/37/Supplement_1/S104.

References1. Siminerio LM, Albanese-O’Neill A, Chiang JL,et al. Care of young children with diabetes in the

child care setting: a position statement of theAmerican Diabetes Association. Diabetes Care2014;37:2834–28422. American Diabetes Association. Diabetesand driving. Diabetes Care 2014;37(Suppl. 1):S972S1033. American Diabetes Association. Diabetesand employment. Diabetes Care 2014;37(Suppl.1):S112–S1174. American Diabetes Association. Diabetescare in the school and day care setting. DiabetesCare 2014;37(Suppl. 1):S91–S965. American Diabetes Association. Diabetesmanagement in correctional institutions.Diabetes Care 2014;37(Suppl. 1):S104–S111


Professional Practice Committeefor the Standards of Medical Carein Diabetesd2015Diabetes Care 2015;38(Suppl. 1):S88–S89 | DOI: 10.2337/dc15-S018

Committee members disclosed the following financial or other conflicts of interest covering the period 12 months before7 September 2014

Member Employment Research grant Other research support

Richard W. Grant, MD, MPH (Chair) Division of Research, KaiserPermanente, Oakland, CA

NIDDK, NHLBI None

Thomas W. Donner, MD Johns Hopkins University School ofMedicine, Baltimore, MD

Novo Nordisk*# None

Judith E. Fradkin, MD National Institutes of Health,Bethesda, MD

None None

Charlotte Hayes, MMSc, MS, RD,CDE, ACSM CES

Private practice: (NF)2 Nutrition andFitness Consulting, Atlanta, GA

None None

William H. Herman, MD, MPH University of Michigan, Ann Arbor, MI None None

William C. Hsu, MD Joslin Diabetes Center, Boston, MA None None

Eileen Kim, MD Kaiser Permanente NorthernCalifornia Region, Oakland, CA

None None

Lori Laffel, MD, MPH Joslin Diabetes Center and HarvardMedical School, Boston, MA

Dexcom, BoehringerIngelheim

None

Rodica Pop-Busui, MD, PhD University of Michigan, Ann Arbor, MI NHLBI, NIDDK, ADA,Bristol-Myers Squibb

None

Neda Rasouli, MD University of Colorado, Denver, CO Novo Nordisk,# Bristol-Myers Squibb,# Merck

Sharp & Dohme,# NIDDK,#Pfizer#

None

Desmond Schatz, MD University of Florida, Gainesville, FL None NIDDK, NIAID, JaebCenter for Health

Research, JDRF, HelmsleyCharitable Trust

Joseph A. Stankaitis, MD, MPH Monroe Plan for Medical Care,Rochester, NY

Milbank Memorial Fund None

Tracey H. Taveira, PharmD,CDOE, CVDOE

University of Rhode Island College ofPharmacy, Kingston, RI; Providence VA

Medical Center, Warren AlpertMedical School of Brown University,

Providence, RI

AHA None

Deborah J. Wexler, MD Massachusetts General Hospital,Boston, MA

NIDDK None

Jane L. Chiang, MD (Staff) ADA, Alexandria, VA None None

Erika Gebel Berg, PhD (Staff) ADA, Alexandria, VA None None

ADA, American Diabetes Association; AHA, American Heart Association; MEDCAC, Medicare Evidence Development & Coverage AdvisoryCommittee; NHLBI, National Heart, Lung, and Blood Institute; NIAID, National Institute of Allergy and Infectious Diseases; NIDDK, National Instituteof Diabetes and Digestive and Kidney Diseases.*$$10,000 per year from company to individual.#Grant or contract is to university or other employer.


