Standards of Medical Care inDiabetesd2014Diabetes mellitus is a complex, chronic illness requiring continuous medical carewith multifactorial risk reduction strategies beyond glycemic control. Ongoingpatient self-management education and support are critical to preventing acutecomplications and reducing the risk of long-term complications. Significantevidence exists that supports a range of interventions to improve diabetesoutcomes.

The American Diabetes Association’s (ADA’s) Standards of Care are intended toprovide clinicians, patients, researchers, payers, and other interestedindividuals with the components of diabetes care, general treatment goals,and tools to evaluate the quality of care. The Standards of Carerecommendations are not intended to preclude clinical judgment and must beapplied in the context of excellent clinical care and with adjustments forindividual preferences, comorbidities, and other patient factors. Formore detailed information about management of diabetes, refer toreferences 1,2.

The recommendations include screening, diagnostic, and therapeutic actions thatare known or believed to favorably affect health outcomes of patients withdiabetes. Many of these interventions have also been shown to be cost-effective(3). A grading system (Table 1) developed by ADA and modeled after existingmethods was used to clarify and codify the evidence that forms the basis for therecommendations. The letters A, B, C, or E show the evidence level that supportseach recommendation. The Standards of Care conclude with evidence andrecommendations for strategies to improve the process of diabetes care. It mustbe emphasized that clinical evidence and expert recommendations alone cannotimprove patients’ lives, but must be effectively translated into clinicalmanagement.

I. CLASSIFICATION AND DIAGNOSIS

A. ClassificationDiabetes can be classified into four clinical categories:

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

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

c Other specific types of diabetes due to other causes, e.g., genetic defects in b-cellfunction, genetic defects in insulin action, diseases of the exocrine pancreas (suchas cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)

c Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy thatis not clearly overt diabetes)

Some patients cannot be clearly classified as type 1 or type 2 diabetic.Clinical presentation and disease progression vary considerably in both types ofdiabetes. Occasionally, patients diagnosed with type 2 diabetes may presentwith ketoacidosis. Children with type 1 diabetes typically present with thehallmark symptoms of polyuria/polydipsia and occasionally with diabeticketoacidosis (DKA). However, difficulties in diagnosis may occur in children,adolescents, and adults, with the true diagnosis becoming more obviousover time.

Originally approved 1988. Most recent review/revision October 2013.

DOI: 10.2337/dc14-S014

© 2014 by the American Diabetes Association.See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

American Diabetes Association

S14 Diabetes Care Volume 37, Supplement 1, January 2014

POSITION

STATEMEN

T

B. Diagnosis of DiabetesDiabetes is usually diagnosed based onplasma glucose criteria, either thefasting plasma glucose (FPG) or the 2-hplasma glucose (2-h PG) value after a75-g oral glucose tolerance test (OGTT)(4). Recently, an International ExpertCommittee added the A1C (threshold$6.5%) as a third option to diagnosediabetes (5) (Table 2).

A1CThe A1C test should be performedusing a method that is certified by theNational GlycohemoglobinStandardization Program (NGSP) andstandardized or traceable to theDiabetes Control and ComplicationsTrial (DCCT) reference assay. Althoughpoint-of-care (POC) A1C assays may beNGSP-certified, proficiency testing is notmandated for performing the test, souse of these assays for diagnosticpurposes may be problematic.

Epidemiological data show a similarrelationship of A1C with the risk ofretinopathy as seen with FPG and 2-hPG. The A1C has several advantages tothe FPG and OGTT, including greaterconvenience (fasting not required),possibly greater preanalytical stability,and less day-to-day perturbationsduring stress and illness. Theseadvantages must be balanced by greater

cost, the limited availability of A1Ctesting in certain regions of thedeveloping world, and the incompletecorrelation between A1C and averageglucose in certain individuals.

Race/Ethnicity

A1C levels may vary with patients’ race/ethnicity (6,7). Glycation rates may differby race. For example, African Americansmayhave higher rates of glycation, but thisis controversial. A recent epidemiologicalstudy found that, when matched for FPG,African Americans (with and withoutdiabetes) had higher A1C than non-Hispanic whites, but also had higher levelsof fructosamine and glycated albumin andlower levels of 1,5 anhydroglucitol,suggesting that their glycemic burden(particularly postprandially) may behigher (8). Epidemiological studiesforming the framework forrecommending A1C to diagnose diabeteshave all been in adult populations. It isunclear if the same A1C cut point shouldbe used to diagnose children oradolescents with diabetes (9,10).

Anemias/Hemoglobinopathies

Interpreting A1C levels in the presence ofcertain anemias and hemoglobinopathiesis particularly problematic. For patientswith an abnormal hemoglobin but normalred cell turnover, such as sickle cell trait,an A1C assay without interference from

abnormal hemoglobins should be used.An updated list is available at www.ngsp.org/interf.asp. In situations of abnormalred cell turnover, such as pregnancy,recent blood loss or transfusion, or someanemias, only blood glucose criteriashould be used to diagnose diabetes.

Fasting and Two-Hour PlasmaGlucoseIn addition to the A1C test, the FPG and2-h PG may also be used to diagnosediabetes. The current diagnostic criteriafor diabetes are summarized in Table 2.The concordance between the FPG and2-h PG tests is,100%. The concordancebetween A1C and either glucose-basedtest is also imperfect. National Health andNutrition Examination Survey (NHANES)data indicate that the A1C cut point of$6.5% identifies one-third fewer cases ofundiagnosed diabetes than a fastingglucose cut point of$126 mg/dL (7.0mmol/L) (11). Numerous studies haveconfirmed that, at these cut points, the2-h OGTT value diagnoses more screenedpeople with diabetes (12). In reality, alarge portion of the diabetic populationremains undiagnosed. Of note, the lowersensitivity of A1C at the designated cutpoint may be offset by the test’s ability tofacilitate the diagnosis.

As with most diagnostic tests, a testresult should be repeated when feasible

Table 1—ADA evidence grading system for Clinical Practice Recommendations

Level ofevidence Description

A Clear evidence from well-conducted, generalizable RCTs that are adequatelypowered, including:c Evidence from a well-conducted multicenter trialc Evidence from a meta-analysis that incorporated quality ratings in the analysis

Compelling nonexperimental evidence, i.e., “all or none” rule developedby the Center for Evidence-Based Medicine at the University of Oxford

Supportive evidence from well-conducted RCTs that are adequately powered,including:c Evidence from a well-conducted trial at one or more institutionsc Evidence from a meta-analysis that incorporated quality ratings in the analysis

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 as caseseries 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

Table 2—Criteria for the diagnosis ofdiabetesA1C$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). Fastingis defined as no caloric intake for atleast 8 h.*

OR

Two-hour PG $200 mg/dL (11.1 mmol/L)during an OGTT. The test should beperformed as described by the WHO,using a 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, result should be confirmedby repeat testing.

care.diabetesjournals.org Position Statement S15

to rule out laboratory error (e.g., anelevated A1C should be repeated whenfeasible, and not necessarily in 3months).Unless there is a clear clinical diagnosis(e.g., a patient in a hyperglycemic crisis orclassic symptoms of hyperglycemia and arandom plasma glucose$200 mg/dL), itis preferable that the same test berepeated for confirmation, since therewill be a greater likelihood ofconcurrence. For example, if the A1C is7.0% and a repeat result is 6.8%, thediagnosis of diabetes is confirmed. If twodifferent tests (such as A1C and FPG) areboth above the diagnostic threshold, thisalso confirms the diagnosis.

On the other hand, if a patient hasdiscordant results on two differenttests, then the test result that is abovethe diagnostic cut point should berepeated. The diagnosis is made on thebasis of the confirmed test. For example,if a patient meets the diabetes criterion ofthe A1C (two results$6.5%) but not theFPG (,126 mg/dL or 7.0 mmol/L), orvice versa, that person should beconsidered to have diabetes.

Since there is preanalytic and analyticvariability of all the tests, it is possible thatan abnormal result (i.e., above thediagnostic threshold), when repeated,will produce a value below the diagnosticcut point. This is least likely for A1C,somewhat more likely for FPG, and mostlikely for the 2-h PG. Barring a laboratoryerror, such patients will likely have testresults near the margins of the diagnosticthreshold. The health care professionalmight opt to follow the patient closelyand repeat the test in 3–6 months.

C. Categories of Increased Risk forDiabetes (Prediabetes)In 1997 and 2003, the Expert Committeeon Diagnosis and Classification ofDiabetes Mellitus (13,14) recognized agroup of individuals whose glucoselevels did not meet the criteria fordiabetes, but were too high to beconsidered normal. These persons weredefined as having impaired fastingglucose (IFG) (FPG levels 100–125mg/dL[5.6–6.9 mmol/L]), or impaired glucosetolerance (IGT) (2-h PG OGTT values of140–199 mg/dL [7.8–11.0 mmol/L]).It should be noted that theWorld HealthOrganization (WHO) and a number ofother diabetes organizations define thecutoff for IFG at 110 mg/dL (6.1 mmol/L).

“Prediabetes” is the term used forindividuals with IFG and/or IGT,indicating the relatively high risk for thefuture development of diabetes. IFG andIGT should not be viewed as clinicalentities in their own right but rather riskfactors for diabetes and cardiovasculardisease (CVD). IFG and IGT areassociated with obesity (especiallyabdominal or visceral obesity),dyslipidemia with high triglyceridesand/or low HDL cholesterol, andhypertension.

As with the glucose measures, severalprospective studies that used A1C topredict the progression to diabetesdemonstrated a strong, continuousassociation between A1C andsubsequent diabetes. In a systematicreview of 44,203 individuals from 16cohort studies with a follow-up intervalaveraging 5.6 years (range 2.8–12years), those with an A1C between 5.5and 6.0% had a substantially increasedrisk of diabetes (5-year incidences from9 to 25%). An A1C range of 6.0–6.5%had a 5-year risk of developing diabetesbetween 25–50%, and a relative risk(RR) 20 times higher compared with anA1C of 5.0% (15). In a community-basedstudy of African American and non-Hispanic white adults without diabetes,baseline A1Cwas a stronger predictor ofsubsequent diabetes andcardiovascular events than fastingglucose (16). Other analyses suggestthat an A1C of 5.7% is associated withsimilar diabetes risk to the high-riskparticipants in the Diabetes PreventionProgram (DPP) (17).

Hence, it is reasonable to consider anA1C range of 5.7–6.4% as identifyingindividuals with prediabetes. As withthose with IFG and IGT, individuals withan A1C of 5.7–6.4% should be informedof their increased risk for diabetes andCVD and counseled about effectivestrategies to lower their risks (seeSection IV). Similar to glucosemeasurements, the continuum of riskis curvilinear, so as A1C rises, thediabetes risk rises disproportionately(15). Aggressive interventions andvigilant follow-up should be pursuedfor those considered at very high risk(e.g., those with A1Cs .6.0%). Table 3summarizes the categories ofprediabetes.

II. TESTING FOR DIABETES INASYMPTOMATIC PATIENTS

Recommendations

c Testing to detect type 2 diabetes andprediabetes in asymptomatic peopleshould be considered in adults of anyage who are overweight or obese(BMI $25 kg/m2) and who have oneor more additional risk factors fordiabetes (Table 4). In those withoutthese risk factors, testing shouldbegin at age 45 years. B

c If tests are normal, repeat testingat least at 3-year intervals isreasonable. E

c To test for diabetes or prediabetes,the A1C, FPG, or 2-h 75-g OGTT areappropriate. B

c In those identified with prediabetes,identify and, if appropriate, treatother CVD risk factors. B

The same tests are used for bothscreening and diagnosing diabetes.Diabetes may be identified anywherealong the spectrum of clinical scenarios:from a seemingly low-risk individual whohappens to have glucose testing, to ahigher-risk individual whom the providertests because of high suspicion ofdiabetes, and finally, to the symptomaticpatient. The discussion herein is primarilyframed as testing for diabetes inasymptomatic individuals. The sameassays used for testing will also detectindividuals with prediabetes.

A. Testing for Type 2 Diabetes andRisk of Future Diabetes in AdultsPrediabetes and diabetes meetestablished criteria for conditions inwhich early detection is appropriate.Both conditions are common, areincreasing in prevalence, and impose

Table 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(7.8 mmol/L) to 199 mg/dL(11.0 mmol/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.

S16 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

significant public health burdens. There isoften a long presymptomatic phasebefore the diagnosis of type 2 diabetes ismade. Simple tests to detect preclinicaldisease are readily available. The durationof glycemic burden is a strong predictorof adverse outcomes, and effectiveinterventions exist to prevent progressionof prediabetes to diabetes (see Section IV)and to reduce risk of complications ofdiabetes (see Section VI).

Type 2 diabetes is frequently notdiagnosed until complications appear.Approximately one-fourth of the U.S.population may have undiagnoseddiabetes.Mass screening of asymptomaticindividuals has not effectively identifiedthose with prediabetes or diabetes, andrigorous clinical trials to provide suchproof are unlikely to occur. In a largerandomized controlled trial (RCT) inEurope, general practice patients betweenthe ages of 40–69 years were screened fordiabetes, then randomized by practice toroutine diabetes care or intensivetreatment ofmultiple risk factors. After 5.3years of follow-up, CVD risk factors weremodestly but significantly improved withintensive treatment. Incidence of first CVDevent and mortality rates were notsignificantly different between groups(18). This study would seem to addsupport for early treatment of screen-detected diabetes, as risk factor controlwas excellent even in the routinetreatment arm and both groups had lowerevent rates than predicted. The absence

of a control unscreened arm limits theability to definitely prove that screeningimpacts outcomes. Mathematicalmodeling studies suggest that screening,independent of risk factors, beginning atage 30 or 45 years is highly cost-effective(,$11,000 per quality-adjusted life-yeargained) (19).

BMI Cut PointsTesting recommendations for diabetesin asymptomatic, undiagnosed adultsare listed in Table 4. Testing should beconsidered in adults of any age with BMI$25 kg/m2 and one or more of theknown risk factors for diabetes. Inaddition to the listed risk factors, certainmedications, such as glucocorticoidsand antipsychotics (20), are known toincrease the risk of type 2 diabetes.There is compelling evidence that lowerBMI cut points suggest diabetes risk insome racial and ethnic groups. In a largemultiethnic cohort study, for anequivalent incidence rate of diabetesconferred by a BMI of 30 kg/m2 in non-Hispanic whites, the BMI cutoff valuewas 24 kg/m2 in South Asians, 25 kg/m2

in Chinese, and 26 kg/m2 in AfricanAmericans (21). Disparities in screeningrates, not explainable by insurancestatus, are highlighted by evidence thatdespite much higher prevalence of type 2diabetes, ethnic minorities in an insuredpopulation are no more likely than non-Hispanic whites to be screened fordiabetes (22). Because age is a major riskfactor for diabetes, in thosewithout these

risk factors, testing should begin at age45 years.

The A1C, FPG, or the 2-h OGTT areappropriate 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 (23–29)has primarily been demonstratedamong individuals with IGT, not forindividuals with isolated IFG or forindividuals with specific A1C levels.

Testing IntervalThe appropriate interval between testsis not known (30). The rationale for the3-year interval is that false negatives willbe repeated before substantial timeelapses. It is also unlikely that anindividual will develop significantcomplications of diabetes within 3 yearsof a negative test result. In the modelingstudy, repeat screening every 3 or 5 yearswas cost-effective (19).

Community ScreeningTesting should be carried out within thehealth care setting because of the needfor follow-up and discussion of abnormalresults. Community screening outside ahealth care setting is not recommendedbecause people with positive tests maynot seek, or have access to, appropriatefollow-up testing and care. Conversely,there may be failure to ensureappropriate repeat testing for individualswho test negative. Community screeningmay also be poorly targeted; i.e., it mayfail to reach the groups most at risk andinappropriately test those at low risk oreven those already diagnosed.

B. Screening for Type 2 Diabetes inChildren

Recommendation

c Testing to detect type 2 diabetes andprediabetes should be considered inchildren and adolescents who areoverweight and who have two ormore additional risk factors fordiabetes (Table 5). E

In the last decade, the incidence of type 2diabetes in adolescents has increaseddramatically, especially in minoritypopulations (31). As with adultrecommendations, children and youth atincreased risk for the presence or thedevelopment of type 2 diabetes should betested within the health care setting (32).

Table 4—Criteria for testing for diabetes in asymptomatic adult individuals1. Testing should be considered in all adults who are overweight (BMI$25 kg/m2*) 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 ovarian 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. In the absence of the above criteria, testing for diabetes should begin at age 45 years.

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

*At-risk BMI may be lower in some ethnic groups.

care.diabetesjournals.org Position Statement S17

A1C in PediatricsRecent studies question the validity ofA1C in the pediatric population, especiallyin ethnic minorities, and suggest OGTT orFPG as more suitable diagnostic tests(33). However, many of these studies donot recognize that diabetes diagnosticcriteria are based upon long-term healthoutcomes, and validations are notcurrently available in the pediatricpopulation (34). ADA acknowledges thelimited data supporting A1C fordiagnosing diabetes in children andadolescents. However, aside from rareinstances, such as cystic fibrosis andhemoglobinopathies, ADA continues torecommend A1C in this cohort (35,36).The modified recommendations of theADA consensus statement “Type 2Diabetes in Children andAdolescents” aresummarized in Table 5.

C. Screening for Type 1 Diabetes

Recommendation

c Inform type 1 diabetic patients of theopportunity to have their relativesscreened for type 1 diabetes risk in thesetting of a clinical research study. E

Type 1 diabetic patients often presentwith acute symptoms of diabetes and

markedly elevated blood glucose levels,and some cases are diagnosed with life-

threatening ketoacidosis. The incidence

and prevalence of type 1 diabetes isincreasing (31,37,38). Several studiessuggest thatmeasuring islet autoantibodiesin relatives of those with type 1 diabetesmay identify individuals who are at risk fordeveloping type 1 diabetes. Such testing,coupled with education about diabetessymptoms and close follow-up in anobservational clinical study, may enableearlier identification of type 1 diabetesonset. A recent study reported the risk ofprogression to type 1 diabetes from thetime of seroconversion to autoantibodypositivity in three pediatric cohorts fromFinland, Germany, and the U.S. Of the 585children who developed more than twoautoantibodies, nearly 70%developed type1 diabetes within 10 years and 84% within15 years (39,40). These findings are highlysignificant because, while the Germangroup was recruited from offspring ofparents with type 1 diabetes, the Finnishand Colorado groups were recruited fromthe general population. Remarkably, thefindings in all three groups were the same,suggesting that the same sequence ofevents led to clinical disease in both“sporadic” and genetic cases of type 1diabetes. There is evidence to suggest thatearly diagnosis may limit acutecomplications (39) and extend long-termendogenous insulin production (41). Whilethere is currently a lack of acceptedscreening programs, one should considerreferring relatives of those with type 1diabetes for antibody testing for riskassessment in the setting of a clinicalresearch study (http://www2.diabetestrialnet.org).

Widespread clinical testing ofasymptomatic low-risk individuals is notcurrently recommended. Higher-riskindividuals may be screened, but only inthe context of a clinical research setting.Individuals who screen positive will becounseled about the risk of developingdiabetes, diabetes symptoms, and theprevention of DKA. Numerous clinicalstudies arebeing conducted to test variousmethods of preventing type 1 diabetes inthose with evidence of autoimmunity(www.clinicaltrials.gov).

III. DETECTION AND DIAGNOSIS OFGESTATIONAL DIABETES MELLITUS

Recommendations

c Screen for undiagnosed type 2diabetes at the first prenatal visit in

those with risk factors, using standarddiagnostic criteria. B

c Screen for GDM at 24–28 weeks ofgestation in pregnant women notpreviously known to have diabetes. A

c Screen women with GDM forpersistent diabetes at 6–12 weekspostpartum, using the OGTT andnonpregnancy diagnostic criteria. E

c Women with a history of GDM shouldhave lifelong screening for thedevelopment of diabetes orprediabetes at least every 3 years. B

c Women with a history of GDM foundto have prediabetes should receivelifestyle interventions or metforminto prevent diabetes. A

c Further research is needed toestablish a uniform approach todiagnosing GDM. E

For many years, GDM was defined asany degree of glucose intolerance withonset or first recognition duringpregnancy (13), whether or not thecondition persisted after pregnancy,and not excluding the possibility thatunrecognized glucose intolerance mayhave antedated or begun concomitantlywith the pregnancy. This definitionfacilitated a uniform strategy fordetection and classification of GDM, butits limitations were recognized for manyyears. As the ongoing epidemic ofobesity and diabetes has led to moretype 2 diabetes in women ofchildbearing age, the number ofpregnant women with undiagnosedtype 2 diabetes has increased (42).Because of this, it is reasonable toscreen women with risk factors for type2 diabetes (Table 4) at their initialprenatal visit, using standard diagnosticcriteria (Table 2). Women with diabetesin the first trimester should receive adiagnosis of overt, not gestational,diabetes.

GDM carries risks for the mother andneonate. Not all adverse outcomes areof equal clinical importance. TheHyperglycemia and Adverse PregnancyOutcome (HAPO) study (43), a large-scale (;25,000 pregnant women)multinational epidemiological study,demonstrated that risk of adversematernal, fetal, and neonataloutcomes continuously increased as afunction of maternal glycemia at 24–28

Table 5—Testing for type 2 diabetesin asymptomatic children*Criteria

cOverweight (BMI.85th percentile forage and sex, weight for height .85thpercentile, or weight .120% of idealfor height)

Plus any two of the following risk factors:c Family history of type 2 diabetes infirst- or second-degree relative

c Race/ethnicity (Native American,African American, Latino, AsianAmerican, Pacific Islander)

c Signs of insulin resistance orconditions associated with insulinresistance (acanthosis nigricans,hypertension, dyslipidemia,polycystic ovarian syndrome, orsmall-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 ata younger age

Frequency: every 3 years

*Persons aged 18 years and younger.

S18 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

weeks, even within ranges previouslyconsidered normal for pregnancy. Formost complications, there was nothreshold for risk. These results haveled to careful reconsideration of thediagnostic criteria for GDM. GDMscreening can be accomplished witheither of two strategies:

1. “One-step” 2-h 75-g OGTT or2. “Two-step” approach with a 1-h

50-g (nonfasting) screen followedby a 3-h 100-g OGTT for those whoscreen positive (Table 6)

Different diagnostic criteria will identifydifferent magnitudes of maternalhyperglycemia and maternal/fetal risk.

In the 2011 Standards of Care (44), ADAfor the first time recommended that allpregnant women not known to haveprior diabetes undergo a 75-g OGTT at24–28 weeks of gestation based on anInternational Association of Diabetesand Pregnancy Study Groups (IADPSG)consensus meeting (45). Diagnostic cutpoints for the fasting, 1-h, and 2-h PGmeasurements were defined thatconveyed an odds ratio for adverseoutcomes of at least 1.75 comparedwith women with the mean glucoselevels in the HAPO study, a strategyanticipated to significantly increase theprevalence of GDM (from 5–6% to;15–20%), primarily because only oneabnormal value, not two, is sufficient tomake the diagnosis. ADA recognizedthat the anticipated increase in theincidence of GDM diagnosed by thesecriteria would have significant impact onthe costs, medical infrastructurecapacity, and potential for increased“medicalization” of pregnanciespreviously categorized as normal, butrecommended these diagnostic criteriachanges in the context of worrisomeworldwide increases in obesity anddiabetes rates with the intent ofoptimizing gestational outcomes forwomen and their babies. It is importantto note that 80–90% of women in bothof the mild GDM studies (whose glucosevalues overlapped with the thresholdsrecommended herein) could bemanaged with lifestyle therapy alone.The expected benefits to thesepregnancies and offspring are inferredfrom intervention trials that focused onwomen with lower levels of

hyperglycemia than identified using olderGDM diagnostic criteria and that foundmodest benefits including reduced ratesof large-for-gestational-age (LGA) births(46,47). However, while treatment oflower threshold hyperglycemia canreduce LGA, it has not been shown toreduce primary cesarean delivery rates.Data are lacking on how treatment oflower threshold hyperglycemia impactsprognosis of future diabetes for themother and future obesity, diabetes risk,or other metabolic consequences for theoffspring. The frequency of follow-up andblood glucose monitoring for thesewomen has also not yet beenstandardized, but is likely to be lessintensive than for women diagnosed bythe older criteria.

National Institutes of HealthConsensus ReportSince this initial IADPSGrecommendation, the NationalInstitutes of Health (NIH) completed aconsensus development conferenceinvolving a 15-member panel withrepresentatives from obstetrics/gynecology, maternal-fetal medicine,pediatrics, diabetes research,biostatistics, and other related fields(48). Reviewing the same available data,the NIH consensus panel recommendedcontinuation of the “two-step”

approach of screening with a 1-h 50-gglucose 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 NIHpanel’s decision-making process werethe lack of clinical trial interventionsdemonstrating the benefits of the “one-step” strategy and the potentialnegative consequences of identifying alarge new group of women with GDM.Moreover, screening with a 50-g GLTdoes not require fasting and is thereforeeasier to accomplish for many women.Treatment of higher threshold maternalhyperglycemia, as identified by the two-step approach, reduces rates of neonatalmacrosomia, LGA, and shoulder dystocia,without increasing small-for-gestational-age births (49).

How do two different groups of expertsarrive at different GDM screening anddiagnosis recommendations? Becauseglycemic dysregulation exists on acontinuum, the decision to pick a singlebinary threshold for diagnosis requiresbalancing the harms and benefitsassociated with greater versus lessersensitivity. While data from the HAPOstudy demonstrated a correlationbetween increased fasting glucoselevels identified through the “one-step”strategy with increased odds for adverse

Table 6—Screening for and diagnosis of GDM“One-step” (IADPSG consensus)Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 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 exceeded:

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” (NIH consensus)Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h (Step 1), at

24–28 weeks 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), proceed to

100-g OGTT (Step 2). The 100-g OGTT should be performed when the patient is fasting.The diagnosis of GDM is made when at least two of the following four plasma glucose levels

(measured fasting, 1 h, 2 h, 3 h after the OGTT) are met or exceeded:

Carpenter/Coustan or NDDG

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)c 2 h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L)c 3 h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L)

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

care.diabetesjournals.org Position Statement S19

pregnancy outcomes, this largeobservational study was not designedto determine the benefit ofintervention. Moreover, there are noavailable cost-effective analyses toexamine the balance of achievedbenefits versus the increased costsgenerated by this strategy.

The conflicting recommendations fromthese two consensus panels underscoreseveral key points:

1. There are insufficient data tostrongly demonstrate the superiorityof one strategy over the other.

2. The decision of which strategy toimplement must therefore be madebased on the relative values placedon currently unmeasured factors(e.g., cost-benefit estimation,willingness to change practice basedon correlation studies rather thanclinical intervention trial results,relative role of cost considerations,and available infrastructure).

3. Further research is needed to resolvethese uncertainties.

There remains strong consensus thatestablishing a uniform approach todiagnosing GDM will have extensivebenefits for patients, caregivers, andpolicymakers. Longer-term outcomestudies are currently underway.

Because some cases of GDM mayrepresent preexisting undiagnosed type2 diabetes, women with a history ofGDM should be screened for diabetes6–12 weeks postpartum, usingnonpregnant OGTT criteria. Because oftheir antepartum treatment forhyperglycemia, A1C for diagnosis ofpersistent diabetes at the postpartumvisit is not recommended (50). Womenwith a history of GDM have a greatlyincreased subsequent diabetes risk (51)and should be followed up withsubsequent screening for thedevelopment of diabetes orprediabetes, as outlined in Section II.Lifestyle interventions or metforminshould be offered to women with ahistory of GDM who developprediabetes, as discussed in Section IV.In the prospective Nurses’ Health StudyII, subsequent diabetes risk after ahistory of GDM was significantly lowerin women who followed healthy eating

patterns. Adjusting for BMI moderately,but not completely, attenuated thisassociation (52).

IV. PREVENTION/DELAY OF TYPE 2DIABETES

Recommendations

c Patients with IGT A, IFG E, or an A1C5.7–6.4% E should be referred to aneffective ongoing support programtargeting weight loss of 7% of bodyweight and increasing physicalactivity to at least 150 min/week ofmoderate activity such as walking.

c Follow-up counseling appears to beimportant for success. B

c Based on the cost-effectiveness ofdiabetes prevention, such programsshould be covered by third-partypayers. B

c Metformin therapy for prevention oftype 2 diabetes may be consideredin those with IGT A, IFG E, or anA1C 5.7–6.4% E, especially for thosewith BMI .35 kg/m2, aged,60 years, and women with priorGDM. A

c At least annual monitoring for thedevelopment of diabetes in thosewith prediabetes is suggested. E

c Screening for and treatment ofmodifiable risk factors for CVD issuggested. B

RCTs have shown that individuals at highrisk for developing type 2 diabetes (IFG,IGT, or both) can significantly decreasethe rate of diabetes onset withparticular interventions (23–29). Theseinclude intensive lifestyle modificationprograms that have been shown to bevery effective (;58% reduction after3 years) and pharmacological agentsmetformin, a-glucosidase inhibitors,orlistat, and thiazolidinediones, each ofwhich has been shown to decreaseincident diabetes to various degrees.Follow-up of all three large studies oflifestyle intervention has shownsustained reduction in the rate ofconversion to type 2 diabetes, with 43%reduction at 20 years in the Da Qingstudy (53), 43% reduction at 7 years inthe Finnish Diabetes Prevention Study(DPS) (54), and 34% reduction at 10years in the U.S. Diabetes PreventionProgram Outcomes Study (DPPOS) (55).A cost-effectiveness model suggestedthat lifestyle interventions as delivered

in the DPP are cost-effective (56), andactual cost data from the DPP andDPPOS confirm that lifestyleinterventions are highly cost-effective(57). Group delivery of the DPPintervention in community settings hasthe potential to be significantly lessexpensive while still achieving similarweight loss (58). The Centers for DiseaseControl and Prevention (CDC) helpscoordinate the National DiabetesPrevention Program, a resource designedto bring evidence-based lifestyle changeprograms for preventing type 2 diabetesto communities (http://www.cdc.gov/diabetes/prevention/index.htm).

Given the clinical trial results and theknown risks of progression ofprediabetes to diabetes, persons withan A1C of 5.7–6.4%, IGT, or IFG shouldbe counseled on lifestyle changes withgoals similar to those of the DPP (7%weight loss and moderate physicalactivity of at least 150 min/week).Metformin has a strong evidence baseand demonstrated long-term safety aspharmacological therapy for diabetesprevention (59). For other drugs, cost,side effects, and lack of a persistenteffect require consideration (60).

MetforminMetformin was less effective thanlifestyle modification in the DPP andDPPOS, but may be cost-saving over a10-year period (57). It was as effective aslifestyle modification in participantswith a BMI $35 kg/m2, but notsignificantly better than placebo inthose over age 60 years (23). In the DPP,for women with a history of GDM,metformin and intensive lifestylemodification led to an equivalent 50%reduction in diabetes risk (61).Metformin therefore might reasonablybe recommended for very-high-riskindividuals (e.g., history of GDM, veryobese, and/or those with more severeor progressive hyperglycemia).

People with prediabetes often haveother cardiovascular risk factors, such asobesity, hypertension, anddyslipidemia, and are at increased riskfor CVD events. While treatment goalsare the same as for other patientswithout diabetes, increased vigilance iswarranted to identify and treat theseand other risk factors (e.g., smoking).

S20 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

V. DIABETES CARE

A. Initial EvaluationA complete medical evaluation shouldbe performed to classify the diabetes,detect the presence of diabetescomplications, review previoustreatment and risk factor control inpatients with established diabetes,assist in formulating a managementplan, and provide a basis for continuingcare. Laboratory tests appropriate tothe evaluation of each patient’smedical condition should becompleted. A focus on the componentsof comprehensive care (Table 7) will

enable the health care team tooptimally manage the patient withdiabetes.

B. ManagementPeople with diabetes should receivemedical care from a team that mayinclude physicians, nurse practitioners,physician’s assistants, nurses, dietitians,pharmacists, and mental healthprofessionals with expertise in diabetes.In this collaborative and integratedteam approach, the individuals withdiabetes must also assume an activerole in their care.

The management plan should beformulated as a collaborativetherapeutic alliance among the patientand family, the physician, and othermembers of the health care team. Avariety of strategies and techniquesshould be used to provide adequateeducation and development ofproblem-solving skills in the numerousaspects of diabetes management.Treatment goals and plans should beindividualized and take patientpreferences into account. Themanagement plan should recognizediabetes self-management education(DSME) and ongoing diabetes support asintegral components of care. Indeveloping the plan, considerationshould be given to the patient’s age,school or work schedule and conditions,physical activity, eating patterns, socialsituation and cultural factors, presenceof diabetes complications, healthpriorities, and other medical conditions.

C. Glycemic Control

1. Assessment of Glycemic Control

Two primary techniques are availablefor health providers and patients toassess the effectiveness of themanagement plan on glycemic control:patient self-monitoring of blood glucose(SMBG) or interstitial glucose, and A1C.

a. Glucose Monitoring

Recommendations

c Patients on multiple-dose insulin(MDI) or insulin pump therapy shoulddo SMBG prior to meals and snacks,occasionally postprandially, atbedtime, prior to exercise, when theysuspect low blood glucose, aftertreating low blood glucose until theyare normoglycemic, and prior tocritical tasks such as driving. B

c When prescribed as part of a broadereducational context, SMBG resultsmay be helpful to guide treatmentdecisions and/or patient self-management for patients using lessfrequent insulin injections ornoninsulin therapies. E

c When prescribing SMBG, ensure thatpatients receive ongoing instructionand regular evaluation of SMBGtechnique and SMBG results, as wellas their ability to use SMBG data toadjust therapy. E

c When used properly, continuousglucose monitoring (CGM) in

Table 7—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 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 episodes

c Hypoglycemia awarenessc Any severe hypoglycemia: frequency and cause

c History of diabetes-related complicationsc Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history offoot lesions; autonomic, including sexual dysfunction and gastroparesis)

c Macrovascular: CHD, cerebrovascular disease, and PADc Other: psychosocial problems,* dental disease*

Physical examinationc Height, weight, BMIc Blood pressure determination, including orthostatic measurements when indicatedc Fundoscopic examination*c Thyroid palpationc Skin examination (for acanthosis nigricans and insulin injection sites)c Comprehensive foot examination

c 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 2–3 monthsc If not performed/available within past year

c Fasting lipid profile, including total, LDL, and HDL cholesterol and triglyceridesc Liver function testsc Test for urine albumin excretion with spot urine albumin-to-creatinine ratioc Serum creatinine and calculated GFRc 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 MNTc DSMEc Dentist for comprehensive periodontal examinationc Mental health professional, if needed

*See appropriate referrals for these categories.

care.diabetesjournals.org Position Statement S21

conjunction with intensive insulinregimens is a useful tool to lower A1Cin selected adults (aged $25 years)with type 1 diabetes. A

c Although the evidence for A1Clowering is less strong in children,teens, and younger adults, CGM maybe helpful in these groups. Successcorrelates with adherence to ongoinguse of the device. C

c CGM may be a supplemental tool toSMBG in those with hypoglycemiaunawareness and/or frequenthypoglycemic episodes. E

Major clinical trials of insulin-treatedpatients that demonstrated the benefitsof intensive glycemic control ondiabetes complications have includedSMBG as part of multifactorialinterventions, suggesting that SMBG is acomponent of effective therapy. SMBGallows patients to evaluate theirindividual response to therapy andassess whether glycemic targets arebeing achieved. Results of SMBG can beuseful in preventing hypoglycemia andadjusting medications (particularlyprandial insulin doses), medicalnutrition therapy (MNT), and physicalactivity. Evidence also supports acorrelation between SMBG frequencyand lower A1C (62).

SMBG frequency and timing should bedictated by the patient’s specific needsand goals. SMBG is especially importantfor patients treated with insulin tomonitor for and prevent asymptomatichypoglycemia and hyperglycemia. Mostpatients with type 1 diabetes or onintensive insulin regimens (MDI orinsulin pump therapy) should considerSMBG prior to meals and snacks,occasionally postprandially, at bedtime,prior to exercise, when they suspect lowblood glucose, after treating low bloodglucose until they are normoglycemic,and prior to critical tasks such as driving.For many patients, this will requiretesting 6–8 times daily, althoughindividual needs may vary. A databasestudy of almost 27,000 children andadolescents with type 1 diabetesshowed that, after adjustment formultiple confounders, increased dailyfrequency of SMBG was significantlyassociated with lower A1C (20.2% peradditional test per day, leveling off atfive tests per day) and with fewer acute

complications (63). For patients onnonintensive insulin regimens, such asthose with type 2 diabetes on basalinsulin, when to prescribe SMBG and thetesting frequency are unclear becausethere is insufficient evidence for testingin this cohort.

Several randomized trials have calledinto question the clinical utility and cost-effectiveness of routine SMBG innoninsulin-treated patients (64–66).A recent meta-analysis suggested thatSMBG reduced A1C by 0.25% at6 months (67), but a Cochrane reviewconcluded that the overall effect ofSMBG in such patients is minimal up to6 months after initiation and subsidesafter 12 months (68). A keyconsideration is that SMBG alone doesnot lower blood glucose level; to beuseful, the information must beintegrated into clinical and self-management plans.

SMBG accuracy is instrument and userdependent (69), so it is important toevaluate each patient’s monitoringtechnique, both initially and at regularintervals thereafter. Optimal use ofSMBG requires proper review andinterpretation of the data, both by thepatient and provider. Among patientswho checked their blood glucose at leastonce daily, many reported taking noaction when results were high or low(70). In one study of insulin-naıvepatients with suboptimal initial glycemiccontrol, use of structured SMBG (apaper tool to collect and interpret7-point SMBG profiles over 3 days atleast quarterly) reduced A1C by 0.3%more than an active control group (71).Patients should be taught how to useSMBG data to adjust food intake,exercise, or pharmacological therapy toachieve specific goals. The ongoing needfor and frequency of SMBG should bereevaluated at each routine visit.

Continuous Glucose MonitoringReal-time CGM through themeasurement of interstitial glucose(which correlates well with plasmaglucose) is available. These sensorsrequire calibration with SMBG, and thelatter are still required for making acutetreatment decisions. CGM devices havealarms for hypo- and hyperglycemicexcursions. A 26-week randomized trial

of 322 type 1 diabetic patients showedthat adults aged$25 years usingintensive insulin therapy and CGMexperienced a 0.5% reduction in A1C(from;7.6 to 7.1%) comparedwith usualintensive insulin therapy with SMBG (72).Sensor use in those ,25 years of age(children, teens, and adults) did not resultin significant A1C lowering, and there wasno significant difference in hypoglycemiain any group. The greatest predictor ofA1C lowering for all age-groups wasfrequency of sensor use, whichwas lowerin younger age-groups. In a smaller RCT of129 adults and childrenwith baseline A1C,7.0%, outcomes combining A1C andhypoglycemia favored the group usingCGM, suggesting that CGM is alsobeneficial for individuals with type 1diabetes who have already achievedexcellent control (72).

Overall, meta-analyses suggest thatcompared with SMBG, CGM use isassociated with A1C lowering by;0.26% (73). The technology may beparticularly useful in those withhypoglycemia unawareness and/orfrequent hypoglycemic episodes,although studies have not shownsignificant reductions in severehypoglycemia (73). A CGM deviceequippedwith an automatic low glucosesuspend feature was recently approvedby the U.S. Food and DrugAdministration (FDA). The ASPIRE trialof 247 patients showed that sensor-augmented insulin pump therapy with alow glucose suspend significantlyreduced nocturnal hypoglycemia,without increasing A1C levels for thoseover 16 years of age (74). These devicesmay offer the opportunity to reducesevere hypoglycemia for those with ahistory of nocturnal hypoglycemia. CGMforms the underpinning for the “artificialpancreas” or the closed-loop system.However, before CGM is widely adopted,data must be reported and analyzedusing a standard universal template thatis predictable and intuitive (75).

b. A1C

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 inpatients whose therapy has changed

S22 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

or who are not meeting glycemicgoals. E

c Use of POC testing for A1C providesthe opportunity for more timelytreatment changes. E

A1C reflects average glycemia overseveral months (69) and has strongpredictive value for diabetescomplications (76,77). Thus, A1C testingshould be performed routinely in allpatients with diabetes: at initialassessment and as part of continuingcare. Measurement approximatelyevery 3 months determines whether apatient’s glycemic targets have beenreached and maintained. The frequencyof A1C testing should be dependent onthe clinical situation, the treatmentregimen used, and the clinician’sjudgment. Some patients with stableglycemia well within target may do wellwith testing only twice per year.Unstable or highly intensively managedpatients (e.g., pregnant type 1 diabeticwomen) may require testing morefrequently than every 3 months.

A1C LimitationsAs mentioned above, the A1C test issubject to certain limitations.Conditions that affect erythrocyteturnover (hemolysis, blood loss) andhemoglobin variants must beconsidered, particularly when the A1Cresult does not correlate with thepatient’s clinical situation (69). A1C alsodoes not provide a measure of glycemicvariability or hypoglycemia. For patientsprone to glycemic variability, especiallytype 1 diabetic patients or type 2diabetic patients with severe insulindeficiency, glycemic control is bestevaluated by the combination of resultsfrom self-monitoring and the A1C. TheA1C may also confirm the accuracy ofthe patient’s meter (or the patient’sreported SMBG results) and theadequacy of the SMBG testing schedule.

A1C and Plasma GlucoseTable 8 contains the correlationbetween A1C levels and mean plasmaglucose levels based on data from theinternational A1C-Derived AverageGlucose (ADAG) trial using frequentSMBG and CGM in 507 adults (83% non-Hispanic whites) with type 1, type 2,and no diabetes (78). The ADA and theAmerican Association for Clinical

Chemistry have determined that thecorrelation (r5 0.92) is strong enough tojustify reporting both the A1C result andan estimated average glucose (eAG)result when a clinician orders the A1Ctest. The table in pre-2009 versions of theStandards of Medical Care in Diabetesdescribing the correlation between A1Cand mean glucose was derived fromrelatively sparse data (one 7-point profileover 1 day per A1C reading) in theprimarily non-Hispanic white type 1diabetic participants in the DCCT (79).Clinicians should note that the numbersin the table are now different becausethey are based on;2,800 readings perA1C in the ADAG trial.

In the ADAG study, there were nosignificant differences among racial andethnic groups in the regression linesbetween A1C and mean glucose,although there was a trend toward adifference between the African/AfricanAmerican and non-Hispanic whitecohorts. A small study comparing A1C toCGM data in type 1 diabetic childrenfound a highly statistically significantcorrelation between A1C andmean bloodglucose, although the correlation (r50.7) was significantly lower than in theADAG trial (80). Whether there aresignificant differences in how A1C relatesto average glucose in children or inAfrican American patients is an area forfurther study (33,81). For the time being,the question has not led to differentrecommendations about testing A1C or

to different interpretations of the clinicalmeaning of given levels of A1C in thosepopulations.

For patients in whom A1C/eAG andmeasured blood glucose appeardiscrepant, clinicians should consider thepossibilities of hemoglobinopathy oraltered red cell turnover, and theoptionsofmore frequent and/or different timingof SMBG or use of CGM. Other measuresof chronic glycemia such as fructosamineare available, but their linkage toaverage glucose and their prognosticsignificance are not as clear as for A1C.

2. Glycemic Goals in Adults

Recommendations

c Lowering A1C to below or around 7%has been shown to reducemicrovascular complications ofdiabetes and, if implemented soonafter the diagnosis of diabetes, isassociated with long-term reductionin macrovascular disease.Therefore, a reasonable A1C goal formany nonpregnant adults is ,7%. B

c Providers might reasonably suggestmore stringent A1C goals (such as,6.5%) for selected individualpatients, if this can be achievedwithout significant hypoglycemia orother adverse effects of treatment.Appropriate patients might includethose with short duration of diabetes,long life expectancy, and nosignificant CVD. C

c Less stringent A1C goals (such as,8%)may be appropriate for patients with ahistory of severehypoglycemia, limitedlife expectancy, advancedmicrovascular or macrovascularcomplications, and extensive comorbidconditions and in those with long-standing diabetes in whom the generalgoal is difficult to attain despite DSME,appropriate glucose monitoring, andeffective doses of multiple glucose-lowering agents including insulin. B

Diabetes Control and ComplicationsTrial/Epidemiology of DiabetesInterventions and ComplicationsHyperglycemia defines diabetes, andglycemic control is fundamental todiabetes management. The DCCT study(76), a prospective RCT of intensiveversus standard glycemic control inpatients with relatively recentlydiagnosed type 1 diabetes showeddefinitively that improved glycemic

Table 8—Correlation of A1C withaverage glucose

A1C (%)

Mean plasma glucose

mg/dL mmol/L

6 126 7.0

7 154 8.6

8 183 10.2

9 212 11.8

10 240 13.4

11 269 14.9

12 298 16.5

These estimates are based on ADAG data of;2,700 glucose measurements over 3months per A1C measurement in 507 adultswith type 1, type 2, and no diabetes. Thecorrelation between A1C and averageglucose was 0.92 (ref. 78). A calculator forconverting A1C results into eAG, in eithermg/dL or mmol/L, is available at http://professional.diabetes.org/eAG.

care.diabetesjournals.org Position Statement S23

control is associated with significantlydecreased rates of microvascular(retinopathy and nephropathy) andneuropathic complications. Follow-upof the DCCT cohorts in the Epidemiologyof Diabetes Interventions andComplications (EDIC) study (82,83)demonstrated persistence of thesemicrovascular benefits in previouslyintensively treated subjects, eventhough their glycemic controlapproximated that of previous standardarm subjects during follow-up.

Kumamoto and UK ProspectiveDiabetes StudyThe Kumamoto (84) and UK ProspectiveDiabetes Study (UKPDS) (85,86)confirmed that intensive glycemiccontrol was associated with significantlydecreased rates of microvascular andneuropathic complications in type 2diabetic patients. Long-term follow-upof the UKPDS cohorts showed enduringeffects of early glycemic control onmostmicrovascular complications (87). Threelandmark trials (ACCORD, ADVANCE,and VADT, described in further detailbelow) were designed to examine theimpact of intensive A1C control on CVDoutcomes and showed that lower A1Clevels were associated with reducedonset or progression of microvascularcomplications (88–90).

Epidemiological analyses of the DCCTand UKPDS (76,77) demonstrate acurvilinear relationship betweenA1C and microvascular complications.Such analyses suggest that, on apopulation level, the greatest number ofcomplications will be averted by takingpatients from very poor control to fair/good control. These analyses alsosuggest that further lowering of A1Cfrom 7 to 6% is associated with furtherreduction in the risk of microvascularcomplications, though the absolute riskreductions become much smaller. Giventhe substantially increased risk ofhypoglycemia in type 1 diabetes trials,and now seen in recent type 2 diabetestrials, the risks of lower glycemic targetsmay outweigh the potential benefits onmicrovascular complications on apopulation level. The concerningmortality findings in the ACCORD trial(91) and the relatively much greatereffort required to achieve near-euglycemia should also be considered

when setting glycemic targets.However, based on physician judgmentand patient preferences, select patients,especially those with little comorbidityand long life expectancy, may benefitfrom adopting more intensive glycemictargets (e.g., A1C target,6.5%) as longas significant hypoglycemia does notbecome a barrier.

Cardiovascular Disease OutcomesCVD is a more common cause of deaththan microvascular complications inpopulations with diabetes. However, itis less clearly impacted by hyperglycemialevels or intensity of glycemic control. Inthe DCCT, there was a trend toward lowerrisk of CVD events with intensive control.In the 9-year post-DCCT follow-up of theEDIC cohort, participants previouslyrandomized to the intensive arm had asignificant 57% reduction in the risk ofnonfatal myocardial infarction (MI),stroke, or CVD death comparedwith thosepreviously in the standard arm (92). Thebenefit of intensive glycemic control in thistype 1 diabetic cohort has recently beenshown to persist for several decades (93).

In type 2 diabetes, there is evidence thatmore intensive treatment of glycemia innewly diagnosedpatientsmay reduce long-term CVD rates. During the UKPDS trial,there was a 16% reduction in CVD events(combined fatal or nonfatal MI and suddendeath) in the intensive glycemic controlarm that did not reach statisticalsignificance (P5 0.052), and there was nosuggestion of benefit on other CVDoutcomes (e.g., stroke). However, after10 years of follow-up, those originallyrandomized to intensive glycemic controlhad significant long-term reductions in MI(15% with sulfonylurea or insulin as initialpharmacotherapy, 33% with metformin asinitial pharmacotherapy) and in all-causemortality (13% and 27%, respectively) (87).

The Action to Control Cardiovascular Riskin Diabetes (ACCORD), Action in Diabetesand Vascular Disease: Preterax andDiamicron Modified Release ControlledEvaluation (ADVANCE), and the VeteransAffairs Diabetes Trial (VADT) studiessuggested no significant reduction in CVDoutcomeswith intensive glycemic controlin participants who had more advancedtype 2 diabetes than UKPDS participants.All three trials were conducted inparticipants with more long-standingdiabetes (mean duration 8–11 years) and

either known CVD or multiplecardiovascular risk factors. Details ofthese studies are reviewed extensively inan ADA position statement (94).

ACCORDThe ACCORD study participants hadeither known CVD or two or more majorcardiovascular risk factors and wererandomized to intensive glycemiccontrol (goal A1C ,6%) or standardglycemic control (goal A1C 7–8%). Theglycemic control comparison was haltedearly due to an increased mortality ratein the intensive compared with thestandard arm (1.41 vs. 1.14%/year;hazard ratio [HR] 1.22 [95% CI 1.01–1.46]); with a similar increase incardiovascular deaths. Initial analysis ofthe ACCORD data (evaluating variablesincluding weight gain, use of any specificdrug or drug combination, andhypoglycemia) did not identify a clearexplanation for the excess mortality inthe intensive arm (91). A subsequentanalysis showed no increase in mortalityin the intensive arm participants whoachieved A1C levels below 7%, nor inthose who lowered their A1C quicklyafter trial enrollment. There was no A1Clevel at which intensive versus standardarm participants had significantlylower mortality. The highest risk formortality was observed in intensive armparticipants with the highest A1C levels(95). Severe hypoglycemia wassignificantly more likely in participantsrandomized to the intensive glycemiccontrol arm. Unlike the DCCT, wherelower achieved A1C levels were relatedto significantly increased rates of severehypoglycemia, in ACCORD every 1%decline in A1C from baseline to 4months into the trial was associatedwith a significant decrease in the rate ofsevere hypoglycemia in both arms (95).

ADVANCEThe primary outcome of ADVANCEwas acombination of microvascular events(nephropathy and retinopathy) andmajor adverse cardiovascular events(MI, stroke, and cardiovascular death).Intensive glycemic control (A1C ,6.5%,vs. treatment to local standards)significantly reduced the primary endpoint, primarily due to a significantreduction in the microvascularoutcome, specifically development ofalbuminuria (.300 mg/24 h), with

S24 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

no significant reduction in themacrovascular outcome. There was nodifference in overall or cardiovascularmortality between the two arms (89).

VADTThe primary outcome of the VADT was acomposite of CVD events. The trialrandomized type 2 diabetic participantswho were uncontrolled on insulin or onmaximal dose oral agents (median entryA1C 9.4%) to a strategy of intensiveglycemic control (goal A1C ,6.0%) orstandard glycemic control, with aplanned A1C separation of at least 1.5%.The cumulative primary outcome wasnonsignificantly lower in the intensivearm (88). An ancillary study of the VADTdemonstrated that intensive glycemiccontrol significantly reduced theprimary CVD outcome in individualswith less atherosclerosis at baseline butnot in persons with more extensivebaseline atherosclerosis (96). A post hocanalysis showed that mortality in theintensive versus standard glycemiccontrol arm was related to duration ofdiabetes at study enrollment. Thosewith diabetes duration less than 15years had a mortality benefit in theintensive arm, while those with durationof 20 years or more had higher mortalityin the intensive arm (97).

The evidence for a cardiovascularbenefit of intensive glycemic controlprimarily rests on long-term follow-upof study cohorts treated early in thecourse of type 1 and type 2 diabetes,and a subset analyses of ACCORD,ADVANCE, and VADT. A group-levelmeta-analysis of the latter three trialssuggests that glucose lowering has amodest (9%) but statistically significantreduction in major CVD outcomes,primarily nonfatal MI, with nosignificant effect on mortality. However,heterogeneity of the mortality effectsacross studies was noted. A prespecifiedsubgroup analysis suggested that majorCVD outcome reduction occurred inpatients without known CVD at baseline(HR 0.84 [95% CI 0.74–0.94]) (98).Conversely, the mortality findings inACCORD and subgroup analyses of theVADT suggest that the potential risks ofintensive glycemic control mayoutweigh its benefits in some patients.Those with long duration of diabetes,known history of severe hypoglycemia,

advanced atherosclerosis, and advancedage/frailty may benefit from lessaggressive targets. Providers should bevigilant in preventing severehypoglycemia in patients with advanceddisease and should not aggressivelyattempt to achieve near-normal A1Clevels in patients in whom such targetscannot be safely and reasonablyachieved. Severe or frequenthypoglycemia is an absolute indicationfor the modification of treatmentregimens, including setting higherglycemic goals. Many factors, includingpatient preferences, should be taken intoaccount when developing a patient’sindividualized goals (99) (Fig. 1).

Glycemic GoalsRecommended glycemic goals for manynonpregnant adults are shown inTable 9. The recommendations arebased on those for A1C values, withblood glucose levels that appear tocorrelate with achievement of an A1C of,7%. The issue of pre- versuspostprandial SMBG targets is complex(100). Elevated postchallenge (2-hOGTT) glucose values have been

associated with increased cardiovascularrisk independent of FPG in someepidemiological studies. In diabeticsubjects, surrogate measures of vascularpathology, such as endothelialdysfunction, are negatively affected bypostprandial hyperglycemia (101). It isclear that postprandial hyperglycemia,like preprandial hyperglycemia,contributes to elevated A1C levels, withits relative contribution being greater atA1C levels that are closer to 7%. However,outcome studies have clearly shownA1C to be the primary predictor ofcomplications, and landmark glycemiccontrol trials such as theDCCT andUKPDSrelied overwhelmingly on preprandialSMBG. Additionally, an RCT in patientswith known CVD found no CVD benefit ofinsulin regimens targeting postprandialglucose compared with those targetingpreprandial glucose (102). A reasonablerecommendation for postprandial testingand targets is that for individuals whohave premeal glucose values withintarget but have A1C values abovetarget, monitoring postprandial plasmaglucose (PPG) 1–2 h after the start of themeal and treatment aimed at reducing

Figure 1—Approach to management of hyperglycemia. Depiction of the elements of decisionmaking used to determine appropriate efforts to achieve glycemic targets. Characteristics/predicaments toward the left justify more stringent efforts to lower A1C, whereas those towardthe right are compatible with less stringent efforts. Where possible, such decisions should bemade in conjunction with the patient, reflecting his or her preferences, needs, and values. This“scale” is not designed to be applied rigidly but to be used as a broad construct to help guideclinical decisions. Adapted with permission from Ismail-Beigi et al. (99).

care.diabetesjournals.org Position Statement S25

PPG values to ,180 mg/dL may helplower A1C.

Glycemic goals for children are providedin Section VIII.A.1.a.

Glycemic Goals in Pregnant WomenThe goals for glycemic control forwomen with GDM are based onrecommendations from the FifthInternational Workshop-Conference onGestational Diabetes Mellitus (103) andhave the following targets for maternalcapillary glucose concentrations:

c Preprandial: #95 mg/dL (5.3mmol/L), and either:

c 1-h postmeal: #140 mg/dL(7.8 mmol/L) or

c 2-h postmeal: #120 mg/dL(6.7 mmol/L)

For women with preexisting type 1 ortype 2 diabetes who become pregnant,the following are recommended asoptimal glycemic goals, if they can beachieved without excessivehypoglycemia (104):

c Premeal, bedtime, and overnightglucose 60–99 mg/dL (3.3–5.4 mmol/L)

c Peak postprandial glucose 100–129mg/dL (5.4–7.1 mmol/L)

c A1C ,6.0%

D. Pharmacological and OverallApproaches to Treatment

1. Insulin Therapy for Type 1 Diabetes

c Most people with type 1 diabetesshould be treated with MDI injections

(three to four injections per day of basaland prandial insulin) or continuoussubcutaneous insulin infusion (CSII). A

c Most people with type 1 diabetesshould be educated in how to matchprandial insulin dose to carbohydrateintake, premeal blood glucose, andanticipated activity. E

c Most people with type 1 diabetesshould use insulin analogs to reducehypoglycemia risk. A

Screening

c Consider screening those with type 1diabetes for other autoimmunediseases (thyroid, vitamin B12deficiency, celiac) as appropriate. B

The DCCT clearly showed that intensiveinsulin therapy (three or more injectionsper day of insulin, or CSII (or insulinpump therapy) was a key part ofimproved glycemia and betteroutcomes (76,92). The study was carriedout with short- and intermediate-actinghuman insulins. Despite bettermicrovascular outcomes, intensiveinsulin therapy was associated with ahigh rate of severe hypoglycemia (62episodes per 100 patient-years oftherapy). Since the DCCT, a number ofrapid-acting and long-acting insulinanalogs have been developed. Theseanalogs are associated with lesshypoglycemia with equal A1C loweringin type 1 diabetes (105,106).

Recommended therapy for type 1diabetes consists of the followingcomponents:

1. Use MDI injections (3–4 injectionsper day of basal and prandial insulin)or CSII therapy.

2. Match prandial insulin tocarbohydrate intake, premealblood glucose, and anticipatedactivity.

3. For most patients (especiallywith hypoglycemia), use insulinanalogs.

4. For patients with frequentnocturnal hypoglycemia and/orhypoglycemia unawareness, use ofsensor-augmented low glucosesuspend threshold pump may beconsidered.

There are excellent reviews to guidethe initiation and management ofinsulin therapy to achieve desiredglycemic goals (105,107,108). Althoughmost studies of MDI versus pumptherapy have been small and of shortduration, a systematic review andmeta-analysis concluded that therewere no systematic differences in A1Cor severe hypoglycemia rates inchildren and adults between the twoforms of intensive insulin therapy (73).Recently, a large randomized trial intype 1 diabetic patients with nocturnalhypoglycemia reported that sensor-augmented insulin pump therapy withthe threshold-suspend feature reducednocturnal hypoglycemia, withoutincreasing glycated hemoglobin values(74). Overall, intensive managementthrough pump therapy/CGM and activepatient/family participation should bestrongly encouraged (109–111). Forselected individuals who havemastered carbohydrate counting,education on the impact of protein andfat on glycemic excursions can beincorporated into diabetesmanagement (112).

ScreeningBecause of the increased frequency ofother autoimmune diseases in type 1diabetes, screening for thyroiddysfunction, vitamin B12 deficiency, andceliac disease should be consideredbased on signs and symptoms. Periodicscreening in asymptomatic individualshas been recommended, but theeffectiveness and optimal frequency areunclear.

Table 9—Summary of glycemic recommendations for many nonpregnantadults with diabetesA1C ,7.0%*

Preprandial capillary plasma glucose 70–130 mg/dL* (3.9–7.2 mmol/L)

Peak postprandial capillary plasma glucose† ,180 mg/dL* (,10.0 mmol/L)c *Goals should be individualized based on:

c duration of diabetesc age/life expectancyc comorbid conditionsc known CVD or advanced microvascularcomplications

c hypoglycemia unawarenessc individual patient considerations

c More or less stringent glycemic goalsmay be appropriate for individual patients

c Postprandial glucose may be targeted if A1Cgoals are not met despite reachingpreprandial glucose goals

†Postprandial glucose measurements should be made 1–2 h after the beginning of the meal,generally peak levels in patients with diabetes.

S26 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

2. Pharmacological Therapy for

Hyperglycemia in Type 2 Diabetes

Recommendations

c Metformin, if not contraindicatedand if tolerated, is the preferredinitial pharmacological agent for type2 diabetes. A

c In newly diagnosed type 2 diabeticpatients with markedly symptomaticand/or elevated blood glucose levelsor A1C, consider insulin therapy, withor without additional agents, fromthe outset. E

c If noninsulin monotherapy atmaximum tolerated dose does notachieve or maintain the A1C targetover 3 months, add a second oralagent, a glucagon-like peptide 1 (GLP-1) receptor agonist, or insulin. A

c A patient-centered approach shouldbe used to guide choice ofpharmacological agents.

Considerations include efficacy, cost,potential side effects, effects onweight, comorbidities, hypoglycemiarisk, and patient preferences. E

c Due to the progressive nature of type2 diabetes, insulin therapy iseventually indicated for manypatients with type 2 diabetes. B

The ADA and the European Association forthe Study of Diabetes (EASD) formed ajoint task force to evaluate the data anddevelop recommendations for the use ofantihyperglycemic agents in type 2diabetic patients (113). This 2012 positionstatement is less prescriptive than prioralgorithms and discusses advantages anddisadvantages of the available medicationclasses and considerations for their use. Apatient-centered approach is stressed,including patient preferences, cost andpotential side effects of each class, effects

on body weight, and hypoglycemia risk.The position statement reaffirmsmetformin as the preferred initial agent,barring contraindication or intolerance,either in addition to lifestyle counselingand support for weight loss and exercise,or when lifestyle efforts alone have notachieved or maintained glycemic goals.Metformin has a long-standing evidencebase for efficacy and safety, is inexpensive,and may reduce risk of cardiovascularevents (87). When metformin fails toachieve or maintain glycemic goals,another agent should be added. Althoughthere are numerous trials comparingdual therapy to metformin alone, fewdirectly compare drugs as add-ontherapy. Comparative effectivenessmeta-analyses (114) suggest thatoverall, each new class of noninsulinagents added to initial therapy lowersA1C around 0.9–1.1%.

Figure 2—Antihyperglycemic therapy in type2diabetes: general recommendations.DPP-4-i, DPP-4 inhibitor; Fx’s, bone fractures; GI, gastrointestinal; GLP-1-RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea; TZD, thiazolidinedione. For further details, see ref. 113. Adapted with permission.

care.diabetesjournals.org Position Statement S27

Many patients with type 2 diabeteseventually require and benefit frominsulin therapy. The progressive natureof type 2 diabetes and its therapiesshould be regularly and objectivelyexplained to patients. Providers shouldavoid using insulin as a threat ordescribing it as a failure or punishment.Equipping patients with an algorithm forself-titration of insulin doses based onSMBG results improves glycemic controlin type 2 diabetic patients initiatinginsulin (115). Refer to the ADA-EASDposition statement for more details onpharmacotherapy for hyperglycemia intype 2 diabetes (113) (Fig. 2).

E. Medical Nutrition Therapy

General Recommendations

c Nutrition therapy is recommendedfor all people with type 1 and type 2diabetes as an effective componentof the overall treatment plan. A

c Individuals who have prediabetes ordiabetes should receiveindividualized MNT as needed toachieve treatment goals, preferablyprovided by a registered dietitianfamiliar with the components ofdiabetes MNT. A

c Because diabetes nutrition therapycan result in cost savings B andimproved outcomes such asreduction in A1C A, nutrition therapyshould be adequately reimbursed byinsurance and other payers. E

Energy Balance, Overweight, and Obesity

c For overweight or obese adults withtype 2 diabetes or at risk for diabetes,reducing energy intake whilemaintaining a healthful eatingpattern is recommended to promoteweight loss. A

c Modest weight loss may provideclinical benefits (improved glycemia,blood pressure, and/or lipids) in someindividuals with diabetes, especiallythose early in the disease process. Toachieve modest weight loss,intensive lifestyle interventions(counseling about nutrition therapy,physical activity, and behaviorchange) with ongoing support arerecommended. A

Eating Patterns and Macronutrient

Distribution

c Evidence suggests that there is not anideal percentage of calories from

carbohydrate, protein, and fat for allpeople with diabetes B; therefore,macronutrient distribution should bebased on individualized assessmentof current eating patterns,preferences, and metabolic goals. E

c A variety of eating patterns(combinations of different foods orfood groups) are acceptable for themanagement of diabetes. Personalpreference (e.g., tradition, culture,religion, health beliefs and goals,economics) and metabolic goalsshould be considered whenrecommending one eating patternover another. E

Carbohydrate Amount and Quality

c Monitoring carbohydrate intake,whether by carbohydrate countingor experience-based estimation,remains a key strategy in achievingglycemic control. B

c For good health, carbohydrate intakefrom vegetables, fruits, whole grains,legumes, and dairy products shouldbe advised over intake from othercarbohydrate sources, especiallythose that contain added fats, sugars,or sodium. B

c Substituting low-glycemic load foodsfor higher-glycemic load foods maymodestly improve glycemic control. C

c People with diabetes should consumeat least the amount of fiber andwholegrains recommended for the generalpublic. C

c While substituting sucrose-containing foods for isocaloricamounts of other carbohydrates mayhave similar blood glucose effects,consumption should be minimized toavoid displacing nutrient-dense foodchoices. A

c People with diabetes and those at riskfor diabetes should limit or avoidintake of sugar-sweetened beverages(from any caloric sweetener includinghigh-fructose corn syrup and sucrose)to reduce risk for weight gain andworsening of cardiometabolic riskprofile. B

Dietary Fat Quantity and Quality

c Evidence is inconclusive for an idealamount of total fat intake for peoplewith diabetes; therefore, goals shouldbe individualized. C Fat qualityappears to be far more importantthan quantity. B

c In people with type 2 diabetes, aMediterranean-style, MUFA-richeating pattern may benefit glycemiccontrol and CVD risk factors andcan therefore be recommended asan effective alternative to a lower-fat, higher-carbohydrate eatingpattern. B

c As recommended for the generalpublic, an increase in foodscontaining long-chain n-3 fatty acids(EPA and DHA) (from fatty fish)and n-3 linolenic acid (ALA) isrecommended for individuals withdiabetes because of their beneficialeffects on lipoproteins, prevention ofheart disease, and associations withpositive health outcomes inobservational studies. B

c The amount of dietary saturated fat,cholesterol, and trans fatrecommended for people withdiabetes is the same as thatrecommended for the generalpopulation. C

Supplements for Diabetes Management

c There is no clear evidence of benefitfrom vitamin or mineralsupplementation in people withdiabetes who do not have underlyingdeficiencies. C

c Routine supplementation withantioxidants, such as vitamins E and Cand carotene, is not advised because oflack of evidence of efficacy and concernrelated to long-term safety. A

c Evidence does not supportrecommending n-3 (EPA and DHA)supplements for people withdiabetes for the prevention ortreatment of cardiovascularevents. A

c There is insufficient evidence tosupport the routine use ofmicronutrients such as chromium,magnesium, and vitamin D toimprove glycemic control in peoplewith diabetes. C

c There is insufficient evidence tosupport the use of cinnamon or otherherbs/supplements for the treatmentof diabetes. C

c It is reasonable for individualizedmeal planning to include optimizationof food choices to meetrecommended daily allowance/dietary reference intake for allmicronutrients. E

S28 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

Alcohol

c If adults with diabetes choose todrink alcohol, they should be advisedto do so in moderation (one drinkper day or less for adult women andtwo drinks per day or less for adultmen). E

c Alcohol consumption may placepeople with diabetes at increased riskfor delayed hypoglycemia, especiallyif taking insulin or insulinsecretagogues. Education andawareness regarding the recognitionand management of delayedhypoglycemia is warranted. C

Sodium

c The recommendation for the generalpopulation to reduce sodium to,2,300 mg/day is also appropriatefor people with diabetes. B

c For individuals with both diabetesand hypertension, further reductionin sodium intake should beindividualized. B

Primary Prevention of Type 2 Diabetes

c Among individuals at high risk fordeveloping type 2 diabetes,structured programs that emphasizelifestyle changes that includemoderate weight loss (7% of bodyweight) and regular physical activity(150 min/week), with dietarystrategies including reduced caloriesand reduced intake of dietary fat, canreduce the risk for developingdiabetes and are thereforerecommended. A

c Individuals at high risk for type 2diabetes should be encouraged toachieve the U.S. Department ofAgriculture (USDA) recommendationfor dietary fiber (14 g fiber/1,000 kcal)and foods containing whole grains(one-half of grain intake). B

The ADA recently released an updatedposition statement on nutrition therapyfor adults living with diabetes (116).Nutrition therapy is an integralcomponent of diabetes prevention,management, and self-managementeducation. All individuals with diabetesshould receive individualized MNTpreferably provided by a registereddietitian who is knowledgeable andskilled in providing diabetes MNT.Comprehensive group diabeteseducation programs including nutrition

therapy or individualized educationsessions have reported A1C decreasesof 0.3–1% for type 1 diabetes (117–120)and 0.5–2% for type 2 diabetes(85,121–137).

Individuals with type 1 diabetes shouldbe offered intensive insulin therapyeducation using the carbohydrate-counting meal planning approach(117,119,120,124,138–140); thisapproach has been shown to improveglycemic control (139,141). Consistentcarbohydrate intake with respect totime and amount can result in improvedglycemic control for individuals usingfixed daily insulin doses (142,143). Asimple diabetes meal planning approachsuch as portion control or healthful foodchoices may be better suited forindividuals with health literacy andnumeracy concerns (125–127).

Weight loss of 2–8 kg may provideclinical benefits in those with type 2diabetes, especially early in the diseaseprocess (144–146). Weight loss studieshave used a variety of energy-restrictedeating patterns, with no clear evidencethat one eating pattern or optimalmacronutrient distribution was ideal.Although several studies resulted inimprovements in A1C at 1 year(144,145,147–149), not all weight lossinterventions led to 1-year A1Cimprovements (128,150–154). The mostconsistently identified changes incardiovascular risk factors were anincrease in HDL cholesterol (144,145,147,149,153,155), decrease intriglycerides (144,145,149,155,156)and decrease in blood pressure(144,145,147,151,153,155).

Intensive lifestyle programs withfrequent follow-up are required toachieve significant reductions in excessbody weight and improve clinicalindicators (145,146). Several studieshave attempted to identify the optimalmix of macronutrients for meal plans ofpeople with diabetes. However, a recentsystematic review (157) found thatthere was no ideal macronutrientdistribution and that macronutrientproportions should be individualized.Studies show that people with diabeteson average eat about 45% of theircalories from carbohydrate, ;36–40%of calories from fat, and;16–18% from

protein (158–160). A variety of eatingpatterns have been shown to beeffective in managing diabetes,including Mediterranean-style(144,146,169), Dietary Approaches toStop Hypertension (DASH)-style (161),plant-based (vegan or vegetarian) (129),lower-fat (145), andlower-carbohydrate patterns(144,163).

Studies examining the ideal amount ofcarbohydrate intake for people withdiabetes are inconclusive, althoughmonitoring carbohydrate intake andconsidering the available insulin are keystrategies for improving postprandialglucose control (117,142,143,158). Theliterature concerning glycemic indexand glycemic load in individuals withdiabetes is complex, althoughreductions in A1C of 20.2% to 20.5%have been demonstrated in somestudies. In many studies, it is oftendifficult to discern the independenteffect of fiber compared with that ofglycemic index on glycemic control andother outcomes. Improvements in CVDrisk measures are mixed (164). Recentstudies have shown modest effect offiber on lowering preprandial glucoseand mixed results on improving CVD riskfactors. A systematic review (157) foundconsumption of whole grains was notassociated with improvements in glycemiccontrol in people with type 2 diabetes,although it may reduce systemicinflammation. One study did find apotential benefit of whole grain intake inreducing mortality and CVD (165).

Limited research exists concerning theideal amount of fat for individuals withdiabetes. The Institute of Medicine hasdefined an acceptable macronutrientdistribution range (AMDR) for all adultsfor total fat of 20–35% of energy with notolerable upper intake level defined.This AMDR was based on evidence forCHD risk with a low intake of fat and highintake of carbohydrate, and evidencefor increased obesity and CHD with highintake of fat (166). The type of fattyacids consumed is more important thantotal amount of fat when looking atmetabolic goals and risk of CVD(146,167,168).

Multiple RCTs including patients withtype 2 diabetes have reported improved

care.diabetesjournals.org Position Statement S29

glycemic control and/or blood lipidswhen a Mediterranean-style, MUFA-rich eating pattern was consumed(144,146,151,169–171). Some of thesestudies also included caloric restriction,which may have contributed toimprovements in glycemic control orblood lipids (169,170). The ideal ratio ofn-6 to n-3 fatty acids has not beendetermined; however, PUFA and MUFAare recommended substitutes forsaturated or trans fat (167,172).

A recent systematic review (157)concluded that supplementation withn-3 fatty acids did not improveglycemic control but that higher dosesupplementation decreasedtriglycerides in individuals with type 2diabetes. Six short-duration RCTscomparing n-3 supplements to placebopublished since the systematic reviewreported minimal or no beneficialeffects (173,174) or mixed/inconsistent beneficial effects(175–177) on CVD risk factors andother health issues. Three longer-duration studies also reported mixedoutcomes (178–180). Thus, RCTs donot support recommending n-3supplements for primary or secondaryprevention of CVD. Little evidence hasbeen published about the relationshipbetween dietary intake of saturatedfatty acids and dietary cholesterol andglycemic control and CVD risk in peoplewith diabetes. Therefore, people withdiabetes should follow the guidelinesfor the general population for therecommended intakes of saturated fat,dietary cholesterol, and trans fat (167).

Published data on the effects of plantstanols and sterols on CVD risk inindividuals with diabetes include fourRCTs that reported beneficial effects fortotal, LDL, and non-HDL cholesterol(181–184).

There is limited evidence that the use ofvitamin, mineral, or herbal supplementsis necessary in the management ofdiabetes (185–201).

Limited studies have been published onsodium reduction in people withdiabetes. A recent Cochrane reviewfound that decreasing sodium intakereduces blood pressure in those withdiabetes (202). However, two otherstudies in type 1 diabetes (203) and type

2 diabetes (204) havewarranted cautionfor universal sodium restriction to 1,500mg in this population. For individualswith diabetes and hypertension, setting asodium intake goal of,2,300 mg/dayshould be considered only on anindividual basis. Goal sodium intakerecommendations should take intoaccount palatability, availability, additionalcost of specialty low sodium products, andthe difficulty of achieving both low sodiumrecommendations and a nutritionallyadequate diet (205). For completediscussion and references of allrecommendations, see “Nutrition TherapyRecommendations for the Managementof Adults With Diabetes” (116).

F. Diabetes Self-ManagementEducation and Support

Recommendations

c People with diabetes should receiveDSME and diabetes self-managementsupport (DSMS) according to NationalStandards for Diabetes Self-Management Education and Supportwhen their diabetes is diagnosed andas needed thereafter. B

c Effective self-management andquality of life are the key outcomes ofDSME and DSMS and should bemeasured and monitored as part ofcare. C

c DSME and DSMS should addresspsychosocial issues, since emotionalwell-being is associated with positivediabetes outcomes. C

c DSME and DSMS programs areappropriate venues for people withprediabetes to receive education andsupport to develop and maintainbehaviors that can prevent or delaythe onset of diabetes. C

c Because DSME and DSMS can resultin cost-savings and improvedoutcomes B, DSME and DSMS shouldbe adequately reimbursed by third-party payers. E

DSME and DSMS are the ongoingprocesses of facilitating the knowledge,skill, and ability necessary for diabetesself-care. This process incorporates theneeds, goals, and life experiences of theperson with diabetes. The overallobjectives of DSME and DSMS are tosupport informed decision making, self-care behaviors, problem solving, andactive collaboration with the health care

team to improve clinical outcomes,health status, and quality of life in acost-effective manner (206).

DSME and DSMS are essential elementsof diabetes care (207–209), and the currentNational Standards for Diabetes Self-Management Education and Support (206)are based on evidence for their benefits.Education helps people with diabetesinitiate effective self-management andcope with diabetes when they are firstdiagnosed. Ongoing DSME and DSMS alsohelp people with diabetes maintaineffective self-management throughout alifetime of diabetes as they face newchallenges and treatment advancesbecome available. DSME enables patients(including youth) to optimize metaboliccontrol, prevent and managecomplications, and maximize quality of life,in a cost-effective manner (208,210).

Current best practice of DSME is a skills-based approach that focuses on helpingthose with diabetes make informed self-management choices (206,208). DSMEhas changed from a didactic approachfocusing on providing informationto more theoretically basedempowerment models that focus onhelping those with diabetes makeinformed self-management decisions(208). Diabetes care has shifted to anapproach that is more patient centeredand places the person with diabetes andhis or her family at the center of the caremodel working in collaboration withhealth care professionals. Patient-centered care is respectful of andresponsive to individual patientpreferences, needs, and values andensures that patient values guide alldecision making (211).

Evidence for the Benefits of DiabetesSelf-Management Education andSupportMultiple studies have found that DSMEis associated with improved diabetesknowledge and improved self-carebehavior (206,207), improved clinicaloutcomes such as lower A1C (209,212–216), lower self-reported weight (207),improved quality of life (213,216,217),healthy coping (218,219), and lowercosts (220,221). Better outcomes werereported for DSME interventions thatwere longer and included follow-upsupport (DSMS) (207,222–224), that

S30 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

were culturally (225,226) and ageappropriate (227,228) and were tailoredto individual needs and preferences,and that addressed psychosocial issuesand incorporated behavioral strategies(207,208,218,219,229–231). Bothindividual and group approaches havebeen found effective (232,233). There isgrowing evidence for the role of acommunity health workers (234) andpeer (235–239) and lay leaders (240) indelivering DSME and DSMS as part ofthe DSME/S team (241).

Diabetes education is associated withincreased use of primary and preventiveservices (220,242,243) and lower use ofacute, inpatient hospital services (220).Patients who participate in diabeteseducation are more likely to follow bestpractice treatment recommendations,particularly among the Medicarepopulation, and have lowerMedicare andcommercial claim costs (221,242).

The National Standards for DiabetesSelf-Management Education andSupportThe National Standards for DiabetesSelf-Management Education and Supportare designed to define quality DSME andDSMS and to assist diabetes educatorsin a variety of settings to provideevidence-based education and self-management support (206). Thestandards are reviewed and updatedevery 5 years by a task force representingkey organizations involved in the field ofdiabetes education and care.

Diabetes Self-Management Educationand Support Providers and PeopleWith PrediabetesThe standards for DSME and DSMS alsoapply to the education and support ofpeople with prediabetes. Currently, thereare significant barriers to the provision ofeducation and support to those withprediabetes. However, the strategies forsupporting successful behavior changeand the healthy behaviors recommendedfor people with prediabetes are largelyidentical to those for peoplewith diabetes.As barriers to care are overcome,providers of DSME and DSMS, given theirtraining and experience, are particularlywell equipped to assist people withprediabetes in developing andmaintainingbehaviors that can prevent or delay theonset of diabetes (206,244,245).

Reimbursement for Diabetes Self-Management Education and SupportDSME, when provided by a program thatmeets national standards for DSME andis recognized by ADA or other approvalbodies, is reimbursed as part of theMedicare program as overseen by theCenters for Medicare and MedicaidServices (CMS). DSME is also coveredby most health insurance plans.Although DSMS has been shown to beinstrumental for improving outcomes,as described in “Evidence for theBenefits of Diabetes Self-ManagementEducation and Support,” and can beprovided in formats such as phone callsand via telehealth, it currently haslimited reimbursement as face-to-facevisits included as follow-up to DSME.

G. Physical Activity

Recommendations

c As is the case for all children, childrenwith diabetes or prediabetes shouldbe encouraged to engage in at least60 min of physical activity each day. B

c Adults with diabetes should be advisedto perform at least 150 min/week ofmoderate-intensity aerobic physicalactivity (50–70% of maximum heartrate), spread over at least 3 days/weekwith no more than 2 consecutive dayswithout exercise. A

c In the absence of contraindications,adults with type 2 diabetes should beencouraged to perform resistancetraining at least twice per week. A

Exercise is an important part of thediabetes management plan. Regularexercise has been shown to improveblood glucose control, reducecardiovascular risk factors, contribute toweight loss, and improve well-being.Furthermore, regular exercise mayprevent type 2 diabetes in high-riskindividuals (23–25). Structured exerciseinterventions of at least 8 weeks’duration have been shown to lower A1Cby an average of 0.66% in people withtype 2 diabetes, even with no significantchange in BMI (246). There areconsiderable data for the healthbenefits (e.g., increased cardiovascularfitness, muscle strength, improvedinsulin sensitivity, etc.) of regularphysical activity for those with type 1diabetes (247). Higher levels of exerciseintensity are associated with greater

improvements in A1C and in fitness(248). Other benefits include slowingthe decline in mobility amongoverweight patients with diabetes(249). A joint position statement of ADAand the American College of SportsMedicine summarizes the evidence forthe benefits of exercise in people withtype 2 diabetes (250).

Frequency and Type of ExerciseThe U.S. Department of Health andHuman Services’ Physical ActivityGuidelines for Americans (251) suggestthat adults over age 18 years do 150min/week of moderate-intensity, or 75min/week of vigorous aerobic physicalactivity, or an equivalent combination ofthe two. In addition, the guidelinessuggest that adults also do muscle-strengthening activities that involve allmajor muscle groups 2 or more days/week. The guidelines suggest that adultsover age 65 years, or those withdisabilities, follow the adult guidelines ifpossible or (if this is not possible) be asphysically active as they are able.Studies included in the meta-analysis ofeffects of exercise interventions onglycemic control (246) had amean of 3.4sessions/week, with a mean of 49 min/session. The DPP lifestyle intervention,which included 150 min/week ofmoderate-intensity exercise, had abeneficial effect on glycemia in thosewith prediabetes. Therefore, it seemsreasonable to recommend that peoplewith diabetes follow the physicalactivity guidelines for the generalpopulation.

Progressive resistance exerciseimproves insulin sensitivity in older menwith type 2 diabetes to the same oreven a greater extent as aerobicexercise (252). Clinical trials haveprovided strong evidence for the A1Clowering value of resistance training inolder adults with type 2 diabetes(253,254), and for an additive benefit ofcombined aerobic and resistanceexercise in adults with type 2 diabetes(255,256). In the absence ofcontraindications, patients with type 2diabetes should be encouraged to do atleast two weekly sessions of resistanceexercise (exercise with free weights orweight machines), with each sessionconsisting of at least one set of five or

care.diabetesjournals.org Position Statement S31

more different resistance exercisesinvolving the large muscle groups (250).

Pre-exercise Evaluation of theDiabetic PatientAs discussedmore fully in Section VI.A.5,the area of screening asymptomaticdiabetic patients for coronary arterydisease (CAD) remains unclear. An ADAconsensus statement on this issueconcluded that routine screening is notrecommended (257). Providers shoulduse clinical judgment in this area.Certainly, high-risk patients should beencouraged to start with short periodsof low-intensity exercise and increasethe intensity and duration slowly.Providers should assess patients forconditions that might contraindicatecertain types of exercise or predisposeto injury, such as uncontrolledhypertension, severe autonomicneuropathy, severe peripheralneuropathy or history of foot lesions,and unstable proliferative retinopathy.The patient’s age and previous physicalactivity level should be considered. Fortype 1 diabetic patients, the providershould customize the exercise regimento the individual’s needs. Those withcomplications may require a morethorough evaluation (247).

Exercise in the Presence ofNonoptimal Glycemic Control

Hyperglycemia.When people with type 1diabetes are deprived of insulin for12–48 h and are ketotic, exercise canworsen hyperglycemia and ketosis(258); therefore, vigorous activityshould be avoided in the presence ofketosis. However, it is not necessary topostpone exercise based simply onhyperglycemia, provided the patientfeels well and urine and/or bloodketones are negative.

Hypoglycemia. In individuals takinginsulin and/or insulin secretagogues,physical activity can cause hypoglycemiaif medication dose or carbohydrateconsumption is not altered. Forindividuals on these therapies, addedcarbohydrate should be ingested if pre-exercise glucose levels are ,100 mg/dL(5.6 mmol/L). Hypoglycemia is lesscommon in diabetic individuals who arenot treated with insulin or insulinsecretagogues, and no preventivemeasures for hypoglycemia are usuallyadvised in these cases.

Exercise in the Presence of SpecificLong-Term Complications of Diabetes

Retinopathy. In the presence ofproliferative diabetic retinopathy(PDR) or severe non-PDR (NPDR),vigorous aerobic or resistanceexercise may be contraindicatedbecause of the risk of triggeringvitreous hemorrhage or retinaldetachment (259).

Peripheral Neuropathy. Decreased painsensation and a higher pain threshold inthe extremities result in increased risk ofskin breakdown and infection and ofCharcot joint destruction with someforms of exercise. However, studieshave shown that moderate-intensitywalkingmay not lead to increased risk offoot ulcers or reulceration in those withperipheral neuropathy (260). Inaddition, 150 min/week of moderateexercise was reported to improveoutcomes in patients with milder formsof neuropathy (260a). All individualswith peripheral neuropathy should wearproper footwear and examine their feetdaily to detect lesions early. Anyonewith a foot injury or open sore should berestricted to non–weight-bearingactivities.

Autonomic Neuropathy. Autonomicneuropathy can increase the risk ofexercise-induced injury or adverseevent through decreased cardiacresponsiveness to exercise, posturalhypotension, impaired thermoregulation,impaired night vision due to impairedpapillary reaction, and highersusceptibility to hypoglycemia (454).Cardiovascular autonomic neuropathy(CAN) is also an independent riskfactor for cardiovascular death andsilent myocardial ischemia (261).Therefore, individuals with diabeticautonomic neuropathy shouldundergo cardiac investigation beforebeginning physical activity moreintense than that to which they areaccustomed.

Albuminuria and Nephropathy. Physicalactivity can acutely increase urinaryprotein excretion. However, there is noevidence that vigorous exerciseincreases the rate of progression ofdiabetic kidney disease and likely noneed for any specific exerciserestrictions for people with diabetickidney disease (262).

H. Psychosocial Assessment and Care

Recommendations

c It is reasonable to include assessmentof the patient’s psychological and socialsituation as an ongoing part of themedical management of diabetes. B

c Psychosocial screening and follow-upmay include, but are not limited to,attitudes about the illness,expectations for medicalmanagement and outcomes, affect/mood, general and diabetes-relatedquality of life, resources (financial,social, and emotional), andpsychiatric history. E

c Routinely screen for psychosocialproblems such as depression anddiabetes-related distress, anxiety,eating disorders, and cognitiveimpairment. B

Emotional well-being is an important partof diabetes care and self-management.Psychological and social problems canimpair the individual’s (263–265) orfamily’s ability (266) to carry out diabetescare tasks and therefore compromisehealth status. There are opportunities forthe clinician to routinely assesspsychosocial status in a timely andefficient manner so that referral forappropriate services can beaccomplished. A systematic review andmeta-analysis showed that psychosocialinterventions modestly but significantlyimproved A1C (standardized meandifference20.29%) and mental healthoutcomes. However, there was a limitedassociation between the effects on A1Cand mental health, and no interventioncharacteristics predicted benefit on bothoutcomes (267).

ScreeningKey opportunities for routine screening ofpsychosocial status occur at diagnosis,during regularly scheduled managementvisits, during hospitalizations, with thediscovery of complications, or whenproblems with glucose control, quality oflife, or self-management are identified.Patients are likely to exhibit psychologicalvulnerability at diagnosis and when theirmedical status changes, e.g., end of thehoneymoon period, when the need forintensified treatment is evident, andwhen complications are discovered.Depression affects about 20–25% ofpeople with diabetes (268) and increasesthe risk for MI and post-MI (269) and

S32 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

all-cause mortality (270). There appearsto be a bidirectional relationship withboth diabetes (271) and metabolicsyndrome (272) and depression.

Diabetes-related distress is distinct fromclinical depression and is very common(273–276) among people with diabetesand their family members (266).Prevalence is reported as 18–45%, withan incidence of 38–48% over 18 months.High levels of distress are significantlylinked to A1C, self-efficacy, dietary andexercise behaviors (219,274), andmedication taking (277). Other issuesknown to impact self-management andhealth outcomes include but are notlimited to attitudes about the illness,expectations for medical managementand outcomes, anxiety, general anddiabetes-related quality of life, resources(financial, social, and emotional) (278)and psychiatric history (279,280).Screening tools are available for a numberof these areas (229,281,282).

Referral to Mental Health SpecialistIndications for referral to a mentalhealth specialist familiar with diabetesmanagement may include grossdisregard for the medical regimen (byself or others) (283), depression,possibility of self-harm, debilitatinganxiety (alone or with depression),indications of an eating disorder (284),or cognitive functioning thatsignificantly impairs judgment. It ispreferable to incorporatepsychological assessment andtreatment into routine care rather thanwaiting for a specific problem ordeterioration in metabolic orpsychological status (229,273). In therecent DAWN2 study, significantdiabetes-related distress was reportedby 44.6% of the participants, but only23.7% reported that their health careteam asked them how diabetesimpacted their life (273).

Although the clinician may not feelqualified to treat psychologicalproblems (285), using the patient-provider relationship as a foundationcan increase the likelihood that thepatient will accept referral for otherservices. Collaborative careinterventions and use of a teamapproach have demonstrated efficacy indiabetes and depression (286,287), and

interventions to enhance self-management and address severedistress have demonstrated efficacy indiabetes-related distress (219).

I. When Treatment Goals Are Not MetSome people with diabetes and theirhealth care providers may not achievethe desired treatment goals (Table 9).Rethinking the treatment regimen mayrequire assessment of barriers includingincome, health literacy, diabetes-related distress, depression, andcompeting demands, including thoserelated to family responsibilities anddynamics. Other strategies may includeculturally appropriate and enhancedDSME and DSMS, comanagement with adiabetes team, referral to a medicalsocial worker for assistance withinsurance coverage, assessingmedication-taking behaviors, or changein pharmacological therapy. Initiation ofor increase in SMBG, use of CGM,frequent contact with the patient, orreferral to a mental health professionalor physician with special expertise indiabetes may be useful.

J. Intercurrent IllnessThe stress of illness, trauma, and/orsurgery frequently aggravates glycemiccontrol and may precipitate DKA ornonketotic hyperosmolar state, life-threatening conditions that requireimmediate medical care to preventcomplications and death. Any conditionleading to deterioration in glycemiccontrol necessitates more frequentmonitoring of blood glucose and (inketosis-prone patients) urine or bloodketones. If accompanied by ketosis,vomiting, or alteration in level ofconsciousness, marked hyperglycemiarequires temporary adjustment of thetreatment regimen and immediateinteraction with the diabetes care team.The patient treated with noninsulintherapies or MNT alone maytemporarily require insulin. Adequatefluid and caloric intake must be assured.Infection or dehydration is more likelyto necessitate hospitalization of theperson with diabetes than the personwithout diabetes.

The hospitalized patient should betreated by a physician with expertise indiabetes management. For furtherinformation onmanagement of patients

with hyperglycemia in the hospital, seeSection IX.A. For further information onmanagement of DKA or hyperglycemicnonketotic hyperosmolar state, refer tothe ADA statement on hyperglycemiccrises (288).

K. Hypoglycemia

Recommendations

c Individuals at risk for hypoglycemiashould be asked about symptomaticand asymptomatic hypoglycemia ateach encounter. C

c Glucose (15–20 g) is the preferredtreatment for the consciousindividual with hypoglycemia,although any form of carbohydratethat contains glucose may be used.After 15 min of treatment, if SMBGshows continued hypoglycemia, thetreatment should be repeated. OnceSMBG returns to normal, theindividual should consume a meal orsnack to prevent recurrence ofhypoglycemia. E

c Glucagon should be prescribed forall individuals at significant risk ofsevere hypoglycemia, and caregiversor family members of theseindividuals should be instructed onits administration. Glucagonadministration is not limited tohealth care professionals. E

c Hypoglycemia unawareness or one ormore episodes of severe hypoglycemiashould trigger re-evaluation of thetreatment regimen. E

c Insulin-treated patients withhypoglycemia unawareness or anepisode of severe hypoglycemiashould be advised to raise theirglycemic targets to strictly avoidfurther hypoglycemia for at leastseveral weeks, to partially reversehypoglycemia unawareness andreduce risk of future episodes. A

c Ongoing assessment of cognitivefunction is suggested with increasedvigilance for hypoglycemia by theclinician, patient, and caregivers iflow cognition and/or decliningcognition is found. B

Hypoglycemia is the leading limitingfactor in the glycemic management oftype 1 and insulin-treated type 2diabetes (289). Mild hypoglycemia maybe inconvenient or frightening topatients with diabetes. Severe

care.diabetesjournals.org Position Statement S33

hypoglycemia can cause acute harm tothe person with diabetes or others,especially if it causes falls, motor vehicleaccidents, or other injury. A large cohortstudy suggested that among olderadults with type 2 diabetes, a history ofsevere hypoglycemia was associatedwith greater risk of dementia (290).Conversely, in a substudy of theACCORD trial, cognitive impairment atbaseline or decline in cognitive functionduring the trial was significantlyassociated with subsequent episodes ofsevere hypoglycemia (291). Evidencefrom the DCCT/EDIC trial, whichinvolved younger adults andadolescents with type 1 diabetes,suggested no association of frequencyof severe hypoglycemia with cognitivedecline (292), as discussed in SectionVIII.A.1.a.

As described in Section V.b.2, severehypoglycemia was associated withmortality in participants in both thestandard and intensive glycemia armsof the ACCORD trial, but therelationships with achieved A1C andtreatment intensity were notstraightforward. An association ofsevere hypoglycemia with mortalitywas also found in the ADVANCE trial(293). An association of self-reportedsevere hypoglycemia with 5-yearmortality has also been reported inclinical practice (294).