PROFESSIONALPRACTICECOMMITTEE

MemberSpeakers’ bureau/

honorariaOwnershipinterest Consultant/advisory board Other

R.W.G. None None None None

T.W.D. None None None None

J.E.F. None None None None

C.H. Scherer ClinicalCommunications

None Emory University, Emory DiabetesCourse at Grady, Team Novo Nordisk

Receives royalties from the ADA,Academy of Nutrition and Dietetics(Chair, Legislative and Public Policy

Committee)

W.H.H. None None AstraZeneca, Novo Nordisk (self andspouse), Merck Sharp & Dohme,* GIDynamics, Boehringer Ingelheim

National Committee for QualityAssurance (Chair, Diabetes Panel),Centers for Medicare & MedicaidServices (member, MEDCAC),

Diabetic Medicine (Editor for theAmericas)

W.C.H. None None Novo Nordisk None

E.K. None None None None

L.L. None None Johnson & Johnson, Eli Lilly, Sanofi,Bristol-Myers Squibb, Menarini,

Novo Nordisk, AstraZeneca, LifeScan/Animas, Boehringer Ingelheim,

Dexcom

None

R.P.-B. None None Acorda Therapeutics, AstraZeneca,T1D Exchange

None

N.R. None None None None

D.S. None None Daiichi Sankyo, Andromeda Biotech ADA Board of Directors, ADA officer

J.A.S. None None TPG National Payor Roundtable,Amgen, Celgene, Gilead, SalixPharmaceuticals, Janssen

Pharmaceuticals, Bayer, Medtronic

National Committee for QualityAssurance (physician surveyor and

member of ReconsiderationCommittee), New York State

Department of Health MedicaidRedesign Team’s Evidence-BasedBenefit Review Workgroup, Boardmember (Chair-Elect) for St. Ann’sCommunity, Rochester, NY, a non-profit senior living/long-term care

organization

T.H.T. None None None None

D.J.W. None None None Diabetes Care (Editorial Board)

J.L.C. None None None None

E.G.B. None None None None

care.diabetesjournals.org Professional Practice Committee S89

Index

A1C. see also glycemic targetsCGM, S34children and adolescents, S35, S71glycemic target determination, S37goals, S35limitations, S34–S35macrovascular complications, S36mean glucose levels, S35microvascular complications, S35–S36race/ethnicity differences, S9, S35recommendations, S34, S35, S37SMBG, S33–S34testing, S8–S10, S12, S34–S35

acarbose, S44ACCORD trial, S19, S36, S38, S50, S53A1C Derived Average Glucose (ADAG) trial,S35, S37

ACE inhibitors, S49–S51, S55, S58–S60,S72, S78

acute coronary syndrome, S54, S55adolescents. see children andadolescents

ADVANCE-BP trial, S50, S51ADVANCE trial, S36, S38advocacy, S5, S86–S87African Americans, S9, S11, S12, S24, S35age. see older adultsAIM-HIGH trial, S53albiglutide, S45albuminuria, S25, S58–S60, S73alcohol, S23, S51alogliptin, S44amlodipine, S51amputations, S63–S64amylin mimetics, S45anemia, S9angiotensin receptor blockers (ARBs),S49–S51, S55, S58–S60, S72, S78

ankle-brachial index (ABI), S63, S64antihypertensive medications, S51,S59, S78

antiplatelet agents, S54–S55, S61Antithrombotic Trialists’ (ATT) Collaboration, S54Asian Americans, S9–S12aspart, S43, S45aspirin resistance, S55aspirin therapy, S54–S55, S61assisted living. see hospital careautoimmune disease, S10–S11Automation to Simulate Pancreatic InsulinResponse (ASPIRE) trial, S34

autonomic neuropathy, S25, S62–S63

bariatric surgery, S46–S47benazepril, S51biguanides, S31, S32, S42–S44bile acid sequestrants, S42, S44, S53b-blockers, S51, S55blood pressure control. see hypertensionbody mass index (BMI), S12bromocriptine, S42, S45

calcium channel blockers, S51, S59canagliflozin, S45cancer, S18carbohydrates, S21–S23

cardiovascular diseaseA1C relationship to, S36autonomic neuropathy, S25, S62–S63children and adolescents, S72dietary fat management, S23–S24patient-centeredness, S5pharmacological therapy, S51–S55, S59postprandial plasma glucose testing, S37revisions summary, S4risk calculator, S52risk factors, S10, S12, S25, S32risk management, S49–S55screening, S31, S55testing frequency, S9