In 2013, ADA and The Endocrine Societypublished a consensus report on theimpact and treatment of hypoglycemiaon diabetic patients. Severehypoglycemia was defined as an eventrequiring assistance of another person.Young children with type 1 diabetes andthe elderly were noted as particularlyvulnerable due to their limited ability torecognize hypoglycemic symptoms andeffectively communicate their needs.The report recommended that short-acting insulin sliding scales, often used inlong-term care facilities, should beavoided and complex regimenssimplified. Individualized patienteducation, dietary intervention (e.g.,bedtime snack to prevent overnighthypoglycemia), exercise management,medication adjustment, glucosemonitoring, and routine clinicalsurveillance may improve patientoutcomes (295).

Hypoglycemia treatment requiresingestion of glucose- or carbohydrate-containing foods. The acute glycemicresponse correlates better with theglucose content than with thecarbohydrate content of the food. Pureglucose is the preferred treatment, butany form of carbohydrate that containsglucose will raise blood glucose. Addedfatmay retard and thenprolong the acuteglycemic response. Ongoing insulinactivity or insulin secretagoguesmay leadto recurrent hypoglycemia unless furtherfood is ingested after recovery.

GlucagonThose in close contact with, or havingcustodial care of, people withhypoglycemia-prone diabetes (familymembers, roommates, schoolpersonnel, child care providers,correctional institution staff, orcoworkers) should be instructed on useof glucagon kits. An individual does notneed to be a health care professional tosafely administer glucagon. A glucagonkit requires a prescription. Care shouldbe taken to ensure that glucagon kits arenot expired.

Hypoglycemia PreventionHypoglycemia prevention is a criticalcomponent of diabetes management.SMBG and, for some patients, CGM arekey tools to assess therapy and detectincipient hypoglycemia. Patients shouldunderstand situations that increase theirrisk of hypoglycemia, such as whenfasting for tests or procedures, during orafter intense exercise, and during sleep,and that hypoglycemia may increase therisk of harm to self or others, such as withdriving. Teaching people with diabetes tobalance insulin use, carbohydrate intake,and exercise is a necessary but notalways sufficient strategy for prevention.In type 1 diabetes and severely insulin-deficient type 2 diabetes, hypoglycemiaunawareness, or hypoglycemia-associated autonomic failure, canseverely compromise stringent diabetescontrol and quality of life. The deficientcounter-regulatory hormone release andautonomic responses in this syndromeare both risk factors for, and caused by,hypoglycemia. A corollary to this “viciouscycle” is that several weeks of avoidanceof hypoglycemia has been demonstratedto improve counter-regulation andawareness to some extent in many

patients (296). Hence, patients with oneormore episodes of severe hypoglycemiamay benefit from at least short-termrelaxation of glycemic targets.

L. Bariatric Surgery

Recommendations

c Bariatric surgery may be consideredfor adults with BMI .35 kg/m2 andtype 2 diabetes, especially if diabetesor associated comorbidities aredifficult to control with lifestyle andpharmacological therapy. B

c Patients with type 2 diabetes whohave undergone bariatric surgeryneed lifelong lifestyle support andmedical 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 patients withBMI,35 kg/m2 outside of a researchprotocol. E

c The long-term benefits, cost-effectiveness, and risks of bariatricsurgery in individuals with type 2diabetes should be studied in well-designed controlled trials withoptimal medical and lifestyle therapyas the comparator. E

Bariatric and metabolic surgeries, eithergastric banding or procedures that involvebypassing, transposing, or resectingsections of the small intestine, when partof a comprehensive team approach, canbe an effective weight loss treatment forsevere obesity, and national guidelinessupport its consideration for people withtype 2 diabetes who have BMI exceeding35 kg/m2.

AdvantagesBariatric surgery has been shown to leadto near- or complete normalization ofglycemia in ;40–95% of patients withtype 2 diabetes, depending on the studyand the surgical procedure (297–300).A meta-analysis of bariatric surgerystudies involving 3,188 patients withdiabetes reported that 78% hadremission of diabetes (normalization ofblood glucose levels in the absence ofmedications) and that the remissionrates were sustained in studies that hadfollow-up exceeding 2 years (301).Remission rates tend to be lower withprocedures that only constrict the

S34 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

stomach and higher with those thatbypass portions of the small intestine.Additionally, intestinal bypass proceduresmay have glycemic effects that areindependent of their effects on weight,perhaps involving the incretin axis.

There is also evidence for diabetesremission following bariatric surgery inpersons with type 2 diabetes who areless severely obese. One randomizedtrial compared adjustable gastricbanding to “best available”medical andlifestyle therapy in subjects with type 2diabetes and BMI 30–40 kg/m2 (302).Overall, 73% of surgically treatedpatients achieved “remission” of theirdiabetes, compared with 13% of thosetreated medically. The latter group lostonly 1.7% of body weight, suggestingthat their therapy was not optimal.Overall the trial had 60 subjects, andonly 13 had a BMI under 35 kg/m2,making it difficult to generalize theseresults widely to diabetic patients whoare less severely obese or with longerduration of diabetes. In a recentnonrandomized study of 66 people withBMI 30–35 kg/m2, 88% of participantshad remission of their type 2 diabetesup to 6 years after surgery (303).

DisadvantagesBariatric surgery is costly in the shortterm and has associated risks. Morbidityand mortality rates directly related to thesurgery have been reduced considerablyin recent years, with 30-day mortalityrates now 0.28%, similar to those oflaparoscopic cholecystectomy (304).Longer-term concerns include vitaminand mineral deficiencies, osteoporosis,and rare but often severe hypoglycemiafrom insulin hypersecretion. Cohortstudies attempting to match subjectssuggest that the procedure may reducelonger-term mortality rates (305).Retrospective analyses and modelingstudies suggest that these proceduresmay be cost-effective for patients withtype 2 diabetes, when one considersreduction in subsequent health care costs(297,306–308).

Caution about the benefits of bariatricsurgery is warranted. A propensityscore-adjusted analyses of olderseverely obese patients with highbaseline mortality in Veterans AffairsMedical Centers found that bariatricsurgery was not associated with

decreased mortality compared withusual care (mean follow-up 6.7 years)(309). A study that followed patientswho had undergone laparoscopicadjustable gastric banding (LAGB) for12 years found that 60% were satisfiedwith the procedure. Nearly one out ofthree patients experienced band erosion,and almost half had required removal oftheir bands. The authors’ conclusion wasthat “LAGB appears to result in relativelypoor long-term outcomes” (310).Understanding the mechanisms ofglycemic improvement, long-termbenefits, and risks of bariatric surgery inindividuals with type 2 diabetes,especially those who are not severelyobese, will require well designed clinicaltrials, with optimal medical and lifestyletherapy, and cardiovascular risk factors asthe comparator.

M. Immunization

Recommendations

c Annually provide an influenza vaccineto all diabetic patients $6 months ofage. C

c Administer pneumococcalpolysaccharide vaccine to all diabeticpatients $2 years of age. A one-timerevaccination is recommended forindividuals .65 years of age whohave been immunized .5 years ago.Other indications for repeatvaccination include nephroticsyndrome, chronic renal disease, andother immunocompromised states,such as after transplantation. C

c Administer hepatitis B vaccination tounvaccinated adults with diabetes whoare aged 19–59 years. C

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

Influenza and pneumonia are common,preventable infectious diseasesassociated with high mortality andmorbidity in the elderly and in peoplewith chronic diseases. Though there arelimited studies reporting the morbidityand mortality of influenza andpneumococcal pneumonia specifically inpeople with diabetes, observationalstudies of patients with a variety ofchronic illnesses, including diabetes,show that these conditions areassociated with an increase in

hospitalizations for influenza and itscomplications. People with diabetesmay be at increased risk of thebacteremic form of pneumococcalinfection and have been reported tohave a high risk of nosocomialbacteremia, which has a mortality rateas high as 50% (311).

Safe and effective vaccines that greatlyreduce the risk of serious complicationsfrom these diseases are available(312,313). In a case-control series,influenza vaccine was shown to reducediabetes-related hospital admission byas much as 79% during flu epidemics(312). There is sufficient evidence tosupport that people with diabeteshave appropriate serologic and clinicalresponses to these vaccinations.The CDC Advisory Committee onImmunization Practices recommendsinfluenza and pneumococcal vaccines forall individuals with diabetes (http://www.cdc.gov/vaccines/recs/).

Hepatitis B VaccineLate in 2012, the Advisory Committeeon Immunization Practices of the CDCrecommended that all previouslyunvaccinated adults with diabetes aged19–59 years be vaccinated againsthepatitis B virus (HBV) as soon aspossible after a diagnosis of diabetes ismade. Additionally, after assessing riskand likelihood of an adequate immuneresponse, vaccinations for those aged60 years and over should also beconsidered (314). At least 29 outbreaksof HBV in long-term care facilities andhospitals have been reported to theCDC, with the majority involving adultswith diabetes receiving “assisted bloodglucose monitoring,” in which suchmonitoring is done by a health careprofessional with responsibility formore than one patient. HBV is highlytransmissible and stable for longperiods of time on surfaces such aslancing devices and blood glucosemeters, even when no blood is visible.Blood sufficient to transmit the virushas also been found in the reservoirs ofinsulin pens, resulting in warningsagainst sharing such devices betweenpatients.

CDC analyses suggest that, excludingpersons with HBV-related riskbehaviors, acute HBV infection is abouttwice as high among adults with

care.diabetesjournals.org Position Statement S35

diabetes aged 23 years and overcompared with adults without diabetes.Seroprevalence of antibody to HBV coreantigen, suggesting past or currentinfection, is 60% higher among adultswith diabetes than those without, andthere is some evidence that diabetesimparts a higher HBV case fatality rate.The age differentiation in therecommendations stems from CDCeconomic models suggesting thatvaccination of adults with diabeteswho were aged 20–59 years would costan estimated $75,000 per quality-adjusted life-year saved, while cost perquality-adjusted life-year savedincreased significantly at higher ages.In addition to competing causes ofmortality in older adults, the immuneresponse to the vaccine declines withage (314).

These new recommendations regardingHBV vaccinations serve as a reminder toclinicians that children and adults withdiabetes need a number of vaccinations,both those specifically indicatedbecause of diabetes as well as thoserecommended for the generalpopulation (http://www.cdc.gov/vaccines/recs/).

VI. PREVENTION ANDMANAGEMENT OF DIABETESCOMPLICATIONS

For prevention and management ofdiabetes complications in children andadolescents, please refer to Section VIII.Diabetes Care in Specific Populations.

A. Cardiovascular DiseaseCVD is the major cause of morbidity andmortality for individuals with diabetes,and the largest contributor to the directand indirect costs of diabetes. Thecommon conditions coexistingwith type2 diabetes (e.g., hypertension anddyslipidemia) are clear risk factors forCVD, and diabetes itself confersindependent risk. Numerous studieshave shown the efficacy of controllingindividual cardiovascular risk factors inpreventing or slowing CVD in peoplewith diabetes. Large benefits are seenwhenmultiple risk factors are addressedglobally (315,316). There is evidencethat measures of 10-year CHD riskamong U.S. adults with diabetes haveimproved significantly over the pastdecade (317).

1. Hypertension/Blood Pressure Control

Recommendations

Screening and Diagnosis

c Blood pressure should be measuredat every routine visit. Patients foundto have elevated blood pressureshould have blood pressureconfirmed on a separate day. B

Goals

c People with diabetes andhypertension should be treated to asystolic blood pressure (SBP) goal of,140 mmHg. B

c Lower systolic targets, such as ,130mmHg, may be appropriate forcertain individuals, such as youngerpatients, if it can be achieved withoutundue treatment burden. C

c Patients with diabetes should betreated to a diastolic blood pressure(DBP) ,80 mmHg. B

Treatment

c Patients with blood pressure.120/80mmHg should be advised on lifestylechanges to reduce blood pressure. B

c Patients with confirmed bloodpressure higher than 140/80 mmHgshould, in addition to lifestyletherapy, have prompt initiation andtimely subsequent titration ofpharmacological therapy to achieveblood pressure goals. B

c Lifestyle therapy for elevated bloodpressure consists of weight loss, ifoverweight; DASH-style dietarypattern including reducing sodiumand increasing potassium intake;moderation of alcohol intake; andincreased physical activity. B

c Pharmacological therapy for patientswith diabetes and hypertensionshould comprise a regimen thatincludes either an ACE inhibitor or anangiotensin receptor blocker (ARB). Ifone class is not tolerated, the othershould be substituted. C

c Multiple-drug therapy (two or moreagents at maximal doses) is generallyrequired to achieve blood pressuretargets. B

c Administer one or moreantihypertensive medications atbedtime. A

c If ACE inhibitors, ARBs, or diureticsare used, serum creatinine/estimatedglomerular filtration rate (eGFR) andserum potassium levels should bemonitored. E

c In pregnant patients with diabetesand chronic hypertension, bloodpressure target goals of 110–129/65–79 mmHg are suggested in theinterest of long-term maternal healthand minimizing impaired fetalgrowth. ACE inhibitors and ARBs arecontraindicated during pregnancy. E

Hypertension is a common comorbidityof diabetes, affecting the majority ofpatients, with prevalence depending ontype of diabetes, age, obesity, andethnicity. Hypertension is a major riskfactor for both CVD and microvascularcomplications. In type 1 diabetes,hypertension is often the result ofunderlying nephropathy, while in type 2diabetes it usually coexists with othercardiometabolic risk factors.

Screening and DiagnosisBlood pressure measurement should bedone by a trained individual and followthe guidelines established fornondiabetic individuals: measurementin the seated position, with feet on thefloor and arm supported at heart level,after 5 min of rest. Cuff size should beappropriate for the upper armcircumference. Elevated values shouldbe confirmed on a separate day.

Home blood pressure self-monitoring and24-h ambulatory blood pressuremonitoring may provide additionalevidence of “white coat” and maskedhypertension and other discrepanciesbetween office and “true” blood pressure.Studies in nondiabetic populations foundthat home measurements may bettercorrelate with CVD risk than officemeasurements (318,319). However, mostof the evidence of benefits ofhypertension treatment in people withdiabetes is based on officemeasurements.

Treatment GoalsEpidemiological analyses show thatblood pressures .115/75 mmHg areassociated with increasedcardiovascular event rates andmortalityin individuals with diabetes (320–322)and that SBP .120 mmHg predict long-term end-stage renal disease (ESRD).Randomized clinical trials havedemonstrated the benefit (reduction ofCHD events, stroke, and nephropathy)of lowering blood pressure to ,140mmHg systolic and ,80 mmHgdiastolic in individuals with diabetes

S36 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

(320,323–325). There is limited evidencefor the benefits of lower SBP targets.

The ACCORD trial examined whether alower SBP of ,120 mmHg providesgreater cardiovascular protectionthan an SBP level of 130–140 mmHg inpatients with type 2 diabetes at high riskfor CVD (326). The HR for the primaryend point (nonfatal MI, nonfatal stroke,and CVD death) in the intensive (bloodpressure 11/64 on 3.4 medications)versus standard group (blood pressure143/70 on 2.1 medications) was 0.88(95% CI 0.73–1.06; P 5 0.20). Of theprespecified secondary end points, onlystroke and nonfatal stroke werestatistically significantly reduced byintensive blood pressure treatment.The number needed to treat to preventone stroke over the course of 5 yearswith intensive blood pressuremanagement was 89. Serious adverseevent rates (including syncope andhyperkalemia) were higher withintensive targets (3.3% vs. 1.3%; P 50.001). Albuminuria rates were reducedwith more intensive blood pressuregoals, but there were no differences inrenal function nor in othermicrovascular complications.

The ADVANCE trial (treatment with anACE inhibitor and a thiazide-type diuretic)showed a reduced death rate but not inthe composite macrovascular outcome.However, the ADVANCE trial had nospecified targets for the randomizedcomparison and the mean SBP in theintensive group (135 mmHg) was not aslow as themean SBP even in the ACCORDstandard-therapy group (327). Post hocanalysis of achieved blood pressure inseveral hypertension treatment trialshave suggested no benefit of lowerachieved SBP. As an example, among6,400 patients with diabetes and CADenrolled in one trial, “tight control”(achieved SBP ,130 mmHg) was notassociated with improved cardiovascularoutcomes compared with “usual care”(achieved SBP 130–140 mmHg) (328).Similar findings emerged from an analysisof another trial. Those with SBP (,115mmHg) had increased rates of CVDevents, although they had lower rates ofstroke (329).

Observational data, including thatderived from clinical trials, may be

inappropriate for defining bloodpressure targets, since sicker patientsmay have low blood pressures or,conversely, healthier or more adherentpatients may achieve goals morereadily. A recent meta-analysis ofrandomized trials of adults with type 2diabetes comparing prespecified bloodpressure targets found no significantreduction in mortality or nonfatal MI.There was a statistically significant 35%relative reduction in stroke, but theabsolute risk reduction was only 1%(330). Microvascular complicationswere not examined. Another meta-analysis that included both trialscomparing blood pressure goals andtrials comparing treatment strategiesconcluded that a systolic treatment goalof 130–135mmHgwas acceptable.Withgoals ,130 mmHg, there were greaterreductions in stroke, a 10% reduction inmortality, but no reduction of otherCVD events and increased rates ofserious adverse events. SBP ,130mmHg was associated with reducedonset and progression of albuminuria.However, there was heterogeneity inthe measure, rates of more advancedrenal disease outcomes were notaffected, and there were no significantchanges in retinopathy or neuropathy(331).

The clear body of evidence that SBP.140 mmHg is harmful suggests thatclinicians should promptly initiate andtitrate therapy in an ongoing fashion toachieve and maintain SBP ,140 mmHgin virtually all patients. Additionally,patients with long life expectancy (inwhom there may be renal benefits fromlong-term stricter blood pressurecontrol) or those in whom stroke risk is aconcern might, as part of shareddecision making, appropriately havelower systolic targets such as ,130mmHg. This is especially true if it can beachieved with few drugs and withoutside effects of therapy.

Treatment StrategiesAlthough there are no well-controlledstudies of diet and exercise in thetreatment of elevated blood pressure orhypertension in individuals withdiabetes, the DASH study in nondiabeticindividuals has shown antihypertensiveeffects similar to pharmacologicalmonotherapy. Lifestyle therapy consists

of reducing sodium intake (,1,500 mg/day) and excess body weight; increasingconsumption of fruits, vegetables (8–10servings per day), and low-fat dairyproducts (2–3 servings per day);avoiding excessive alcohol consumption(no more than 2 servings per day in menand no more than 1 serving per day inwomen) (332); and increasing activitylevels (320). These nonpharmacologicalstrategies may also positively affectglycemia and lipid control and as a resultshould be encouraged in those witheven mildly elevated blood pressure.Their effects on cardiovascular eventshave not been established.Nonpharmacological therapy isreasonable in diabetic individuals withmildly elevated blood pressure (SBP.120 mmHg or DBP.80 mmHg). If theblood pressure is confirmed to be$140mmHg systolic and/or $80 mmHgdiastolic, pharmacological therapyshould be initiated along withnonpharmacological therapy (320).

Lowering of blood pressure withregimens based on a variety ofantihypertensive drugs, including ACEinhibitors, ARBs, b-blockers, diuretics,and calcium channel blockers, has beenshown to be effective in reducingcardiovascular events. Several studiessuggested that ACE inhibitors may besuperior to dihydropyridine calciumchannel blockers in reducingcardiovascular events (333–335).However, several studies have shownno specific advantage to ACE inhibitorsas initial treatment of hypertension inthe general hypertensive population,but rather an advantage oncardiovascular outcomes of initialtherapy with low-dose thiazidediuretics (320,336,337).

In people with diabetes, inhibitors of therenin-angiotensin system (RAS) mayhave unique advantages for initial orearly therapy of hypertension. In anonhypertension trial of high-riskindividuals, including a large subset withdiabetes, an ACE inhibitor reduced CVDoutcomes (338). In patients withcongestive heart failure (CHF), includingdiabetic subgroups, ARBs have beenshown to reduce major CVD outcomes(339–342), and in type 2 diabeticpatients with significant nephropathy,ARBs were superior to calcium channel

care.diabetesjournals.org Position Statement S37

blockers for reducing heart failure (343).Though evidence for distinctadvantages of RAS inhibitors on CVDoutcomes in diabetes remainsconflicting (323,337), the high CVDrisks associated with diabetes, and thehigh prevalence of undiagnosed CVD,may still favor recommendations fortheir use as first-line hypertensiontherapy in people with diabetes (320).

The blood pressure arm of the ADVANCEtrial demonstrated that routineadministration of a fixed combination ofthe ACE inhibitor perindopril and thediuretic indapamide significantlyreduced combined microvascular andmacrovascular outcomes, as well as CVDand total mortality. The improvedoutcomes could also have been due tolower achieved blood pressure in theperindopril-indapamide arm (327).Another trial showed a decrease inmorbidity andmortality in those receivingbenazepril and amlodipine versusbenazepril and hydrochlorothiazide(HCTZ). The compelling benefits of RASinhibitors in diabetic patients withalbuminuria or renal insufficiencyprovide additional rationale for theseagents (see Section VI.B). If needed toachieve blood pressure targets,amlodipine, HCTZ, or chlorthalidone canbe added. If eGFR is ,30 mL/min/m2,a loop diuretic, rather than HCTZ orchlorthalidone should be prescribed.Titration of and/or addition of furtherblood pressure medications should bemade in timely fashion to overcomeclinical inertia in achieving bloodpressure targets.

Health information technologypotentially can be used as a safe andeffective tool to enable attainment ofblood pressure goals. Using atelemonitoring intervention to directtitrations of antihypertensivemedications between medical officevisits has been demonstrated to have aprofound impact on SBP control (344).

An important caveat is that mostpatients with hypertension requiremultiple-drug therapy to reachtreatment goals (320). Identifying andaddressing barriers to medicationadherence (such as cost and sideeffects) should routinely be done. Ifblood pressure is refractory despite

confirmed adherence to optimal dosesof at least three antihypertensive agentsof different classifications, one of whichshould be a diuretic, clinicians shouldconsider an evaluation for secondaryforms of hypertension. Growingevidence suggests that there is anassociation between increase in sleep-time blood pressure and incidence ofCVD events. A recent RCT of 448participants with type 2 diabetes andhypertension demonstrated reducedcardiovascular events and mortalitywith median follow-up of 5.4 years if atleast one antihypertensive medicationwas given at bedtime (345).

Pregnancy and AntihypertensivesIn a pregnancy complicated by diabetesand chronic hypertension, target bloodpressure goals of SBP 110–129 mmHgand DBP 65–79 mmHg are reasonable,as they contribute to improved long-term maternal health. Lower bloodpressure levels may be associated withimpaired fetal growth. Duringpregnancy, treatment with ACEinhibitors and ARBs is contraindicated,since they may cause fetal damage.Antihypertensive drugs known to beeffective and safe in pregnancy includemethyldopa, labetalol, diltiazem,clonidine, and prazosin. Chronic diureticuse during pregnancy has beenassociated with restricted maternalplasma volume, which may reduceuteroplacental perfusion (346).

2. Dyslipidemia/Lipid Management

Recommendations

Screening

c In most adult patients with diabetes,measure fasting lipid profile at leastannually. B

c In adults with low-risk lipid values(LDL cholesterol ,100 mg/dL, HDLcholesterol .50 mg/dL, andtriglycerides ,150 mg/dL), lipidassessments may be repeated every 2years. E

Treatment Recommendations and Goals

c Lifestyle modification focusing on thereduction of saturated fat, trans fat, andcholesterol intake; increase of n-3 fattyacids, viscous fiber and plant stanols/sterols; weight loss (if indicated); andincreased physical activity should berecommended to improve the lipidprofile in patients with diabetes. A

c Statin therapy should be added tolifestyle therapy, regardless of baselinelipid levels, for diabetic patients:

c with overt CVD Ac without CVDwhoare over the ageof 40years and have one or more other CVDrisk factors (family history of CVD,hypertension, smoking, dyslipidemia,or albuminuria). A

c For lower-risk patients than the above(e.g., without overt CVD and under theage of 40 years), statin therapy shouldbe considered in addition to lifestyletherapy if LDL cholesterol remainsabove 100 mg/dL or in those withmultiple CVD risk factors. C

c In individuals without overt CVD,the goal is LDL cholesterol ,100mg/dL (2.6 mmol/L). B

c In individuals with overt CVD, a lowerLDL cholesterol goal of ,70 mg/dL(1.8 mmol/L), with a high dose of astatin, is an option. B

c If drug-treatedpatients donot reach theabove targets on maximum toleratedstatin therapy, a reduction in LDLcholesterol of;30–40% from baselineis an alternative therapeutic goal. B

c Triglyceride levels ,150 mg/dL (1.7mmol/L) and HDL cholesterol .40mg/dL (1.0 mmol/L) in men and .50mg/dL (1.3 mmol/L) in women aredesirable. C However, LDLcholesterol–targeted statin therapyremains the preferred strategy. A

c Combination therapy has been shownnot to provide additionalcardiovascular benefit above statintherapy alone and is not generallyrecommended. A

c Statin therapy is contraindicated inpregnancy. B

Evidence for Benefits of Lipid-Lowering TherapyPatients with type 2 diabetes have anincreased prevalence of lipidabnormalities, contributing to their highrisk of CVD. Multiple clinical trials havedemonstrated significant effects ofpharmacological (primarily statin)therapy on CVD outcomes in subjectswith CHD and for primary CVDprevention (347,348). Subanalyses ofdiabetic subgroups of larger trials(349–353) and trials specifically insubjects with diabetes (354,355) showedsignificant primary and secondaryprevention of CVD events1/2 CHD

S38 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

deaths in diabetic patients. Meta-analyses including data from over18,000 patients with diabetes from14 randomized trials of statin therapy(mean follow-up 4.3 years),demonstrate a 9% proportionalreduction in all-cause mortality, and13% reduction in vascular mortality,for each mmol/L reduction in LDLcholesterol (356). As in those withoutdiabetes, absolute reductions in “hard”CVD outcomes (CHD death andnonfatal MI) are greatest in peoplewith high baseline CVD risk (knownCVD and/or very high LDL cholesterollevels), but the overall benefits ofstatin therapy in people with diabetesat moderate or high risk for CVD areconvincing (357,358).

Diabetes With Statin UseThere is an increased risk of incidentdiabetes with statin use (359,360),which may be limited to those withdiabetes risk factors. These patientsmay benefit additionally from diabetesscreening when on statin therapy. In ananalysis of one of the initial studiessuggesting that statins are linked to riskof diabetes, the cardiovascular eventrate reduction with statins outweighedthe risk of incident diabetes even forpatients at highest risk for diabetes(361). The absolute risk increase wassmall (over 5 years of follow-up, 1.2% ofparticipants on placebo developeddiabetes and 1.5% on rosuvastatin)(362). A meta-analysis of 13 randomizedstatin 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 caseof diabetes, while simultaneouslypreventing 5.4 vascular events amongthose255patients (360). The relative risk-benefit ratio favoring statins is furthersupported by meta-analysis of individualdata of over 170,000 persons from 27randomized trials. This demonstratedthat individuals at low risk of vasculardisease, including those undergoingprimary prevention, received benefitsfrom statins that included reductions inmajor vascular events and vascular deathwithout increase in incidence of cancer ordeaths from other causes (348).

Low levels of HDL cholesterol, oftenassociated with elevated triglyceride

levels, are the most prevalent pattern ofdyslipidemia in persons with type 2diabetes. However, the evidence basefor drugs that target these lipid fractionsis significantly less robust than that forstatin therapy (363). Nicotinic acid hasbeen shown to reduce CVD outcomes(364), although the study was done in anondiabetic cohort. Gemfibrozil hasbeen shown to decrease rates of CVDevents in subjects without diabetes(365,366) and in a subgroup with diabetesin one of the larger trials (365). However,in a large trial specific to diabetic patients,fenofibrate failed to reduce overallcardiovascular outcomes (367).

Combination TherapyCombination therapy, with a statinand a fibrate or statin and niacin, may beefficacious for treatment for all threelipid fractions, but this combination isassociated with an increased risk forabnormal transaminase levels, myositis,or rhabdomyolysis. The risk ofrhabdomyolysis is higher with higherdoses of statins and with renalinsufficiency and seems to be lowerwhenstatins are combined with fenofibratethan gemfibrozil (368). In the ACCORDstudy, the combination of fenofibrate andsimvastatin did not reduce the rate of fatalcardiovascular events, nonfatal MI, ornonfatal stroke, as compared withsimvastatin alone, in patients with type 2diabetes who were at high risk for CVD.Prespecified subgroup analyses suggestedheterogeneity in treatment effectsaccording to sex, with a benefit ofcombination therapy formenandpossibleharm for women, and a possible benefitfor patients with both triglyceride level$204 mg/dL and HDL cholesterol level#34 mg/dL (369). The AIM-HIGH trialrandomized over 3,000 patients (aboutone-third with diabetes) with establishedCVD, low levels of HDL cholesterol, andtriglyceride levels of 150–400 mg/dL tostatin therapy plus extended releaseniacin or matching placebo. The trial washalted early due to lack of efficacy on theprimary CVD outcome (first event of thecomposite of death from coronary heartdisease (CHD), nonfatal MI, ischemicstroke, hospitalization for an acutecoronary syndrome, or symptom-drivencoronary or cerebral revascularization)and a possible increase in ischemic strokein those on combination therapy (370).

Hence, combination lipid-loweringtherapy cannot be broadlyrecommended.

Dyslipidemia Treatment and TargetLipid LevelsUnless they have severehypertriglyceridemia at risk forpancreatitis, for most diabetic patientsthe first priority of dyslipidemia therapyis to lower LDL cholesterol to ,100mg/dL (2.60 mmol/L) (371). Lifestyleintervention, including MNT, increasedphysical activity, weight loss, andsmoking cessation, may allow somepatients to reach lipid goals. Nutritionintervention should be tailoredaccording to each patient’s age,diabetes type, pharmacologicaltreatment, lipid levels, and othermedical conditions. Recommendationsshould focus on the reduction ofsaturated fat, cholesterol, and transunsaturated fat intake and increases inn-3 fatty acids, viscous fiber (such as inoats, legumes, and citrus), and plantstanols/sterols. Glycemic control can alsobeneficially modify plasma lipid levels,particularly in patients with very hightriglycerides and poor glycemic control.

In those with clinical CVD or over age40 years with other CVD risk factors,pharmacological treatment should beadded to lifestyle therapy regardless ofbaseline lipid levels. Statins are thedrugs of choice for LDL cholesterollowering and cardioprotection. Inpatients other than those describedabove, statin treatment should beconsidered if there is an inadequate LDLcholesterol response to lifestylemodifications and improved glucosecontrol or if the patient has increasedcardiovascular risk (e.g., multiplecardiovascular risk factors or longdiabetes duration).

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 HeartProtection Study (lower age limit 40years), the subgroup of ;600 patientswith type 1 diabetes had aproportionately similar reduction in riskto patients with type 2 diabetes,although not statistically significant(350). Although the data are notdefinitive, similar lipid-lowering goalsfor both type 1 and type 2 diabetic

care.diabetesjournals.org Position Statement S39

patients should be considered,particularly if they have othercardiovascular risk factors.

Alternative Lipoprotein GoalsMost trials of statins and CVD outcometested specific doses of statins againstplacebo or other statins, rather thanaiming for specific LDL cholesterol goals(372). Placebo-controlled trials generallyachieved LDL cholesterol reductions of30–40% from baseline. Hence, LDLcholesterol lowering of this magnitude isan acceptable outcome for patients whocannot reach LDL cholesterol goals due tosevere baseline elevations in LDLcholesterol and/or intolerance ofmaximal, or any, statin doses.Additionally for those with baseline LDLcholesterol minimally above 100 mg/dL,prescribing statin therapy to lower LDLcholesterol about 30–40% from baselineis probably more effective thanprescribing just enough to get LDLcholesterol slightly below 100 mg/dL.

Clinical trials in high-risk patients, suchas those with acute coronary syndromesor previous cardiovascular events (373–375), have demonstrated that moreaggressive therapy with high doses ofstatins to achieve an LDL cholesterol of,70mg/dL led to a significant reductionin further events. A reduction in LDLcholesterol to,70mg/dL is an option invery-high-risk diabetic patients withovert CVD (371). Some expertsrecommend a greater focus on non-HDLcholesterol, apolipoprotein B (apoB), orlipoprotein particle measurements toassess residual CVD risk in statin-treatedpatients who are likely to have small LDLparticles, such as people with diabetes(376), but it is unclear whether clinicalmanagement would change with thesemeasurements.

In individual patients, the high variableresponse seen with LDL cholesterollowering with statins is poorlyunderstood (377). Reduction of CVDevents with statins correlates veryclosely with LDL cholesterol lowering(347). If initial attempts to prescribe astatin leads to side effects, cliniciansshould attempt to find a dose oralternative statin that is tolerable.There is evidence for significant LDLcholesterol lowering from evenextremely low, less than daily, statindoses (378). When maximally tolerated

doses of statins fail to significantly lowerLDL cholesterol (,30% reduction fromthe patient’s baseline), there is nostrong evidence that combinationtherapy should be used to achieveadditional LDL cholesterol lowering.Niacin, fenofibrate, ezetimibe, and bileacid sequestrants all offer additional LDLcholesterol lowering to statins alone.However, there is insufficient evidencethat such combination therapy for LDLcholesterol lowering provides asignificant increment in CVD riskreduction over statin therapy alone.

Treatment of Other LipoproteinFractions or TargetsHypertriglyceridemia should beaddressed with dietary and lifestylechanges. Severe hypertriglyceridemia(.1,000 mg/dL) may warrantimmediate pharmacological therapy(fibric acid derivative, niacin, or fish oil)to reduce the risk of acute pancreatitis.If severe hypertriglyceridemia is absent,then therapy targeting HDL cholesterolor triglycerides lacks the strongevidence base of statin therapy. If theHDL cholesterol is ,40 mg/dL and theLDL cholesterol between 100 and 129mg/dL, a fibrate or niacin might be used,especially if a patient is intolerant tostatins. Niacin is the most effective drugfor raising HDL cholesterol. It cansignificantly increase blood glucose athigh doses, but at modest doses(750–2,000 mg/day), significantimprovements in LDL cholesterol, HDLcholesterol, and triglyceride levels areaccompanied by only modest changes inglucose that are generally amenable toadjustment of diabetes therapy(370,379,380).

Table 10 summarizes commontreatment goals for A1C, bloodpressure, and LDL cholesterol.

3. Antiplatelet Agents

Recommendations

c Consider aspirin therapy (75–162 mg/day) as a primary prevention strategy inthose with type 1 or type 2 diabetes atincreased cardiovascular risk (10-yearrisk.10%). This includes most menaged.50 years or women aged.60years who have at least one additionalmajor risk factor (family history of CVD,hypertension, smoking, dyslipidemia, oralbuminuria). C

c Aspirin should not be recommendedfor CVD prevention for adults withdiabetes at low CVD risk (10-year CVDrisk ,5%, such as in men aged ,50years and women aged ,60 yearswith no major additional CVD riskfactors), since the potential adverseeffects from bleeding likely offset thepotential benefits. C

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

c Use aspirin therapy (75–162 mg/day)as a secondary prevention strategy inthose with diabetes with a history ofCVD. A

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

c Dual antiplatelet therapy isreasonable for up to a year after anacute coronary syndrome. B

Aspirin has been shown to be effectivein reducing cardiovascular morbidityand mortality in high-risk patients with

Table 10—Summary of recommendations for glycemic, blood pressure, and lipidcontrol for most adults with diabetesA1C ,7.0%*

Blood pressure ,140/80 mmHg**

LipidsLDL cholesterol ,100 mg/dL (,2.6 mmol/L)†

Statin therapy for those with history of MI or age over 40plus other risk factors

*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. **Based on patient characteristics and response to therapy,lower SBP targets may be appropriate. †In individuals with overt CVD, a lower LDL cholesterolgoal of ,70 mg/dL (1.8 mmol/L), using a high dose of a statin, is an option.

S40 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

previous MI or stroke (secondaryprevention). Its net benefit in primaryprevention among patients with noprevious cardiovascular events is morecontroversial, both for patients with andwithout a history of diabetes (381,382).Two RCTs of aspirin specifically inpatients with diabetes failed to show asignificant reduction in CVD end points,raising further questions about theefficacy of aspirin for primaryprevention in people with diabetes(190,383).

The Antithrombotic Trialists’ (ATT)collaborators published an individualpatient-level meta-analysis of the sixlarge trials of aspirin for primaryprevention in the general population.These trials collectively enrolled over95,000 participants, including almost4,000 with diabetes. Overall, they foundthat aspirin reduced the risk of vascularevents by 12% (RR 0.88 [95% CI 0.82–0.94]). The largest reduction was fornonfatal MI with little effect on CHDdeath (RR 0.95 [95% CI 0.78–1.15]) ortotal stroke. There was some evidenceof a difference in aspirin effect by sex:aspirin significantly reduced CVD eventsin men, but not in women. Conversely,aspirin had no effect on stroke inmen butsignificantly reduced stroke in women.Notably, sex differences in aspirin’seffects have not been observed in studiesof secondary prevention (381). In the sixtrials examined by the ATT collaborators,the effects of aspirin on major vascularevents were similar for patients with orwithout diabetes: RR 0.88 (95% CI 0.67–1.15) and 0.87 (0.79–0.96), respectively.The confidence interval was wider forthose with diabetes because of theirsmaller number.

Based on the currently availableevidence, aspirin appears to have amodest effect on ischemic vascularevents with the absolute decrease inevents depending on the underlyingCVD risk. The main adverse effectsappear to be an increased risk ofgastrointestinal bleeding. The excessrisk may be as high as 1–5 per 1,000 peryear in real-world settings. In adultswith CVD risk greater than 1% per year,the number of CVD events preventedwill be similar to or greater than thenumber of episodes of bleedinginduced, although these complications

do not have equal effects on long-termhealth (384).

In 2010, a position statement of theADA, the American Heart Association(AHA), and the American College ofCardiology Foundation (ACCF)recommends that low-dose (75–162mg/day) aspirin for primary preventionis reasonable for adults with diabetesand no previous history of vasculardisease who are at increased CVD risk(10-year risk of CVD events over 10%) andwho are 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: 1) smoking,2) hypertension, 3) dyslipidemia,4) familyhistory of premature CVD, and 5)albuminuria (385).

However, aspirin is no longerrecommended 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 beoutweighed by the risks of significantbleeding. Clinical judgment should beused for those at intermediate risk(younger patients with one or more riskfactors or older patients with no riskfactors; those with 10-year CVD risk of5–10%) until further research is available.Aspirin use in patients under the age of21 years is contraindicated due to theassociated risk of Reye syndrome.

Average daily dosages used in mostclinical trials involving patients withdiabetes ranged from 50 to 650 mg butwere mostly in the range of 100 to 325mg/day. There is little evidence tosupport any specific dose, but using thelowest possible dosage may help reduceside effects (386). In the U.S., the mostcommon low dose tablet is 81 mg.Although platelets from patients withdiabetes have altered function, it isunclear 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 areindependent of thromboxane A2 andthus not sensitive to the effects ofaspirin (387). Therefore, while “aspirinresistance” appears higher in thediabetic patients when measured by a

variety of ex vivo and in vitro methods(platelet aggrenometry, measurementof thromboxane B2), these observationsalone are insufficient to empiricallyrecommend higher doses of aspirin beused in the diabetic patient at this time.

A P2Y12 receptor antagonist incombinationwith aspirin should be usedfor at least 1 year in patients followingan acute coronary syndrome. Evidencesupports use of either ticagrelor orclopidogrel if no percutaneous coronaryintervention (PCI) was performed, andthe use of clopidogrel, ticagrelor, orprasugrel if PCI was performed (388).

4. Smoking Cessation

Recommendations

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

c Include smoking cessationcounseling and other forms oftreatment as a routine component ofdiabetes care. B

Results from epidemiological, case-control, and cohort studies provideconvincing evidence to support thecausal link between cigarette smokingand health risks. Much of the workdocumenting the effect of smoking onhealth did not separately discuss resultson subsets of individuals with diabetes,but suggests that the identified risks areat least equivalent to those found in thegeneral population. Other studies ofindividuals with diabetes consistentlydemonstrate that smokers (and personsexposed to second-hand smoke) have aheightened risk of CVD, prematuredeath, and increased rate ofmicrovascular complications ofdiabetes. Smokingmay have a role in thedevelopment of type 2 diabetes. Onestudy in smokers with newly diagnosedtype 2 diabetes found that smokingcessation was associated withamelioration of metabolic parametersand reduced blood pressure andalbuminuria at 1 year (389).

The routine and thorough assessmentof tobacco use is key to prevent smokingor encourage cessation. Numerouslarge randomized clinical trialshave demonstrated the efficacy andcost-effectiveness of brief counselingin smoking cessation, including the useof quitlines, in reducing tobacco use.

care.diabetesjournals.org Position Statement S41

For the patient motivated to quit, theaddition of pharmacological therapy tocounseling is more effective than eithertreatment alone. Special considerationsshould include assessment of levelof nicotine dependence, which isassociated with difficulty in quitting andrelapse (390). Although some patientsmay gain weight in the period shortlyafter smoking cessation, recent researchhas demonstrated that this weight gaindoes not diminish the substantial CVDrisk benefit realized from smokingcessation (391).

5. Cardiovascular Disease

Recommendations

Screening

c In asymptomatic patients, routinescreening for CAD is notrecommended because it does notimprove outcomes as long as CVD riskfactors are treated. A

Treatment

c In patients with known CVD, considerACE inhibitor therapy C and useaspirin and statin therapy A (if notcontraindicated) to reduce the risk ofcardiovascular events.

c In patients with a prior MI, b-blockersshould be continued for at least 2years after the event. B

c In patients with symptomatic heartfailure, avoid thiazolidinedionetreatment. C

c In patients with stable CHF,metformin may be used if renalfunction is normal but should beavoided in unstable or hospitalizedpatients with CHF. B

In all patients with diabetes,cardiovascular risk factors should beassessed at least annually. These riskfactors include dyslipidemia,hypertension, smoking, a positive familyhistory of premature coronary disease,and the presence of albuminuria.Abnormal risk factors should be treatedas described elsewhere in theseguidelines. Intensive lifestyleintervention focusing on weight lossthrough decreased caloric intake andincreased physical activity as performedin the Look AHEAD trial may beconsidered for improving glucosecontrol, fitness, and some CVD riskfactors. However, it is not

recommended to reduce CVD events inoverweight or obese adults with type 2diabetes (155). Patients at increasedCVD risk should receive aspirin and astatin, and ACE inhibitor or ARBtherapy if hypertensive, unless thereare contraindications to a particulardrug class. While clear benefit existsfor ACE inhibitor and ARB therapy inpatients with nephropathy orhypertension, the benefits in patientswith CVD in the absence of theseconditions are less clear, especiallywhen LDL cholesterol is concomitantlycontrolled (392,393).

Candidates for advanced or invasivecardiac testing include those with1) typical or atypical cardiac symptomsand 2) an abnormal resting ECG. Thescreening of asymptomatic patientswith high CVD risk is not recommended(257), in part because these high-riskpatients should already be receivingintensive medical therapy, an approachthat provides similar benefit as invasiverevascularization (394,395). There isalso some evidence that silent MI mayreverse over time, adding to thecontroversy concerning aggressivescreening strategies (396). Finally, arecent randomized observational trialdemonstrated no clinical benefit toroutine screening of asymptomaticpatients with type 2 diabetes andnormal ECGs (397). Despite abnormalmyocardial perfusion imaging in morethan one in five patients, cardiacoutcomes were essentially equal (andvery low) in screened versus unscreenedpatients. Accordingly, the overalleffectiveness, especially the cost-effectiveness, of such an indiscriminatescreening strategy is now questioned.

Despite the intuitive appeal, recentstudies have found that a risk factor–based approach to the initial diagnosticevaluation and subsequent follow-upfor CAD fails to identify which patientswith type 2 diabetes will have silentischemia on screening tests (398,399).The effectiveness of newer noninvasiveCAD screening methods, such ascomputed tomography (CT) and CTangiography, to identify patientsubgroups for different treatmentstrategies remains unproven. Althoughasymptomatic diabetic patients foundto have a higher coronary disease

burden have more future cardiac events(400–402), the role of these testsbeyond risk stratification is not clear.Their routine use leads to radiationexposure and may result in unnecessaryinvasive testing such as coronaryangiography and revascularizationprocedures. The ultimate balance ofbenefit, cost, and risks of such anapproach in asymptomatic patientsremains controversial, particularly inthe modern setting of aggressive CVDrisk factor control.

A systematic review of 34,000 patientsshowed that metformin is as safe asother glucose-lowering treatments inpatients with diabetes and CHF, even inthose with reduced left ventricularejection fraction or concomitant chronickidney disease (CKD); however,metformin should be avoided inhospitalized patients (403).

B. Nephropathy

General Recommendations

c Optimize glucose control to reducethe risk or slow the progression ofnephropathy. A

c Optimize blood pressure control toreduce the risk or slow theprogression of nephropathy. A

Screening

c Perform an annual test to quantitateurine albumin excretion in type 1diabetic patients with diabetesduration of$5 years and in all type 2diabetic patients starting atdiagnosis. B

Treatment

c An ACE inhibitor or ARB for theprimary prevention of diabetic kidneydisease is not recommended indiabetic patients with normal bloodpressure and albumin excretion ,30mg/24 h. B

c Either ACE inhibitors or ARBs (but notboth in combination) arerecommended for the treatment ofthe nonpregnant patient withmodestly elevated (30–299 mg/24 h)C or higher levels (.300 mg/24 h) ofurinary albumin excretion. A

c For people with diabetes and diabetickidney disease (albuminuria.30 mg/24 h), reducing the amount of dietaryprotein below usual intake is notrecommended because it does not

S42 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

alter glycemic measures,cardiovascular risk measures, or thecourse of GFR decline. A

c When ACE inhibitors, ARBs, ordiuretics are used, monitor serumcreatinine and potassium levels forthe development of increasedcreatinine or changes in potassium. E

c Continued monitoring of urinealbumin excretion to assess bothresponse to therapy andprogression of disease isreasonable. E

c When eGFR is ,60 mL/min/1.73 m2,evaluate and manage potentialcomplications of CKD. E

c Consider referral to a physicianexperienced in the care of kidneydisease for uncertainty about theetiology of kidney disease, difficultmanagement issues, or advancedkidney disease. B

To be consistent with newernomenclature intended to emphasizethe continuous nature of albuminuriaas a risk factor, the terms“microalbuminuria” (30–299 mg/24 h)and “macroalbuminuria” (.300mg/24 h) will no longer be used, butrather referred to as persistentalbuminuria at levels 30–299 mg/24 hand levels $300 mg/24 h. Normalalbumin excretion is currently definedas ,30 mg/24 h.