Care of Young Children With Diabetes in theChild Care Setting, S86

celiac disease, S71Charcot foot, S64children and adolescents

A1C goals, S35, S71autoimmune conditions, S71cardiovascular disease, S72celiac disease, S71cognitive impairment, S70DSME/DSMS, S73dyslipidemia, S72family stresses, S74glycemic control, S70–S71hypertension, S71–S72hypoglycemia, S70nephropathy, S72–S73neuropathy, S73pediatric to adult care transition,

S73–S74plasma blood glucose goals, S71psychosocial issues, S74resources, S86retinopathy, S73revisions summary, S4school, child care, S73smoking, S72statins, S72thyroid disease, S71type 1 diabetes, S10–S11, S70–S74type 2 diabetes, S12–S13, S74

chlorthalidone, S51cholesterol. see also dyslipidemia

children and adolescents, S72control, S51monitoring, S53screening, S10, S52treatment, S52, S55

Chronic Care Model (CCM), S5, S6chronic kidney disease, S23, S25, S58–S60classification, diagnosis

overview, S8prediabetes, S9–S10, S12–S13revisions summary, S4testing, S8–S10testing frequency, S9

claudication, S63clinical management

advocacy, S5, S86–S87behavior change support, S6behavior optimization, S6care delivery systems, S6

changes, initiatives, S6demographic changes, S5improvement strategies, S5patient-centeredness, S5regime reevaluation, S6–S7resources, S6

clonidine, S78clopidogrel, S54, S55cognitive impairment, S19, S38, S70colesevelam, S42, S44comorbidities, S17–S19, S26congestive heart failure, S51, S55consensus reports, S1continuous glucose monitoring (CGM), S4,S33, S34

continuous subcutaneous insulin infusion(CSII), S83

contraception, S79coronary heart disease, S55cystic fibrosis–related diabetes, S15

dapagliflozin, S45Da Qing study, S31DAWN2 study, S26day care, S73, S86–S87degludec, S45depression, S18, S26, S67, S74detemir, S45Diabetes and Driving, S86Diabetes and Employment, S86Diabetes Care in the School and Day CareSetting, S86–S87

Diabetes Control and Complications Trial(DCCT), S35, S36, S38, S41, S70

Diabetes Management in CorrectionalInstitutions, S87

Diabetes Prevention Program (DPP),S31, S32

Diabetes Prevention Program OutcomesStudy (DPPOS), S31, S32

diabetes-related distress, S26diabetes self-management education(DSME)

benefits, S6, S20–S21carbohydrate management, S21–S23children and adolescents, S73dietary fat management, S23–S24eating patterns, S21–S23herbal supplements, S23hospital care, S84medical nutrition therapy, S21–S23, S52,

S72, S83micronutrients, S23national standards, S21overview, S17, S20–S21prediabetes, S32protein management, S22, S23, S59recommendations, S20, S31reimbursement, S21sodium, S23, S24, S51weight loss, S21, S55

diabetes self-management support (DSMS).see diabetes self-management education(DSME)

Diabetic Retinopathy Study (DRS), S61diastolic blood pressure goals, S4


INDEX

diet, nutrition, S21–S23diltiazem, S78dipeptidyl peptidase 4 (DPP-4) inhibitors,S42–S44, S46, S68

disordered eating, S74diuretics, S49–S51, S58, S59, S78dopamine-2 agonists, S45driving, S86dulaglutide, S45dyslipidemia. see also cholesterol;triglycerides

children and adolescents, S72control, S51lifestyle modification, S52, S55monitoring recommendations, S4, S53recommendations, S51–S52screening, S51treatment, S52–S55

Early Treatment Diabetic Retinopathy Study(ETDRS), S61

eating abnormalities, S74eating patterns, S21–S23e-cigarettes, S4, S25empagliflozin, S45employment, S86end-stage renal disease (ESRD), S59Epidemiology of Diabetes Interventions andComplications (EDIC) study, S35–S36, S38

erectile dysfunction, S63exenatide/exenatide ER, S45, S82exercise

albuminuria, S25autonomic neuropathy, S25, S62–S63benefits, S24children, S24frequency, type, S24glycemic control, S24hyperglycemia, S25hypoglycemia, S25kidney disease, S23, S25, S58–S60,S72–S73

peripheral neuropathy, S25, S62–S63prediabetes, S24pre-exercise evaluation, S24–S25recommendations, S24retinopathy, S25, S60–S62, S73

ezetimibe, S53

fasting plasma glucose testing, S9fatty liver disease, S18fenofibrate, S53fibrates, S53Finnish Diabetes Prevention Study (DPS), S31foot care, S4, S63–S64foot infections, S64foundations of care revisions summary, S4fractures, S18–S19FRAX score, S18fundus photographs, S61

gastrointestinal neuropathies, S62gastroparesis, S63genitourinary tract disturbances, S62–S63gestational diabetes mellitus (GDM). see alsopregnancy

classification, S8diagnosis, S13–S14glycemic targets, S77, S78management, S78one-step strategy, S13, S14overview, S13, S77

postpartum care, S79recommendations, S13screening, S10two-step strategy, S13–S14

glargine, S45gliclazide, S44glimepiride, S44glipizide, S44glucagon, S38glucagon-like peptide 1 (GLP-1) agonists, S42,S43, S45, S46, S68, S82

a-glucosidase inhibitors, S42, S44glulisine, S43, S45glyburide/glibenclamide, S44glycemic targets. see also A1C

A1C/microvascular complicationsrelationships, S35–S36

determination, S37glycemic control assessment, S33–S35hospital care, S80–S82intercurrent illness, S39mean glucose levels, S35mortality findings, S36older adults, S68pregnancy, S77, S78recommendations, S33, S36–S37revisions summary, S4

glycemic treatment approachesbariatric surgery, S46–S47pharmacological therapy, S41–S46revisions summary, S4

gram-positive cocci, S64

hearing impairment, S19hemoglobinopathies, S9hepatitis B vaccination, S26herbal supplements, S23hospital care

bedside blood glucose monitoring, S83critically ill patients, S80, S81discharge planning, S80, S83DSME, S84glucose abnormalities definitions, S81glycemic targets, S80–S82hyperglycemia, S80–S81hypoglycemia, S80–S82insulin therapy, S80–S82management team, S82medical nutrition therapy, S83medication reconciliation, S83non critically ill patients, S80–S82recommendations, S80self-management, S82–S83sliding scale insulin (SSI), S80, S82structured discharge communication, S83type 1 diabetes, S82

hydrochlorothiazide, S51hyperglycemia

cognitive impairment, S19exercise, S25glycemic target determination, S37hospital care, S80–S81older adults, S67, S68plasma glucose testing, S9postprandial, S37risk factors, S11

Hyperglycemia and Adverse PregnancyOutcome (HAPO) study, S13

hyperglycemic crisis, S9hypertension

children and adolescents, S71–S72diagnosis, S49, S50

diastolic blood pressure, S50–S51goals, S49, S50lifestyle modification, S49, S51older adults, S67overview, S49–S50pharmacological therapy, S49–S51recommendations, S49screening, S10, S49, S50sodium guidelines, S24, S51systolic blood pressure, S50, S59treatment, S49, S50

HypertensionOptimal Treatment (HOT) trial, S50hypertriglyceridemia, S53hypoglycemia