Diabetic nephropathy occurs in 20–40%of patients with diabetes and is thesingle leading cause of ESRD. Persistentalbuminuria in the range of 30–299 mg/24 h has been shown to be an early stageof diabetic nephropathy in type 1diabetes and a marker for developmentof nephropathy in type 2 diabetes. It is awell-established marker of increasedCVD risk (404–406). However, there isincreasing evidence of spontaneousremission of albumin levels 30–299 mg/24 h in up to 40% of patients with type 1diabetes. About 30–40% remain with30–299 mg/24 h and do not progress tomore elevated levels of albuminuria($300 mg/24 h) over 5–10 years offollow-up (407–410). Patients withpersistent albuminuria (30–299 mg/24 h)who progress to more significant levels($300 mg/24 h are likely to progress toESRD (411,412).

A number of interventions have beendemonstrated to reduce the risk andslow the progression of renal disease.Intensive diabetes managementwith the goal of achieving near-normoglycemia has been shown in largeprospective randomized studies todelay the onset and progression ofincreased urinary albumin excretion inpatients with type 1 (413) and type 2(85,86,89,90) diabetes. The UKPDSprovided strong evidence that bloodpressure control can reduce thedevelopment of nephropathy (323). Inaddition, large prospective randomizedstudies in patients with type 1 diabeteshave demonstrated that achievementof lower levels of SBP (,140 mmHg)resulting from treatment using ACEinhibitors provides a selective benefitover other antihypertensive drugclasses in delaying the progression ofincreased urinary albumin excretionand can slow the decline in GFR inpatients with higher levels ofalbuminuria (414,415). In type 2diabetes with hypertension andnormoalbuminuria, RAS inhibition hasbeen demonstrated to delay onset ofelevated albuminuria (416,417). In thelatter study, there was an unexpectedhigher rate of fatal cardiovascularevents with olmesartan among patientswith preexisting CHD.

ACE inhibitors have been shown toreduce major CVD outcomes (i.e., MI,stroke, death) in patients with diabetes(338), thus further supporting the use ofthese agents in patients with elevatedalbuminuria, a CVD risk factor. ARBs donot prevent onset of elevatedalbuminuria in normotensive patientswith type 1 or type 2 diabetes (418,419);however, ARBs have been shown toreduce the progression rate of albuminlevels from 30 to 299 mg/24 h to levels$300 mg/24 h as well as ESRD inpatients with type 2 diabetes (420–422).Some evidence suggests that ARBs have asmaller magnitude of rise in potassiumcompared with ACE inhibitors in peoplewith nephropathy (423).

In the absence of side effects or adverseevents (e.g., hyperkalemia or acutekidney injury), it is suggested to titrateup to the maximum approved dose forthe treatment of hypertension.Combinations of drugs that block the

renin-angiotensin-aldosterone system(e.g., an ACE inhibitor plus an ARB, amineralocorticoid antagonist, or a directrenin inhibitor) provide additionallowering of albuminuria (424–427).However, such combinations have beenfound to provide no additionalcardiovascular benefit and have higheradverse event rates (428). At least onerandomized clinical trial has shown anincrease in adverse events, particularlyimpaired kidney function andhyperkalemia, compared with eitheragent alone, despite a reduction inalbuminuria using combination therapy(410).

Diuretics, calcium channel blockers, andb-blockers should be used as additionaltherapy to further lower blood pressurein patients already treated with ACEinhibitors or ARBs (343) or as alternatetherapy in the rare individual unable totolerate ACE inhibitors or ARBs.

Studies in patients with varying stages ofnephropathy have shown that proteinrestriction of dietary protein helps slowthe progression of albuminuria, GFRdecline, and occurrence of ESRD (429–432), althoughmore recent studies haveprovided conflicting results (157).Dietary protein restriction might beconsidered particularly in patientswhose nephropathy seems to beprogressing despite optimal glucose andblood pressure control and use of ACEinhibitor and/or ARBs (432).

Assessment of Albuminuria Status andRenal FunctionScreening for increased urinary albuminexcretion can be performed bymeasurement of the albumin-to-creatinine ratio in a random spotcollection; 24-h or timed collections aremore burdensome and add little toprediction or accuracy (433,434).Measurement of a spot urine foralbumin alone (whether byimmunoassay or by using a dipstick testspecific for albuminuria) withoutsimultaneously measuring urinecreatinine is less expensive butsusceptible to false-negative and-positive determinations as a result ofvariation in urine concentration due tohydration and other factors.

Abnormalities of albumin excretion andthe linkage between albumin-to-creatinine

care.diabetesjournals.org Position Statement S43

ratio and 24-h albumin excretionare defined in Table 11. Because ofvariability in urinary albuminexcretion, two of three specimenscollected within a 3- to 6-month periodshould be abnormal before considering apatient to have developed increasedurinary albumin excretion or had aprogression in albuminuria. Exercisewithin 24 h, infection, fever, CHF,marked hyperglycemia, and markedhypertension may elevate urinaryalbumin excretion over baselinevalues.

Information on presence of abnormalurine albumin excretion in addition tolevel of GFR may be used to stage CKD.The National Kidney Foundationclassification (Table 12) is primarilybased on GFR levels and may besuperseded by other systems in whichstaging includes other variables such asurinary albumin excretion (435).Studies have found decreased GFR inthe absence of increased urine albuminexcretion in a substantial percentageof adults with diabetes (436).Substantial evidence shows that inpatients with type 1 diabetes andpersistent albumin levels 30–299mg/24 h, screening with albuminexcretion rate alone would miss .20%of progressive disease (410). Serumcreatinine with estimated GFR shouldtherefore be assessed at least annuallyin all adults with diabetes, regardlessof the degree of urine albuminexcretion.

Serum creatinine should be used toestimate GFR and to stage the level ofCKD, if present. eGFR is commonlycoreported by laboratories or can be

estimated using formulae such as the

Modification of Diet in Renal Disease

(MDRD) study equation (437) or the

CKD-EPI equation. GFR calculators areavailable at http://www.nkdep.nih.gov.

The role of continued annualquantitative assessment of albuminexcretion after diagnosis of albuminuriaand institution of ACE inhibitor or ARBtherapy and blood pressure control isunclear. Continued surveillance canassess both response to therapy andprogression of disease. Some suggestthat reducing albuminuria to the normal(,30 mg/g) or near-normal range mayimprove renal and cardiovascularprognosis, but this approach has notbeen formally evaluated in prospectivetrials, and more recent evidencereported spontaneous remission ofalbuminuria in up to 40% of type 1diabetic patients.

Conversely, patients with increasingalbumin levels, declining GFR, increasingblood pressure, retinopathy,macrovascular disease, elevated lipidsand/or uric acid concentrations, ora family history of CKD are more likely toexperience a progression of diabetickidney disease (410).

Complications of kidney diseasecorrelate with level of kidney function.When the eGFR is,60mL/min/1.73m2,screening for complications of CKD isindicated (Table 13). Early vaccinationagainst HBV is indicated in patients likelyto progress to end-stage kidney disease.

Consider referral to a physicianexperienced in the care of kidneydisease when there is uncertainty aboutthe etiology of kidney disease (heavyproteinuria, active urine sediment,absence of retinopathy, rapid decline inGFR, and resistant hypertension). Othertriggers for referral may include difficultmanagement issues (anemia, secondaryhyperparathyroidism, metabolic bonedisease, or electrolyte disturbance) or

advanced kidney disease. The thresholdfor referral may vary depending on thefrequency with which a providerencounters diabetic patients withsignificant kidney disease. Consultationwith a nephrologist when stage 4 CKDdevelops has been found to reduce cost,improve quality of care, and keeppeople off dialysis longer (438).However, nonrenal specialists shouldnot delay educating their patients aboutthe progressive nature of diabetickidney disease, the renal preservationbenefits of aggressive treatment ofblood pressure, blood glucose, andhyperlipidemia, and the potential needfor renal transplant.

C. Retinopathy

General Recommendations

c Optimize glycemic control to reducethe risk or slow the progression ofretinopathy. A

c Optimize blood pressure control toreduce the risk or slow theprogression of retinopathy. A

Screening

c Adults with type 1 diabetes shouldhave an initial dilated andcomprehensive eye examination byan ophthalmologist or optometristwithin 5 years after the onset ofdiabetes. B

c Patients with type 2 diabetes shouldhave an initial dilated andcomprehensive eye examination byan ophthalmologist or optometristshortly after the diagnosis ofdiabetes. B

c If there is no evidence of retinopathyfor one or more eye exams, thenexams every 2 years may beconsidered. If diabetic retinopathy ispresent, subsequent examinationsfor type 1 and type 2 diabetic patients

Table 11—Definitions ofabnormalities in albumin excretion

CategorySpot collection

(mg/mg creatinine)

Normal ,30

Increased urinaryalbumin excretion*

$30

*Historically, ratios between 30 and 299have been called microalbuminuria andthose 300 or greater have been calledmacroalbuminuria (or clinical albuminuria).

Table 12—Stages of chronic kidney disease

Stage DescriptionGFR (mL/min/1.73 m2 body

surface area)

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 defined as abnormalities on pathologic, urine, blood, or imaging tests. Adaptedfrom Levey et al. (434).

S44 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

should be repeated annually by anophthalmologist or optometrist. Ifretinopathy is progressing or sightthreatening, then examinations willbe required more frequently. B

c High-quality fundus photographs candetect most clinically significantdiabetic retinopathy. Interpretationof the images should be performedby a trained eye care provider. Whileretinal photography may serve as ascreening tool for retinopathy, it isnot a substitute for a comprehensiveeye exam, which should beperformed at least initially and atintervals thereafter as recommendedby an eye care professional. E

c Women with preexisting diabeteswho are planning pregnancy or whohave become pregnant should have acomprehensive eye examinationand be counseled on the risk ofdevelopment and/or progressionof diabetic retinopathy. Eyeexamination should occur in the firsttrimester with close follow-upthroughout pregnancy and for 1 yearpostpartum. B

Treatment

c Promptly refer patients with any levelof macular edema, severe NPDR, orany PDR to an ophthalmologist who isknowledgeable and experienced inthe management and treatment ofdiabetic retinopathy. A

c Laser photocoagulation therapy isindicated to reduce the risk of vision

loss in patients with high-risk PDR,clinically significant macular edema,and in some cases severe NPDR. A

c Anti-vascular endothelial growthfactor (VEGF) therapy is indicated fordiabetic macular edema. A

c The presence of retinopathy is not acontraindication to aspirin therapyfor cardioprotection, as this therapydoes not increase the risk of retinalhemorrhage. A

Diabetic retinopathy is a highly specificvascular complication of both type 1 andtype 2 diabetes, with prevalencestrongly related to the duration ofdiabetes. Diabetic retinopathy is themost frequent cause of new cases ofblindness among adults aged 20–74years. Glaucoma, cataracts, and otherdisorders of the eye occur earlier andmore frequently in people withdiabetes.

In addition to duration of diabetes,factors that increase the risk of, or areassociated with, retinopathy includechronic hyperglycemia (439),nephropathy (440), and hypertension(441). Intensive diabetes managementwith the goal of achieving near-normoglycemia has been shown in largeprospective randomized studies toprevent and/or delay the onset andprogression of diabetic retinopathy(76,85,86,442). Lowering bloodpressure has been shown to decreasethe progression of retinopathy (323),

although tight targets (systolic ,120mmHg) do not impart additional benefit(442). Several case series and acontrolled prospective study suggestthat pregnancy in type 1 diabeticpatients may aggravate retinopathy(443,444). Laser photocoagulationsurgery can minimize this risk (444).

One of the main motivations forscreening for diabetic retinopathy is thelong-established efficacy of laserphotocoagulation surgery in preventingvisual loss. Two large trials, the DiabeticRetinopathy Study (DRS) in patientswith PDR and the Early TreatmentDiabetic Retinopathy Study (ETDRS) inpatients with macular edema, providethe strongest support for thetherapeutic benefits ofphotocoagulation surgery. The DRS(445) showed that panretinalphotocoagulation surgery reduced therisk of severe vision loss from PDR from15.9% in untreated eyes to 6.4% intreated eyes, with greatest risk-benefitratio in those with baseline disease (discneovascularization or vitreoushemorrhage).

The ETDRS (446) established the benefitof focal laser photocoagulation surgeryin eyes withmacular edema, particularlythose with clinically significant macularedema, with reduction of doubling ofthe visual angle (e.g., 20/50 to 20/100)from 20% in untreated eyes to 8%in treated eyes. The ETDRS alsoverified the benefits of panretinalphotocoagulation for high-risk PDR andin older-onset patients with severeNPDR or less-than-high-risk PDR.

Laser photocoagulation surgery in bothtrials was beneficial in reducing the riskof further visual loss, but generally notbeneficial in reversing alreadydiminished acuity. Recombinantmonoclonal neutralizing antibody toVEGF improves vision and reduces theneed for laser photocoagulation inpatients with macular edema (447).Other emerging therapies forretinopathy include sustainedintravitreal delivery of fluocinolone(448) and the possibility of preventionwith fenofibrate (449,450).

The preventive effects of therapy andthe fact that patients with PDR ormacular edema may be asymptomatic

Table 13—Management of CKD in diabetes

GFR Recommended

All patients Yearly measurement of creatinine, urinary albumin excretion, potassium

45–60 Referral to a nephrologist if possibility for nondiabetic kidney disease exists(duration of type 1 diabetes ,10 years, heavy proteinuria, abnormalfindings on renal ultrasound, resistant hypertension, rapid fall in GFR, oractive urinary sediment on ultrasound)

Consider need for dose adjustment of medicationsMonitor eGFR every 6 monthsMonitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus,parathyroid hormone at least yearly

Assure vitamin D sufficiencyConsider bone density testingReferral for dietary counseling

30–44 Monitor eGFR every 3 monthsMonitor electrolytes, bicarbonate, calcium, phosphorus, parathyroidhormone, hemoglobin, albumin, weight every 3–6 months

Consider need for dose adjustment of medications

,30 Referral to a nephrologist

Adapted from http://www.kidney.org/professionals/KDOQI/guideline_diabetes.

care.diabetesjournals.org Position Statement S45

provide strong support for a screeningprogram to detect diabeticretinopathy. Because retinopathy isestimated to take at least 5 years todevelop after the onset ofhyperglycemia, patients with type 1diabetes should have an initial dilatedand comprehensive eye examinationwithin 5 years after the diabetes (451).Patients with type 2 diabetes, whomay have had years of undiagnoseddiabetes and who have a significantrisk of prevalent diabetic retinopathyat time of diagnosis should have aninitial dilated and comprehensive eyeexamination. Examinations should beperformed by an ophthalmologist oroptometrist who is knowledgeableand experienced in diagnosingdiabetic retinopathy. Subsequentexaminations for type 1 and type 2diabetic patients are generallyrepeated annually. Exams every 2 yearsmay be cost-effective after one ormore normal eye exams, and in apopulation with well-controlled type 2diabetes there was essentially no riskof development of significantretinopathy with a 3-year intervalafter a normal examination (452).Examinations will be required morefrequently if retinopathy isprogressing.

Retinal photography, with remotereading by experts, has great potentialin areas where qualified eye careprofessionals are not available. It mayalso enhance efficiency and reduce costswhen the expertise of ophthalmologistscan be used for more complexexaminations and for therapy (453). In-person exams are still necessary whenthe photos are unacceptable and forfollow-up of abnormalities detected.Photos are not a substitute for acomprehensive eye exam, which shouldbe performed at least initially and atintervals thereafter as recommended byan eye care professional. Results of eyeexaminations should be documentedand transmitted to the referring healthcare professional.

D. Neuropathy

Recommendations

c All patients should be screened fordistal symmetric polyneuropathy(DPN) starting at diagnosis of type 2diabetes and 5 years after the

diagnosis of type 1 diabetes and atleast annually thereafter, usingsimple clinical tests. B

c Electrophysiological testing orreferral to a neurologist is rarelyneeded, except in situationswhere the clinical features areatypical. E

c Screening for signs and symptoms ofCAN should be instituted at diagnosisof type 2 diabetes and 5 years afterthe diagnosis of type 1 diabetes.Special testing is rarely needed andmay not affect management oroutcomes. E

c Medications for the relief of specificsymptoms related to painful DPN andautonomic neuropathy arerecommended because they mayreduce pain B and improve quality oflife. E

The diabetic neuropathies areheterogeneous with diverse clinicalmanifestations. They may be focal ordiffuse. The most prevalentneuropathies are chronic sensorimotorDPN and autonomic neuropathy.Although DPN is a diagnosis ofexclusion, complex investigations orreferral for neurology consultation toexclude other conditions is rarelyneeded.

The early recognition and appropriatemanagement of neuropathy in thepatient with diabetes is important for anumber of reasons:

1. Nondiabetic neuropathies may bepresent in patients with diabetes andmay be treatable.

2. A number of treatment options existfor symptomatic diabeticneuropathy.

3. Up to 50% of DPN may beasymptomatic and patients are atrisk for insensate injury to their feet.

4. Autonomic neuropathy andparticularly CAN is an independentrisk factor for cardiovascularmortality (261,454).

Specific treatment for the underlyingnerve damage is currently notavailable, other than improvedglycemic control, which may modestlyslow progression in type 2 diabetes(90) but not reverse neuronal loss.

Effective symptomatic treatments areavailable for the neuropathic pain ofDPN such as neuropathic pain (455)and for limited symptoms ofautonomic neuropathy.

Diagnosis of Neuropathy

Distal Symmetric Polyneuropathy. Patientswith diabetes should be screenedannually for DPN symptoms usingsimple clinical tests. Symptoms varyaccording to the class of sensory fibersinvolved. The most common symptomsare induced by the involvement of smallfibers and include pain, dysesthesias(unpleasant abnormal sensations ofburning and tingling associated withperipheral nerve lesions), andnumbness. Clinical tests includeassessment of vibration thresholdusing a 128-Hz tuning fork, pinpricksensation and light touch perceptionusing a 10-g monofilament, and anklereflexes. Assessment should follow thetypical DPN pattern, starting distally(the dorsal aspect of the hallux) on bothsides and move proximally untilthreshold is detected. Several clinicalinstruments that combine more thanone test have .87% sensitivity indetecting DPN (83,456,457).

In patients with severe or atypicalneuropathy, causes other than diabetesshould always be considered, such asneurotoxic medications, heavy metalpoisoning, alcohol abuse, vitamin B12deficiency (especially in those takingmetformin for prolonged periods) (458),renal disease, chronic inflammatorydemyelinating neuropathy, inheritedneuropathies, and vasculitis (459).

Diabetic Autonomic Neuropathy. Thesymptoms and signs of autonomicdysfunction should be elicited carefullyduring the history and physicalexamination. Major clinicalmanifestations of diabetic autonomicneuropathy include resting tachycardia,exercise intolerance, orthostatichypotension, constipation,gastroparesis, erectile dysfunction,sudomotor dysfunction, impairedneurovascular function, and,potentially, autonomic failure inresponse to hypoglycemia.

Cardiovascular Autonomic Neuropathy.

CAN is the most studied and clinicallyimportant form of diabetic autonomic

S46 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

neuropathy because of its associationwith mortality risk independent ofother cardiovascular risk factors(261,397). In early stages CAN may becompletely asymptomatic and detectedby changes in heart rate variability andabnormal cardiovascular reflex tests(R-R response to deep breathing,standing and Valsalva maneuver).Advanced disease may be indicated byresting tachycardia (.100 bpm) andorthostasis (a fall in SBP .20 mmHg orDBP of at least 10 mmHg upon standingwithout an appropriate heart rateresponse). The standard cardiovascularreflex testing, especially the deep-breathing test, is noninvasive, easy toperform, reliable, and reproducible andhas prognostic value. Although somesocieties have developed guidelines forscreening for CAN, the benefits ofsophisticated testing beyond riskstratification are not clear (460).

Gastrointestinal Neuropathies.

Gastrointestinal neuropathies (e.g.,esophageal enteropathy, gastroparesis,constipation, diarrhea, fecalincontinence) may involve any sectionof the gastrointestinal tract. Gastroparesisshould be suspected in individuals witherratic glucose control or with uppergastrointestinal symptoms without otheridentified cause. Evaluation of solid-phasegastric emptying using double-isotopescintigraphymaybedone if symptoms aresuggestive, but test results often correlatepoorly with symptoms. Constipation isthe most common lower-gastrointestinalsymptom but can alternate with episodesof diarrhea.

Genitourinary Tract Disturbances.

Diabetic autonomic neuropathy is alsoassociated with genitourinary tractdisturbances. In men, diabeticautonomic neuropathy may causeerectile dysfunction and/or retrogradeejaculation. Evaluation of bladderdysfunction should be performed forindividuals with diabetes who haverecurrent urinary tract infections,pyelonephritis, incontinence, or apalpable bladder.

Treatment

Glycemic Control. Tight and stableglycemic control, implemented as earlyas possible has been shown toeffectively prevent the development ofDPN and autonomic neuropathy in

patients with type 1 diabetes for manyyears (461–464). While the evidence isnot as strong for type 2 diabetes as fortype 1 diabetes, some studies havedemonstrated a modest slowing ofprogression (90,465) without reversal ofneuronal loss. Several observationalstudies further suggest that neuropathicsymptoms improve not only withoptimization of control but also with theavoidance of extreme blood glucosefluctuations.

Distal Symmetric Polyneuropathy. DPNsymptoms, and especially neuropathicpain, can be severe, have sudden onset,and are associated with lower quality oflife, limited mobility, depression, andsocial dysfunction (466). There is limitedclinical evidence regarding the mosteffective treatments for individualpatient needs given the wide range ofavailable medications (467,468). Twodrugs have been approved for relief ofDPN pain in the U.S.dpregabalin andduloxetinedbut neither of theseaffords complete relief, even when usedin combination. Venlafaxine,amitriptyline, gabapentin, valproate,opioids (morphine sulfate, tramadol,and oxycodone controlled-release) mayalso be effective and could beconsidered for treatment of painfulDPN. Head-to-head treatmentcomparisons and studies that includequality-of-life outcomes are rare, sotreatment decisions must often follow atrial-and-error approach. Given therange of partially effective treatmentoptions, a tailored and step-wisepharmacological strategy with carefulattention to relative symptomimprovement, medication adherence,and medication side effects isrecommended to achieve pain reductionand improve quality of life (455).

Autonomic Neuropathy. An intensivemultifactorial cardiovascular riskintervention targeting glucose, bloodpressure, lipids, smoking, and otherlifestyle factors has been shown to reducethe progression and development of CANamong patients with type 2 diabetes(469).

Orthostatic Hypotension. Treatment oforthostatic hypotension is challenging.The therapeutic goal is to minimizepostural symptoms rather than torestore normotension. Most patients

require the use of both pharmacologicaland nonpharmacological measures(e.g., avoiding medications thataggravate hypotension, usingcompressive garments over the legs andabdomen).

Gastroparesis Symptoms. Gastroparesissymptoms may improve with dietarychanges and prokinetic agents such aserythromycin. Recently, the EuropeanMedicines Agency (www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/07/WC500146614.pdf) decided that risks of extrapyramidalsymptoms with metoclopramideoutweigh benefits. In Europe,metoclopramide use is now restrictedto a maximum use of 5 days and is nolonger indicated for the long-termtreatment of gastroparesis. Although theFDA decision is pending, it is suggestedthat metoclopramide be reserved to onlythe most severe cases that areunresponsive to other therapies. Sideeffects should be closely monitored.

Erectile Dysfunction. Treatments forerectile dysfunction may includephosphodiesterase type 5 inhibitors,intracorporeal or intraurethralprostaglandins, vacuum devices, orpenile prostheses. Interventions forother manifestations of autonomicneuropathy are described in the ADAstatement on neuropathy (468). As withDPN treatments, these interventions donot change the underlying pathologyand natural history of the diseaseprocess, but may have a positive impacton the quality of life of the patient.

E. Foot Care

Recommendations

c For all patients with diabetes,perform an annual comprehensivefoot examination to identify riskfactors predictive of ulcers andamputations. The foot examinationshould include inspection,assessment of foot pulses, and testingfor loss of protective sensation (LOPS)(10-g monofilament plus testing anyone of the following: vibration using128-Hz tuning fork, pinpricksensation, ankle reflexes, or vibrationperception threshold). B

c Provide general foot self-careeducation to all patients withdiabetes. B

care.diabetesjournals.org Position Statement S47

c A multidisciplinary approach isrecommended for individuals withfoot ulcers and high-risk feet,especially those with a history of priorulcer or amputation. B

c Refer patients who smoke, have LOPSand structural abnormalities, or havehistory of prior lower-extremitycomplications to foot care specialistsfor ongoing preventive care andlifelong surveillance. C

c Initial screening for peripheralarterial disease (PAD) shouldinclude a history for claudication andan assessment of the pedal pulses.Consider obtaining an ankle-brachialindex (ABI), as many patients withPAD are asymptomatic. C

c Refer patients with significantclaudication or a positive ABI forfurther vascular assessment andconsider exercise, medications, andsurgical options. C

Amputation and foot ulceration,consequences of diabetic neuropathyand/or PAD, are common and are majorcauses of morbidity and disability inpeople with diabetes. Loss of 10-gmonofilament perception and reducedvibration perception predict footulcers (468). Early recognition andmanagement of risk factors can preventor delay adverse outcomes.

The risk of ulcers or amputations isincreased in people who have thefollowing risk factors:

c Previous amputationc Past foot ulcer historyc Peripheral neuropathyc Foot deformityc Peripheral vascular diseasec Visual impairmentc Diabetic nephropathy (especially

patients on dialysis)c Poor glycemic controlc Cigarette smoking

In 2008, ADA published screeningrecommendations (470). Clinicians areencouraged to review this report forfurther details and practical descriptionsof how to perform components of thecomprehensive foot examination.

ExaminationAll adults with diabetes shouldundergo a comprehensive foot

examination to identify high-riskconditions at least annually. Cliniciansshould ask about history of previousfoot ulceration or amputation,neuropathic or peripheral vascularsymptoms, impaired vision, tobaccouse, and foot care practices. A generalinspection of skin integrity andmusculoskeletal deformities should bedone in a well-lit room. Vascularassessment would include inspectionand assessment of pedal pulses.

The neurological exam recommended isdesigned to identify LOPS rather thanearly neuropathy. The clinicalexamination to identify LOPS is simpleand requires no expensive equipment.Five simple clinical tests (use of a 10-gmonofilament, vibration testing using a128-Hz tuning fork, tests of pinpricksensation, ankle reflex assessment, andtesting vibration perception thresholdwith a biothesiometer), each withevidence from well-conductedprospective clinical cohort studies, areconsidered useful in the diagnosis ofLOPS in the diabetic foot. The task forceagreed that any of the five tests listedcould be used by clinicians to identifyLOPS, although ideally two of theseshould be regularly performed duringthe screening examdnormally the 10-gmonofilament and one other test. Oneor more abnormal tests would suggestLOPS, while at least two normal tests(and no abnormal test) would rule outLOPS. The last test listed, vibrationassessment using a biothesiometer orsimilar instrument, is widely used in theU.S.; however, identification of thepatient with LOPS can easily be carriedout without this or other expensiveequipment.

ScreeningInitial screening for PAD shouldinclude a history for claudication and anassessment of the pedal pulses. Adiagnostic ABI should be performed inany patient with symptoms of PAD. Dueto the high estimated prevalence of PADin patients with diabetes and the factthat many patients with PAD areasymptomatic, an ADA consensusstatement on PAD (471) suggestedthat a screening ABI be performed inpatients over 50 years of age and beconsidered in patients under 50 years ofage who have other PAD risk factors

(e.g., smoking, hypertension,hyperlipidemia, or duration of diabetes.10 years). Refer patients withsignificant symptoms or a positive ABIfor further vascular assessment andconsider exercise, medications, andsurgical options (471).

Patient EducationPatients with diabetes and high-risk footconditions should be educatedregarding their risk factors andappropriate management. Patients atrisk should understand the implicationsof LOPS, the importance of footmonitoring on a daily basis, the propercare of the foot, including nail and skincare, and the selection of appropriatefootwear. Patients with LOPS should beeducated on ways to substitute othersensory modalities (hand palpation,visual inspection) for surveillance ofearly foot problems. Patients’understanding of these issues and theirphysical ability to conduct proper footsurveillance and care should beassessed. Patients with visualdifficulties, physical constraintspreventing movement, or cognitiveproblems that impair their ability toassess the condition of the foot and toinstitute appropriate responses willneed other people, such as familymembers, to assist in their care.

TreatmentPeople with neuropathy or evidence ofincreased plantar pressure (e.g.,erythema, warmth, callus, or measuredpressure) may be adequately managedwithwell-fittedwalking shoes or athleticshoes that cushion the feet andredistribute pressure. Callus can bedebrided 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 withcommercial therapeutic footwear mayneed custom-molded shoes.

Most diabetic foot infections arepolymicrobial, with aerobic gram-positive cocci (GPC), and especiallystaphylococci, the most commoncausative organisms.

S48 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

Wounds without evidence of soft tissueor bone infection do not requireantibiotic therapy.

Empiric antibiotic therapy can benarrowly targeted at GPC in manyacutely infected patients, but those atrisk for infection with antibiotic-resistant organisms or with chronic,previously treated, or severe infectionsrequire broader spectrum regimens andshould be referred to specialized carecenters (472). Foot ulcers and woundcare may require care by a podiatrist,orthopedic or vascular surgeon, orrehabilitation specialist experienced inthe management of individuals withdiabetes. Guidelines for treatment ofdiabetic foot ulcers have recently beenupdated (472).

VII. ASSESSMENT OF COMMONCOMORBID CONDITIONS

Recommendation

c Consider assessing for and addressingcommon comorbid conditions thatmay complicate the management ofdiabetes. B

Improved disease prevention andtreatment efficacy means that patientswith diabetes are living longer, oftenwith multiple comorbidities requiringcomplicated medical regimens (473). Inaddition to the commonly appreciatedcomorbidities of obesity, hypertension,and dyslipidemia, diabetesmanagement is often complicated byconcurrent conditions such as heartfailure, depression and anxiety, arthritis,and other diseases or conditions at rateshigher than those of age-matchedpeople without diabetes. Theseconcurrent conditions present clinicalchallenges related to polypharmacy,prevalent symptoms, and complexity ofcare (474–477).

DepressionAs discussed in Section V.H, depression,anxiety, and other mental healthsymptoms are highly prevalent inpeople with diabetes and are associatedwith worse outcomes.

Obstructive Sleep ApneaAge-adjusted rates of obstructive sleepapnea, a risk factor for CVD, aresignificantly higher (4- to 10-fold) withobesity, especially with central obesity,

in men and women (478). Theprevalence in general populations withtype 2 diabetes may be up to 23% (479)and in obese participants enrolled in theLook AHEAD trial exceeded 80% (480).Treatment of sleep apnea significantlyimproves quality of life and bloodpressure control. The evidence for atreatment effect on glycemic control ismixed (481).

Fatty Liver DiseaseUnexplained elevations of hepatictransaminase concentrations aresignificantly associated with higher BMI,waist circumference, triglycerides, andfasting insulin, and with lower HDLcholesterol. In a prospective analysis,diabetes was significantly associatedwith incident nonalcoholic chronic liverdisease and with hepatocellularcarcinoma (482). Interventions thatimprove metabolic abnormalities inpatients with diabetes (weight loss,glycemic control, treatment withspecific drugs for hyperglycemia ordyslipidemia) are also beneficial forfatty liver disease (483).

CancerDiabetes (possibly only type 2 diabetes)is associated with increased risk ofcancers of the liver, pancreas,endometrium, colon/rectum, breast,and bladder (484). The association mayresult from shared risk factors betweentype 2 diabetes and cancer (obesity, age,physical inactivity) but may also be dueto hyperinsulinemia or hyperglycemia(485,486). Patients with diabetesshould be encouraged to undergorecommended age- and sex-appropriatecancer screenings and to reduce theirmodifiable cancer risk factors (obesity,smoking, physical inactivity).

FracturesAge-matched hip fracture risk issignificantly increased in both type 1(summary RR 6.3) and type 2 diabetes(summary RR 1.7) in both sexes (487).Type 1 diabetes is associated withosteoporosis, but in type 2 diabetesan increased risk of hip fracture isseen despite higher bone mineraldensity (BMD) (488). In three largeobservational studies of older adults,femoral neck BMD T score and theWHOFracture Risk Algorithm (FRAX) scorewere associated with hip and nonspine

fracture, although fracture risk washigher in diabetic participantscompared with participants withoutdiabetes for a given T score and age orfor a given FRAX score risk (489). It isappropriate to assess fracture historyand risk factors in older patients withdiabetes and recommend BMD testing ifappropriate for the patient’s age andsex. Prevention strategies are the sameas for the general population. For type 2diabetic patients with fracture riskfactors, avoiding use ofthiazolidinediones is warranted.

Cognitive ImpairmentDiabetes is associated with significantlyincreased risk and rate of cognitivedecline and increased risk of dementia(490,491). In a 15-year prospectivestudy of community-dwelling peopleover the age of 60 years, the presence ofdiabetes at baseline significantlyincreased the age- and sex-adjustedincidence of all-cause dementia,Alzheimer disease, and vasculardementia compared with rates in thosewith normal glucose tolerance (492).In a substudy of the ACCORD study,there were no differences in cognitiveoutcomes between intensive andstandard glycemic control, althoughthere was significantly less of adecrement in total brain volume by MRIin participants in the intensive arm(493). The effects of hyperglycemia andinsulin on the brain are areas of intenseresearch 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 (494).Treatment in asymptomatic men iscontroversial. The evidence for effectsof testosterone replacement onoutcomes is mixed, and recentguidelines suggest that screening andtreatment of men without symptomsare not recommended (495).

Periodontal DiseasePeriodontal disease is more severe, butnot necessarily more prevalent, inpatients with diabetes than in thosewithout (496). Current evidencesuggests that periodontal diseaseadversely affects diabetes outcomes,although evidence for treatmentbenefits is currently lacking (477).

care.diabetesjournals.org Position Statement S49

Hearing ImpairmentHearing impairment, both highfrequency and low/mid frequency, ismore common in people with diabetes,perhaps due to neuropathy and/orvascular disease. In NHANES analysis,hearing impairment was about twice asgreat in people with diabetes comparedwith those without, after adjusting forage and other risk factors for hearingimpairment (497).

VIII. DIABETES CARE IN SPECIFICPOPULATIONS

A. Children and Adolescents

1. Type 1 Diabetes

Three-quarters of all cases of type 1diabetes are diagnosed in individuals,18 years of age. The provider mustconsider the unique aspects of careand management of children andadolescents with type 1 diabetes, suchas changes in insulin sensitivity relatedto sexual maturity and physical growth,ability to provide self-care, supervisionin child care and school, and uniqueneurological vulnerability tohypoglycemia and DKA. Attention tofamily dynamics, developmental stages,and physiological differences related tosexual maturity are all essential indeveloping and implementing anoptimal diabetes regimen. Due to thepaucity of clinical research in children,the recommendations for children andadolescents are less likely to be basedon clinical trial evidence. However,expert opinion and a review of availableand relevant experimental data aresummarized in the ADA statement oncare of children and adolescents withtype 1 diabetes (498).

The care of a child or adolescent withtype 1 diabetes should be provided by amultidisciplinary team of specialiststrained in pediatric diabetesmanagement. At the very least,education of the child and family shouldbe provided by health care providerstrained and experienced in childhooddiabetes and sensitive to the challengesposed by diabetes in this age-group. It isessential that DSME, MNT, andpsychosocial support be provided atdiagnosis and regularly thereafter byindividuals experienced with theeducational, nutritional, behavioral, andemotional needs of the growing child

and family. The balance between adultsupervision and self-care should bedefined at the first interaction and re-evaluated at each clinic visit. Thisrelationship will evolve as the childreaches physical, psychological, andemotional maturity.

a. Glycemic Control

Recommendation

c Consider age when setting glycemicgoals in children and adolescents withtype 1 diabetes. E

Current standards for diabetesmanagement reflect the need to lowerglucose as safely possible. This shouldbe done with step-wise goals. Specialconsideration should be given to theunique risks of hypoglycemia in youngchildren. For young children (,7 yearsold), glycemic goals may need to bemodified since most at that age have aform of “hypoglycemic unawareness,”including immaturity of and a relativeinability to recognize and respond tohypoglycemic symptoms. This placesthem at greater risk for severehypoglycemia. While it was previouslythought that young children were at riskfor cognitive impairment after episodesof severe hypoglycemia, current datahave not confirmed this (295,499,500).Furthermore, new therapeuticmodalities, such as rapid and long-actinginsulin analogs, technological advances(e.g., low glucose suspend), andeducation may mitigate the incidenceof severe hypoglycemia (501). Inadolescents, the DCCT demonstratedthat near-normalization of blood glucoselevels was more difficult to achievecompared with adults. Nevertheless, theincreased frequency of basal-bolusregimens and insulin pumps in youthfrom infancy through adolescence hasbeen associated with more childrenreaching ADA blood glucose targets(502–504) in those families in whichboth parents and the child with diabetesparticipate jointly to perform therequired diabetes-related tasks.Furthermore, studies documentingneurocognitive imaging differences ofhyperglycemia in children provideanother compelling motivation forachieving glycemic targets (505).

In selecting glycemic goals, the long-term health benefits of achieving a

lower A1C should be balanced againstthe risks of hypoglycemia and thedevelopmental burdens of intensiveregimens in children and youth. Age-specific glycemic and A1C goals arepresented in Table 14.

b. Screening and Management ofComplications

i. Nephropathy

Recommendations

Screening

c Annual screening for albumin levels,with a random spot urine sample foralbumin-to-creatinine ratio (ACR),should be considered for the child atthe start of puberty or at age $10years, whichever is earlier, once theyouth has had diabetes for 5 years. B

Treatment

c Treatment with an ACE inhibitor,titrated to normalization of albuminexcretion, should be consideredwhen elevated ACR is subsequentlyconfirmed on two additionalspecimens from different days. Thisshould be obtained over a 6-monthinterval following efforts to improveglycemic control and normalize bloodpressure for age. E

Recent research demonstrates theimportance of good glycemic and bloodpressue control, especially as diabetesduration increases (506).

ii. Hypertension

Recommendations

Screening

c Blood pressure should be measured ateach routine visit. Children found to havehigh-normal blood pressure orhypertension shouldhavebloodpressureconfirmed on a separate day. B

Treatment

c Initial treatment of high-normalblood pressure (SBP or DBPconsistently above the 90thpercentile for age, sex, and height)includes dietary intervention andexercise, aimed at weight controland increased physical activity, ifappropriate. If target blood pressureis not reached with 3–6 monthsof lifestyle intervention,pharmacological treatment shouldbe considered. E

S50 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

c Pharmacological treatment ofhypertension (SBP or DBPconsistently above the 95thpercentile for age, sex, and height orconsistently .130/80 mmHg, if 95%exceeds that value) should beconsidered as soon as the diagnosis isconfirmed. E

c ACE inhibitors should be consideredfor the initial pharmacologicaltreatment of hypertension, followingappropriate reproductive counselingdue to its potential teratogeniceffects. E

c The goal of treatment is bloodpressure consistently ,130/80 orbelow the 90th percentile forage, sex, and height, whichever islower. E

Blood pressure measurements shouldbe determined correctly, using theappropriate size cuff, and with the childseated and relaxed. Hypertensionshould be confirmed on at least threeseparate days. Normal blood pressurelevels for age, sex, and heightand appropriate methods fordeterminations are available online atwww.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf.

iii. Dyslipidemia

Recommendations

Screening

c If there is a family history ofhypercholesterolemia or a

cardiovascular event before age 55years, or if family history is unknown,then consider obtaining a fasting lipidprofile in children.2 years of age soonafter the diagnosis (after glucosecontrol has been established). If familyhistory is not of concern, then considerthefirst lipid screeningat puberty ($10years). For children diagnosed withdiabetes at or after puberty, considerobtaining a fasting lipid profile soonafter the diagnosis (after glucosecontrol has been established). E

c For both age-groups, if lipids areabnormal, annual monitoring isreasonable. If LDL cholesterol valuesare within the accepted risk levels(,100 mg/dL [2.6 mmol/L]), a lipidprofile repeated every 5 years isreasonable. E

Treatment

c Initial therapy may consist ofoptimization of glucose control andMNT using a Step 2 AHA diet aimedat a decrease in the amount ofsaturated fat in the diet. E

c After the age of 10 years, the additionof a statin in patients who, after MNTand lifestyle changes, have LDLcholesterol.160 mg/dL (4.1 mmol/L)or LDL cholesterol.130 mg/dL (3.4mmol/L) and one or more CVD riskfactors is reasonable. E

c The goal of therapy is an LDLcholesterol value ,100 mg/dL(2.6 mmol/L). E

Children diagnosed with type 1 diabeteshave a high risk of early subclinical(507,508) and clinical (509) CVD.Although intervention data are lacking,the AHA categorizes childrenwith type 1diabetes in the highest tier forcardiovascular risk and recommendsboth lifestyle and pharmacologicaltreatment for those with elevated LDLcholesterol levels (510,511). Initialtherapy should be with a Step 2 AHAdiet, which restricts saturated fat to 7%of total calories and restricts dietarycholesterol to 200 mg/day. Data fromrandomized clinical trials in children asyoung as 7 months of age indicate thatthis diet is safe and does not interferewith normal growth and development(512,513). Abnormal results from arandom lipid panel should be confirmedwith a fasting lipid panel. Evidence hasshown that improved glucose controlcorrelates with a more favorable lipidprofile. However, improved glycemiccontrol alone will not reverse significantdyslipidemia (514). Neither long-termsafety nor cardiovascular outcomeefficacy of statin therapy has beenestablished for children. However,studies have shown short-term safetyequivalent to that seen in adults andefficacy in lowering LDL cholesterollevels, improving endothelial functionand causing regression of carotidintimal thickening (515–517). Statinsare not approved for use under the ageof 10 years, and statin treatment

Table 14—Plasma blood glucose and A1C goals for type 1 diabetes by age-group

Values by age (years)

Plasma blood glucose goal range(mg/dL)

A1C RationaleBefore meals Bedtime/overnight

Toddlers and preschoolers (0–6) 100–180 110–200 ,8.5% c Vulnerability to hypoglycemiac Insulin sensitivityc Unpredictability in dietary intake and physical activityc A lower goal (,8.0%) is reasonable if it can be achievedwithout excessive hypoglycemia

School age (6–12) 90–180 100–180 ,8% c Vulnerability of hypoglycemiac A lower goal (,7.5%) is reasonable if it can be achievedwithout excessive hypoglycemia

Adolescents and young adults (13–19) 90–130 90–150 ,7.5% c A lower goal (,7.0%) is reasonable if it can be achievedwithout excessive hypoglycemia

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 bemeasured when there is a discrepancy between preprandial blood glucose values and A1C levels andto help assess glycemia in those on basal-bolus regimens.

care.diabetesjournals.org Position Statement S51

should generally not be used inchildren with type 1 diabetes priorto this age. For postpubertal girls,issues of pregnancy prevention areparamount, since statins are category Xin pregnancy (see Section VIII.B formore information).

iv. Retinopathy

Recommendations

c An initial dilated and comprehensiveeye examination should beconsidered for the child at the start ofpuberty or at age $10 years,whichever is earlier, once the youthhas had diabetes for 3–5 years. B

c After the initial examination, annualroutine follow-up is generallyrecommended. Less frequentexaminations may be acceptable onthe advice of an eye careprofessional. E

Although retinopathy (like albuminuria)most commonly occurs after the onsetof puberty and after 5–10 years ofdiabetes duration (518), it has beenreported in prepubertal children andwith diabetes duration of only 1–2years. Referrals should be made to eyecare professionals with expertise indiabetic retinopathy, an understandingof retinopathy risk in the pediatricpopulation, and experience incounseling the pediatric patient andfamily on the importance of earlyprevention/intervention.

v. Celiac Disease

Recommendations

c Consider screening children with type1 diabetes for celiac disease bymeasuring IgA antitissuetransglutaminase or antiendomysialantibodies, with documentation ofnormal total serum IgA levels, soonafter the diagnosis of diabetes. E

c Testing should be considered inchildren with a positive family historyof celiac disease, growth failure,failure to gain weight, weight loss,diarrhea, flatulence, abdominal pain,or signs of malabsorption or inchildren with frequent unexplainedhypoglycemia or deterioration inglycemic control. E

c Consider referral to a gastroenterologistfor evaluation with possible endoscopyand biopsy for confirmation of celiac

disease in asymptomatic children withpositive antibodies. E

c Children with biopsy-confirmedceliac disease should be placed on agluten-free diet and haveconsultation with a dietitianexperienced in managing bothdiabetes and celiac disease. B

Celiac disease is an immune-mediateddisorder that occurs with increasedfrequency in patients with type 1diabetes (1–16% of individualscompared with 0.3–1% in the generalpopulation) (519,520). Symptoms ofceliac disease include diarrhea, weightloss or poor weight gain, growthfailure, abdominal pain, chronicfatigue, malnutrition due tomalabsorption, and othergastrointestinal problems, andunexplained hypoglycemia or erraticblood glucose concentrations.

ScreeningScreening for celiac disease includesmeasuring serum levels of tissuetransglutaminase or antiendomysialantibodies, then small-bowel biopsy inantibody-positive children. Europeanguidelines on screening for celiac diseasein children (not specific to children withtype 1 diabetes) suggested that biopsymay not be necessary in symptomaticchildren with positive antibodies, as longas further testing such as genetic or HLAtesting was supportive, but thatasymptomatic at-risk children shouldhave biopsies (521). One small study thatincluded childrenwith andwithout type 1diabetes suggested that antibody-positive but biopsy-negative childrenwere similar clinically to those who werebiopsy-positive.