A1C goals, S35, S37CGM, S34children and adolescents, S70exercise, S25hospital care, S80–S82nocturnal, S34older adults, S68overview, S38pregnancy, S78prevention, S38, S82recommendations, S38treatment, S38

hypoglycemia unawarenessCGM, S33, S34children and adolescents, S70effects, characterization, S38recommendations, S38

immune-mediated diabetes, S10–S11immunization recommendations, S4,S26–S27

impaired fasting glucose (IFG), S10, S31impaired glucose tolerance (IGT), S10, S31incretin-based therapies, S42indapamide, S50, S51infections, S64influenza vaccine, S26–S27insulin

basal–bolus, S43, S45, S46, S70,S71, S82

combination therapy, S42glycemic targets, S38hospital care, S80–S82hypoglycemia treatment, S38intensive insulin regimens, S34MDI, S41older adults, S68pregnancy, S78recommendations, S33sliding scale insulin (SSI), S80, S82type 1 diabetes, S41type 2 diabetes, S42–S46

insulin dependent diabetes, S10–S11insulin pump therapy, S33, S41, S43, S83insulin resistance, S10, S78insulin secretagogues, S38, S68International Association of the Diabetesand Pregnancy Study Groups(IADPSG), S13

jail, S87juvenile-onset diabetes, S10–S11

kidney disease, S23, S25, S58–S60, S72–S73Kumamoto Study, S36

labetalol, S78lactation, S79

care.diabetesjournals.org Index S91

laser photocoagulation therapy, S61–S62lifestyle modifications

dyslipidemia, S52, S55hypertension, S49, S51type 2 diabetes, S31, S42

linagliptin, S44liraglutide, S45lispro, S43, S45lixisenatide, S45Look AHEAD trial, S18, S55loss of protective sensation (LOPS),S63, S64

macrovascular complications, S35, S36, S51macular edema, S61management planning, S17–S19, S26maturity-onset diabetes of the young(MODY), S14

medical evaluation, S17, S18, S24–S25medical nutrition therapy, S21–S23, S52, S72,S83

Medicare/Medicaid, S21medications, S12. see also pharmacologicaltherapy; specific medications, conditions

meglitinides, S42, S44mental health specialist referrals, S26metformin, S31, S32, S42–S44, S55, S59,S68

methyldopa, S78microvascular complications

A1C goals, S35A1C relationship to, S35–S36erectile dysfunction, S63gastroparesis, S63glycemic control, S63kidney disease, S23, S25, S58–S60,S72–S73

neuropathy, S25, S62–S63, S73orthostatic hypotension, S63patient education, S64pharmacological therapy, S51retinopathy, S25, S60–S62, S73revisions summary, S4risk factors, S11

miglitol, S44monogenic diabetes syndromes, S14–S15myocardial infarction (MI), S36, S50, S54, S55,S59

nateglinide, S44National Diabetes Education Program (NDEP),S6, S74

National Diabetes Prevention Program, S31National Institutes of Health (NIH),S13–S14

neonatal diabetes, S14nephropathy, S23, S25, S58–S60, S72–S73neuropathy, S25, S62–S63, S73niacin, S53NICE-SUGAR trial, S81nonproliferative diabetic retinopathy(NPDR), S61

nursing home. see hospital care

obstructive sleep apnea, S18older adults

A1C levels, S9depression screening, S67diabetes complications screening, S67glycemic targets, S68hyperglycemia, S67, S68hypertension, S67

hypoglycemia, S68pharmacological therapy, S68–S69recommendations, S67sodium guidelines, S24statin therapy, S52, S53treatment goals, S67–S68type 2 diabetes screening, S12

orthostatic hypotension, S63overweight, obesity, S9, S10, S21, S55,S78–S79

Patient-Centered Medical Home, S6perindopril, S50, S51periodontal disease, S19peripheral arterial disease, S63, S64peripheral neuropathy, S25, S62–S63pharmacological therapy

cardiovascular disease, S51–S55, S59hypertension, S49–S51microvascular complications, S51older adults, S68–S69prediabetes, S32type 2 diabetes, S31–S32, S42–S46

pioglitazone, S44, S46pneumococcal polysaccharide vaccine 23(PPSV23), S26, S27

polycystic ovary syndrome, S10position statements, S1pramlintide, S41–S42, S45prasugrel, S55prazosin, S78prediabetes