TreatmentBiopsy-negative children had benefitsfrom a gluten-free diet, but worseningon a usual diet (522). This was a smallstudy, and children with type 1 diabetesalready follow a careful diet. However, itis difficult to advocate for notconfirming the diagnosis by biopsybefore recommending a lifelong gluten-free diet, especially in asymptomaticchildren. In symptomatic children withtype 1 diabetes and celiac disease,gluten-free diets reduce symptoms andrates of hypoglycemia (523).

vi. Hypothyroidism

Recommendations

c Consider screening children with type1 diabetes for antithyroid peroxidaseand antithyroglobulin antibodiessoon after diagnosis. E

c Measuring thyroid-stimulatinghormone (TSH) concentrations soonafter diagnosis of type 1 diabetes,after metabolic control has beenestablished, is reasonable. If normal,consider rechecking every 1–2 years,especially if the patient developssymptoms of thyroid dysfunction,thyromegaly, an abnormal growthrate, or unusual glycemic variation. E

Autoimmune thyroid disease is themostcommon autoimmune disorderassociated with diabetes, occurring in17–30% of patients with type 1 diabetes(524). About one-quarter of type 1diabetic children have thyroidautoantibodies at the time of diagnosis(525), and the presence of thyroidautoantibodies is predictive of thyroiddysfunction, generally hypothyroidismbut less commonly hyperthyroidism(526). Subclinical hypothyroidism maybe associated with increased risk ofsymptomatic hypoglycemia (527) andwith reduced linear growth (528).Hyperthyroidism alters glucosemetabolism, potentially resulting indeterioration of metabolic control.

c. Self-Management

No matter how sound the medicalregimen, it can only be as good as theability of the family and/or individual toimplement it. Family involvementremains an important component ofoptimal diabetes managementthroughout childhood and adolescence.Health care providers who care forchildren and adolescents, therefore,must be capable of evaluating theeducational, behavioral, emotional, andpsychosocial factors that impactimplementation of a treatment plan andmust work with the individual andfamily to overcome barriers or redefinegoals as appropriate.

d. School and Day Care

Since a large portion of a child’s day isspent in school, close communicationwith and cooperation of school or daycare personnel is essential for optimal

S52 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

diabetes management, safety, andmaximal academic opportunities. Seethe ADA position statement “DiabetesCare in the School and Day Care Setting”(529) for further discussion.

e. Transition From Pediatric to AdultCare

Recommendations

c As teens transition into emergingadulthood, health care providersand families must recognize theirmany vulnerabilities B andprepare the developing teen,beginning in early to midadolescence and at least 1 year priorto the transition. E

c Both pediatricians and adult healthcare providers should assist inproviding support and links toresources for the teen and emergingadult. B

Care and close supervision of diabetesmanagement is increasingly shiftedfrom parents and other older adultsthroughout childhood and adolescence;however, the shift from pediatrics toadult health care providers often occursvery abruptly as the older teen entersthe next developmental stage referredto as emerging adulthood (530),a critical period for young people whohave diabetes. During this period ofmajor life transitions, youth begin tomove out of their parents’ home andmust become more fully responsible fortheir diabetes care including the manyaspects of self-management, makingmedical appointments, and financinghealth care once they are no longercovered under their parents healthinsurance (531,532). In addition tolapses in health care, this is also a periodof deterioration in glycemic control,increased occurrence of acutecomplications, psycho-social-emotional-behavioral issues, andemergence of chronic complications(531–534).

Though scientific evidence continues tobe limited, it is clear that early andongoing attention be given tocomprehensive and coordinatedplanning for seamless transition of allyouth from pediatric to adult healthcare (531,532). A comprehensivediscussion regarding the challengesfaced during this period, including

specific recommendations, is foundin the ADA position statement“Diabetes Care for Emerging Adults:Recommendations for Transition FromPediatric to Adult Diabetes CareSystems” (532).

The National Diabetes EducationProgram (NDEP) has materials availableto facilitate the transition process(http://ndep.nih.gov/transitions/), andThe Endocrine Society in collaborationwith ADA and other organizations hasdeveloped transition tools for cliniciansand youth/families (http://www.endo-society.org/clinicalpractice/transition_of_care.cfm).

2. Type 2 Diabetes

The CDC recently published projectionsfor type 2 diabetes prevalence using theSEARCH database. Assuming a 2.3%annual increase, the prevalence of type2 diabetes in those under 20 years of agewill quadruple in 40 years (31,38). Giventhe current obesity epidemic,distinguishing between type 1 and type2 diabetes in children can be difficult.Autoantigens and ketosis may bepresent in a substantial number ofpatients with features of type 2 diabetes(including obesity and acanthosisnigricans). Such a distinction atdiagnosis is critical since treatmentregimens, educational approaches,dietary counsel, and outcomes willdiffer markedly between the twodiagnoses.

Type 2 diabetes has a significantincidence of comorbidities alreadypresent at the time of diagnosis (535). Itis recommended that blood pressuremeasurement, a fasting lipid profile,assessment for albumin excretion, anddilated eye examination be performedat diagnosis. Thereafter, screeningguidelines and treatmentrecommendations for hypertension,dyslipidemia, albumin excretion, andretinopathy in youth with type 2diabetes are similar to those for youthwith type 1 diabetes. Additionalproblems that may need to beaddressed include polycystic ovariandisease and the various comorbiditiesassociatedwith pediatric obesity such assleep apnea, hepatic steatosis,orthopedic complications, andpsychosocial concerns. The ADAconsensus statement on this subject

(32) provides guidance on theprevention, screening, and treatment oftype 2 diabetes and its comorbidities inyoung people.

3. Monogenic Diabetes Syndromes

Monogenic forms of diabetes(neonatal diabetes or maturity-onsetdiabetes of the young) represent asmall fraction of children with diabetes(,5%), but readily availablecommercial genetic testing nowenables a true genetic diagnosis withincreasing frequency. It is importantto correctly diagnose one of themonogenic forms of diabetes, as thesechildren may be incorrectly diagnosedwith type 1 or type 2 diabetes, leadingto suboptimal treatment regimens anddelays in diagnosing other familymembers.

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

c Diabetes diagnosedwithin the first sixmonths of life.

c Strong family history of diabetes butwithout typical features of type 2diabetes (nonobese, low-risk ethnicgroup).

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

c Diabetes but with negative auto-antibodies without signs of obesity orinsulin resistance.

A recent international consensusdocument discusses in further detail thediagnosis and management of childrenwith monogenic forms of diabetes(536).

B. Preconception Care

Recommendations

c A1C levels should be as close tonormal as possible (,7%) in anindividual patient before conceptionis attempted. B

c Starting at puberty, preconceptioncounseling should be incorporated inthe routine diabetes clinic visit for allwomen of childbearing potential. B

c Women with diabetes who arecontemplating pregnancy should beevaluated and, if indicated, treated fordiabetic retinopathy, nephropathy,neuropathy, and CVD. B

care.diabetesjournals.org Position Statement S53

c Medications used by such womenshould be evaluated prior toconception, since drugs commonlyused to treat diabetes and itscomplications may becontraindicated or not recommendedin pregnancy, including statins, ACEinhibitors, ARBs, and most noninsulintherapies. E

c Since many pregnancies areunplanned, consider the potentialrisks and benefits of medications thatare contraindicated in pregnancy inall women of childbearing potentialand counsel women using suchmedications accordingly. E

Major congenital malformations remainthe leading cause of mortality andserious morbidity in infants of motherswith type 1 and type 2 diabetes.Observational studies indicate that therisk of malformations increasescontinuously with increasing maternalglycemia during the first 6–8 weeks ofgestation, as defined by first-trimesterA1C concentrations. There is nothreshold for A1C values below whichrisk disappears entirely. However,malformation rates above the 1–2%background rate of nondiabeticpregnancies appear to be limited topregnancies in which first-trimester A1Cconcentrations are .1% above thenormal range for a nondiabeticpregnant woman.

Preconception CarePreconception care of diabetes appearsto reduce the risk of congenitalmalformations. Five nonrandomizedstudies compared rates of majormalformations in infants betweenwomen who participated inpreconception diabetes care programsand women who initiated intensivediabetes management after they werealready pregnant. The preconceptioncare programs were multidisciplinaryand designed to train patients indiabetes self-management with diet,intensified insulin therapy, and SMBG.Goals were set to achieve normal bloodglucose concentrations, and .80% ofsubjects achieved normal A1Cconcentrations before they becamepregnant. In all five studies, theincidence of major congenitalmalformations in women who

participated in preconception care(range 1.0–1.7% of infants) was muchlower than the incidence in women whodid not participate (range 1.4–10.9% ofinfants) (104). One limitation of thesestudies is that participation inpreconception care was self-selectedrather than randomized. Thus, it isimpossible to be certain that the lowermalformation rates resulted fully fromimproved diabetes care. Nonetheless,the evidence supports the concept thatmalformations can be reduced orprevented by careful management ofdiabetes before pregnancy (537).

Planned pregnancies greatly facilitatepreconception diabetes care.Unfortunately, nearly two-thirds ofpregnancies in womenwith diabetes areunplanned, potentially leading tomalformations in infants of diabeticmothers. To minimize the occurrence ofthese devastating malformations,beginning at the onset of puberty or atdiagnosis, all women with diabetes withchildbearing potential should receive1) education about the risk ofmalformations associated withunplanned pregnancies and poormetabolic control and 2) use of effectivecontraception at all times, unless thepatient has good metabolic control andis actively trying to conceive. A recentstudy showed that preconceptioncounseling using simple educationaltools enabled adolescent girls to makewell-informed decisions lasting up to 9months (538).

Women contemplating pregnancy needto be seen frequently by amultidisciplinary team experienced indiabetes management both before andduring pregnancy. The goals ofpreconception care are to 1) involve andempower the patient on diabetesmanagement, 2) achieve the lowest A1Ctest results possible without excessivehypoglycemia, 3) assure effectivecontraception until stable andacceptable glycemia is achieved, and 4)identify, evaluate, and treat long-termdiabetes complications such asretinopathy, nephropathy, neuropathy,hypertension, and CHD (104).

Drugs Contraindicated in PregnancyDrugs commonly used in the diabetestreatment may be relatively or

absolutely contraindicated duringpregnancy. Statins are category X(contraindicated for use in pregnancy)and should be discontinued beforeconception, as should ACE inhibitors(539). ARBs are category C (risk cannotbe ruled out) in the first trimester butcategory D (positive evidence of risk) inlater pregnancy and should generally bediscontinued before pregnancy. Sincemany pregnancies are unplanned,health care professionals caring for anywoman of childbearing potential shouldconsider the potential risks and benefitsof medications that are contraindicatedin pregnancy. Women usingmedications such as statins or ACEinhibitors need ongoing family planningcounseling. Among the oral antidiabeticagents, metformin and acarbose areclassified as category B (no evidence ofrisk in humans) and all others ascategory C. Potential risks and benefitsof oral antidiabetic agents in thepreconception period must be carefullyweighed, recognizing that data areinsufficient to establish the safety ofthese agents in pregnancy.

For further discussion of preconceptioncare, see the ADA consensus statementon preexisting diabetes and pregnancy(104) and the position statement (540).

C. Older Adults

Recommendations

c Older adults who are functional,cognitively intact, and havesignificant life expectancy shouldreceive diabetes care with goalssimilar to those developed foryounger adults. E

c Glycemic goals for some older adultsmight reasonably be relaxed, usingindividual criteria, but hyperglycemialeading to symptoms or risk of acutehyperglycemic complications shouldbe avoided in all patients. E

c Other cardiovascular risk factorsshould be treated in older adults withconsideration of the time frame ofbenefit and the individual patient.Treatment of hypertension isindicated in virtually all older adults,and lipid and aspirin therapy maybenefit those with life expectancy atleast equal to the time frame ofprimary or secondary preventiontrials. E

S54 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

c Screening for diabetes complicationsshould be individualized in olderadults, but particular attentionshould be paid to complicationsthat would lead to functionalimpairment. E

Diabetes is an important healthcondition for the aging population; atleast 20% of patients over the age of 65years have diabetes, and this numbercan be expected to grow rapidly in thecoming decades. Older individuals withdiabetes have higher rates of prematuredeath, functional disability, andcoexisting illnesses such ashypertension, CHD, and stroke thanthose without diabetes. Older adultswith diabetes are also at greater riskthan other older adults for severalcommon geriatric syndromes, such aspolypharmacy, depression, cognitiveimpairment, urinary incontinence,injurious falls, and persistent pain.

A consensus report on diabetesand older adults (541) influencedthe following discussion andrecommendations. The care of older

adults with diabetes is complicated bytheir clinical and functionalheterogeneity. Some older individualsdeveloped diabetes years earlier andmay have significant complications;others who are newly diagnosed mayhave had years of undiagnosed diabeteswith resultant complications or mayhave truly recent-onset disease and fewor no complications. Some older adultswith diabetes are frail and have otherunderlying chronic conditions,substantial diabetes-relatedcomorbidity, or limited physical orcognitive functioning. Other olderindividuals with diabetes have littlecomorbidity and are active. Lifeexpectancies are highly variable for thispopulation, but often longer thanclinicians realize. Providers caring forolder adults with diabetes must take thisheterogeneity into consideration whensetting and prioritizing treatment goals(Table 15).

There are few long-term studies in olderadults demonstrating the benefits ofintensive glycemic, blood pressure, andlipid control. Patients who can be

expected to live long enough to reap thebenefits of long-term intensive diabetesmanagement, who have good cognitiveand functional function, and who chooseto do so via shared decision making maybe treated using therapeuticinterventions and goals similar to thosefor younger adults with diabetes. As withall patients, DSME and ongoing DSMS arevital components of diabetes care forolder adults and their caregivers.

For patients with advanced diabetescomplications, life-limiting comorbidillness, or substantial cognitive orfunctional impairment, it is reasonableto set less intensive glycemic targetgoals. These patients are less likely tobenefit from reducing the risk ofmicrovascular complications and morelikely to suffer serious adverse effectsfrom hypoglycemia. However, patientswith poorly controlled diabetes may besubject to acute complications ofdiabetes, including dehydration, poorwound healing, and hyperglycemichyperosmolar coma. Glycemic goals at aminimum should avoid theseconsequences.

Table 15—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adultswith diabetes

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 ,140/80 Statin unlesscontraindicated or 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 ,140/80 Statin unlesscontraindicated or 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/caregiver 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 goal may be set for an individual if achievable without recurrent or severe hypoglycemia or unduetreatment burden. *Coexisting chronic illnesses are conditions serious enough to require medications or lifestyle management and may includearthritis, cancer, CHF, depression, emphysema, falls, hypertension, incontinence, stage 3 or worse CKD,MI, and stroke. Bymultiple, wemean at leastthree, but many patients may have five or more (132). **The presence of a single end-stage chronic illness such as stage 3-4 CHF or oxygen-dependent lung disease, CKD requiring dialysis, or uncontrolled metastatic cancer may cause significant symptoms or impairment of functionalstatus and significantly reduce life expectancy. †A1C of 8.5% equates to an eAG of ;200 mg/dL. Looser glycemic targets than this may exposepatients to acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome, and poor wound healing.

care.diabetesjournals.org Position Statement S55

Although hyperglycemia control may beimportant in older individuals withdiabetes, greater reductions in morbidityand mortality may result from control ofother cardiovascular risk factors rather thanfrom tight glycemic control alone. There isstrong evidence from clinical trials of thevalueof treatinghypertension in theelderly(542,543). There is less evidence for lipid-lowering and aspirin therapy, although thebenefits of these interventions for primaryand secondary prevention are likely toapply to older adults whose lifeexpectancies equal or exceed the timeframes seen in clinical trials.

Special care is required in prescribingand monitoring pharmacologicaltherapy in older adults. Costs may be asignificant factor, especially sinceolder adults tend to be on manymedications. Metformin may becontraindicated because of renalinsufficiency or significant heart failure.Thiazolidinediones, if used at all, shouldbe used very cautiously in those with, orat risk for, CHF, and have also beenassociated with fractures. Sulfonylureas,other insulin secretagogues, and insulincan cause hypoglycemia. Insulin userequires that patients or caregivers havegood visual and motor skills andcognitive ability. DPP-4 inhibitors havefew side effects, but their costs may be abarrier to some older patients; the latteris also the case for GLP-1 agonists.

Screening for diabetes complications inolder adults also should beindividualized. Particular attentionshould be paid to complications that candevelop over short periods of time and/or that would significantly impairfunctional status, such as visual andlower-extremity complications.

D. Cystic Fibrosis–Related Diabetes

Recommendations

c Annual screening for CFRD with OGTTshould begin by age 10 years in allpatients with cystic fibrosis who do nothave CFRD. B A1C as a screening testfor CFRD is not recommended. B

c During a period of stable health, thediagnosis of CFRD can be made incystic fibrosis patients according tousual glucose criteria. E

c Patients with CFRD should be treatedwith insulin to attain individualizedglycemic goals. A

c Annual monitoring for complicationsof diabetes is recommended,beginning 5 years after the diagnosisof CFRD. E

CFRD is the most common comorbidityin persons with cystic fibrosis, occurringin about 20% of adolescents and 40–50% of adults. Diabetes in thispopulation is associated with worsenutritional status, more severeinflammatory lung disease, and greatermortality from respiratory failure.Insulin insufficiency related to partialfibrotic destruction of the islet mass isthe primary defect in CFRD. Geneticallydetermined function of the remainingb-cells and insulin resistance associatedwith infection and inflammation mayalso play a role. Encouraging datasuggest that improved screening(544,545) and aggressive insulin therapyhave narrowed the gap in mortalitybetween cystic fibrosis patients withand without diabetes, and haveeliminated the sex difference inmortality (546). Recent trials comparinginsulin with oral repaglinide showed nosignificant difference between thegroups. Insulin remains the most widelyused therapy for CFRD (547).

Recommendations for the clinicalmanagement of CFRD can be found inthe recent ADA position statement onthis topic (548).

IX. DIABETES CARE IN SPECIFICSETTINGS

A. Diabetes Care in the Hospital

Recommendations

c Diabetes discharge planning shouldstart at hospital admission, and cleardiabetes management instructionsshould be provided at discharge. E

c The sole use of sliding scale insulin inthe inpatient hospital setting isdiscouraged. E

c All patients with diabetes admitted tothe hospital should have theirdiabetes clearly identified in themedical record. E

c All patients with diabetes should havean order for blood glucose monitoring,with results available to all members ofthe health care team. E

c Goals for blood glucose levels:

� Critically ill patients: Insulintherapy should be initiated for

treatment of persistenthyperglycemia starting at athreshold of no greater than 180mg/dL (10 mmol/L). Once insulintherapy is started, a glucose rangeof 140–180 mg/dL (7.8–10mmol/L)is recommended for the majority ofcritically ill patients. A

� More stringent goals, such as 110–140 mg/dL (6.1–7.8 mmol/L) maybe appropriate for selectedpatients, as long as this can beachieved without significanthypoglycemia. C

� Critically ill patients require anintravenous insulin protocol thathas demonstrated efficacy andsafety in achieving the desiredglucose range without increasingrisk for severe hypoglycemia. E

� Non–critically ill patients: There isno clear evidence for specificblood glucose goals. If treatedwith insulin, the premeal bloodglucose targets generally ,140mg/dL (7.8 mmol/L) with randomblood glucose ,180 mg/dL (10.0mmol/L) are reasonable,provided these targets can besafely achieved. More stringenttargets may be appropriate instable patients with previoustight glycemic control. Lessstringent targets may beappropriate in those with severecomorbidities. E

� Scheduled subcutaneous insulinwith basal, nutritional, andcorrectional components is thepreferred method for achievingand maintaining glucose control innon–critically ill patients. C

� Glucose monitoring should beinitiated in any patient not knownto be diabetic who receivestherapy associated with high riskfor hyperglycemia, includinghigh-dose glucocorticoidtherapy, initiation of enteral orparenteral nutrition, or othermedications such as octreotide orimmunosuppressive medications. BIf hyperglycemia is documentedand persistent, consider treatingsuch patients to the same glycemicgoals as in patients with knowndiabetes. E

� A hypoglycemia managementprotocol should be adopted and

S56 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

implemented by each hospital orhospital system. A plan forpreventing and treatinghypoglycemia should beestablished for each patient.Episodes of hypoglycemia in thehospital should be documented inthe medical record and tracked. E

� Consider obtaining an A1C inpatients with diabetes admitted tothe hospital if the result of testingin the previous 2–3 months is notavailable. E

� Consider obtaining an A1C inpatients with risk factors forundiagnosed diabetes who exhibithyperglycemia in the hospital. E

� Patients with hyperglycemia in thehospital who do not have a priordiagnosis of diabetes should haveappropriate plans for follow-uptesting and care documented atdischarge. E

Hyperglycemia in the hospital canrepresent previously known diabetes,previously undiagnosed diabetes, orhospital-related hyperglycemia (fastingblood glucose $126 mg/dL or randomblood glucose $200 mg/dL occurringduring the hospitalization that reverts tonormal after hospital discharge). Thedifficulty distinguishing between thesecond and third categories during thehospitalization may be overcome bymeasuring an A1C in undiagnosedpatients with hyperglycemia, as long asconditions interfering with A1C utility(hemolysis, blood transfusion) have notoccurred. Hyperglycemia managementin the hospital has been consideredsecondary in importance to thecondition that prompted admission.However, a body of literature nowsupports targeted glucose control in thehospital setting for potential improvedclinical outcomes. Hyperglycemia in thehospital may result from stress,decompensation of type 1 or type 2 orother forms of diabetes, and/or may beiatrogenic due to withholding ofantihyperglycemic medications oradministration of hyperglycemia-provoking agents such asglucocorticoids or vasopressors.

There is substantial observationalevidence linking hyperglycemia inhospitalized patients (with or without

diabetes) to poor outcomes. Cohortstudies as well as a few early RCTssuggested that intensive treatment ofhyperglycemia improved hospitaloutcomes (549–551). In general, thesestudies were heterogeneous in terms ofpatient population, blood glucosetargets and insulin protocols used,provision of nutritional support and theproportion of patients receiving insulin,which limits the ability to makemeaningful comparisons among them.Trials in critically ill patients have failedto show a significant improvement inmortality with intensive glycemiccontrol (552,553) or have even shownincreased mortality risk (554).Moreover, these recent RCTs havehighlighted the risk of severehypoglycemia resulting from suchefforts (552–557).

The largest study to date, NICE-SUGAR, a multicenter, multinationalRCT, compared the effect of intensiveglycemic control (target 81–108 mg/dL,mean blood glucose attained115 mg/dL) to standard glycemiccontrol (target 144–180 mg/dL, meanblood glucose attained 144 mg/dL) onoutcomes among 6,104 critically illparticipants, almost all of whomrequired mechanical ventilation (554).Ninety-day mortality was significantlyhigher in the intensive versus theconventional group in both surgical andmedical patients, as was mortality fromcardiovascular causes. Severehypoglycemia was also more commonin the intensively treated group (6.8%vs. 0.5%; P, 0.001). The precise reasonfor the increased mortality in thetightly controlled group is unknown.The study results lie in stark contrastto a 2001 single-center study thatreported a 42% relative reductionin intensive care unit (ICU) mortality incritically ill surgical patients treatedto a target blood glucose of 80–110mg/dL(549). Importantly, the control group inNICE-SUGAR had reasonably good bloodglucose management, maintained at amean glucose of 144 mg/dL, only29 mg/dL above the intensively managedpatients. This study’s findings do notdisprove the notion that glycemic controlin the ICU is important. However, they dostrongly suggest that it may not benecessary to target blood glucose values

,140 mg/dL and that a highly stringenttarget of,110 mg/dL may actually bedangerous.

In a meta-analysis of 26 trials (N 513,567), which included the NICE-SUGAR data, the pooled RR of deathwith intensive insulin therapy was 0.93as compared with conventional therapy(95% CI 0.83–1.04) (557). Approximatelyhalf of these trials reportedhypoglycemia, with a pooled RR ofintensive therapy of 6.0 (95% CI 4.5–8.0). The specific ICU setting influencedthe findings, with patients in surgicalICUs appearing to benefit from intensiveinsulin therapy (RR 0.63 [95% CI 0.44–0.91]), while those in other medical andmixed critical care settings did not. Itwas concluded that, overall, intensiveinsulin therapy increased the risk ofhypoglycemia but provided no overallbenefit on mortality in the critically ill,although a possible mortality benefit topatients admitted to the surgical ICUwas suggested.

1. Glycemic Targets in Hospitalized

Patients

Definition of Glucose Abnormalities inthe Hospital SettingHyperglycemia in the hospital has beendefined as any blood glucose.140 mg/dL (7.8 mmol/L). Levels that aresignificantly and persistently above thismay require treatment in hospitalizedpatients. A1C values .6.5% suggest, inundiagnosed patients, that diabetespreceded hospitalization (558).Hypoglycemia has been defined as anyblood glucose,70mg/dL (3.9 mmol/L).This is the standard definition inoutpatients and correlates with theinitial threshold for the release ofcounter-regulatory hormones. Severehypoglycemia in hospitalized patientshas been defined by many as ,40 mg/dL (2.2 mmol/L), although this is lowerthan the ;50 mg/dL (2.8 mmol/L) levelat which cognitive impairment begins innormal individuals (559). Both hyper-and hypoglycemia among inpatients areassociated with adverse short- andlong-term outcomes. Early recognitionand treatment of mild to moderatehypoglycemia (40–69 mg/dL [2.2–3.8mmol/L]) can prevent deterioration to amore severe episode with potentialadverse sequelae (560).

care.diabetesjournals.org Position Statement S57

Critically Ill PatientsBased on the weight of the availableevidence, for the majority of critically illpatients in the ICU setting, insulininfusion should be used to controlhyperglycemia, with a starting thresholdof no higher than 180 mg/dL (10.0mmol/L). Once intravenous insulin isstarted, the glucose level should bemaintained between 140 and 180mg/dL(7.8 and 10.0 mmol/L). Greater benefitmaybe realized at the lower end of thisrange. Although strong evidence islacking, lower glucose targets may beappropriate in selected patients. Onesmall study suggested that ICU patientstreated to targets of 120–140 had lessnegative nitrogen balance than thosetreated to higher targets (561).However, targets ,110 mg/dL(6.1 mmol/L) are not recommended.Insulin infusion protocols withdemonstrated safety and efficacy,resulting in low rates of hypoglycemia,are highly recommended (560).

Non–critically Ill PatientsWith no prospective RCT data to informspecific glycemic targets in non–critically ill patients, recommendationsare based on clinical experience andjudgment (562). For the majority ofnon–critically ill patients treated withinsulin, premeal glucose targets shouldgenerally be ,140 mg/dL (7.8 mmol/L)with randomblood glucose,180mg/dL(10.0 mmol/L), as long as these targetscan be safely achieved. To avoidhypoglycemia, consideration should begiven to reassessing the insulin regimenif blood glucose levels fall below100 mg/dL (5.6 mmol/L). Modifying theregimen is required when blood glucosevalues are ,70 mg/dL (3.9 mmol/L),unless the event is easily explained byother factors (such as a missed meal).There is some evidence that systematicattention to hyperglycemia in theemergency room leads to betterglycemic control in the hospital forthose subsequently admitted (563).

Patients with a prior history ofsuccessful tight glycemic control in theoutpatient setting who are clinicallystablemay bemaintainedwith a glucoserange below the aforementioned cutpoints. Conversely, higher glucoseranges may be acceptable in terminallyill patients or in patients with severe

comorbidities, as well as in those inpatient-care settings where frequentglucose monitoring or close nursingsupervision is not feasible.

Clinical judgment, combined withongoing assessment of the patient’sclinical status, including changes in thetrajectory of glucose measures, theseverity of illness, nutritional status, orconcomitant medications that mightaffect glucose levels (e.g., steroids,octreotide) must be incorporated intothe day-to-day decisions regardinginsulin dosing (560).

2. Antihyperglycemic Agents in

Hospitalized Patients

Inmost clinical situations in the hospital,insulin therapy is the preferred methodof glycemic control (560). In the ICU,intravenous infusion is the preferredroute of insulin administration. Whenthe patient is transitioned offintravenous insulin to subcutaneoustherapy, precautions should be taken toprevent hyperglycemia escape(564,565). Outside of critical care units,scheduled subcutaneous insulin thatdelivers basal, nutritional, andcorrectional (supplemental)components is recommended. Typicaldosing schemes are based on bodyweight, with some evidence thatpatients with renal insufficiency shouldbe treated with lower doses (566).

The sole use of sliding scale insulin isstrongly discouraged in hospitalizedpatients. A more physiological insulinregimen including basal, prandial, andcorrectional insulin is recommended.The insulin regimen must alsoincorporate prandial carbohydrateintake (567). For type 1 diabeticpatients, dosing insulin solely based onpremeal glucose would likely deliversuboptimal insulin doses and maypotentially lead to DKA. It increases bothhypoglycemia and hyperglycemia risksand has been shown in a randomizedtrial to be associated with adverseoutcomes in general surgery patientswith type 2 diabetes (568). The reader isreferred to publications and reviewsthat describe currently available insulinpreparations and protocols and provideguidance in use of insulin therapy inspecific clinical settings includingparenteral nutrition (569), enteral tube

feedings and with high doseglucocorticoid therapy (560).

There are no data on the safety andefficacy of oral agents and injectablenoninsulin therapies such as GLP-1analogs and pramlintide in the hospital.They appear to have a limited role inhyperglycemia management inconjunction with acute illness.Continuation of these agents may beappropriate in selected stable patientswho are expected to consume meals atregular intervals. They may be initiatedor resumed in anticipation of dischargeonce the patient is clinically stable.Specific caution is required withmetformin, due to the possibility that acontraindication may develop duringthe hospitalization, such as renalinsufficiency, unstable hemodynamicstatus, or need for an imaging study thatrequires a radiocontrast dye.

3. Preventing Hypoglycemia

Patients with or without diabetes mayexperience hypoglycemia in the hospitalsetting in association with alterednutritional state, heart failure, renal orliver disease, malignancy, infection, orsepsis. Additional triggering eventsleading to iatrogenic hypoglycemiainclude sudden reduction ofcorticosteroid dose, altered ability ofthe patient to report symptoms,reduced oral intake, emesis, new NPOstatus, inappropriate timing of short- orrapid-acting insulin in relation to meals,reduced infusion rate of intravenousdextrose, and unexpected interruptionof enteral feedings or parenteralnutrition.

Despite the preventable nature ofmany inpatient episodes ofhypoglycemia, institutions are morelikely to have nursing protocols forhypoglycemia treatment than for itsprevention. Tracking such episodesand analyzing their causes areimportant quality improvementactivities (295).

4. Diabetes Care Providers in the

Hospital

Inpatient diabetes management may beeffectively championed and/or providedby primary care physicians,endocrinologists, intensivists, orhospitalists. Involvement ofappropriately trained specialists or

S58 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

specialty teams may reduce length ofstay, improve glycemic control, andimprove outcomes (560). Standardizedorders for scheduled and correction-dose insulin should be implemented,and sole reliance on a sliding scaleregimen strongly discouraged. Ashospitals move to comply with“meaningful use” regulations forelectronic health records, as mandatedby the Health Information TechnologyAct, efforts should be made to assurethat all components of structuredinsulin order sets are incorporated intoelectronic insulin order sets (570,571).

A team approach is needed to establishhospital pathways. To achieve glycemictargets associated with improvedhospital outcomes, hospitals will needmultidisciplinary support to developinsulin management protocols thateffectively and safely enableachievement of glycemic targets (572).

5. Self-Management in the Hospital

Diabetes self-management in the hospitalmay be appropriate for competent youthand adult patientswho have a stable levelof consciousness and reasonably stabledaily insulin requirements, successfullyconduct self-management of diabetes athome, have physical skills needed tosuccessfully self-administer insulin andperform SMBG, have adequate oralintake, are proficient in carbohydratecounting, use multiple daily insulininjections or insulin pump therapy, andunderstand sick-day management. Thepatient and physician, in consultationwith nursing staff, must agree thatpatient self-management is appropriatewhile hospitalized.

Patients who use CSII pump therapy inthe outpatient setting can be candidatesfor diabetes self-management in thehospital, provided that they have themental and physical capacity to do so(560). A hospital policy and proceduresdelineating inpatient guidelines for CSIItherapy are advisable, and availabilityof hospital personnel with expertise inCSII therapy is essential. It is importantthat nursing personnel document basalrates and bolus doses taken on a dailybasis.

6. MNT in the Hospital

The goals of MNT are to optimizeglycemic control, provide adequate

calories to meet metabolic demands,and create a discharge plan for follow-up care (551,573). The ADA does notendorse any single meal plan orspecified percentages of macronutrients,and the term “ADA diet” should nolonger be used. Current nutritionrecommendations adviseindividualization based on treatmentgoals, physiological parameters, andmedication use. Consistentcarbohydrate meal plans are preferredby many hospitals since they facilitatematching the prandial insulin dose to theamount of carbohydrate consumed(574). Because of the complexity ofnutrition issues in the hospital, aregistered dietitian, knowledgeable andskilled in MNT, should serve as aninpatient team member. The dietitian isresponsible for integrating informationabout the patient’s clinical condition,eating, and lifestyle habits and forestablishing treatment goals in order todetermine a realistic plan for nutritiontherapy (116).

7. Bedside Blood Glucose Monitoring

Bedside POC blood glucose monitoringis used to guide insulin dosing. In thepatient receiving nutrition, the timingof glucose monitoring should matchcarbohydrate exposure. In the patientnot receiving nutrition, glucosemonitoring is performed every 4–6 h(575,576). More frequent blood glucosetesting ranging from every 30 min toevery 2 h is required for patients onintravenous insulin infusions.

Safety standards should be establishedfor blood glucose monitoringprohibiting sharing of finger-sticklancing devices, lancets, needles, andmeters to reduce the risk oftransmission of blood-borne diseases.Shared lancing devices carry essentiallythe same risk as sharing syringes andneedles (577).

Accuracy of blood glucosemeasurements using POC meters haslimitations that must be considered.Although the FDA allows a 1/2 20%error for blood glucose meters,questions about the appropriateness ofthese criteria have been raised (388).Glucose measures differ significantlybetween plasma and whole blood, termsthat are often used interchangeably andcan lead to misinterpretation. Most

commercially available capillary bloodglucose meters introduce a correctionfactor of;1.12 to report a “plasma-adjusted” value (578).

Significant discrepancies betweencapillary, venous, and arterial plasmasamples have been observed in patientswith low or high hemoglobinconcentrations, hypoperfusion, and thepresence of interfering substancesparticularly maltose, as contained inimmunoglobulins (579). Analyticalvariability has been described withseveral meters (580). Increasinglynewer generation POC blood glucosemeters correct for variation inhematocrit and for interferingsubstances. Any glucose result thatdoes not correlate with the patient’sstatus should be confirmed throughconventional laboratory sampling ofplasma glucose. The FDA has becomeincreasingly concerned about the use ofPOC blood glucose meters in thehospital and is presently reviewingmatters related to their use.

8. Discharge Planning and DSME

Transition from the acute care settingis a high-risk time for all patients, notjust those with diabetes or newhyperglycemia. Although there is anextensive literature concerning safetransition within and from the hospital,little of it is specific to diabetes (581).Diabetes discharge planning is not aseparate entity, but is an important partof an overall discharge plan. As such,discharge planning begins atadmission to the hospital and isupdated as projected patient needschange.

Inpatients may be discharged to variedsettings, including home (with or withoutvisiting nurse services), assisted living,rehabilitation, or skilled nursing facilities.The latter two sites are generally staffedby health professionals, so diabetesdischarge planning will be limited tocommunication of medication and dietorders. For the patient who is dischargedto assisted living or to home, the optimalprogram will need to consider the typeand severity of diabetes, the effects of thepatient’s illness on blood glucose levels,and the capacities and desires of thepatient. Smooth transition to outpatientcare should be ensured. The Agency forHealthcare Research and Quality

care.diabetesjournals.org Position Statement S59

recommends that, at a minimum,discharge plans include the following:

c Medication reconciliation: thepatient’s medications must be cross-checked to ensure that no chronicmedications were stopped and toensure the safety of newprescriptions.c Prescriptions for new or changed

medication should be filled andreviewed with the patient andfamily at or before discharge

c Structured dischargecommunication: Information onmedication changes, pending testsand studies, and follow-up needsmust be accurately and promptlycommunicated to outpatientphysicians.c Discharge summaries should be

transmitted to the primary physicianas soon as possible after discharge.

c Appointment keeping behavior isenhanced when the inpatient teamschedules outpatient medicalfollow-up prior to discharge. Ideallythe inpatient care providers or casemanagers/discharge planners willschedule follow-up visit(s) withthe appropriate professionals,including primary care provider,endocrinologist, and diabeteseducator (582).

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,people with diabetes should be taughtat a time and place conducive tolearning: as an outpatient in arecognized program of diabeteseducation. For the hospitalized patient,diabetes “survival skills” education isgenerally a feasible approach to providesufficient information and training toenable safe care at home. Patientshospitalized because of a crisis relatedto diabetesmanagement or poor care athome require education to preventsubsequent episodes of hospitalization.Assessing the need for a home healthreferral or referral to an outpatientdiabetes education program should bepart of discharge planning for allpatients.

DSME should start upon admission or assoon as feasible, especially in those newto insulin therapy or in whom thediabetes regimen has been substantiallyaltered during the hospitalization.

It is recommended that the followingareas of knowledge be reviewed andaddressed prior to hospital discharge:

c Identification of the health careprovider who will provide diabetescare after discharge

c Level of understanding related to thediagnosis of diabetes, SMBG, andexplanationof homebloodglucose goals

c Definition, recognition, treatment,and prevention of hyperglycemia andhypoglycemia

c Information on consistent eatingpatterns

c When and how to take bloodglucose–lowering medicationsincluding insulin administration (ifgoing home on insulin)

c Sick-day managementc Proper use and disposal of needles

and syringes

It is important that patients be providedwith appropriate durable medicalequipment, medication, supplies andprescriptions at the time of discharge inorder to avoid a potentially dangeroushiatus in care. These supplies/prescriptions should include thefollowing:

c Insulin (vials or pens) if neededc Syringes or pen needles (if needed)c Oral medications (if needed)c Blood glucose meter and stripsc Lancets and lancing devicec Urine ketone strips (type 1)c Glucagon emergency kit (insulin

treated)c Medical alert application/charm

More expanded diabetes education canbe arranged in the community. Anoutpatient follow-up visit with theprimary care provider, endocrinologist,or diabetes educator within 1 month ofdischarge is advised for all patientshaving hyperglycemia in the hospital.Clear communication with outpatientproviders either directly or via hospitaldischarge summaries facilitates safetransitions to outpatient care. Providinginformation regarding the cause or the

plan for determining the cause ofhyperglycemia, related complicationsand comorbidities, and recommendedtreatments can assist outpatientproviders as they assume ongoingcare.

B. Diabetes and EmploymentAny person with diabetes, whetherinsulin treated or noninsulin treated,should be eligible for any employmentfor which he or she is otherwisequalified. Employment decisions shouldnever be based on generalizations orstereotypes regarding the effects ofdiabetes. When questions arise aboutthe medical fitness of a person withdiabetes for a particular job, a healthcare professional with expertise intreating diabetes should perform anindividualized assessment. See the ADAposition statement on diabetes andemployment (583).

C. Diabetes and DrivingA large percentage of people withdiabetes in the U.S. and elsewhereseek a license to drive, either forpersonal or employment purposes.There has been considerable debatewhether, and the extent to which,diabetes may be a relevant factor indetermining the driver ability andeligibility for a license.

People with diabetes are subject to agreat variety of licensing requirementsapplied by both state and federaljurisdictions, which may lead to loss ofemployment or significant restrictionson a person’s license. Presence of amedical condition that can lead tosignificantly impaired consciousness orcognition may lead to drivers beingevaluated for fitness to drive. Fordiabetes, this typically arises whenthe person has had a hypoglycemicepisode behind the wheel, even ifthis did not lead to a motor vehicleaccident.

Epidemiological and simulator datasuggest that people with insulin-treateddiabetes have a small increase in risk ofmotor vehicle accidents, primarily dueto hypoglycemia and decreasedawareness of hypoglycemia. Thisincrease (RR 1.12–1.19) is much smallerthan the risks associated with teenagemale drivers (RR 42), driving at night(RR 142), driving on rural roads

S60 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

compared with urban roads (RR 9.2),and obstructive sleep apnea (RR 2.4), allof which are accepted for unrestrictedlicensure.

The ADA position statement on diabetesand driving (584) recommends againstblanket restrictions based on thediagnosis of diabetes and urgesindividual assessment by a health careprofessional knowledgeable in diabetesif restrictions on licensure are beingconsidered. Patients should beevaluated for decreased awareness ofhypoglycemia, hypoglycemia episodeswhile driving, or severe hypoglycemia.Patients with retinopathy or peripheralneuropathy require assessment todetermine if those complicationsinterfere with operation of a motorvehicle. Health care professionalsshould be cognizant of the potential riskof driving with diabetes and counseltheir patients about detecting andavoiding hypoglycemia while driving.

D. Diabetes Management inCorrectional InstitutionsPeople with diabetes in correctionalfacilities should receive care that meetsnational standards. Because it isestimated that nearly 80,000 inmateshave diabetes, correctional institutionsshould have written policies andprocedures for the management ofdiabetes and for training of medical andcorrectional staff in diabetes carepractices. See the ADA positionstatement on diabetes management incorrectional institutions (585) forfurther discussion.

X. STRATEGIES FOR IMPROVINGDIABETES CARE

Recommendations

c Care should be aligned withcomponents of the Chronic CareModel (CCM) to ensure productiveinteractions between a preparedproactive practice team and aninformed activated patient. A

c When feasible, care systems shouldsupport team-based care, communityinvolvement, patient registries, andembedded decision support tools tomeet patient needs. B

c Treatment decisions should be timelyand based on evidence-basedguidelines that are tailored to

individual patient preferences,prognoses, and comorbidities. B

c A patient-centered communicationstyle should be used thatincorporates patient preferences,assesses literacy and numeracy,and addresses cultural barriers tocare. B

There has been steady improvement inthe proportion of diabetic patientsachieving recommended levels of A1C,blood pressure, and LDL cholesterol inthe last 10 years, both in primary caresettings and in endocrinology practices.Mean A1C nationally has declined from7.82% in 1999–2000 to 7.18% in 2004based on NHANES data (586). This hasbeen accompanied by improvements inlipids and blood pressure control and ledto substantial reductions in end-stagemicrovascular complications in thosewith diabetes. Nevertheless, between33.4 to 48.7% of patients with diabetesstill do not meet targets for glycemic,blood pressure, and cholesterol control,and only 14.3% meet targets for thecombination of all three measures andnonsmoking status (317). Evidence alsosuggests that progress in risk factorcontrol (particularly tobacco use) maybe slowing (317,587). Certain patientgroups, such as patients with complexcomorbidities, financial or other socialhardships, and/or limited Englishproficiency, may present particularchallenges to goal-based care (588,589).Persistent variation in quality ofdiabetes care across providers andacross practice settings even afteradjusting for patient factors indicatesthat there remains potential forsubstantial further improvements indiabetes care.

While numerous interventions toimprove adherence to therecommended standards have beenimplemented, amajor barrier to optimalcare is a delivery system that too often isfragmented, lacks clinical informationcapabilities, often duplicates services,and is poorly designed for thecoordinated delivery of chronic care.The CCM has been shown to be aneffective framework for improving thequality of diabetes care (590). The CCMincludes six core elements for theprovision of optimal care of patients

with chronic disease: 1) delivery systemdesign (moving from a reactive to aproactive care delivery system whereplanned visits are coordinated through ateam-based approach, 2) self-management support, 3) decisionsupport (basing care on evidence-based, effective care guidelines),4) clinical information systems (usingregistries that can provide patient-specific and population-based supportto the care team), 5) communityresources and policies (identifying ordeveloping resources to supporthealthy lifestyles), and 6) healthsystems (to create a quality-orientedculture). Redefinition of the roles of theclinic staff and promoting self-management on the part of the patientare fundamental to the successfulimplementation of the CCM (591).Collaborative, multidisciplinary teamsare best suited to provide such care forpeople with chronic conditions such asdiabetes and to facilitate patients’performance of appropriate self-management (222,224,287,592).

NDEP maintains an online resource(www.betterdiabetescare.nih.gov) tohelp health care professionals designand implement more effective healthcare delivery systems for those withdiabetes. Three specific objectives, withreferences to literature that outlinespractical strategies to achieve each, areoutlined below.

Objective 1: Optimize Provider andTeam BehaviorThe care team should prioritize timelyand appropriate intensification oflifestyle and/or pharmaceuticaltherapy of patients who have notachieved beneficial levels of bloodpressure, lipid, or glucose control (593).Strategies such as explicit goal settingwith patients (594); identifying andaddressing language, numeracy, orcultural barriers to care (595–598);integrating evidence-based guidelinesand clinical information tools into theprocess of care (599–601); andincorporating care management teamsincluding nurses, pharmacists, andother providers (602–604) have eachbeen shown to optimize provider andteam behavior and thereby catalyzereduction in A1C, blood pressure, andLDL cholesterol.

care.diabetesjournals.org Position Statement S61

Objective 2: Support Patient BehaviorChangeSuccessful diabetes care requires asystematic approach to supportingpatients’ behavior change efforts,including 1) healthy lifestyle changes(physical activity, healthy eating,nonuse of tobacco, weightmanagement, effective coping);2) disease self-management (medicationtaking and management and self-monitoring of glucose and bloodpressure when clinically appropriate);and 3) prevention of diabetescomplications (self-monitoring of foothealth; active participation in screeningfor eye, foot, and renal complications;and immunizations). High-quality DSMEhas been shown to improve patient self-management, satisfaction, and glucosecontrol (242,605), as has delivery ofongoing DSMS, so that gains achievedduring DSME are sustained (606–608).National DSME standards call for anintegrated approach that includesclinical content and skills, behavioralstrategies (goal setting, problemsolving) and addressing emotionalconcerns in each needed curriculumcontent area.

Objective 3: Change the System ofCareThe most successful practices have aninstitutional priority for providing highquality of care (609). Changes that havebeen shown to increase quality ofdiabetes care include basing care onevidence-based guidelines (610),expanding the role of teams and staff(602,611), redesigning the processes ofcare (612), implementing electronichealth record tools (613,614), activatingand educating patients (615,616), andidentifying and/or developing andengaging community resources andpublic policy that support healthylifestyles (617). Recent initiatives suchas the Patient-Centered Medical Homeshow promise to improve outcomesthrough coordinated primary care andoffer new opportunities for team-based chronic disease care (618).Alterations in reimbursement thatreward the provision of appropriateand high-quality care rather thanvisit-based billing (619) and that canaccommodate the need to personalizecare goals may provide additional

incentives to improve diabetescare (620).

It is clear that optimal diabetesmanagement requires an organized,systematic approach and involvementof a coordinated team of dedicatedhealth care professionals working in anenvironment where patient-centeredhigh-quality care is a priority.

References1. American Diabetes Association. Medical

Management of Type 1 Diabetes.Alexandria, VA, American DiabetesAssociation, 2012

2. American Diabetes Association. MedicalManagement of Type 2 Diabetes.Alexandria, VA, American DiabetesAssociation, 2012

3. Li R, Zhang P, Barker LE, Chowdhury FM,Zhang X. Cost-effectiveness ofinterventions to prevent and controldiabetes mellitus: a systematic review.Diabetes Care 2010;33:1872–1894

4. American Diabetes Association. Diagnosisand classification of diabetes mellitus.Diabetes Care 2014;37(Suppl. 1):S81–S90

5. International Expert Committee.International Expert Committee report onthe role of the A1C assay in the diagnosisof diabetes. Diabetes Care 2009;32:1327–1334

6. Ziemer DC, Kolm P, Weintraub WS, et al.Glucose-independent, black-whitedifferences in hemoglobin A1c levels:a cross-sectional analysis of 2 studies. AnnIntern Med 2010;152:770–777

7. Kumar PR, Bhansali A, Ravikiran M, et al.Utility of glycated hemoglobin indiagnosing type 2 diabetes mellitus:a community-based study. J ClinEndocrinol Metab 2010;95:2832–2835

8. Selvin E, Steffes MW, Ballantyne CM,Hoogeveen RC, Coresh J, Brancati FL.Racial differences in glycemic markers:a cross-sectional analysis of community-based data. Ann Intern Med 2011;154:303–309

9. Nowicka P, Santoro N, Liu H, et al. Utility ofhemoglobin A(1c) for diagnosingprediabetes and diabetes in obesechildren and adolescents. Diabetes Care2011;34:1306–1311

10. Garcıa de Guadiana Romualdo L, GonzalezMorales M, Albaladejo Oton MD. Thevalue of hemoglobin A1c for diagnosis ofdiabetes mellitus and other changes incarbohydrate metabolism in women withrecent gestational diabetes mellitus.Endocrinology Nutrition 2012;59:362–366[in Spanish]

11. Cowie CC, Rust KF, Byrd-Holt DD, et al.Prevalence of diabetes and high risk fordiabetes using A1C criteria in the U.S.

population in 1988–2006. Diabetes Care2010;33:562–568

12. Picon MJ, Murri M, Mu~noz A, Fernandez-Garcıa JC, Gomez-Huelgas R, Tinahones FJ.Hemoglobin A1c versus oral glucosetolerance test in postpartum diabetesscreening. Diabetes Care 2012;35:1648–1653

13. Expert Committee on the Diagnosis andClassification of Diabetes Mellitus. Reportof the Expert Committee on the Diagnosisand Classification of Diabetes Mellitus.Diabetes Care 1997;20:1183–1197

14. Genuth S, Alberti KG, Bennett P, et al.;Expert Committee on the Diagnosis andClassification of DiabetesMellitus. Follow-up report on the diagnosis of diabetesmellitus. Diabetes Care 2003;26:3160–3167

15. Zhang X, Gregg EW, Williamson DF, et al.A1C level and future risk of diabetes:a systematic review. Diabetes Care 2010;33:1665–1673

16. Selvin E, SteffesMW, Zhu H, et al. Glycatedhemoglobin, diabetes, and cardiovascularrisk in nondiabetic adults. N Engl J Med2010;362:800–811

17. Ackermann RT, Cheng YJ, Williamson DF,Gregg EW. Identifying adults at high riskfor diabetes and cardiovascular diseaseusing hemoglobin A1c National Health andNutrition Examination Survey 2005–2006.Am J Prev Med 2011;40:11–17

18. Griffin SJ, Borch-Johnsen K, Davies MJ,et al. Effect of early intensivemultifactorial therapy on 5-yearcardiovascular outcomes in individuals withtype 2 diabetes detected by screening(ADDITION-Europe): a cluster-randomisedtrial. Lancet 2011;378:156–167

19. Kahn R, Alperin P, Eddy D, et al. Age atinitiation and frequency of screening todetect type 2 diabetes: a cost-effectiveness analysis. Lancet 2010;375:1365–1374

20. Erickson SC, Le L, Zakharyan A, et al. New-onset treatment-dependent diabetesmellitus and hyperlipidemia associatedwith atypical antipsychotic use in olderadults without schizophrenia or bipolardisorder. J Am Geriatr Soc 2012;60:474–479

21. Chiu M, Austin PC, Manuel DG, Shah BR,Tu JV. Deriving ethnic-specific BMI cutoffpoints for assessing diabetes risk.Diabetes Care 2011;34:1741–1748

22. Sheehy A, Pandhi N, Coursin DB, et al.Minority status and diabetes screening inan ambulatory population. Diabetes Care2011;34:1289–1294

23. Knowler WC, Barrett-Connor E, Fowler SE,et al.; Diabetes Prevention ProgramResearch Group. Reduction in theincidence of type 2 diabetes with lifestyleintervention or metformin. N Engl J Med2002;346:393–403

S62 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

24. Tuomilehto J, Lindstrom J, Eriksson JG,et al.; Finnish Diabetes Prevention StudyGroup. Prevention of type 2 diabetesmellitus by changes in lifestyle amongsubjects with impaired glucosetolerance. N Engl J Med 2001;344:1343–1350

25. Pan XR, Li GW, Hu YH, et al. Effects of dietand exercise in preventing NIDDM inpeople with impaired glucose tolerance.The Da Qing IGT and Diabetes Study.Diabetes Care 1997;20:537–544

26. Buchanan TA, Xiang AH, Peters RK, et al.Preservation of pancreatic beta-cellfunction and prevention of type 2 diabetesby pharmacological treatment of insulinresistance in high-risk Hispanic women.Diabetes 2002;51:2796–2803

27. Chiasson JL, Josse RG, Gomis R, HanefeldM, Karasik A, Laakso M; STOP-NIDDM TrialResearch Group. Acarbose for preventionof type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002;359:2072–2077

28. Gerstein HC, Yusuf S, Bosch J, et al.;DREAM (Diabetes REduction Assessmentwith ramipril and rosiglitazoneMedication) Trial Investigators. Effect ofrosiglitazone on the frequency of diabetesin patients with impaired glucosetolerance or impaired fasting glucose:a randomised controlled trial. Lancet2006;368:1096–1105

29. Ramachandran A, Snehalatha C, Mary S,Mukesh B, Bhaskar AD, Vijay V; IndianDiabetes Prevention Programme (IDPP).The Indian Diabetes PreventionProgramme shows that lifestylemodification and metformin prevent type2 diabetes in Asian Indian subjects withimpaired glucose tolerance (IDPP-1).Diabetologia 2006;49:289–297

30. Johnson SL, Tabaei BP, Herman WH. Theefficacy and cost of alternative strategiesfor systematic screening for type 2 diabetesin the U.S. population 45–74 years of age.Diabetes Care 2005;28:307–311

31. Imperatore G, Boyle JP, Thompson TJ,et al.; SEARCH for Diabetes in Youth StudyGroup. Projections of type 1 and type 2diabetes burden in the U.S. populationaged ,20 years through 2050: dynamicmodeling of incidence, mortality, andpopulation growth. Diabetes Care 2012;35:2515–2520

32. American Diabetes Association. Type 2diabetes in children and adolescents.Diabetes Care 2000;23:381–389

33. Buse JB, Kaufman FR, Linder B, Hirst K, ElGhormli L, Willi S; HEALTHY Study Group.Diabetes screening with hemoglobin A(1c)versus fasting plasma glucose in amultiethnic middle-school cohort.Diabetes Care 2013;36:429–435

34. Kapadia C, Zeitler P; Drugs andTherapeutics Committee of the Pediatric

Endocrine Society. Hemoglobin A1cmeasurement for the diagnosis of type 2diabetes in children. Int J PediatrEndocrinol 2012;2012:31

35. Kester LM, Hey H, Hannon TS. Usinghemoglobin A1c for prediabetes anddiabetes diagnosis in adolescents: canadult recommendations be upheld forpediatric use?J Adolesc Health 2012;50:321–323

36. Wu EL, Kazzi NG, Lee JM. Cost-effectiveness of screening strategies foridentifying pediatric diabetes mellitus anddysglycemia. JAMA Pediatr 2013;167:32–39

37. Lipman TH, Levitt Katz LE, Ratcliffe SJ, et al.Increasing incidence of type 1 diabetes inyouth: twenty years of the PhiladelphiaPediatric Diabetes Registry. Diabetes Care2013;36:1597–1603

38. Pettitt DJ, Talton J, Dabelea D, et al.Prevalence of diabetes mellitus in U.S.youth in 2009: the SEARCH for Diabetes inYouth Study. Diabetes Care. 16 September2013 [Epub ahead of print]

39. Ziegler AG, Rewers M, Simell O, et al.Seroconversion to multiple isletautoantibodies and risk of progression todiabetes in children. JAMA 2013;309:2473–2479

40. Sosenko JM, Skyler JS, Palmer JP, et al.;Type 1 Diabetes TrialNet Study Group;Diabetes Prevention Trial-Type 1 StudyGroup. The prediction of type 1 diabetesby multiple autoantibody levels and theirincorporation into an autoantibody riskscore in relatives of type 1 diabeticpatients. Diabetes Care 2013;36:2615–2620

41. Sorensen JS, Johannesen J, Pociot F, et al.;the Danish Society for Diabetes inChildhood and Adolescence. Residualb-cell function 3 to 6 years after onset oftype 1 diabetes reduces risk of severehypoglycemia in children and adolescents.Diabetes Care 2013;36:3454–3459

42. Lawrence JM, Contreras R, Chen W, SacksDA. Trends in the prevalence ofpreexisting diabetes and gestationaldiabetes mellitus among a racially/ethnically diverse population of pregnantwomen, 1999–2005. Diabetes Care 2008;31:899–904

43. Metzger BE, Lowe LP, Dyer AR, et al.;HAPO Study Cooperative Research Group.Hyperglycemia and adverse pregnancyoutcomes. N Engl J Med 2008;358:1991–2002

44. American Diabetes Association. Standardsof medical care in diabetesd2011.Diabetes Care 2011;34(Suppl. 1):S11–S61

45. Metzger BE, Gabbe SG, Persson B, et al.;International Association of Diabetes andPregnancy Study Groups Consensus Panel.International Association of Diabetesand Pregnancy Study Groups

recommendations on the diagnosisand classification of hyperglycemiain pregnancy. Diabetes Care 2010;33:676–682

46. Landon MB, Spong CY, Thom E, et al.;Eunice Kennedy Shriver National Instituteof Child Health and Human DevelopmentMaternal-Fetal Medicine Units Network.A multicenter, randomized trial oftreatment for mild gestational diabetes.N Engl J Med 2009;361:1339–1348

47. Crowther CA, Hiller JE, Moss JR, McPheeAJ, Jeffries WS, Robinson JS; AustralianCarbohydrate Intolerance Study inPregnant Women (ACHOIS) Trial Group.Effect of treatment of gestational diabetesmellitus on pregnancy outcomes. N Engl JMed 2005;352:2477–2486

48. Vandorsten JP, Dodson WC, Espeland MA,et al. NIH consensus developmentconference: diagnosing gestationaldiabetes mellitus. NIH Consens State SciStatements 2013;29:1–31

49. Horvath K, Koch K, Jeitler K, et al. Effects oftreatment in women with gestationaldiabetes mellitus: systematic review andmeta-analysis. BMJ 2010;340:c1395

50. Kim C, Herman WH, Cheung NW,Gunderson EP, Richardson C. Comparisonof hemoglobin A1c with fasting plasmaglucose and 2-h postchallenge glucose forrisk stratification among women withrecent gestational diabetes mellitus.Diabetes Care 2011;34:1949–1951

51. Kim C, Newton KM, Knopp RH. Gestationaldiabetes and the incidence of type 2diabetes: a systematic review. DiabetesCare 2002;25:1862–1868

52. Tobias DK, Hu FB, Chavarro J, Rosner B,Mozaffarian D, Zhang C. Healthful dietarypatterns and type 2 diabetes mellitus riskamong women with a history ofgestational diabetes mellitus. Arch InternMed 2012;172:1566–1572

53. Li G, Zhang P, Wang J, et al. The long-termeffect of lifestyle interventions to preventdiabetes in the China Da Qing DiabetesPrevention Study: a 20-year follow-upstudy. Lancet 2008;371:1783–1789

54. Lindstrom J, Ilanne-Parikka P, Peltonen M,et al.; Finnish Diabetes Prevention StudyGroup. Sustained reduction in theincidence of type 2 diabetes by lifestyleintervention: follow-up of the FinnishDiabetes Prevention Study. Lancet 2006;368:1673–1679

55. Knowler WC, Fowler SE, Hamman RF,et al.; Diabetes Prevention ProgramResearch Group. 10-year follow-up ofdiabetes incidence and weight loss in theDiabetes Prevention Program OutcomesStudy. Lancet 2009;374:1677–1686

56. HermanWH, Hoerger TJ, Brandle M, et al.;Diabetes Prevention Program ResearchGroup. The cost-effectiveness of lifestylemodification or metformin in preventing

care.diabetesjournals.org Position Statement S63

type 2 diabetes in adults with impairedglucose tolerance. Ann Intern Med 2005;142:323–332

57. Diabetes Prevention Program ResearchGroup. The 10-year cost-effectiveness oflifestyle intervention or metformin fordiabetes prevention: an intent-to-treatanalysis of the DPP/DPPOS. Diabetes Care2012;35:723–730

58. Ackermann RT, Finch EA, Brizendine E,Zhou H, Marrero DG. Translating theDiabetes Prevention Program into thecommunity. The DEPLOY Pilot Study. Am JPrev Med 2008;35:357–363

59. Diabetes Prevention Program ResearchGroup. Long-term safety, tolerability, andweight loss associated with metformin inthe Diabetes Prevention ProgramOutcomes Study. Diabetes Care 2012;35:731–737

60. DREAM Trial Investigators. Incidence ofdiabetes following ramipril orrosiglitazone withdrawal. Diabetes Care2011;34:1265–1269

61. Ratner RE, Christophi CA, Metzger BE,et al.; Diabetes Prevention ProgramResearch Group. Prevention of diabetes inwomen with a history of gestationaldiabetes: effects of metformin andlifestyle interventions. J Clin EndocrinolMetab 2008;93:4774–4779

62. Miller KM, Beck RW, Bergenstal RM, et al.;T1D Exchange Clinic Network. Evidenceof a strong association between frequencyof self-monitoring of blood glucose andhemoglobin A1c levels in T1D Exchangeclinic registry participants. Diabetes Care2013;36:2009–2014

63. Ziegler R, Heidtmann B, Hilgard D, Hofer S,Rosenbauer J, Holl R; DPV-Wiss-Initiative.Frequency of SMBG correlates with HbA1cand acute complications in children andadolescents with type 1 diabetes. PediatrDiabetes 2011;12:11–17

64. Farmer A, Wade A, Goyder E, et al. Impactof self monitoring of blood glucose in themanagement of patients with non-insulintreated diabetes: open parallel grouprandomised trial. BMJ 2007;335:132

65. O’KaneMJ, Bunting B, CopelandM, CoatesVE; ESMON Study Group. Efficacy of selfmonitoring of blood glucose in patientswith newly diagnosed type 2 diabetes(ESMON study): randomised controlledtrial. BMJ 2008;336:1174–1177

66. Simon J, Gray A, Clarke P, Wade A, Neil A,Farmer A; Diabetes Glycaemic Educationand Monitoring Trial Group. Costeffectiveness of self monitoring of bloodglucose in patients with non-insulintreated type 2 diabetes: economicevaluation of data from the DiGEM trial.BMJ 2008;336:1177–1180

67. Willett LR. ACP Journal Club. Meta-analysis: self-monitoring in non-insulin-treated type 2 diabetes improved HbA1c

by 0.25%. Ann Intern Med 2012;156:JC6–JC12

68. Malanda UL, Welschen LMC, Riphagen II,Dekker JM, Nijpels G, Bot SD. Self-monitoring of blood glucose in patientswith type 2 diabetes mellitus who are notusing insulin. Cochrane Database Syst Rev2012;(1):CD005060

69. Sacks DB, Arnold M, Bakris GL, et al.;National Academy of ClinicalBiochemistry. Position statementexecutive summary: guidelines andrecommendations for laboratory analysisin the diagnosis and management ofdiabetes mellitus. Diabetes Care 2011;34:1419–1423

70. Wang J, Zgibor J, Matthews JT, Charron-Prochownik D, Sereika SM, Siminerio L.Self-monitoring of blood glucose isassociated with problem-solving skills inhyperglycemia and hypoglycemia.Diabetes Educ 2012;38:207–218

71. Polonsky WH, Fisher L, Schikman CH, et al.Structured self-monitoring of bloodglucose significantly reduces A1C levels inpoorly controlled, noninsulin-treated type2 diabetes: results from the StructuredTesting Program study. Diabetes Care2011;34:262–267

72. Tamborlane WV, Beck RW, Bode BW,et al.; Juvenile Diabetes ResearchFoundation Continuous GlucoseMonitoring Study Group. Continuousglucose monitoring and intensivetreatment of type 1 diabetes. N Engl J Med2008;359:1464–1476

73. Yeh HC, Brown TT, Maruthur N, et al.Comparative effectiveness and safety ofmethods of insulin delivery and glucosemonitoring for diabetes mellitus:a systematic review and meta-analysis.Ann Intern Med 2012;157:336–347

74. Bergenstal RM, Klonoff DC, Garg SK, et al.;ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption forreduction of hypoglycemia. N Engl J Med2013;369:224–232

75. Bergenstal RM, Ahmann AJ, Bailey T, et al.Recommendations for standardizingglucose reporting and analysis to optimizeclinical decision making in diabetes: theAmbulatory Glucose Profile (AGP).Diabetes Technol Ther 2013;15:198–211

76. The Diabetes Control and ComplicationsTrial Research Group. The effect ofintensive treatment of diabetes on thedevelopment and progression of long-term complications in insulin-dependentdiabetes mellitus. N Engl J Med 1993;329:977–986

77. Stratton IM, Adler AI, Neil HA, et al.Association of glycaemia withmacrovascular and microvascularcomplications of type 2 diabetes (UKPDS35): prospective observational study. BMJ2000;321:405–412

78. Nathan DM, Kuenen J, Borg R, Zheng H,Schoenfeld D, Heine RJ; A1c-DerivedAverage Glucose Study Group. Translatingthe A1C assay into estimated averageglucose values. Diabetes Care 2008;31:1473–1478

79. Rohlfing CL, Wiedmeyer HM, Little RR,England JD, Tennill A, Goldstein DE.Defining the relationship between plasmaglucose and HbA(1c): analysis of glucoseprofiles and HbA(1c) in the DiabetesControl and Complications Trial. DiabetesCare 2002;25:275–278

80. Wilson DM, Kollman; Diabetes Research inChildren Network (DirecNet) Study Group.Relationship of A1C to glucoseconcentrations in children with type 1diabetes: assessments by high-frequencyglucose determinations by sensors.Diabetes Care 2008;31:381–385

81. Kamps JL, Hempe JM, Chalew SA. Racialdisparity in A1C independent of meanblood glucose in children with type 1diabetes. Diabetes Care 2010;33:1025–1027

82. The Diabetes Control and ComplicationsTrial/Epidemiology of DiabetesInterventions and Complications ResearchGroup. Retinopathy and nephropathy inpatients with type 1 diabetes four yearsafter a trial of intensive therapy. N Engl JMed 2000;342:381–389

83. Martin CL, Albers J, Herman WH, et al.;DCCT/EDIC Research Group. Neuropathyamong the diabetes control andcomplications trial cohort 8 years aftertrial completion. Diabetes Care 2006;29:340–344

84. Ohkubo Y, Kishikawa H, Araki E, et al.Intensive insulin therapy prevents theprogression of diabetic microvascularcomplications in Japanese patients withnon-insulin-dependent diabetes mellitus:a randomized prospective 6-year study.Diabetes Res Clin Pract 1995;28:103–117

85. UK Prospective Diabetes Study (UKPDS)Group. Effect of intensive blood-glucosecontrol with metformin on complicationsin overweight patients with type 2diabetes (UKPDS 34). Lancet 1998;352:854–865

86. UK Prospective Diabetes Study (UKPDS)Group. Intensive blood-glucose controlwith sulphonylureas or insulin comparedwith conventional treatment and risk ofcomplications in patients with type 2diabetes (UKPDS 33). Lancet 1998;352:837–853

87. Holman RR, Paul SK, Bethel MA,MatthewsDR, Neil HA. 10-year follow-up of intensiveglucose control in type 2 diabetes. N Engl JMed 2008;359:1577–1589

88. Duckworth W, Abraira C, Moritz T, et al.;VADT Investigators. Glucose control andvascular complications in veterans withtype 2 diabetes. N Engl J Med 2009;360:129–139

S64 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

89. Patel A, MacMahon S, Chalmers J, et al.;ADVANCE Collaborative Group. Intensiveblood glucose control and vascularoutcomes in patients with type 2 diabetes.N Engl J Med 2008;358:2560–2572

90. Ismail-Beigi F, Craven T, Banerji MA, et al.;ACCORD trial group. Effect of intensivetreatment of hyperglycaemia onmicrovascular outcomes in type 2diabetes: an analysis of the ACCORDrandomised trial. Lancet 2010;376:419–430

91. Gerstein HC,MillerME, Byington RP, et al.;Action to Control Cardiovascular Risk inDiabetes Study Group. Effects of intensiveglucose lowering in type 2 diabetes. N EnglJ Med 2008;358:2545–2559

92. Nathan DM, Cleary PA, Backlund JY, et al.;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventionsand Complications (DCCT/EDIC) StudyResearch Group. Intensive diabetestreatment and cardiovascular disease inpatients with type 1 diabetes. N Engl JMed 2005;353:2643–2653

93. Nathan DM, Zinman B, Cleary PA, et al.;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventionsand Complications (DCCT/EDIC) ResearchGroup. Modern-day clinical course of type1 diabetes mellitus after 30 years’duration: the Diabetes Control andComplications Trial/Epidemiology ofDiabetes Interventions and Complicationsand Pittsburgh Epidemiology of DiabetesComplications experience (1983–2005).Arch Intern Med 2009;169:1307–1316

94. Skyler JS, Bergenstal R, Bonow RO, et al.;American Diabetes Association; AmericanCollege of Cardiology Foundation;American Heart Association. Intensiveglycemic control and the prevention ofcardiovascular events: implications of theACCORD, ADVANCE, and VA DiabetesTrials: a position statement of theAmerican Diabetes Association and ascientific statement of the AmericanCollege of Cardiology Foundation and theAmerican Heart Association. DiabetesCare 2009;32:187–192

95. Riddle MC, Ambrosius WT, Brillon DJ,et al.; Action to Control CardiovascularRisk in Diabetes Investigators.Epidemiologic relationships between A1Cand all-cause mortality during a median3.4-year follow-up of glycemic treatmentin the ACCORD trial. Diabetes Care 2010;33:983–990

96. Reaven PD, Moritz TE, Schwenke DC, et al.Intensive glucose lowering therapyreduces cardiovascular disease eventsin Veterans Affairs Diabetes Trialparticipants with lower calcified coronaryatherosclerosis. Diabetes 2009;58:2642–2648

97. DuckworthWC, Abraira C,Moritz TE, et al.;Investigators of the VADT. The duration of

diabetes affects the response to intensiveglucose control in type 2 subjects: the VADiabetes Trial. J Diabetes Complications2011;25:355–361

98. Turnbull FM, Abraira C, Anderson RJ, et al.;Control Group. Intensive glucose controland macrovascular outcomes in type 2diabetes [published correction appears inDiabetologia 2009;52:2470]. Diabetologia2009;52:2288–2298

99. Ismail-Beigi F, Moghissi E, Tiktin M, HirschIB, Inzucchi SE, Genuth S. Individualizingglycemic targets in type 2 diabetesmellitus: implications of recent clinicaltrials. Ann Intern Med 2011;154:554–559

100. American Diabetes Association.Postprandial blood glucose. Diabetes Care2001;24:775–778

101. Ceriello A, Taboga C, Tonutti L, et al.Evidence for an independent andcumulative effect of postprandialhypertriglyceridemia and hyperglycemiaon endothelial dysfunction and oxidativestress generation: effects of short- andlong-term simvastatin treatment.Circulation 2002;106:1211–1218

102. Raz I, Wilson PW, Strojek K, et al. Effects ofprandial versus fasting glycemia oncardiovascular outcomes in type 2diabetes: the HEART2D trial. DiabetesCare 2009;32:381–386

103. Metzger BE, Buchanan TA, Coustan DR,et al. Summary and recommendations ofthe Fifth International Workshop-Conference on Gestational DiabetesMellitus. Diabetes Care 2007;30(Suppl. 2):S251–S260

104. Kitzmiller JL, Block JM, Brown FM, et al.Managing preexisting diabetes forpregnancy: summary of evidence andconsensus recommendations for care.Diabetes Care 2008;31:1060–1079

105. DeWitt DE, Hirsch IB. Outpatient insulintherapy in type 1 and type 2 diabetesmellitus: scientific review. JAMA 2003;289:2254–2264

106. Rosenstock J, Dailey G, Massi-BenedettiM, Fritsche A, Lin Z, Salzman A. Reducedhypoglycemia risk with insulin glargine:ameta-analysis comparing insulin glarginewith human NPH insulin in type 2diabetes. Diabetes Care 2005;28:950–955

107. American Diabetes Association. IntensiveDiabetes Management. Alexandria, VA,American Diabetes Association, 2009

108. Mooradian AD, Bernbaum M, Albert SG.Narrative review: a rational approach tostarting insulin therapy. Ann Intern Med2006;145:125–134

109. Wood JR,Miller KM,Maahs DM, et al.; T1DExchange Clinic Network. Most youth withtype 1 diabetes in the T1D Exchange ClinicRegistry do not meet American DiabetesAssociation or International Society forPediatric and Adolescent Diabetes clinical

guidelines. Diabetes Care 2013;36:2035–2037

110. Kmietowicz Z. Insulin pumps improvecontrol and reduce complications inchildren with type 1 diabetes. BMJ 2013;347:f5154

111. Phillip M, Battelino T, Atlas E, et al.Nocturnal glucose control with an artificialpancreas at a diabetes camp. N Engl J Med2013;368:824–833

112. Wolpert HA, Atakov-Castillo A, Smith SA,Steil GM. Dietary fat acutely increasesglucose concentrations and insulinrequirements in patients with type 1diabetes: implications for carbohydrate-based bolus dose calculation and intensivediabetes management. Diabetes Care2013;36:810–816

113. Inzucchi SE, Bergenstal RM, Buse JB, et al.;American Diabetes Association (ADA);European Association for the Study ofDiabetes (EASD). Management ofhyperglycemia in type 2 diabetes:a patient-centered approach. Positionstatement of the American DiabetesAssociation (ADA) and the EuropeanAssociation for the Study of Diabetes(EASD). Diabetes Care 2012;35:1364–1379

114. Bennett WL, Maruthur NM, Singh S, et al.Comparative effectiveness and safety ofmedications for type 2 diabetes: anupdate including new drugs and 2-drugcombinations. Ann Intern Med 2011;154:602–613

115. Blonde L,MerilainenM, Karwe V, Raskin P;TITRATE Study Group. Patient-directedtitration for achieving glycaemic goalsusing a once-daily basal insulin analogue:an assessment of two different fastingplasma glucose targetsdthe TITRATEstudy. Diabetes Obes Metab 2009;11:623–631

116. Evert AB, Boucher JL, Cypress M, et al.Nutrition therapy recommendations for themanagement of adults with diabetes.Diabetes Care 2014;37(Suppl. 1):S120–S143

117. DAFNE Study Group. Training in flexible,intensive insulin management to enabledietary freedom in people with type 1diabetes: Dose Adjustment for NormalEating (DAFNE) randomised controlledtrial. BMJ 2002;325:746

118. Kulkarni K, Castle G, Gregory R, et al.; theDiabetes Care and Education DieteticPractice Group. Nutrition PracticeGuidelines for Type 1 Diabetes Mellituspositively affect dietitian practices andpatient outcomes. J Am Diet Assoc 1998;98:62–70

119. Rossi MC, Nicolucci A, Di Bartolo P, et al.Diabetes Interactive Diary: a newtelemedicine system enabling flexible dietand insulin therapy while improvingquality of life: an open-label,international, multicenter, randomizedstudy. Diabetes Care 2010;33:109–115

care.diabetesjournals.org Position Statement S65

120. Laurenzi A, Bolla AM, Panigoni G, et al.Effects of carbohydrate counting onglucose control and quality of life over24 weeks in adult patients with type 1diabetes on continuous subcutaneousinsulin infusion: a randomized,prospective clinical trial (GIOCAR).Diabetes Care 2011;34:823–827

121. Ash S, Reeves MM, Yeo S, Morrison G,Carey D, Capra S. Effect of intensivedietetic interventions on weight andglycaemic control in overweight men withtype II diabetes: a randomised trial. Int JObes Relat Metab Disord 2003;27:797–802

122. Rickheim PL, Weaver TW, Flader JL,Kendall DM. Assessment of group versusindividual diabetes education:a randomized study. Diabetes Care 2002;25:269–274

123. Miller CK, Edwards L, Kissling G, Sanville L.Nutrition education improves metabolicoutcomes among older adults withdiabetes mellitus: results from arandomized controlled trial. Prev Med2002;34:252–259

124. Scavone G, Manto A, Pitocco D, et al.Effect of carbohydrate counting andmedical nutritional therapy on glycaemiccontrol in type 1 diabetic subjects: a pilotstudy. Diabet Med 2010;27:477–479

125. Goldhaber-Fiebert JD, Goldhaber-FiebertSN, Tristan ML, Nathan DM. Randomizedcontrolled community-based nutritionand exercise intervention improvesglycemia and cardiovascular risk factors intype 2 diabetic patients in rural Costa Rica.Diabetes Care 2003;26:24–29

126. Ziemer DC, Berkowitz KJ, Panayioto RM,et al. A simple meal plan emphasizinghealthy food choices is as effective as anexchange-based meal plan for urbanAfrican Americans with type 2 diabetes.Diabetes Care 2003;26:1719–1724

127. Takahashi M, Araki A, Ito H. Developmentof a new method for simple dietaryeducation in elderly patients withdiabetes mellitus. Nihon Rohen IgakkaiZasshi 2002;39:527–532 [in Japanese]

128. Wolf AM, Conaway MR, Crowther JQ,et al.; Improving Control with Activity andNutrition (ICAN) Study. Translatinglifestyle intervention to practice in obesepatients with type 2 diabetes: ImprovingControl with Activity and Nutrition (ICAN)study. Diabetes Care 2004;27:1570–1576

129. Barnard ND, Cohen J, Jenkins DJ, et al.A low-fat vegan diet improves glycemiccontrol and cardiovascular risk factors in arandomized clinical trial in individuals withtype 2 diabetes. Diabetes Care 2006;29:1777–1783

130. Nield L, Moore HJ, Hooper L, et al. Dietaryadvice for treatment of type 2 diabetesmellitus in adults. Cochrane Database SystRev 2007;(3):CD004097

131. Davis RM, Hitch AD, Salaam MM, HermanWH, Zimmer-Galler IE, Mayer-Davis EJ.TeleHealth improves diabetes self-management in an underservedcommunity: Diabetes TeleCare. DiabetesCare 2010;33:1712–1717

132. Huang MC, Hsu CC, Wang HS, Shin SJ.Prospective randomized controlled trial toevaluate effectiveness of registereddietitian-led diabetes management onglycemic and diet control in a primary caresetting in Taiwan. Diabetes Care 2010;33:233–239

133. Al-Shookri A, Khor GL, Chan YM, Loke SC,Al-Maskari M. Effectiveness of medicalnutrition treatment delivered by dietitianson glycaemic outcomes and lipid profilesof Arab, Omani patients with type 2diabetes. Diabet Med 2012;29:236–244

134. Coppell KJ, Kataoka M, Williams SM,Chisholm AW, Vorgers SM, Mann JI.Nutritional intervention in patients withtype 2 diabetes who are hyperglycaemicdespite optimised drugtreatmentdLifestyle Over and AboveDrugs in Diabetes (LOADD) study:randomised controlled trial. BMJ 2010;341:c3337

135. Tan MY, Magarey JM, Chee SS, Lee LF, TanMH. A brief structured educationprogramme enhances self-care practicesand improves glycaemic control inMalaysianswith poorly controlled diabetes.Health Educ Res 2011;26:896–907

136. Battista MC, Labonte M, Menard J, et al.Dietitian-coached management incombination with annual endocrinologistfollow up improves global metabolic andcardiovascular health in diabeticparticipants after 24 months. Appl PhysiolNutr Metab 2012;37:610–620

137. Franz MJ, Monk A, Barry B, et al.Effectiveness of medical nutrition therapyprovided by dietitians in the managementof non-insulin-dependent diabetesmellitus: a randomized, controlled clinicaltrial. J Am Diet Assoc 1995;95:1009–1017

138. Graber AL, Elasy TA, Quinn D, Wolff K,Brown A. Improving glycemic control inadults with diabetes mellitus: sharedresponsibility in primary care practices.South Med J 2002;95:684–690

139. Samann A, Muhlhauser I, Bender R, KloosCh, Muller UA. Glycaemic control andsevere hypoglycaemia following trainingin flexible, intensive insulin therapy toenable dietary freedom in people withtype 1 diabetes: a prospectiveimplementation study. Diabetologia 2005;48:1965–1970

140. Lowe J, Linjawi S, Mensch M, James K,Attia J. Flexible eating and flexible insulindosing in patients with diabetes: Resultsof an intensive self-management course.Diabetes Res Clin Pract 2008;80:439–443

141. McIntyre HD, Knight BA, Harvey DM, NoudMN, Hagger VL, Gilshenan KS. Dose

adjustment for normal eating (DAFNE)dan audit of outcomes in Australia. Med JAust 2010;192:637–640

142. Wolever TM, Hamad S, Chiasson JL, et al.Day-to-day consistency in amount andsource of carbohydrate intake associatedwith improved blood glucose control intype 1 diabetes. J Am Coll Nutr 1999;18:242–247

143. Rabasa-Lhoret R, Garon J, Langelier H,Poisson D, Chiasson JL. Effects of mealcarbohydrate content on insulinrequirements in type 1 diabetic patientstreated intensively with the basal-bolus(ultralente-regular) insulin regimen.Diabetes Care 1999;22:667–673

144. Esposito K, Maiorino MI, Ciotola M, et al.Effects of a Mediterranean-style diet onthe need for antihyperglycemic drugtherapy in patients with newly diagnosedtype 2 diabetes: a randomized trial. AnnIntern Med 2009;151:306–314

145. Pi-Sunyer X, Blackburn G, Brancati FL,et al.; Look AHEAD Research Group.Reduction in weight and cardiovasculardisease risk factors in individuals with type2 diabetes: one-year results of the LookAHEAD trial. Diabetes Care 2007;30:1374–1383

146. Estruch R, Ros E, Salas-Salvado J, et al.;PREDIMED Study Investigators. Primaryprevention of cardiovascular diseasewith a Mediterranean diet. N Engl J Med2013;368:1279–1290

147. Metz JA, Stern JS, Kris-Etherton P, et al. Arandomized trial of improved weight losswith a prepared meal plan in overweightand obese patients: impact oncardiovascular risk reduction. Arch InternMed 2000;160:2150–2158

148. West DS, DiLillo V, Bursac Z, Gore SA,Greene PG. Motivational interviewingimproves weight loss in women with type2 diabetes. Diabetes Care 2007;30:1081–1087

149. Larsen RN, Mann NJ, Maclean E, Shaw JE.The effect of high-protein, low-carbohydrate diets in the treatment oftype 2 diabetes: a 12 month randomisedcontrolled trial. Diabetologia 2011;54:731–740

150. Li Z, Hong K, Saltsman P, et al. Long-termefficacy of soy-based meal replacementsvs an individualized diet plan in obesetype II DM patients: relative effects onweight loss, metabolic parameters, andC-reactive protein. Eur J Clin Nutr 2005;59:411–418

151. Brehm BJ, Lattin BL, Summer SS, et al.One-year comparison of a high-monounsaturated fat diet with a high-carbohydrate diet in type 2 diabetes.Diabetes Care 2009;32:215–220

152. Davis NJ, Tomuta N, Schechter C, et al.Comparative study of the effects of a1-year dietary intervention of a

S66 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

low-carbohydrate diet versus a low-fat dieton weight and glycemic control in type 2diabetes.DiabetesCare 2009;32:1147–1152

153. Guldbrand H, Dizdar B, Bunjaku B, et al. Intype 2 diabetes, randomisation to adviceto follow a low-carbohydrate diettransiently improves glycaemic controlcompared with advice to follow a low-fatdiet producing a similar weight loss.Diabetologia 2012;55:2118–2127

154. Krebs JD, Elley CR, Parry-Strong A, et al.The Diabetes Excess Weight Loss (DEWL)Trial: a randomised controlled trial ofhigh-protein versus high-carbohydratediets over 2 years in type 2 diabetes.Diabetologia 2012;55:905–914

155. Wing RR, Bolin P, Brancati FL, et al.; LookAHEAD Research Group. Cardiovasculareffects of intensive lifestyle interventionin type 2 diabetes. N Engl J Med 2013;369:145–154

156. Li TY, Brennan AM, Wedick NM,Mantzoros C, Rifai N, Hu FB. Regularconsumption of nuts is associated with alower risk of cardiovascular disease inwomen with type 2 diabetes. J Nutr 2009;139:1333–1338

157. Wheeler ML, Dunbar SA, Jaacks LM, et al.Macronutrients, food groups, and eatingpatterns in the management of diabetes:a systematic review of the literature,2010. Diabetes Care 2012;35:434–445

158. Delahanty LM, Nathan DM, Lachin JM,et al.; Diabetes Control and ComplicationsTrial/Epidemiology of Diabetes.Association of diet with glycatedhemoglobin during intensive treatment oftype 1 diabetes in the Diabetes Controland Complications Trial. Am J Clin Nutr2009;89:518–524

159. Vitolins MZ, Anderson AM, Delahanty L,et al.; Look AHEAD Research Group. Actionfor Health in Diabetes (Look AHEAD) trial:baseline evaluation of selected nutrientsand food group intake. J Am Diet Assoc2009;109:1367–1375

160. Oza-Frank R, Cheng YJ, Narayan KM, GreggEW. Trends in nutrient intake amongadults with diabetes in the United States:1988–2004. J Am Diet Assoc 2009;109:1173–1178

161. Azadbakht L, Fard NR, Karimi M, et al.Effects of the Dietary Approaches to StopHypertension (DASH) eating plan oncardiovascular risks among type 2 diabeticpatients: a randomized crossover clinicaltrial. Diabetes Care 2011;34:55–57

162. Turner-McGrievy GM, Barnard ND, CohenJ, Jenkins DJ, Gloede L, Green AA. Changesin nutrient intake and dietary qualityamong participants with type 2 diabetesfollowing a low-fat vegan diet or aconventional diabetes diet for 22 weeks.J Am Diet Assoc 2008;108:1636–1645

163. Stern L, Iqbal N, Seshadri P, et al. Theeffects of low-carbohydrate versus

conventional weight loss diets in severelyobese adults: one-year follow-up of arandomized trial. Ann Intern Med 2004;140:778–785

164. Thomas D, Elliott EJ. Low glycaemic index,or low glycaemic load, diets for diabetesmellitus. Cochrane Database Syst Rev2009;(1):CD006296

165. He M, van Dam RM, Rimm E, Hu FB, Qi L.Whole-grain, cereal fiber, bran, and germintake and the risks of all-cause andcardiovascular disease-specific mortalityamong women with type 2 diabetesmellitus. Circulation 2010;121:2162–2168

166. Institute of Medicine. Dietary ReferenceIntakes: Energy, Carbohydrate, Fiber, Fat,Fatty Acids, Cholesterol, Protein, andAmino Acids. Washington, D.C., NationalAcademies Press, 2002

167. U.S. Department of Health and HumanServices. U.S. Department of Agriculture:Dietary Guideline for Americans, 2010.[article online], 2013. Available fromwww.health.gov/dietaryguidelines/.Accessed 1 October 2013

168. Ros E. Dietary cis-monounsaturated fattyacids and metabolic control in type 2diabetes. Am J Clin Nutr 2003;78(Suppl.):617S–625S

169. Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrateMediterranean diet improvescardiovascular risk factors and diabetescontrol among overweight patients withtype 2 diabetes mellitus: a 1-yearprospective randomized interventionstudy. Diabetes Obes Metab 2010;12:204–209

170. Shai I, Schwarzfuchs D, Henkin Y, et al.;Dietary Intervention RandomizedControlled Trial (DIRECT) Group. Weightloss with a low-carbohydrate,Mediterranean, or low-fat diet. N Engl JMed 2008;359:229–241

171. Brunerova L, Smejkalova V, Potockova J,Andel M. A comparison of the influenceof a high-fat diet enriched inmonounsaturated fatty acids andconventional diet on weight loss andmetabolic parameters in obese non-diabetic and type 2 diabetic patients.Diabet Med 2007;24:533–540

172. Harris WS, Mozaffarian D, Rimm E, et al.Omega-6 fatty acids and risk forcardiovascular disease: a science advisoryfrom the American Heart AssociationNutrition Subcommittee of the Council onNutrition, Physical Activity, andMetabolism; Council on CardiovascularNursing; and Council on Epidemiology andPrevention. Circulation 2009;119:902–907

173. Crochemore IC, Souza AF, de Souza AC,Rosado EL. v-3 Polyunsaturated fatty acidsupplementation does not influence bodycomposition, insulin resistance, andlipemia in women with type 2 diabetes

and obesity. Nutr Clin Pract 2012;27:553–560

174. Bot M, Pouwer F, Assies J, Jansen EH,Beekman AT, de Jonge P. Supplementationwith eicosapentaenoic omega-3 fatty aciddoes not influence serum brain-derivedneurotrophic factor in diabetes mellituspatients with major depression:a randomized controlled pilot study.Neuropsychobiology 2011;63:219–223

175. Mas E, Woodman RJ, Burke V, et al. Theomega-3 fatty acids EPA and DHAdecrease plasma F(2)-isoprostanes:results from two placebo-controlledinterventions. Free Radic Res 2010;44:983–990

176. Wong CY, Yiu KH, Li SW, et al. Fish-oilsupplement has neutral effects onvascular and metabolic function butimproves renal function in patients withtype 2 diabetes mellitus. Diabet Med2010;27:54–60

177. Malekshahi Moghadam A, SaedisomeoliaA, Djalali M, Djazayery A, Pooya S, SojoudiF. Efficacy of omega-3 fatty acidsupplementation on serum levels oftumour necrosis factor-alpha, C-reactiveprotein and interleukin-2 in type 2diabetes mellitus patients. Singapore MedJ 2012;53:615–619

178. Holman RR, Paul S, Farmer A, Tucker L,Stratton IM, Neil HA; Atorvastatin inFactorial with Omega-3 EE90 RiskReduction in Diabetes Study Group.Atorvastatin in Factorial with Omega-3EE90 Risk Reduction in Diabetes(AFORRD): a randomised controlled trial.Diabetologia 2009;52:50–59

179. Kromhout D, Geleijnse JM, de Goede J,et al. n-3 Fatty acids, ventriculararrhythmia-related events, and fatalmyocardial infarction in postmyocardialinfarction patients with diabetes.Diabetes Care 2011;34:2515–2520

180. Bosch J, Gerstein HC, Dagenais GR, et al.;ORIGIN Trial Investigators. n-3 Fatty acidsand cardiovascular outcomes in patientswith dysglycemia. N Engl J Med 2012;367:309–318

181. HallikainenM, Kurl S, Laakso M, MiettinenTA, Gylling H. Plant stanol esters lower LDLcholesterol level in statin-treatedsubjects with type 1 diabetes byinterfering the absorption and synthesisof cholesterol. Atherosclerosis 2011;217:473–478

182. HallikainenM, Lyyra-Laitinen T, Laitinen T,Moilanen L, Miettinen TA, Gylling H.Effects of plant stanol esters on serumcholesterol concentrations, relativemarkers of cholesterol metabolism andendothelial function in type 1 diabetes.Atherosclerosis 2008;199:432–439

183. Lau VW, Journoud M, Jones PJ. Plantsterols are efficacious in lowering plasmaLDL and non-HDL cholesterol inhypercholesterolemic type 2 diabetic and

care.diabetesjournals.org Position Statement S67

nondiabetic persons. Am J Clin Nutr 2005;81:1351–1358

184. Lee YM, Haastert B, ScherbaumW, HaunerH. A phytosterol-enriched spreadimproves the lipid profile of subjects withtype 2 diabetes mellitusda randomizedcontrolled trial under free-livingconditions. Eur J Nutr 2003;42:111–117

185. Stampfer MJ, Hennekens CH, Manson JE,Colditz GA, Rosner B, Willett WC. VitaminE consumption and the risk of coronarydisease in women. N Engl J Med 1993;328:1444–1449

186. Yochum LA, Folsom AR, Kushi LH. Intake ofantioxidant vitamins and risk of deathfrom stroke in postmenopausal women.Am J Clin Nutr 2000;72:476–483

187. Hasanain B, Mooradian AD. Antioxidantvitamins and their influence in diabetesmellitus. Curr Diab Rep 2002;2:448–456

188. Lonn E, Yusuf S, Hoogwerf B, et al.; HOPEStudy; MICRO-HOPE Study. Effects ofvitamin E on cardiovascular andmicrovascular outcomes in high-riskpatients with diabetes: results of theHOPE study and MICRO-HOPE substudy.Diabetes Care 2002;25:1919–1927

189. Miller ER 3rd, Pastor-Barriuso R, Dalal D,Riemersma RA, Appel LJ, Guallar E.Meta-analysis: high-dosage vitamin Esupplementation may increase all-causemortality. Ann Intern Med 2005;142:37–46

190. Belch J, MacCuish A, Campbell I, et al.;Prevention of Progression of ArterialDisease and Diabetes Study Group;Diabetes Registry Group; Royal College ofPhysicians Edinburgh. The Prevention ofProgression of Arterial Disease andDiabetes (POPADAD) trial: factorialrandomised placebo controlled trial ofaspirin and antioxidants in patientswith diabetes and asymptomaticperipheral arterial disease. BMJ 2008;337:a1840

191. Kataja-Tuomola MK, Kontto JP, MannistoS, Albanes D, Virtamo JR. Effect of alpha-tocopherol and beta-carotenesupplementation on macrovascularcomplications and total mortality fromdiabetes: results of the ATBC Study. AnnMed 2010;42:178–186

192. Balk EM, Tatsioni A, Lichtenstein AH, Lau J,Pittas AG. Effect of chromiumsupplementation on glucose metabolismand lipids: a systematic review ofrandomized controlled trials. DiabetesCare 2007;30:2154–2163

193. Rodrıguez-Moran M, Guerrero-Romero F.Oral magnesium supplementationimproves insulin sensitivity and metaboliccontrol in type 2 diabetic subjects:a randomized double-blind controlledtrial. Diabetes Care 2003;26:1147–1152

194. de Valk HW, Verkaaik R, van Rijn HJ,Geerdink RA, Struyvenberg A. Oral

magnesium supplementation in insulin-requiring type 2 diabetic patients. DiabetMed 1998;15:503–507