classification, diagnosis, S9–S10,S12–S13

DSME/DSMS, S32exercise, S24pharmacological therapy, S32

pre-exercise medical evaluation, S24–S25pregnancy

A1C testing, S9, S78antihypertensive medications, S51,

S78contraception, S79GDM (see gestational diabetes mellitus

[GDM])glycemic targets, S77, S78hypertension, S50hypoglycemia, S78insulin, S78insulin resistance, S78lactation, S79medications contraindicated, S77, S78metabolic physiology, S78overweight, obesity, S78–S79postpartum care, S79preconception counseling, S77recommendations, S77retinopathy, S25, S60–S62, S73revisions summary, S4screening, S10statins, S72

prison, S87Professional Practice Committee, S3,S88–S89

proliferative diabetic retinopathy, S61protein, S22, S23, S59psychosocial screening, care, S25–S26P2Y12 receptor antagonist, S55

race/ethnicity, S9, S12, S35. see also AfricanAmericans; Asian Americans

RAS inhibitors, S51, S59

repaglinide, S44retinal photography, S61retinopathy, S25, S60–S62, S73revisions summary, S4Reye syndrome, S54risk management, S4, S6, S9, S11rosiglitazone, S44

SAVOR-TIMI 53 trial, S68–S69saxagliptin, S44, S68–S69school, S73, S86–S87scientific evidence grading,S1–S2

scientific statements, S1self-monitoring of blood glucose(SMBG)

basal insulin/oral agents, S34intensive insulin regimens, S34optimization, S33–S34overview, S33recommendations, S33

sickle cell trait, S9sitagliptin, S44, S82skilled nursing facilities. see hospital caresliding scale insulin (SSI), S80, S82smoking, S4, S25, S63, S72sodium, S23, S24, S51sodium–glucose cotransporter 2 (SGLT2)inhibitors, S42, S43, S45, S46

Standards of Care recommendations, S1Staphylococci, S64statins, S4, S52–S55, S72stroke, S36, S54, S59sulfonylureas

A1C/CVD relationships, S36combination therapy, S42, S43older adults, S68type 2 diabetes, S43, S44, S46

testosterone levels, S19thiazolidinediones, S43, S44, S46thyroid disease, S71ticagrelor, S55triglycerides, S10, S52, S53. see alsodyslipidemia

2-hour plasma glucose testing, S9type 1 diabetes

A1C/mean glucose relationship,S35

autoimmune conditions, S71carbohydrate management, S21CGM, S33, S34children and adolescents, S10–S11,

S70–S74classification, S8diagnosis, S10–S11glycemic control,

S70–S71hospital care, S82hypoglycemia, S38insulin, S41pharmacological therapy, S41–S42pregnancy, S78–S79progression estimates, S11retinopathy, S25, S60–S62, S73SMBG, S34statin therapy, S53testing, S11

type 2 diabetesA1C goals, S35A1C/macrovascular complications

relationships, S36

S92 Index Diabetes Care Volume 38, Supplement 1, January 2015

children and adolescents, S12–S13,S74

classification, S8combination therapy, S42, S43community screening, S12comorbidities, S74diagnosis, S11–S13diagnostic tests, S12hypoglycemia, S38ketoacidosis, S11lifestyle modifications, S31, S42

overview, S11pharmacological therapy, S31–S32,

S42–S46pregnancy, S78–S79prevention, delay of,

S31–S32recommendations, S11, S31retinopathy, S25, S60–S62, S73risk factors, S11–S12screening, S12, S31testing interval, S12

UK Prospective Diabetes Study (UKPDS),S36, S59

ulcers, S63–S64

vascular endothelial growth factor (VEGF),S61, S62

vascular pathology measures, S37Veterans Affairs Diabetes Trial (VADT), S36vildagliptin, S44

weight loss, S21, S55

care.diabetesjournals.org Index S93

Standards of medical care in diabetes—2015

Health & Medicine

Transcript of Standards of medical care in diabetes—2015