195. Jorde R, Figenschau Y. Supplementationwith cholecalciferol does not improveglycaemic control in diabetic subjects withnormal serum 25-hydroxyvitamin D levels.Eur J Nutr 2009;48:349–354

196. Patel P, Poretsky L, Liao E. Lack of effect ofsubtherapeutic vitamin D treatment onglycemic and lipid parameters in type 2diabetes: a pilot prospective randomizedtrial. J Diabetes 2010;2:36–40

197. Parekh D, Sarathi V, Shivane VK, BandgarTR, Menon PS, Shah NS. Pilot study toevaluate the effect of short-termimprovement in vitamin D status onglucose tolerance in patients with type 2diabetes mellitus. Endocr Pract 2010;16:600–608

198. Nikooyeh B, Neyestani TR, Farvid M, et al.Daily consumption of vitamin D- orvitamin D1 calcium-fortified yogurt drinkimproved glycemic control in patientswith type 2 diabetes: a randomized clinicaltrial. Am J Clin Nutr 2011;93:764–771

199. Soric MM, Renner ET, Smith SR. Effect ofdaily vitamin D supplementation onHbA1c in patients with uncontrolled type2 diabetes mellitus: a pilot study. JDiabetes 2012;4:104–105

200. LeachMJ, Kumar S. Cinnamon for diabetesmellitus. Cochrane Database Syst Rev2012;(9):CD007170

201. Yeh GY, Eisenberg DM, Kaptchuk TJ,Phillips RS. Systematic review of herbs anddietary supplements for glycemic controlin diabetes. Diabetes Care 2003;26:1277–1294

202. Bray GA, Vollmer WM, Sacks FM,Obarzanek E, Svetkey LP, Appel LJ; DASHCollaborative Research Group. A furthersubgroup analysis of the effects of theDASH diet and three dietary sodium levelson blood pressure: results of the DASH-Sodium Trial. Am J Cardiol 2004;94:222–227

203. Thomas MC, Moran J, Forsblom C, et al.;FinnDiane Study Group. The associationbetween dietary sodium intake, ESRD, andall-cause mortality in patients with type 1diabetes. Diabetes Care 2011;34:861–866

204. Ekinci EI, Clarke S, Thomas MC, et al.Dietary salt intake and mortality inpatients with type 2 diabetes. DiabetesCare 2011;34:703–709

205. Maillot M, Drewnowski A. A conflictbetween nutritionally adequate diets andmeeting the 2010 dietary guidelines forsodium. Am J Prev Med 2012;42:174–179

206. Haas L, Maryniuk M, Beck J, et al.; 2012Standards Revision Task Force. Nationalstandards for diabetes self-managementeducation and support. Diabetes Care2014;37(Suppl. 1):S144–S153

207. Norris SL, Engelgau MM, Narayan KM.Effectiveness of self-managementtraining in type 2 diabetes:a systematic review of randomizedcontrolled trials. Diabetes Care 2001;24:561–587

208. Marrero DG, Ard J, Delamater AM, et al.Twenty-first century behavioral medicine:a context for empowering clinicians andpatients with diabetes: a consensusreport. Diabetes Care 2013;36:463–470

209. Norris SL, Lau J, Smith SJ, Schmid CH,Engelgau MM. Self-managementeducation for adults with type 2 diabetes:a meta-analysis of the effect on glycemiccontrol. Diabetes Care 2002;25:1159–1171

210. Martin D, Lange K, Sima A, et al.; SWEETgroup. Recommendations for age-appropriate education of children andadolescents with diabetes and theirparents in the European Union. PediatrDiabetes 2012;13(Suppl. 16):20–28

211. Committee on Quality of Health Care inAmerica. Institute of Medicine. Crossingthe Quality Chasm: A New Health Systemfor the 21st Century. Washington,National Academy Press, 2001

212. Barker JM, Goehrig SH, Barriga K, et al.;DAISY study. Clinical characteristics ofchildren diagnosed with type 1 diabetesthrough intensive screening andfollow-up. Diabetes Care 2004;27:1399–1404

213. Heinrich E, Nicolaas C, de Vries NK. Self-management interventions for type 2diabetes: a systematic review. EurDiabetes Nurs 2010;7:71–76

214. Frosch DL, Uy V, Ochoa S, Mangione CM.Evaluation of a behavior supportintervention for patients with poorlycontrolled diabetes. Arch Intern Med2011;171:2011–2017

215. McGowan P. The efficacy of diabetespatient education and self-managementeducation in type 2 diabetes. Can JDiabetes 2011;35:46–53

216. Cooke D, Bond R, Lawton J, et al.; U.K.NIHR DAFNE Study Group. Structuredtype 1 diabetes education deliveredwithin routine care: impact on glycemiccontrol and diabetes-specific quality oflife. Diabetes Care 2013;36:270–272

217. Cochran J, Conn VS. Meta-analysis ofquality of life outcomes following diabetesself-management training. Diabetes Educ2008;34:815–823

218. Thorpe CT, Fahey LE, Johnson H,Deshpande M, Thorpe JM, Fisher EB.Facilitating healthy coping in patients withdiabetes: a systematic review. DiabetesEduc 2013;39:33–52

219. Fisher L, Hessler D, Glasgow RE, et al.REDEEM: a pragmatic trial to reducediabetes distress. Diabetes Care 2013;36:2551–2558

S68 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

220. Robbins JM, Thatcher GE, Webb DA,Valdmanis VG. Nutritionist visits, diabetesclasses, and hospitalization rates andcharges: the Urban Diabetes Study.Diabetes Care 2008;31:655–660

221. Duncan I, Ahmed T, Li QE, et al. Assessingthe value of the diabetes educator.Diabetes Educ 2011;37:638–657

222. Piatt GA, Anderson RM, Brooks MM, et al.3-year follow-up of clinical and behavioralimprovements following a multifaceteddiabetes care intervention: results of arandomized controlled trial. DiabetesEduc 2010;36:301–309

223. Tang TS, Funnell MM, Brown MB,Kurlander JE. Self-management support in“real-world” settings: an empowerment-based intervention. Patient Educ Couns2010;79:178–184

224. Renders CM, Valk GD, Griffin S, WagnerEH, Eijk JT, Assendelft WJ. Interventions toimprove the management of diabetesmellitus in primary care, outpatient andcommunity settings. Cochrane DatabaseSyst Rev 2001;(1):CD001481

225. Glazier RH, Bajcar J, Kennie NR, Willson K.A systematic review of interventions toimprove diabetes care in sociallydisadvantaged populations. Diabetes Care2006;29:1675–1688

226. Hawthorne K, Robles Y, Cannings-John R,Edwards AG. Culturally appropriate healtheducation for type 2 diabetes mellitus inethnic minority groups. CochraneDatabase Syst Rev 2008;(3):CD006424

227. Sarkisian CA, Brown AF, Norris KC, WintzRL, Mangione CM. A systematic review ofdiabetes self-care interventions for older,African American, or Latino adults.Diabetes Educ 2003;29:467–479

228. Chodosh J, Morton SC, Mojica W, et al.Meta-analysis: chronic disease self-management programs for older adults.Ann Intern Med 2005;143:427–438

229. Peyrot M, Rubin RR. Behavioral andpsychosocial interventions in diabetes:a conceptual review. Diabetes Care 2007;30:2433–2440

230. Anderson DR, Christison-Legay J, Proctor-Gray E. Self-management goal setting in acommunity health center: the impact ofgoal attainment on diabetes outcomes.Diabetes Spectrum 2010;23:97–105

231. Naik AD, Palmer N, Petersen NJ, et al.Comparative effectiveness of goal settingin diabetes mellitus group clinics:randomized clinical trial. Arch Intern Med2011;171:453–459

232. Deakin T, McShane CE, Cade JE, WilliamsRD. Group based training for self-management strategies in people withtype 2 diabetes mellitus. CochraneDatabase Syst Rev 2005;(2):CD003417

233. Duke SA, Colagiuri S, Colagiuri R.Individual patient education for people

with type 2 diabetes mellitus. CochraneDatabase Syst Rev 2009;(1):CD005268

234. Shah M, Kaselitz E, Heisler M. The role ofcommunity health workers in diabetes:update on current literature. Curr DiabRep 2013;13:163–171

235. Heisler M, Vijan S, Makki F, Piette JD.Diabetes control with reciprocal peersupport versus nurse care management:a randomized trial. Ann Intern Med 2010;153:507–515

236. Heisler M. Different models to mobilizepeer support to improve diabetes self-management and clinical outcomes:evidence, logistics, evaluationconsiderations and needs for futureresearch [retraction of: Heisler M. In: FamPract 2012;29:497]. Fam Pract 2010;27(Suppl. 1):i23–i32

237. Long JA, Jahnle EC, Richardson DM,Loewenstein G, Volpp KG. Peer mentoringand financial incentives to improveglucose control in African Americanveterans: a randomized trial. Ann InternMed 2012;156:416–424

238. Dale JR, Williams SM, Bowyer V. Whatis the effect of peer support on diabetesoutcomes in adults? A systematicreview. Diabet Med 2012;29:1361–1377

239. Moskowitz D, ThomDH, Hessler D, GhorobA, Bodenheimer T. Peer coaching toimprove diabetes self-management:which patients benefit most?J Gen InternMed 2013;28:938–942

240. Foster G, Taylor SJ, Eldridge SE, Ramsay J,Griffiths CJ. Self-management educationprogrammes by lay leaders for peoplewith chronic conditions. CochraneDatabase Syst Rev 2007;(4):CD005108

241. Siminerio L, Ruppert KM, Gabbay RA. Whocan provide diabetes self-managementsupport in primary care? Findings from arandomized controlled trial. DiabetesEduc 2013;39:705–713

242. Duncan I, Birkmeyer C, Coughlin S, Li QE,Sherr D, Boren S. Assessing the value ofdiabetes education. Diabetes Educ 2009;35:752–760

243. Johnson TM, Murray MR, Huang Y.Associations between self-managementeducation and comprehensive diabetesclinical care. Diabetes Spectrum 2010;23:41–46

244. Kramer MK, McWilliams JR, Chen HY,Siminerio LM. A community-baseddiabetes prevention program: evaluationof the group lifestyle balance programdelivered by diabetes educators. DiabetesEduc 2011;37:659–668

245. Piatt GA, Seidel MC, Powell RO, Zgibor JC.Comparative effectiveness of lifestyleintervention efforts in the community:results of the Rethinking Eating andACTivity (REACT) study. Diabetes Care2013;36:202–209

246. Boule NG, Haddad E, Kenny GP, Wells GA,Sigal RJ. Effects of exercise on glycemiccontrol and body mass in type 2 diabetesmellitus: a meta-analysis of controlledclinical trials. JAMA 2001;286:1218–1227

247. Colberg SR, Riddell MC. Physical Activity:Regulation of Glucose Metabolism,Clinicial Management Strategies, andWeight Control. Alexandria, VA, AmericanDiabetes Association, 2013

248. Boule NG, Kenny GP, Haddad E, Wells GA,Sigal RJ. Meta-analysis of the effect ofstructured exercise training oncardiorespiratory fitness in type 2diabetes mellitus. Diabetologia 2003;46:1071–1081

249. Rejeski WJ, Ip EH, Bertoni AG, et al.; LookAHEAD Research Group. Lifestyle changeand mobility in obese adults with type 2diabetes. N Engl J Med 2012;366:1209–1217

250. Colberg SR, Sigal RJ, Fernhall B, et al.;American College of Sports Medicine;American Diabetes Association. Exerciseand type 2 diabetes. The American Collegeof Sports Medicine and the AmericanDiabetes Association: joint positionstatement. Diabetes Care 2010;33:2692–2696

251. U.S. Department of Health and HumanServices. Physical Activity Guidelines forAmericans [article online], 2008. Availablefrom http://www.health.gov/paguidelines/guidelines/default.aspx

252. Cauza E, Hanusch-Enserer U, Strasser B,et al. The relative benefits of enduranceand strength training on the metabolicfactors and muscle function of peoplewith type 2 diabetes mellitus. Arch PhysMed Rehabil 2005;86:1527–1533

253. Dunstan DW, Daly RM, Owen N, et al.High-intensity resistance trainingimproves glycemic control in olderpatients with type 2 diabetes. DiabetesCare 2002;25:1729–1736

254. Castaneda C, Layne JE, Munoz-Orians L,et al. A randomized controlled trial ofresistance exercise training to improveglycemic control in older adults with type2 diabetes. Diabetes Care 2002;25:2335–2341

255. Sigal RJ, Kenny GP, Wasserman DH,Castaneda-Sceppa C. Physical activity/exercise and type 2 diabetes. DiabetesCare 2004;27:2518–2539

256. Church TS, Blair SN, Cocreham S, et al.Effects of aerobic and resistance trainingon hemoglobin A1c levels in patients withtype 2 diabetes: a randomized controlledtrial. JAMA 2010;304:2253–2262

257. Bax JJ, Young LH, Frye RL, Bonow RO,Steinberg HO, Barrett EJ; AmericanDiabetes Association. Screening forcoronary artery disease in patients withdiabetes. Diabetes Care 2007;30:2729–2736

care.diabetesjournals.org Position Statement S69

258. Berger M, Berchtold P, Cuppers HJ, et al.Metabolic and hormonal effects ofmuscular exercise in juvenile typediabetics. Diabetologia 1977;13:355–365

259. Aiello LP,Wong J, Cavallerano J, Bursell SE,Aiello LM. Retinopathy. In Handbook ofExercise in Diabetes. 2nd ed.Ruderman N,Devlin JT, Kriska A, Eds. Alexandria, VA,American Diabetes Association, 2002, p.401–413

260. Lemaster JW, Reiber GE, Smith DG,Heagerty PJ, Wallace C. Daily weight-bearing activity does not increase the riskof diabetic foot ulcers. Med Sci SportsExerc 2003;35:1093–1099

260a. Smith AG, Russell J, Feldman EL, et al.Lifestyle intervention for pre-diabeticneuropathy. Diabetes Care 2006;29;1294–1299

261. Pop-Busui R, Evans GW, Gerstein HC,et al.; Action to Control CardiovascularRisk in Diabetes Study Group. Effects ofcardiac autonomic dysfunction onmortality risk in the Action to ControlCardiovascular Risk in Diabetes(ACCORD) trial. Diabetes Care 2010;33:1578–1584

262. Mogensen CE. Nephropathy. In Handbookof Exercise in Diabetes. 2nd ed.RudermanN, Devlin JT, Kriska A, Eds. Alexandria, VA,American Diabetes Association, 2002, p.433–449

263. Anderson RJ, Grigsby AB, Freedland KE,et al. Anxiety and poor glycemic control:a meta-analytic review of the literature.Int J Psychiatry Med 2002;32:235–247

264. Delahanty LM, Grant RW, Wittenberg E,et al. Association of diabetes-relatedemotional distress with diabetestreatment in primary care patients withtype 2 diabetes. Diabet Med 2007;24:48–54

265. Anderson RJ, Freedland KE, Clouse RE,Lustman PJ. The prevalence of comorbiddepression in adults with diabetes:a meta-analysis. Diabetes Care 2001;24:1069–1078

266. Kovacs Burns K, Nicolucci A, Holt RI, et al.;DAWN2 Study Group. Diabetes Attitudes,Wishes and Needs second study(DAWN2�): cross-national benchmarkingindicators for family members living withpeople with diabetes. Diabet Med 2013;30:778–788

267. Harkness E, Macdonald W, Valderas J,Coventry P, Gask L, Bower P. Identifyingpsychosocial interventions that improveboth physical and mental health inpatients with diabetes: a systematicreview and meta-analysis. Diabetes Care2010;33:926–930

268. Bot M, Pouwer F, Zuidersma M, van MelleJP, de Jonge P. Association of coexistingdiabetes and depression with mortalityafter myocardial infarction. Diabetes Care2012;35:503–509

269. Scherrer JF, Garfield LD, Chrusciel T, et al.Increased risk of myocardial infarction indepressed patients with type 2 diabetes.Diabetes Care 2011;34:1729–1734

270. Sullivan MD, O’Connor P, Feeney P, et al.Depression predicts all-cause mortality:epidemiological evaluation from theACCORD HRQL substudy. Diabetes Care2012;35:1708–1715

271. Chen PC, Chan YT, Chen HF, Ko MC, Li CY.Population-based cohort analyses of thebidirectional relationship between type 2diabetes and depression. Diabetes Care2013;36:376–382

272. Pan A, Keum N, Okereke OI, et al.Bidirectional association betweendepression and metabolic syndrome:a systematic review and meta-analysis ofepidemiological studies. Diabetes Care2012;35:1171–1180

273. Nicolucci A, Kovacs Burns K, Holt RI, et al.;DAWN2 Study Group. Diabetes Attitudes,Wishes and Needs second study(DAWN2�): cross-national benchmarkingof diabetes-related psychosocialoutcomes for people with diabetes.Diabet Med 2013;30:767–777

274. Fisher L, Hessler DM, Polonsky WH,Mullan J. When is diabetes distressclinically meaningful? Establishing cutpoints for the Diabetes Distress Scale.Diabetes Care 2012;35:259–264

275. Fisher L, SkaffMM,Mullan JT, et al. Clinicaldepression versus distress among patientswith type 2 diabetes: not just a question ofsemantics. Diabetes Care 2007;30:542–548

276. Fisher L, Glasgow RE, Strycker LA. Therelationship between diabetes distressand clinical depression with glycemiccontrol among patients with type 2diabetes. Diabetes Care 2010;33:1034–1036

277. Aikens JE. Prospective associationsbetween emotional distress and pooroutcomes in type 2 diabetes. DiabetesCare 2012;35:2472–2478

278. Gary TL, Safford MM, Gerzoff RB, et al.Perception of neighborhood problems,health behaviors, and diabetes outcomesamong adults with diabetes in managedcare: the Translating Research Into Actionfor Diabetes (TRIAD) study. Diabetes Care2008;31:273–278

279. Katon W, Fan MY, Unutzer J, Taylor J,Pincus H, SchoenbaumM. Depression anddiabetes: a potentially lethal combination.J Gen Intern Med 2008;23:1571–1575

280. Zhang X, Norris SL, Gregg EW, Cheng YJ,Beckles G, Kahn HS. Depressive symptomsand mortality among persons with andwithout diabetes. Am J Epidemiol 2005;161:652–660

281. Fisher L, Glasgow RE, Mullan JT, Skaff MM,Polonsky WH. Development of a briefdiabetes distress screening instrument.Ann Fam Med 2008;6:246–252

282. McGuire BE, Morrison TG, Hermanns N,et al. Short-form measures of diabetes-related emotional distress: the ProblemAreas in Diabetes Scale (PAID)-5 andPAID-1. Diabetologia 2010;53:66–69

283. Rubin RR, Peyrot M. Psychological issuesand treatments for people with diabetes. JClin Psychol 2001;57:457–478

284. Young-Hyman DL, Davis CL. Disorderedeating behavior in individuals withdiabetes: importance of context,evaluation, and classification. DiabetesCare 2010;33:683–689

285. Beverly EA, Hultgren BA, Brooks KM,Ritholz MD, Abrahamson MJ, Weinger K.Understanding physicians’ challengeswhen treating type 2 diabetic patients’social and emotional difficulties:a qualitative study. Diabetes Care 2011;34:1086–1088

286. Ciechanowski P. Diapression: anintegrated model for understanding theexperience of individuals with co-occuringdiabetes and depression. Clin Diabetes2011;29:43–50

287. Katon WJ, Lin EH, Von Korff M, et al.Collaborative care for patients withdepression and chronic illnesses. N Engl JMed 2010;363:2611–2620

288. Kitabchi AE, Umpierrez GE, Miles JM,Fisher JN. Hyperglycemic crises in adultpatients with diabetes. Diabetes Care2009;32:1335–1343

289. Cryer PE. Hypoglycaemia: the limitingfactor in the glycaemic management oftype I and type II diabetes. Diabetologia2002;45:937–948

290. Whitmer RA, Karter AJ, Yaffe K,Quesenberry CP Jr, Selby JV. Hypoglycemicepisodes and risk of dementia in olderpatients with type 2 diabetesmellitus. JAMA2009;301:1565–1572

291. Punthakee Z, Miller ME, Launer LJ, et al.;ACCORD Group of Investigators; ACCORD-MIND Investigators. Poor cognitivefunction and risk of severe hypoglycemiain type 2 diabetes: post hoc epidemiologicanalysis of the ACCORD trial. DiabetesCare 2012;35:787–793

292. Jacobson AM, Musen G, Ryan CM, et al.;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventionsand Complications Study Research Group.Long-term effect of diabetes and itstreatment on cognitive function. N Engl JMed 2007;356:1842–1852

293. Zoungas S, Patel A, Chalmers J, et al.;ADVANCE Collaborative Group. Severehypoglycemia and risks of vascular eventsand death. N Engl J Med 2010;363:1410–1418

294. McCoy RG, Van Houten HK, Ziegenfuss JY,Shah ND, Wermers RA, Smith SA.Increased mortality of patients withdiabetes reporting severe hypoglycemia.Diabetes Care 2012;35:1897–1901

S70 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

295. Seaquist ER, Anderson J, Childs B, et al.Hypoglycemia and diabetes: a report of aworkgroup of the American DiabetesAssociation and The Endocrine Society.Diabetes Care 2013;36:1384–1395

296. Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes.N Engl J Med 2004;350:2272–2279

297. Ikramuddin S, Korner J, LeeWJ, et al. Roux-en-Y gastric bypass vs intensive medicalmanagement for the control of type 2diabetes, hypertension, andhyperlipidemia: the Diabetes SurgeryStudy randomized clinical trial. JAMA2013;309:2240–2249

298. Schauer PR, Kashyap SR, Wolski K, et al.Bariatric surgery versus intensive medicaltherapy in obese patients with diabetes.N Engl J Med 2012;366:1567–1576

299. Mingrone G, Panunzi S, De Gaetano A,et al. Bariatric surgery versus conventionalmedical therapy for type 2 diabetes.N Engl J Med 2012;366:1577–1585

300. Dorman RB, Serrot FJ,Miller CJ, et al. Case-matched outcomes in bariatric surgery fortreatment of type 2 diabetes in themorbidly obese patient. Ann Surg 2012;255:287–293

301. Buchwald H, Estok R, Fahrbach K, et al.Weight and type 2 diabetes after bariatricsurgery: systematic review and meta-analysis. Am J Med 2009;122:248–256.e5

302. Dixon JB, O’Brien PE, Playfair J, et al.Adjustable gastric banding andconventional therapy for type 2 diabetes:a randomized controlled trial. JAMA 2008;299:316–323

303. Cohen RV, Pinheiro JC, Schiavon CA, SallesJE, Wajchenberg BL, Cummings DE. Effectsof gastric bypass surgery in patients withtype 2 diabetes and only mild obesity.Diabetes Care 2012;35:1420–1428

304. Buchwald H, Estok R, Fahrbach K, Banel D,Sledge I. Trends in mortality in bariatricsurgery: a systematic review and meta-analysis. Surgery 2007;142:621–632;discussion 632–635

305. Sjostrom L, Narbro K, Sjostrom CD, et al.;Swedish Obese Subjects Study. Effects ofbariatric surgery on mortality in Swedishobese subjects. N Engl J Med 2007;357:741–752

306. Hoerger TJ, Zhang P, Segel JE, Kahn HS,Barker LE, Couper S. Cost-effectiveness ofbariatric surgery for severely obese adultswith diabetes. Diabetes Care 2010;33:1933–1939

307. Makary MA, Clark JM, Shore AD, et al.Medication utilization and annual healthcare costs in patients with type 2 diabetesmellitus before and after bariatric surgery[published correction appears in Arch Surg2011;146:659]. Arch Surg 2010;145:726–731

308. Keating CL, Dixon JB, Moodie ML, PeetersA, Playfair J, O’Brien PE. Cost-efficacy of

surgically induced weight loss for themanagement of type 2 diabetes:a randomized controlled trial. DiabetesCare 2009;32:580–584

309. Maciejewski ML, Livingston EH, Smith VA,et al. Survival among high-risk patientsafter bariatric surgery. JAMA 2011;305:2419–2426

310. Himpens J, Cadiere GB, Bazi M, Vouche M,Cadiere B, Dapri G. Long-term outcomesof laparoscopic adjustable gastricbanding. Arch Surg 2011;146:802–807

311. Smith SA, Poland GA. Use of influenza andpneumococcal vaccines in people withdiabetes. Diabetes Care 2000;23:95–108

312. Colquhoun AJ, Nicholson KG, Botha JL,Raymond NT. Effectiveness of influenzavaccine in reducing hospital admissions inpeople with diabetes. Epidemiol Infect1997;119:335–341

313. Bridges CB, Fukuda K, Uyeki TM, Cox NJ,Singleton JA; Centers for Disease Controland Prevention, Advisory Committee onImmunization Practices. Prevention andcontrol of influenza. Recommendations ofthe Advisory Committee on ImmunizationPractices (ACIP). MMWR Recomm Rep2002;51(RR-3):1–31

314. Centers for Disease Control andPrevention. Use of hepatitis B vaccinationfor adults with diabetes mellitus:recommendations of the AdvisoryCommitte on Immunization Practices(ACIP). MMWR Morb Mortal Wkly Rep2011;60:1709–1711

315. Buse JB, Ginsberg HN, Bakris GL, et al.;American Heart Association; AmericanDiabetes Association. Primary preventionof cardiovascular diseases in people withdiabetes mellitus: a scientific statementfrom the American Heart Association andthe American Diabetes Association.Diabetes Care 2007;30:162–172

316. Gaede P, Lund-Andersen H, Parving HH,Pedersen O. Effect of a multifactorialintervention on mortality in type 2diabetes. N Engl J Med 2008;358:580–591

317. AliMK, Bullard KM, Saaddine JB, Cowie CC,Imperatore G, Gregg EW. Achievement ofgoals in U.S. diabetes care, 1999–2010. NEngl J Med 2013;368:1613–1624

318. Bobrie G, Genes N, Vaur L, et al. Is“isolated home” hypertension as opposedto “isolated office” hypertension a sign ofgreater cardiovascular risk?Arch InternMed 2001;161:2205–2211

319. Sega R, Facchetti R, Bombelli M, et al.Prognostic value of ambulatory and homeblood pressures compared with officeblood pressure in the general population:follow-up results from the PressioniArteriose Monitorate e Loro Associazioni(PAMELA) study. Circulation 2005;111:1777–1783

320. Chobanian AV, Bakris GL, Black HR, et al.;National Heart, Lung, and Blood Institute

Joint National Committee onPrevention, Detection, Evaluation, andTreatment of High Blood Pressure;National High Blood Pressure EducationProgram Coordinating Committee. TheSeventh Report of the Joint NationalCommittee on Prevention, Detection,Evaluation, and Treatment of High BloodPressure: the JNC 7 report. JAMA 2003;289:2560–2572

321. Lewington S, Clarke R, Qizilbash N, Peto R,Collins R; Prospective StudiesCollaboration. Age-specific relevance ofusual blood pressure to vascularmortality: a meta-analysis of individualdata for one million adults in 61prospective studies. Lancet 2002;360:1903–1913

322. Stamler J, Vaccaro O, Neaton JD,Wentworth D. Diabetes, other risk factors,and 12-yr cardiovascular mortality formen screened in the Multiple Risk FactorIntervention Trial. Diabetes Care 1993;16:434–444

323. UK Prospective Diabetes Study Group.Tight blood pressure control and risk ofmacrovascular and microvascularcomplications in type 2 diabetes: UKPDS38. BMJ 1998;317:703–713

324. Hansson L, Zanchetti A, Carruthers SG,et al.; HOT Study Group. Effects ofintensive blood-pressure lowering andlow-dose aspirin in patients withhypertension: principal results of theHypertension Optimal Treatment (HOT)randomised trial. Lancet 1998;351:1755–1762

325. Adler AI, Stratton IM, Neil HA, et al.Association of systolic blood pressure withmacrovascular and microvascularcomplications of type 2 diabetes (UKPDS36): prospective observational study. BMJ2000;321:412–419

326. Cushman WC, Evans GW, Byington RP,et al.; ACCORD Study Group. Effects ofintensive blood-pressure control in type 2diabetes mellitus. N Engl J Med 2010;362:1575–1585

327. Patel A, MacMahon S, Chalmers J, et al.;ADVANCE Collaborative Group. Effectsof a fixed combination of perindopril andindapamide on macrovascular andmicrovascular outcomes in patients withtype 2 diabetes mellitus (the ADVANCEtrial): a randomised controlled trial.Lancet 2007;370:829–840

328. Cooper-DeHoff RM, Gong Y, HandbergEM, et al. Tight blood pressure control andcardiovascular outcomes amonghypertensive patients with diabetes andcoronary artery disease. JAMA 2010;304:61–68

329. Sleight P, Redon J, Verdecchia P, et al.;ONTARGET investigators. Prognostic valueof blood pressure in patients with highvascular risk in the Ongoing TelmisartanAlone and in combination with Ramipril

care.diabetesjournals.org Position Statement S71

Global Endpoint Trial study. J Hypertens2009;27:1360–1369

330. McBrien K, Rabi DM, Campbell N, et al.Intensive and standard blood pressuretargets in patients with type 2 diabetesmellitus: systematic review and meta-analysis. Arch Intern Med 2012;172:1296–1303

331. Bangalore S, Kumar S, Lobach I, MesserliFH. Blood pressure targets in subjects withtype 2 diabetes mellitus/impaired fastingglucose: observations from traditional andbayesian random-effectsmeta-analyses ofrandomized trials. Circulation 2011;123:2799–2810

332. Sacks FM, Svetkey LP, Vollmer WM, et al.;DASH-Sodium Collaborative ResearchGroup. Effects on blood pressure ofreduced dietary sodium and the DietaryApproaches to Stop Hypertension (DASH)diet. N Engl J Med 2001;344:3–10

333. Tatti P, Pahor M, Byington RP, et al.Outcome results of the Fosinopril VersusAmlodipine Cardiovascular EventsRandomized Trial (FACET) in patients withhypertension and NIDDM. Diabetes Care1998;21:597–603

334. Estacio RO, Jeffers BW, Hiatt WR,Biggerstaff SL, Gifford N, Schrier RW. Theeffect of nisoldipine as compared withenalapril on cardiovascular outcomes inpatients with non-insulin-dependentdiabetes and hypertension. N Engl J Med1998;338:645–652

335. Schrier RW, Estacio RO, Mehler PS, HiattWR. Appropriate blood pressure control inhypertensive and normotensive type 2diabetes mellitus: a summary of the ABCDtrial. Nat Clin Pract Nephrol 2007;3:428–438

336. ALLHAT Officers and Coordinators for theALLHAT Collaborative Research Group.Major outcomes in high-risk hypertensivepatients randomized to angiotensin-converting enzyme inhibitor or calciumchannel blocker vs diuretic: theAntihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial(ALLHAT). JAMA 2002;288:2981–2997

337. Psaty BM, Smith NL, Siscovick DS, et al.Health outcomes associated withantihypertensive therapies used as first-line agents. A systematic review andmeta-analysis. JAMA 1997;277:739–745

338. Heart Outcomes Prevention EvaluationStudy Investigators. Effects of ramipril oncardiovascular and microvascularoutcomes in people with diabetesmellitus: results of the HOPE study andMICRO-HOPE substudy. Lancet 2000;355:253–259

339. McMurray JJ, Ostergren J, Swedberg K,et al.; CHARM Investigators andCommittees. Effects of candesartan inpatients with chronic heart failure andreduced left-ventricular systolic functiontaking angiotensin-converting-enzyme

inhibitors: the CHARM-Added trial. Lancet2003;362:767–771

340. Pfeffer MA, Swedberg K, Granger CB,et al.; CHARM Investigators andCommittees. Effects of candesartan onmortality and morbidity in patients withchronic heart failure: the CHARM-Overallprogramme. Lancet 2003;362:759–766

341. Granger CB, McMurray JJ, Yusuf S, et al.;CHARM Investigators and Committees.Effects of candesartan in patients withchronic heart failure and reduced left-ventricular systolic function intolerant toangiotensin-converting-enzymeinhibitors: the CHARM-Alternative trial.Lancet 2003;362:772–776

342. Lindholm LH, Ibsen H, Dahlof B, et al.; LIFEStudy Group. Cardiovascular morbidityand mortality in patients with diabetes inthe Losartan Intervention For Endpointreduction in hypertension study (LIFE):a randomised trial against atenolol. Lancet2002;359:1004–1010

343. Berl T, Hunsicker LG, Lewis JB, et al.;Irbesartan Diabetic Nephropathy Trial.Collaborative Study Group. Cardiovascularoutcomes in the Irbesartan DiabeticNephropathy Trial of patients with type 2diabetes and overt nephropathy. AnnIntern Med 2003;138:542–549

344. McManus RJ, Mant J, Bray EP, et al.Telemonitoring and self-management inthe control of hypertension (TASMINH2):a randomised controlled trial. Lancet2010;376:163–172

345. Hermida RC, Ayala DE, Mojon A,Fernandez JR. Influence of time of day ofblood pressure-lowering treatment oncardiovascular risk in hypertensivepatients with type 2 diabetes. DiabetesCare 2011;34:1270–1276

346. Sibai BM. Treatment of hypertension inpregnant women. N Engl J Med 1996;335:257–265

347. Baigent C, Keech A, Kearney PM, et al.;Cholesterol Treatment Trialists’ (CTT)Collaborators. Efficacy and safety ofcholesterol-lowering treatment:prospective meta-analysis of data from90,056 participants in 14 randomised trialsof statins. Lancet 2005;366:1267–1278

348. Mihaylova B, Emberson J, Blackwell L,et al.; Cholesterol Treatment Trialists’(CTT) Collaborators. The effects oflowering LDL cholesterol with statintherapy in people at low risk of vasculardisease: meta-analysis of individual datafrom 27 randomised trials. Lancet 2012;380:581–590

349. Pyorala K, Pedersen TR, Kjekshus J,Faergeman O, Olsson AG, Thorgeirsson G.Cholesterol lowering with simvastatinimproves prognosis of diabetic patientswith coronary heart disease. A subgroupanalysis of the Scandinavian SimvastatinSurvival Study (4S). Diabetes Care 1997;20:614–620

350. Collins R, Armitage J, Parish S, Sleigh P,Peto R; Heart Protection StudyCollaborative Group. MRC/BHF HeartProtection Study of cholesterol-loweringwith simvastatin in 5963 people withdiabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005–2016

351. Goldberg RB, Mellies MJ, Sacks FM, et al.;The Care Investigators. Cardiovascularevents and their reduction withpravastatin in diabetic and glucose-intolerant myocardial infarction survivorswith average cholesterol levels: subgroupanalyses in the Cholesterol And RecurrentEvents (CARE) trial. Circulation 1998;98:2513–2519

352. Shepherd J, Barter P, Carmena R, et al.Effect of lowering LDL cholesterolsubstantially below currentlyrecommended levels in patients withcoronary heart disease and diabetes: theTreating to New Targets (TNT) study.Diabetes Care 2006;29:1220–1226

353. Sever PS, Poulter NR, Dahlof B, et al.Reduction in cardiovascular events withatorvastatin in 2,532 patients with type 2diabetes: Anglo-Scandinavian CardiacOutcomes TrialdLipid-Lowering Arm(ASCOT-LLA). Diabetes Care 2005;28:1151–1157

354. Knopp RH, d’Emden M, Smilde JG, PocockSJ. Efficacy and safety of atorvastatin inthe prevention of cardiovascular endpoints in subjects with type 2 diabetes: theAtorvastatin Study for Prevention ofCoronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus(ASPEN). Diabetes Care 2006;29:1478–1485

355. Colhoun HM, Betteridge DJ, DurringtonPN, et al.; CARDS investigators. Primaryprevention of cardiovascular disease withatorvastatin in type 2 diabetes in theCollaborative Atorvastatin Diabetes Study(CARDS): multicentre randomisedplacebo-controlled trial. Lancet 2004;364:685–696

356. Kearney PM, Blackwell L, Collins R, et al.;Cholesterol Treatment Trialists’ (CTT)Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people withdiabetes in 14 randomised trials ofstatins: a meta-analysis. Lancet 2008;371:117–125

357. Taylor F, Huffman MD, Macedo AF, et al.Statins for the primary prevention ofcardiovascular disease. CochraneDatabase Syst Rev 2013;(1):CD004816

358. Carter AA, Gomes T, Camacho X, JuurlinkDN, Shah BR, Mamdani MM. Risk ofincident diabetes among patients treatedwith statins: population based study. BMJ2013;346:f2610

359. Rajpathak SN, Kumbhani DJ, Crandall J,Barzilai N, Alderman M, Ridker PM. Statintherapy and risk of developing type 2

S72 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

diabetes: a meta-analysis. Diabetes Care2009;32:1924–1929

360. Sattar N, Preiss D,Murray HM, et al. Statinsand risk of incident diabetes: a collaborativemeta-analysis of randomised statin trials.Lancet 2010;375:735–742

361. Ridker PM, Danielson E, Fonseca FA, et al.;JUPITER Study Group. Rosuvastatin toprevent vascular events in men andwomen with elevated C-reactive protein.N Engl J Med 2008;359:2195–2207

362. Ridker PM, Pradhan A, MacFadyen JG,Libby P, Glynn RJ. Cardiovascular benefitsand diabetes risks of statin therapy inprimary prevention: an analysis from theJUPITER trial. Lancet 2012;380:565–571

363. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutictarget: a systematic review. JAMA 2007;298:786–798

364. Canner PL, Berge KG, Wenger NK, et al.Fifteen year mortality in Coronary DrugProject patients: long-term benefit withniacin. J Am Coll Cardiol 1986;8:1245–1255

365. Rubins HB, Robins SJ, Collins D, et al.;Veterans Affairs High-Density LipoproteinCholesterol Intervention Trial StudyGroup. Gemfibrozil for the secondaryprevention of coronary heart disease inmen with low levels of high-densitylipoprotein cholesterol. N Engl J Med1999;341:410–418

366. Frick MH, Elo O, Haapa K, et al. HelsinkiHeart Study: primary-prevention trial withgemfibrozil in middle-aged men withdyslipidemia. Safety of treatment,changes in risk factors, and incidence ofcoronary heart disease. N Engl J Med1987;317:1237–1245

367. Keech A, Simes RJ, Barter P, et al.; FIELDstudy investigators. Effects of long-termfenofibrate therapy on cardiovascularevents in 9795 people with type 2diabetes mellitus (the FIELD study):randomised controlled trial. Lancet 2005;366:1849–1861

368. Jones PH, Davidson MH. Reporting rate ofrhabdomyolysis with fenofibrate 1 statinversus gemfibrozil 1 any statin. Am JCardiol 2005;95:120–122

369. Ginsberg HN, Elam MB, Lovato LC, et al.;ACCORD Study Group. Effects ofcombination lipid therapy in type 2diabetes mellitus. N Engl J Med 2010;362:1563–1574

370. Boden WE, Probstfield JL, Anderson T,et al.; AIM-HIGH Investigators. Niacin inpatients with low HDL cholesterol levelsreceiving intensive statin therapy. N Engl JMed 2011;365:2255–2267

371. Grundy SM, Cleeman JI, Merz CN, et al.;National Heart, Lung, and Blood Institute;American College of CardiologyFoundation; American Heart Association.Implications of recent clinical trials for the

National Cholesterol Education ProgramAdult Treatment Panel III guidelines.Circulation 2004;110:227–239

372. Hayward RA, Hofer TP, Vijan S. Narrativereview: lack of evidence for recommendedlow-density lipoprotein treatmenttargets: a solvable problem. Ann InternMed 2006;145:520–530

373. Cannon CP, Braunwald E, McCabe CH,et al.; Pravastatin or AtorvastatinEvaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22Investigators. Intensive versus moderatelipid lowering with statins after acutecoronary syndromes. N Engl J Med 2004;350:1495–1504

374. de Lemos JA, Blazing MA,Wiviott SD, et al.Early intensive vs a delayed conservativesimvastatin strategy in patients with acutecoronary syndromes: phase Z of the A to Ztrial. JAMA 2004;292:1307–1316

375. Nissen SE, Tuzcu EM, Schoenhagen P,et al.; REVERSAL Investigators. Effect ofintensive compared with moderate lipid-lowering therapy on progression ofcoronary atherosclerosis: a randomizedcontrolled trial. JAMA 2004;291:1071–1080

376. Brunzell JD, Davidson M, Furberg CD,et al.; American Diabetes Association;American College of CardiologyFoundation. Lipoprotein management inpatients with cardiometabolic risk:consensus statement from the AmericanDiabetes Association and the AmericanCollege of Cardiology Foundation.Diabetes Care 2008;31:811–822

377. Chasman DI, Posada D, Subrahmanyan L,Cook NR, Stanton VP Jr, Ridker PM.Pharmacogenetic study of statin therapyand cholesterol reduction. JAMA 2004;291:2821–2827

378. Meek C, Wierzbicki AS, Jewkes C, et al.Daily and intermittent rosuvastatin 5mgtherapy in statin intolerant patients: anobservational study. Curr Med Res Opin2012;28:371–378

379. ElamMB, Hunninghake DB, Davis KB, et al.Effect of niacin on lipid and lipoproteinlevels and glycemic control in patientswith diabetes and peripheral arterialdisease. The ADMIT study: a randomizedtrial. JAMA 2000;284:1263–1270

380. Grundy SM, Vega GL, McGovernME, et al.;Diabetes Multicenter Research Group.Efficacy, safety, and tolerability of once-daily niacin for the treatment ofdyslipidemia associated with type 2diabetes: results of the assessment ofdiabetes control and evaluation of theefficacy of niaspan trial. Arch Intern Med2002;162:1568–1576

381. Baigent C, Blackwell L, Collins R, et al.;Antithrombotic Trialists’ (ATT)Collaboration. Aspirin in the primary andsecondary prevention of vascular disease:collaborative meta-analysis of individual

participant data from randomised trials.Lancet 2009;373:1849–1860

382. Perk J, De Backer G, Gohlke H, et al.;European Association for CardiovascularPrevention & Rehabilitation (EACPR); ESCCommittee for Practice Guidelines (CPG).European guidelines on cardiovasculardisease prevention in clinical practice(version 2012). The Fifth Joint Task Forceof the European Society of Cardiology andOther Societies on Cardiovascular DiseasePrevention in Clinical Practice (constitutedby representatives of nine societies and byinvited experts). Eur Heart J 2012;33:1635–1701

383. Ogawa H, Nakayama M, Morimoto T,et al.; Japanese Primary Prevention ofAtherosclerosis With Aspirin for Diabetes(JPAD) Trial Investigators. Low-doseaspirin for primary prevention ofatherosclerotic events in patients withtype 2 diabetes: a randomized controlledtrial. JAMA 2008;300:2134–2141

384. Pignone M, Earnshaw S, Tice JA, PletcherMJ. Aspirin, statins, or both drugs for theprimary prevention of coronary heartdisease events inmen: a cost-utility analysis.Ann Intern Med 2006;144:326–336

385. Pignone M, Alberts MJ, Colwell JA, et al.;American Diabetes Association; AmericanHeart Association; American College ofCardiology Foundation. Aspirin forprimary prevention of cardiovascularevents in people with diabetes: a positionstatement of the American DiabetesAssociation, a scientific statement of theAmerican Heart Association, and an expertconsensus document of the AmericanCollege of Cardiology Foundation.Diabetes Care 2010;33:1395–1402

386. Campbell CL, Smyth S, Montalescot G,Steinhubl SR. Aspirin dose for theprevention of cardiovascular disease:a systematic review. JAMA 2007;297:2018–2024

387. Davı G, Patrono C. Platelet activation andatherothrombosis. N Engl JMed 2007;357:2482–2494

388. Vandvik PO, Lincoff AM, Gore JM, et al.Primary and secondary prevention ofcardiovascular disease: AntithromboticTherapy and Prevention of Thrombosis,9th ed: American College of ChestPhysicians Evidence-Based ClinicalPractice Guidelines. Chest 2012;141:e637S–e668S

389. Voulgari C, Katsilambros N, Tentolouris N.Smoking cessation predicts ameliorationof microalbuminuria in newly diagnosedtype 2 diabetes mellitus: a 1-yearprospective study. Metabolism 2011;60:1456–1464

390. Ranney L, Melvin C, Lux L, McClain E, LohrKN. Systematic review: smoking cessationintervention strategies for adults andadults in special populations. Ann InternMed 2006;145:845–856

care.diabetesjournals.org Position Statement S73

391. Clair C, Rigotti NA, Porneala B, et al.Association of smoking cessation andweight change with cardiovasculardisease among adults with and withoutdiabetes. JAMA 2013;309:1014–1021

392. Braunwald E, Domanski MJ, Fowler SE,et al.; PEACE Trial Investigators.Angiotensin-converting-enzymeinhibition in stable coronary arterydisease. N Engl J Med 2004;351:2058–2068

393. Yusuf S, Teo K, Anderson C, et al.;Telmisartan Randomised AssessmeNtStudy in ACE iNtolerant subjects withcardiovascular Disease (TRANSCEND)Investigators. Effects of the angiotensin-receptor blocker telmisartan oncardiovascular events in high-risk patientsintolerant to angiotensin-convertingenzyme inhibitors: a randomisedcontrolled trial. Lancet 2008;372:1174–1183

394. Boden WE, O’Rourke RA, Teo KK, et al.;COURAGE Trial Research Group. Optimalmedical therapy with or without PCI forstable coronary disease. N Engl J Med2007;356:1503–1516

395. Frye RL, August P, Brooks MM, et al.; BARI2D Study Group. A randomized trial oftherapies for type 2 diabetes and coronaryartery disease. N Engl J Med 2009;360:2503–2515

396. Wackers FJ, Chyun DA, Young LH, et al.;Detection of Ischemia in AsymptomaticDiabetics (DIAD) Investigators. Resolutionof asymptomatic myocardial ischemia inpatients with type 2 diabetes in theDetection of Ischemia in AsymptomaticDiabetics (DIAD) study. Diabetes Care2007;30:2892–2898

397. Young LH, Wackers FJ, Chyun DA, et al.;DIAD Investigators. Cardiac outcomesafter screening for asymptomaticcoronary artery disease in patients withtype 2 diabetes: the DIAD study:a randomized controlled trial. JAMA 2009;301:1547–1555

398. Wackers FJ, Young LH, Inzucchi SE, et al.;Detection of Ischemia in AsymptomaticDiabetics Investigators. Detection of silentmyocardial ischemia in asymptomaticdiabetic subjects: the DIAD study.Diabetes Care 2004;27:1954–1961

399. Scognamiglio R, Negut C, Ramondo A,Tiengo A, Avogaro A. Detection ofcoronary artery disease in asymptomaticpatients with type 2 diabetes mellitus.J Am Coll Cardiol 2006;47:65–71

400. Hadamitzky M, Hein F, Meyer T, et al.Prognostic value of coronary computedtomographic angiography in diabeticpatients without known coronary arterydisease. Diabetes Care 2010;33:1358–1363

401. Elkeles RS, Godsland IF, Feher MD, et al.;PREDICT Study Group. Coronary calciummeasurement improves prediction of

cardiovascular events in asymptomaticpatients with type 2 diabetes: the PREDICTstudy. Eur Heart J 2008;29:2244–2251

402. Choi EK, Chun EJ, Choi SI, et al. Assessmentof subclinical coronary atherosclerosis inasymptomatic patients with type 2diabetes mellitus with single photonemission computed tomography andcoronary computed tomographyangiography. Am J Cardiol 2009;104:890–896

403. Eurich DT, Weir DL, Majumdar SR, et al.Comparative safety and effectiveness ofmetformin in patients with diabetesmellitus and heart failure: systematicreview of observational studies involving34,000 patients. Circ Heart Fail 2013;6:395–402

404. Krolewski AS, Niewczas MA, Skupien J,et al. Early progressive renal declineprecedes the onset of microalbuminuriaand its progression to macroalbuminuria.Diabetes Care 2014;37:226–234

405. Garg JP, Bakris GL. Microalbuminuria:marker of vascular dysfunction, risk factorfor cardiovascular disease. Vasc Med2002;7:35–43

406. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al. Very low levels ofmicroalbuminuria are associated withincreased risk of coronary heart diseaseand death independently of renalfunction, hypertension, and diabetes.Circulation 2004;110:32–35

407. de Boer IH, Rue TC, Cleary PA, et al.;Diabetes Control and ComplicationsTrial/Epidemiology of DiabetesInterventions and Complications StudyResearch Group. Long-term renaloutcomes of patients with type 1diabetes mellitus and microalbuminuria:an analysis of the Diabetes Control andComplications Trial/Epidemiology ofDiabetes Interventions andComplications cohort. Arch Intern Med2011;171:412–420

408. Molitch ME, Steffes M, Sun W, et al.;Epidemiology of Diabetes Interventionsand Complications Study Group.Development and progression of renalinsufficiency with and withoutalbuminuria in adults with type 1 diabetesin the Diabetes Control and ComplicationsTrial and the Epidemiology of DiabetesInterventions and Complications Study.Diabetes Care 2010;33:1536–1543

409. de Boer IH, SunW, Cleary PA, et al.; DCCT/EDIC Research Group. Intensive diabetestherapy and glomerular filtration rate intype 1 diabetes. N Engl J Med 2011;365:2366–2376

410. National Kidney Foundation. KDOQIclinical practice guidline for diabetes andCKD: 2012 update. Am J Kidney Dis 2012;60:850–886

411. Gall MA, Hougaard P, Borch-Johnsen K,Parving HH. Risk factors for development

of incipient and overt diabeticnephropathy in patients with non-insulindependent diabetes mellitus: prospective,observational study. BMJ 1997;314:783–788

412. Ravid M, Lang R, Rachmani R, Lishner M.Long-term renoprotective effect ofangiotensin-converting enzyme inhibitionin non-insulin-dependent diabetesmellitus. A 7-year follow-up study. ArchIntern Med 1996;156:286–289

413. The Diabetes Control and Complications(DCCT) Research Group. Effect of intensivetherapy on the development andprogression of diabetic nephropathy inthe Diabetes Control and ComplicationsTrial. Kidney Int 1995;47:1703–1720

414. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD;the Collaborative Study Group. The effectof angiotensin-converting-enzymeinhibition on diabetic nephropathy. N EnglJ Med 1993;329:1456–1462

415. Laffel LM, McGill JB, Gans DJ; NorthAmerican Microalbuminuria Study Group.The beneficial effect of angiotensin-converting enzyme inhibition withcaptopril on diabetic nephropathy innormotensive IDDM patients withmicroalbuminuria. Am J Med 1995;99:497–504

416. Remuzzi G, Macia M, Ruggenenti P.Prevention and treatment of diabeticrenal disease in type 2 diabetes: theBENEDICT study. J Am Soc Nephrol 2006;17(Suppl. 2):S90–S97

417. Haller H, Ito S, Izzo JL Jr, et al.; ROADMAPTrial Investigators. Olmesartan for thedelay or prevention of microalbuminuriain type 2 diabetes. N Engl J Med 2011;364:907–917

418. Bilous R, Chaturvedi N, Sjølie AK,et al. Effect of candesartan onmicroalbuminuria and albumin excretionrate in diabetes: three randomized trials.Ann Intern Med 2009;151:11–20, W3-4

419. Mauer M, Zinman B, Gardiner R, et al.Renal and retinal effects of enalapril andlosartan in type 1 diabetes. N Engl J Med2009;361:40–51

420. Lewis EJ, Hunsicker LG, Clarke WR,et al.; Collaborative Study Group.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patientswith nephropathy due to type 2 diabetes.N Engl J Med 2001;345:851–860

421. Brenner BM, Cooper ME, de Zeeuw D,et al.; RENAAL Study Investigators. Effectsof losartan on renal and cardiovascularoutcomes in patients with type 2 diabetesand nephropathy. N Engl J Med 2001;345:861–869

422. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, ArnerP; Irbesartan in Patients with Type 2Diabetes and Microalbuminuria StudyGroup. The effect of irbesartan on the

S74 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

development of diabetic nephropathy inpatients with type 2 diabetes. N Engl JMed 2001;345:870–878

423. Pepine CJ, Handberg EM, Cooper-DeHoffRM, et al.; INVEST Investigators. A calciumantagonist vs a non-calcium antagonisthypertension treatment strategy forpatients with coronary artery disease. TheInternational Verapamil-TrandolaprilStudy (INVEST): a randomized controlledtrial. JAMA 2003;290:2805–2816

424. Mogensen CE, Neldam S, Tikkanen I, et al.Randomised controlled trial of dualblockade of renin-angiotensin system inpatients with hypertension,microalbuminuria, and non-insulindependent diabetes: the candesartan andlisinopril microalbuminuria (CALM) study.BMJ 2000;321:1440–1444

425. Schjoedt KJ, Jacobsen P, Rossing K,Boomsma F, Parving HH. Dual blockade ofthe renin-angiotensin-aldosterone systemin diabetic nephropathy: the role ofaldosterone. Horm Metab Res 2005;37(Suppl. 1):4–8

426. Schjoedt KJ, Rossing K, Juhl TR, et al.Beneficial impact of spironolactone indiabetic nephropathy. Kidney Int 2005;68:2829–2836

427. Parving HH, Persson F, Lewis JB, Lewis EJ,Hollenberg NK; AVOID StudyInvestigators. Aliskiren combined withlosartan in type 2 diabetes andnephropathy. N Engl J Med 2008;358:2433–2446

428. Yusuf S, Teo KK, Pogue J, et al.; ONTARGETInvestigators. Telmisartan, ramipril, orboth in patients at high risk for vascularevents. N Engl J Med 2008;358:1547–1559

429. Pijls LT, de Vries H, Donker AJ, van Eijk JT.The effect of protein restriction onalbuminuria in patients with type 2diabetes mellitus: a randomized trial.Nephrol Dial Transplant 1999;14:1445–1453

430. Pedrini MT, Levey AS, Lau J, Chalmers TC,Wang PH. The effect of dietary proteinrestriction on the progression of diabeticand nondiabetic renal diseases: a meta-analysis. Ann Intern Med 1996;124:627–632

431. Hansen HP, Tauber-Lassen E, Jensen BR,Parving HH. Effect of dietary proteinrestriction on prognosis in patients withdiabetic nephropathy. Kidney Int 2002;62:220–228

432. Kasiske BL, Lakatua JD, Ma JZ, Louis TA.A meta-analysis of the effects of dietaryprotein restriction on the rate of decline inrenal function. Am J Kidney Dis 1998;31:954–961

433. Eknoyan G, Hostetter T, Bakris GL, et al.Proteinuria and other markers of chronickidney disease: a position statement ofthe National Kidney Foundation (NKF) andthe National Institute of Diabetes and

Digestive and Kidney Diseases (NIDDK).Am J Kidney Dis 2003;42:617–622

434. Levey AS, Coresh J, Balk E, et al.; NationalKidney Foundation. National KidneyFoundation practice guidelines for chronickidney disease: evaluation, classification,and stratification. Ann Intern Med 2003;139:137–147

435. Kramer H, Molitch ME. Screening forkidney disease in adults with diabetes.Diabetes Care 2005;28:1813–1816

436. Kramer HJ, Nguyen QD, Curhan G, Hsu CY.Renal insufficiency in the absence ofalbuminuria and retinopathy amongadults with type 2 diabetes mellitus. JAMA2003;289:3273–3277

437. Levey AS, Bosch JP, Lewis JB, Greene T,Rogers N, Roth D; Modification of Diet inRenal Disease Study Group. A moreaccurate method to estimate glomerularfiltration rate from serum creatinine:a new prediction equation. Ann InternMed 1999;130:461–470

438. Levinsky NG. Specialist evaluation inchronic kidney disease: too little, too late.Ann Intern Med 2002;137:542–543

439. Klein R. Hyperglycemia and microvascularand macrovascular disease in diabetes.Diabetes Care 1995;18:258–268

440. Estacio RO, McFarling E, Biggerstaff S,Jeffers BW, Johnson D, Schrier RW. Overtalbuminuria predicts diabetic retinopathyin Hispanics with NIDDM. Am J Kidney Dis1998;31:947–953

441. Leske MC, Wu SY, Hennis A, et al.;Barbados Eye Study Group.Hyperglycemia, blood pressure, and the9-year incidence of diabetic retinopathy:the Barbados Eye Studies. Ophthalmology2005;112:799–805

442. Chew EY, AmbrosiusWT, Davis MD, et al.;ACCORD Study Group; ACCORD EyeStudy Group. Effects of medicaltherapies on retinopathy progression intype 2 diabetes. N Engl J Med 2010;363:233–244

443. Fong DS, Aiello LP, Ferris FL 3rd, Klein R.Diabetic retinopathy. Diabetes Care 2004;27:2540–2553

444. Diabetes Control and ComplicationsTrial Research Group. Effect ofpregnancy on microvascularcomplications in the diabetes control andcomplications trial. Diabetes Care 2000;23:1084–1091

445. The Diabetic Retinopathy Study ResearchGroup. Preliminary report on effects ofphotocoagulation therapy. Am JOphthalmol 1976;81:383–396

446. ETDRS. Photocoagulation for diabeticmacular edema. Early Treatment DiabeticRetinopathy Study report number 1. EarlyTreatment Diabetic Retinopathy Studyresearch group. Arch Ophthalmol 1985;103:1796–1806

447. NguyenQD, BrownDM,Marcus DM, et al.;RISE and RIDE Research Group.Ranibizumab for diabetic macular edema:results from 2 phase III randomized trials:RISE and RIDE. Ophthalmology 2012;119:789–801

448. Pearson PA, Comstock TL, Ip M, et al.Fluocinolone acetonide intravitrealimplant for diabetic macular edema:a 3-year multicenter, randomized,controlled clinical trial. Ophthalmology2011;118:1580–1587

449. Chew EY, Ambrosius WT. Update of theACCORD Eye Study. N Engl J Med 2011;364:188–189

450. Keech AC, Mitchell P, Summanen PA,et al.; FIELD study investigators. Effect offenofibrate on the need for lasertreatment for diabetic retinopathy (FIELDstudy): a randomised controlled trial.Lancet 2007;370:1687–1697

451. Hooper P, Boucher MC, Cruess A, et al.Canadian Ophthalmological Societyevidence-based clinical practiceguidelines for themanagement of diabeticretinopathy. Can J Ophthalmol 2012;47(Suppl.):S1–S30, S31–S54

452. Agardh E, Tababat-Khani P. Adopting3-year screening intervals for sight-threatening retinal vascular lesions in type2 diabetic subjects without retinopathy.Diabetes Care 2011;34:1318–1319

453. Ahmed J, Ward TP, Bursell SE, Aiello LM,Cavallerano JD, Vigersky RA. Thesensitivity and specificity of nonmydriaticdigital stereoscopic retinal imaging indetecting diabetic retinopathy. DiabetesCare 2006;29:2205–2209

454. Spallone V, Ziegler D, Freeman R, et al.;Toronto Consensus Panel on DiabeticNeuropathy. Cardiovascular autonomicneuropathy in diabetes: clinical impact,assessment, diagnosis, and management.Diabetes Metab Res Rev 2011;27:639–653

455. Bril V, England J, Franklin GM, et al.;American Academy of Neurology;American Association of Neuromuscularand Electrodiagnostic Medicine; AmericanAcademy of Physical Medicine andRehabilitation. Evidence-based guideline:treatment of painful diabetic neuropathy:report of the American Academy ofNeurology, the American Association ofNeuromuscular and ElectrodiagnosticMedicine, and the American Academy ofPhysical Medicine and Rehabilitation[published correction appears inNeurology 2011;77:603]. Neurology 2011;76:1758–1765

456. Pop-Busui R, Lu J, Brooks MM, et al.Impact of glycemic control strategies onthe progression of diabetic peripheralneuropathy in the Bypass AngioplastyRevascularization Investigation 2 Diabetes(BARI 2D) cohort. Diabetes Care 2013;36:3208–3215

care.diabetesjournals.org Position Statement S75

457. Herman WH, Pop-Busui R, Braffett BH,et al.; DCCT/EDIC Research Group. Use ofthe Michigan Neuropathy ScreeningInstrument as a measure of distalsymmetrical peripheral neuropathy intype 1 diabetes: results from the DiabetesControl and Complications Trial/Epidemiology of Diabetes Interventionsand Complications. Diabet Med 2012;29:937–944

458. Wile DJ, Toth C. Association of metformin,elevated homocysteine, andmethylmalonic acid levels and clinicallyworsened diabetic peripheral neuropathy.Diabetes Care 2010;33:156–161

459. Freeman R. Not all neuropathy in diabetesis of diabetic etiology: differentialdiagnosis of diabetic neuropathy. CurrDiab Rep 2009;9:423–431

460. Spallone V, Bellavere F, Scionti L, et al.;Diabetic Neuropathy Study Group of theItalian Society of Diabetology.Recommendations for the use ofcardiovascular tests in diagnosing diabeticautonomic neuropathy. Nutr MetabCardiovasc Dis 2011;21:69–78

461. Diabetes Control and Complications Trial(DCCT) Research Group. Effect of intensivediabetes treatment on nerve conductionin the Diabetes Control and ComplicationsTrial. Ann Neurol 1995;38:869–880

462. CDC Study Group. The effect of intensivediabetes therapy on measures ofautonomic nervous system function inthe Diabetes Control and ComplicationsTrial (DCCT). Diabetologia 1998;41:416–423

463. Albers JW, Herman WH, Pop-Busui R,et al.; Diabetes Control and ComplicationsTrial /Epidemiology of DiabetesInterventions and Complications ResearchGroup. Effect of prior intensive insulintreatment during the Diabetes Controland Complications Trial (DCCT) onperipheral neuropathy in type 1 diabetesduring the Epidemiology of DiabetesInterventions and Complications (EDIC)Study. Diabetes Care 2010;33:1090–1096

464. Pop-Busui R, Low PA, Waberski BH, et al.;DCCT/EDIC Research Group. Effects ofprior intensive insulin therapy on cardiacautonomic nervous system function intype 1 diabetes mellitus: the DiabetesControl and Complications Trial/Epidemiology of Diabetes Interventionsand Complications study (DCCT/EDIC).Circulation 2009;119:2886–2893

465. Callaghan BC, Little AA, Feldman EL,Hughes RA. Enhanced glucose control forpreventing and treating diabeticneuropathy. Cochrane Database Syst Rev2012;(6):CD007543

466. Sadosky A, Schaefer C, Mann R, et al.Burden of illness associated with painfuldiabetic peripheral neuropathy amongadults seeking treatment in the US: resultsfrom a retrospective chart review and

cross-sectional survey. Diabetes MetabSyndr Obes 2013;6:79–92

467. Snedecor SJ, Sudharshan L, Cappelleri JC,Sadosky A, Mehta S, Botteman M.Systematic review and meta-analysis ofpharmacological therapies for painfuldiabetic peripheral neuropathy. PainPract. 28 March 2013 [Epub ahead ofprint]

468. Boulton AJ, Vinik AI, Arezzo JC, et al.;American Diabetes Association. Diabeticneuropathies: a statement by theAmerican Diabetes Association. DiabetesCare 2005;28:956–962

469. Gaede P, Vedel P, Larsen N, Jensen GV,Parving HH, Pedersen O. Multifactorialintervention and cardiovascular disease inpatients with type 2 diabetes. N Engl JMed 2003;348:383–393

470. Boulton AJ, Armstrong DG, Albert SF,et al.; American Diabetes Association;American Association of ClinicalEndocrinologists. Comprehensive footexamination and risk assessment: a reportof the task force of the foot care interestgroupof theAmericanDiabetes Association,with endorsement by the AmericanAssociation of Clinical Endocrinologists.Diabetes Care 2008;31:1679–1685

471. American Diabetes Association.Peripheral arterial disease in people withdiabetes. Diabetes Care 2003;26:3333–3341

472. Lipsky BA, Berendt AR, Cornia PB, et al.;Infectious Diseases Society of America.2012 Infectious Diseases Society ofAmerica clinical practice guideline for thediagnosis and treatment of diabetic footinfections. Clin Infect Dis 2012;54:e132–e173

473. Selvin E, Coresh J, Brancati FL. The burdenand treatment of diabetes in elderlyindividuals in the U.S. Diabetes Care 2006;29:2415–2419

474. Grant RW, Ashburner JM, Hong CS, ChangY, Barry MJ, Atlas SJ. Defining patientcomplexity from the primary carephysician’s perspective: a cohort study[published correction appears in AnnIntern Med 2012;157:152]. Ann InternMed 2011;155:797–804

475. Tinetti ME, Fried TR, Boyd CM. Designinghealth care for the most common chronicconditiondmultimorbidity. JAMA 2012;307:2493–2494

476. Sudore RL, Karter AJ, Huang ES, et al.Symptom burden of adults with type 2diabetes across the disease course:Diabetes & Aging Study. J Gen Intern Med2012;27:1674–1681

477. Borgnakke WS, Ylostalo PV, Taylor GW,Genco RJ. Effect of periodontal diseaseon diabetes: systematic review ofepidemiologic observational evidence.J Periodontol 2013;84(Suppl.):S135–S152

478. Li C, Ford ES, Zhao G, Croft JB, Balluz LS,Mokdad AH. Prevalence of self-reportedclinically diagnosed sleep apnea accordingto obesity status in men and women:National Health and NutritionExamination Survey, 2005–2006. PrevMed 2010;51:18–23

479. West SD, Nicoll DJ, Stradling JR.Prevalence of obstructive sleep apnoea inmenwith type 2 diabetes. Thorax 2006;61:945–950

480. Foster GD, Sanders MH, Millman R, et al.;Sleep AHEAD Research Group. Obstructivesleep apnea among obese patients withtype 2 diabetes. Diabetes Care 2009;32:1017–1019

481. Shaw JE, Punjabi NM, Wilding JP, AlbertiKG, Zimmet PZ; International DiabetesFederation Taskforce on Epidemiologyand Prevention. Sleep-disorderedbreathing and type 2 diabetes: a reportfrom the International DiabetesFederation Taskforce on Epidemiologyand Prevention. Diabetes Res Clin Pract2008;81:2–12

482. El-Serag HB, Tran T, Everhart JE. Diabetesincreases the risk of chronic liver diseaseand hepatocellular carcinoma.Gastroenterology 2004;126:460–468

483. American GastroenterologicalAssociation. AmericanGastroenterological Association medicalposition statement: nonalcoholic fattyliver disease. Gastroenterology 2002;123:1702–1704

484. Suh S, Kim KW. Diabetes and cancer: isdiabetes causally related to cancer?Diabetes Metab J 2011;35:193–198

485. International Diabetes Federation. OralHealth for People with Diabetes. Brussels,International Diabetes Federation, 2009

486. Giovannucci E, Harlan DM, Archer MC,et al. Diabetes and cancer: a consensusreport. Diabetes Care 2010;33:1674–1685

487. Janghorbani M, Van Dam RM, Willett WC,Hu FB. Systematic review of type 1 andtype 2 diabetes mellitus and risk offracture. Am J Epidemiol 2007;166:495–505

488. Vestergaard P. Discrepancies in bonemineral density and fracture risk inpatients with type 1 and type 2diabetesda meta-analysis. OsteoporosInt 2007;18:427–444

489. Schwartz AV, Vittinghoff E, Bauer DC,et al.; Study of Osteoporotic Fractures(SOF) Research Group; OsteoporoticFractures in Men (MrOS) Research Group;Health, Aging, and Body Composition(Health ABC) Research Group. Associationof BMD and FRAX score with risk offracture in older adults with type 2diabetes. JAMA 2011;305:2184–2192

490. Cukierman T, Gerstein HC, Williamson JD.Cognitive decline and dementia indiabetesdsystematic overview of

S76 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

prospective observational studies.Diabetologia 2005;48:2460–2469

491. Biessels GJ, Staekenborg S, Brunner E,Brayne C, Scheltens P. Risk of dementia indiabetes mellitus: a systematic review.Lancet Neurol 2006;5:64–74

492. Ohara T, Doi Y, Ninomiya T, et al. Glucosetolerance status and risk of dementia inthe community: the Hisayama study.Neurology 2011;77:1126–1134

493. Launer LJ, Miller ME, Williamson JD, et al.;ACCORD MIND investigators. Effects ofintensive glucose lowering on brainstructure and function in people with type2 diabetes (ACCORDMIND): a randomisedopen-label substudy. Lancet Neurol 2011;10:969–977

494. Dhindsa S, Miller MG, McWhirter CL, et al.Testosterone concentrations in diabeticand nondiabetic obese men. DiabetesCare 2010;33:1186–1192

495. Bhasin S, Cunningham GR, Hayes FJ, et al.;Task Force, Endocrine Society.Testosterone therapy in men withandrogen deficiency syndromes: anEndocrine Society clinical practiceguideline. J Clin Endocrinol Metab 2010;95:2536–2559

496. Khader YS, Dauod AS, El-Qaderi SS,Alkafajei A, Batayha WQ. Periodontalstatus of diabetics compared withnondiabetics: a meta-analysis. J DiabetesComplications 2006;20:59–68

497. Bainbridge KE, Hoffman HJ, Cowie CC.Diabetes and hearing impairment in theUnited States: audiometric evidence fromthe National Health and NutritionExamination Survey, 1999 to 2004. AnnIntern Med 2008;149:1–10

498. Silverstein J, Klingensmith G, Copeland KC,et al.; American Diabetes Association.Care of children and adolescents with type1 diabetes: a statement of the AmericanDiabetes Association. Diabetes Care 2005;28:186–212

499. Wysocki T, Harris MA, Mauras N, et al.Absence of adverse effects of severehypoglycemia on cognitive function inschool-aged children with diabetes over 18months. Diabetes Care 2003;26:1100–1105

500. Blasetti A, Chiuri RM, Tocco AM, et al.The effect of recurrent severehypoglycemia on cognitive performancein children with type 1 diabetes: a meta-analysis. J Child Neurol 2011;26:1383–1391

501. CooperMN, O’Connell SM, Davis EA, JonesTW. A population-based study of riskfactors for severe hypoglycaemia in acontemporary cohort of childhood-onsettype 1 diabetes. Diabetologia 2013;56:2164–2170

502. Zuijdwijk CS, Cuerden M, Mahmud FH.Social determinants of health on glycemiccontrol in pediatric type 1 diabetes.J Pediatr 2013;162:730–735

503. Nimri R, Weintrob N, Benzaquen H, OfanR, Fayman G, Phillip M. Insulin pumptherapy in youth with type 1 diabetes:a retrospective paired study. Pediatrics2006;117:2126–2131

504. Doyle EA, Weinzimer SA, Steffen AT,Ahern JA, Vincent M, Tamborlane WV. Arandomized, prospective trial comparingthe efficacy of continuous subcutaneousinsulin infusion with multiple dailyinjections using insulin glargine. DiabetesCare 2004;27:1554–1558

505. Perantie DC, Wu J, Koller JM, et al.Regional brain volume differencesassociated with hyperglycemia and severehypoglycemia in youth with type 1diabetes. Diabetes Care 2007;30:2331–2337

506. Daniels M, DuBose SN, Maahs DM, et al.;T1D Exchange Clinic Network. Factorsassociatedwithmicroalbuminuria in 7,549children and adolescents with type 1diabetes in the T1D Exchange clinicregistry. Diabetes Care 2013;36:2639–2645

507. Hortenhuber T, Rami-Mehar B, Satler M,et al. Endothelial progenitor cells arerelated to glycemic control in childrenwith type 1 diabetes over time. DiabetesCare 2013;36:1647–1653

508. Haller MJ, Samyn M, Nichols WW, et al.Radial artery tonometry demonstratesarterial stiffness in children with type 1diabetes. Diabetes Care 2004;27:2911–2917

509. Orchard TJ, Forrest KY, Kuller LH, BeckerDJ; Pittsburgh Epidemiology of DiabetesComplications Study. Lipid and bloodpressure treatment goals for type 1diabetes: 10-year incidence data from thePittsburgh Epidemiology of DiabetesComplications Study. Diabetes Care 2001;24:1053–1059

510. Kavey RE, Allada V, Daniels SR, et al.Cardiovascular risk reduction in high-riskpediatric patients: a scientific statementfrom the American Heart AssociationExpert Panel on Population andPrevention Science; the Councils onCardiovascular Disease in the Young,Epidemiology and Prevention, Nutrition,Physical Activity and Metabolism, HighBlood Pressure Research, CardiovascularNursing, and the Kidney in Heart Disease;and the Interdisciplinary Working Groupon Quality of Care and OutcomesResearch: endorsed by the AmericanAcademy of Pediatrics. Circulation 2006;114:2710–2738

511. McCrindle BW, Urbina EM, Dennison BA,et al. Drug therapy of high-risk lipidabnormalities in children andadolescents: a scientific statement fromthe American Heart AssociationAtherosclerosis, Hypertension, andObesity in Youth Committee, Council ofCardiovascular Disease in the Young, with

the Council on Cardiovascular Nursing.Circulation 2007;115:1948–1967

512. Salo P, Viikari J, Hamalainen M, et al.Serum cholesterol ester fatty acids in7- and 13-month-old children in aprospective randomized trial of a low-saturated fat, low-cholesterol diet: theSTRIP baby project. Special Turku coronaryRisk factor Intervention Project forchildren. Acta Paediatr 1999;88:505–512

513. The Dietary Intervention Study in Children(DISC); Writing Group for the DISCCollaborative Research Group. Efficacyand safety of lowering dietary intake of fatand cholesterol in children with elevatedlow-density lipoprotein cholesterol. JAMA1995;273:1429–1435

514. Maahs DM, Dabelea D, D’Agostino RB Jr,et al.; SEARCH for Diabetes in Youth Study.Glucose control predicts 2-year change inlipid profile in youth with type 1 diabetes.J Pediatr 2013;162:101–107.e1

515. McCrindle BW, Ose L, Marais AD.Efficacy and safety of atorvastatin inchildren and adolescents with familialhypercholesterolemia or severehyperlipidemia: a multicenter,randomized, placebo-controlled trial.J Pediatr 2003;143:74–80

516. de Jongh S, Lilien MR, op’t Roodt J, StroesES, Bakker HD, Kastelein JJ. Early statintherapy restores endothelial function inchildren with familialhypercholesterolemia. J Am Coll Cardiol2002;40:2117–2121

517. Wiegman A, Hutten BA, de Groot E,et al. Efficacy and safety of statintherapy in children with familialhypercholesterolemia: a randomizedcontrolled trial. JAMA 2004;292:331–337

518. Cho YH, Craig ME, Hing S, et al.Microvascular complications assessmentin adolescents with 2- to 5-yr duration oftype 1 diabetes from 1990 to 2006. PediatrDiabetes 2011;12:682–689

519. Holmes GK. Screening for coeliac diseasein type 1 diabetes. Arch Dis Child 2002;87:495–498

520. Rewers M, Liu E, Simmons J, Redondo MJ,Hoffenberg EJ. Celiac disease associatedwith type 1 diabetes mellitus. EndocrinolMetab Clin North Am 2004;33:197–214

521. Husby S, Koletzko S, Korponay-Szabo IR,et al.; ESPGHANWorking Group on CoeliacDisease Diagnosis; ESPGHANGastroenterology Committee; EuropeanSociety for Pediatric Gastroenterology,Hepatology, and Nutrition. EuropeanSociety for Pediatric Gastroenterology,Hepatology, and Nutrition guidelines forthe diagnosis of coeliac disease. J PediatrGastroenterol Nutr 2012;54:136–160

522. Kurppa K, Ashorn M, Iltanen S, et al.Celiac disease without villous atrophyin children: a prospective study. J Pediatr2010;157:373–380.e1

care.diabetesjournals.org Position Statement S77

523. Abid N, McGlone O, Cardwell C, McCallionW, Carson D. Clinical andmetabolic effectsof gluten free diet in children with type 1diabetes and coeliac disease. PediatrDiabetes 2011;12:322–325

524. Roldan MB, Alonso M, Barrio R. Thyroidautoimmunity in children and adolescentswith Type 1 diabetes mellitus. DiabetesNutr Metab 1999;12:27–31

525. Triolo TM, Armstrong TK, McFann K, et al.Additional autoimmune disease found in33% of patients at type 1 diabetes onset.Diabetes Care 2011;34:1211–1213

526. Kordonouri O, Deiss D, Danne T, Dorow A,Bassir C, Gruters-Kieslich A. Predictivity ofthyroid autoantibodies for thedevelopment of thyroid disorders inchildren and adolescents with type 1diabetes. Diabet Med 2002;19:518–521

527. Mohn A, Di Michele S, Di Luzio R, Tumini S,Chiarelli F. The effect of subclinicalhypothyroidism on metabolic control inchildren and adolescents with type 1diabetes mellitus. Diabet Med 2002;19:70–73

528. Chase HP, Garg SK, Cockerham RS, WilcoxWD, Walravens PA. Thyroid hormonereplacement and growth of children withsubclinical hypothyroidism and diabetes.Diabet Med 1990;7:299–303

529. American Diabetes Association. Diabetescare in the school and day care setting.Diabetes Care 2014;37(Suppl. 1):S91–S96

530. Arnett JJ. Emerging adulthood. A theory ofdevelopment from the late teens throughthe twenties. Am Psychol 2000;55:469–480

531. Weissberg-Benchell J, Wolpert H,Anderson BJ. Transitioning from pediatricto adult care: a new approach to the post-adolescent young person with type 1diabetes. Diabetes Care 2007;30:2441–2446

532. Peters A, Laffel L, the American DiabetesAssociation Transitions Working Group.Diabetes care for emerging adults:recommendations for transition frompediatric to adult diabetes care systems:a position statement of the AmericanDiabetes Association, with representationby the American College of OsteopathicFamily Physicians, the American Academyof Pediatrics, the American Association ofClinical Endocrinologists, the AmericanOsteopathic Association, the Centers forDisease Control and Prevention, Childrenwith Diabetes, The Endocrine Society, theInternational Society for Pediatric andAdolescent Diabetes, Juvenile DiabetesResearch Foundation International, theNational Diabetes Education Program, andthe Pediatric Endocrine Society (formerlyLawson Wilkins Pediatric EndocrineSociety). Diabetes Care 2011;34:2477–2485

533. Bryden KS, Peveler RC, Stein A, Neil A,Mayou RA, Dunger DB. Clinical and

psychological course of diabetes fromadolescence to young adulthood:a longitudinal cohort study. Diabetes Care2001;24:1536–1540

534. Laing SP, Jones ME, Swerdlow AJ, BurdenAC, Gatling W. Psychosocial andsocioeconomic risk factors for prematuredeath in young peoplewith type 1 diabetes.Diabetes Care 2005;28:1618–1623

535. Eppens MC, Craig ME, Cusumano J, et al.Prevalence of diabetes complications inadolescents with type 2 compared withtype 1 diabetes. Diabetes Care 2006;29:1300–1306

536. Hattersley A, Bruining J, Shield J, NjolstadP, Donaghue KC. The diagnosis andmanagement of monogenic diabetes inchildren and adolescents. PediatrDiabetes 2009;10(Suppl. 12):33–42

537. Kitzmiller JL,Wallerstein R, Correa A, KwanS. Preconception care for women withdiabetes and prevention of majorcongenital malformations. Birth DefectsRes A Clin Mol Teratol 2010;88:791–803

538. Charron-Prochownik D, Sereika SM,Becker D, et al. Long-term effects of thebooster-enhanced READY-Girlspreconception counseling program onintentions and behaviors for familyplanning in teens with diabetes. DiabetesCare 2013;36:3870–3874

539. Cooper WO, Hernandez-Diaz S, ArbogastPG, et al. Major congenital malformationsafter first-trimester exposure to ACEinhibitors. N Engl J Med 2006;354:2443–2451

540. American Diabetes Association.Preconception care of women withdiabetes. Diabetes Care 2004;27(Suppl.1):S76–S78

541. Kirkman MS, Briscoe VJ, Clark N, et al.Diabetes in older adults. Diabetes Care2012;35:2650–2664

542. Curb JD, Pressel SL, Cutler JA, et al.;Systolic Hypertension in the ElderlyProgram Cooperative Research Group.Effect of diuretic-based antihypertensivetreatment on cardiovascular disease riskin older diabetic patients with isolatedsystolic hypertension. JAMA 1996;276:1886–1892

543. Beckett NS, Peters R, Fletcher AE, et al.;HYVET Study Group. Treatment ofhypertension in patients 80 years of age orolder. N Engl J Med 2008;358:1887–1898

544. Kern AS, Prestridge AL. Improvingscreening for cystic fibrosis-relateddiabetes at a pediatric cystic fibrosisprogram. Pediatrics 2013;132:e512–e518

545. Waugh N, Royle P, Craigie I, et al.Screening for cystic fibrosis-relateddiabetes: a systematic review. HealthTechnol Assess 2012;16:iii–iv, 1–179

546. Moran A, Dunitz J, Nathan B, Saeed A,Holme B, Thomas W. Cystic fibrosis-related

diabetes: current trends in prevalence,incidence, and mortality. Diabetes Care2009;32:1626–1631

547. Onady GM, Stolfi A. Insulin and oral agentsfor managing cystic fibrosis-relateddiabetes. Cochrane Database Syst Rev2013;(7):CD004730

548. Moran A, Brunzell C, Cohen RC, et al.;CFRD Guidelines Committee. Clinical careguidelines for cystic fibrosis-relateddiabetes: a position statement of theAmerican Diabetes Association and aclinical practice guideline of the CysticFibrosis Foundation, endorsed by thePediatric Endocrine Society. Diabetes Care2010;33:2697–2708

549. van den Berghe G, Wouters P, Weekers F,et al. Intensive insulin therapy in criticallyill patients. N Engl J Med 2001;345:1359–1367

550. Malmberg K, Norhammar A, Wedel H,Ryden L. Glycometabolic state atadmission: important risk marker ofmortality in conventionally treatedpatients with diabetes mellitus and acutemyocardial infarction: long-term resultsfrom the Diabetes and Insulin-GlucoseInfusion in Acute Myocardial Infarction(DIGAMI) study. Circulation 1999;99:2626–2632

551. Clement S, Braithwaite SS, Magee MF,et al.; American Diabetes AssociationDiabetes in Hospitals Writing Committee.Management of diabetes andhyperglycemia in hospitals [publishedcorrection appears in Diabetes Care 2004;27:856 and 2044;27:155]. Diabetes Care2004;27:553–591

552. Wiener RS, Wiener DC, Larson RJ. Benefitsand risks of tight glucose control incritically ill adults: a meta-analysis. JAMA2008;300:933–944

553. Brunkhorst FM, Engel C, Bloos F, et al.;German Competence Network Sepsis(SepNet). Intensive insulin therapy andpentastarch resuscitation in severe sepsis.N Engl J Med 2008;358:125–139

554. Finfer S, Chittock DR, Su SY, et al.; NICE-SUGAR Study Investigators. Intensiveversus conventional glucose control incritically ill patients. N Engl J Med 2009;360:1283–1297

555. Krinsley JS, Grover A. Severehypoglycemia in critically ill patients: riskfactors and outcomes. Crit Care Med2007;35:2262–2267

556. Van den Berghe G, Wilmer A, Hermans G,et al. Intensive insulin therapy in themedicalICU. N Engl J Med 2006;354:449–461

557. Griesdale DE, de Souza RJ, van Dam RM,et al. Intensive insulin therapy andmortality among critically ill patients:a meta-analysis including NICE-SUGARstudy data. CMAJ 2009;180:821–827

558. Saudek CD, Herman WH, Sacks DB,Bergenstal RM, Edelman D, Davidson MB.

S78 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014

A new look at screening and diagnosingdiabetes mellitus. J Clin Endocrinol Metab2008;93:2447–2453

559. Cryer PE, Davis SN, Shamoon H.Hypoglycemia in diabetes. Diabetes Care2003;26:1902–1912

560. Moghissi ES, Korytkowski MT, DiNardo M,et al.; American Association of ClinicalEndocrinologists; American DiabetesAssociation. American Association ofClinical Endocrinologists and AmericanDiabetes Association consensusstatement on inpatient glycemic control.Diabetes Care 2009;32:1119–1131

561. Hsu CW, Sun SF, Lin SL, Huang HH, WongKF. Moderate glucose control results inless negative nitrogen balances in medicalintensive care unit patients:a randomized, controlled study. Crit Care2012;16:R56

562. Umpierrez GE, Hellman R, KorytkowskiMT, et al.; Endocrine Society.Management of hyperglycemia inhospitalized patients in non-critical caresetting: an Endocrine Society clinicalpractice guideline. J Clin Endocrinol Metab2012;97:16–38

563. Bernard JB, Munoz C, Harper J, MurielloM, Rico E, Baldwin D. Treatment ofinpatient hyperglycemia beginning in theemergency department: a randomizedtrial using insulins aspart and detemircompared with usual care. J Hosp Med2011;6:279–284

564. Czosnowski QA, Swanson JM, Lobo BL,Broyles JE, Deaton PR, Finch CK.Evaluation of glycemic control followingdiscontinuation of an intensive insulinprotocol. J Hosp Med 2009;4:28–34

565. Shomali MI, Herr DL, Hill PC, PehlivanovaM, Sharretts JM, Magee MF. Conversionfrom intravenous insulin to subcutaneousinsulin after cardiovascular surgery:transition to target study. DiabetesTechnol Ther 2011;13:121–126

566. Baldwin D, Zander J, Munoz C, et al. Arandomized trial of two weight-baseddoses of insulin glargine and glulisine inhospitalized subjects with type 2 diabetesand renal insufficiency. Diabetes Care2012;35:1970–1974

567. Draznin B, Gilden J, Golden SH, et al.;PRIDE investigators. Pathways to qualityinpatient management of hyperglycemiaand diabetes: a call to action. DiabetesCare 2013;36:1807–1814

568. Umpierrez GE, Smiley D, Jacobs S, et al.Randomized study of basal-bolus insulintherapy in the inpatient management ofpatients with type 2 diabetes undergoinggeneral surgery (RABBIT 2 surgery).Diabetes Care 2011;34:256–261

569. Pasquel FJ, Spiegelman R, McCauley M,et al. Hyperglycemia during totalparenteral nutrition: an important markerof poor outcome and mortality in

hospitalized patients. Diabetes Care 2010;33:739–741

570. Schnipper JL, Liang CL, Ndumele CD,PendergrassML. Effects of a computerizedorder set on the inpatient management ofhyperglycemia: a cluster-randomizedcontrolled trial. Endocr Pract 2010;16:209–218

571. Wexler DJ, Shrader P, Burns SM, CaglieroE. Effectiveness of a computerized insulinorder template in general medicalinpatients with type 2 diabetes: a clusterrandomized trial. Diabetes Care 2010;33:2181–2183

572. Furnary AP, Braithwaite SS. Effects ofoutcome on in-hospital transition fromintravenous insulin infusion tosubcutaneous therapy. Am J Cardiol 2006;98:557–564

573. Schafer RG, Bohannon B, Franz MJ, et al.;American Diabetes Association. Diabetesnutrition recommendations for healthcare institutions. Diabetes Care 2004;27(Suppl. 1):S55–S57

574. Curll M, Dinardo M, Noschese M,Korytkowski MT. Menu selection,glycaemic control and satisfaction withstandard and patient-controlledconsistent carbohydrate meal plans inhospitalised patients with diabetes. QualSaf Health Care 2010;19:355–359

575. Korytkowski MT, Salata RJ, Koerbel GL,et al. Insulin therapy and glycemic controlin hospitalized patients with diabetesduring enteral nutrition therapy:a randomized controlled clinical trial.Diabetes Care 2009;32:594–596

576. Umpierrez GE. Basal versus sliding-scaleregular insulin in hospitalized patients withhyperglycemia during enteral nutritiontherapy. Diabetes Care 2009;32:751–753

577. Klonoff DC, Perz JF. Assisted monitoring ofblood glucose: special safety needs for anew paradigm in testing glucose. JDiabetes Sci Tech 2010;4:1027–1031

578. D’Orazio P, Burnett RW, Fogh-Andersen N,et al.; International Federation of ClinicalChemistry Scientific Division WorkingGroup on Selective Electrodes and Point ofCare Testing. Approved IFCCrecommendation on reporting results forblood glucose (abbreviated). Clin Chem2005;51:1573–1576

579. Dungan K, Chapman J, Braithwaite SS,Buse J. Glucose measurement:confounding issues in setting targets forinpatient management. Diabetes Care2007;30:403–409

580. Boyd JC, Bruns DE. Quality specificationsfor glucose meters: assessment bysimulation modeling of errors in insulindose. Clin Chem 2001;47:209–214

581. Shepperd S, McClaran J, Phillips CO, et al.Discharge planning from hospital to home.Cochrane Database Syst Rev 2010;(1):CD000313

582. Agency for Healthcare Research andQuality. Adverse Events after hospitaldischarge [Internet], 2010. Available fromhttp://psnet.ahrq.gov/primer.aspx?primerID511

583. American Diabetes Association. Diabetesand employment. Diabetes Care 2014;37(Suppl. 1):S112–S117

584. American Diabetes Association. Diabetesand driving. Diabetes Care 2014;37(Suppl. 1):S97–S103

585. American Diabetes Association. Diabetesmanagement in correctional institutions.Diabetes Care 2014;37(Suppl. 1):S104–S111

586. Hoerger TJ, Segel JE, Gregg EW, SaaddineJB. Is glycemic control improving in U.S.adults?Diabetes Care 2008;31:81–86

587. Wang J, Geiss LS, Cheng YJ, et al. Long-term and recent progress in bloodpressure levels among U.S. adults withdiagnosed diabetes, 1988–2008. DiabetesCare 2011;34:1579–1581

588. Kerr EA, Heisler M, Krein SL, et al. Beyondcomorbidity counts: how do comorbiditytype and severity influence diabetespatients’ treatment priorities and self-management? J Gen Intern Med 2007;22:1635–1640

589. Fernandez A, Schillinger D, Warton EM,et al. Language barriers, physician-patientlanguage concordance, and glycemiccontrol among insured Latinos withdiabetes: the Diabetes Study of NorthernCalifornia (DISTANCE). J Gen Intern Med2011;26:170–176

590. Stellefson M, Dipnarine K, Stopka C. Thechronic care model and diabetesmanagement in US primary care settings:a systematic review. Prev Chronic Dis2013;10:E26

591. Coleman K, Austin BT, Brach C,Wagner EH.Evidence on the chronic care model in thenew millennium. Health Aff (Millwood)2009;28:75–85

592. Parchman ML, Zeber JE, Romero RR, PughJA. Risk of coronary artery disease in type2 diabetes and the delivery of careconsistent with the chronic care model inprimary care settings: a STARNet study.Med Care 2007;45:1129–1134

593. Davidson MB. How our current medicalcare system fails people with diabetes:lack of timely, appropriate clinicaldecisions. Diabetes Care 2009;32:370–372

594. Grant RW, Pabon-Nau L, Ross KM, YouattEJ, Pandiscio JC, Park ER. Diabetes oralmedication initiation and intensification:patient views compared with currenttreatment guidelines. Diabetes Educ 2011;37:78–84

595. Schillinger D, Piette J, Grumbach K, et al.Closing the loop: physiciancommunication with diabetic patientswho have low health literacy. Arch InternMed 2003;163:83–90

care.diabetesjournals.org Position Statement S79

596. Rosal MC, Ockene IS, Restrepo A, et al.Randomized trial of a literacy-sensitive,culturally tailored diabetes self-management intervention for low-incomeLatinos: Latinos en Control. Diabetes Care2011;34:838–844

597. Osborn CY, Cavanaugh K, Wallston KA,et al. Health literacy explains racialdisparities in diabetes medicationadherence. J Health Commun 2011;16(Suppl. 3):268–278

598. Rothman R, Malone R, Bryant B, Horlen C,DeWalt D, Pignone M. The relationshipbetween literacy and glycemic control in adiabetes disease-management program.Diabetes Educ 2004;30:263–273

599. O’Connor PJ, Sperl-Hillen JM, Rush WA,et al. Impact of electronic health recordclinical decision support on diabetes care:a randomized trial. Ann Fam Med 2011;9:12–21

600. Garg AX, Adhikari NK, McDonald H, et al.Effects of computerized clinical decisionsupport systems on practitionerperformance and patient outcomes:a systematic review. JAMA 2005;293:1223–1238

601. Smith SA, Shah ND, Bryant SC, et al.;Evidens ResearchGroup. Chronic caremodeland shared care indiabetes: randomized trialof an electronic decision support system.Mayo Clin Proc 2008;83:747–757

602. Jaffe MG, Lee GA, Young JD, Sidney S, GoAS. Improved blood pressure controlassociated with a large-scale hypertensionprogram. JAMA 2013;310:699–705

603. Davidson MB, Ansari A, Karlan VJ. Effectof a nurse-directed diabetes diseasemanagement program on urgent care/emergency room visits andhospitalizations in a minority population.Diabetes Care 2007;30:224–227

604. Stone RA, Rao RH, Sevick MA, et al. Activecare management supported by home

telemonitoring in veterans with type 2diabetes: the DiaTel randomizedcontrolled trial. Diabetes Care 2010;33:478–484

605. Berikai P, Meyer PM, Kazlauskaite R, SavoyB, Kozik K, Fogelfeld L. Gain in patients’knowledge of diabetes managementtargets is associated with better glycemiccontrol. Diabetes Care 2007;30:1587–1589

606. Funnell MM, Brown TL, Childs BP, et al.National Standards for Diabetes Self-Management Education. Diabetes Care2007;30:1630–1637

607. Klein S, Sheard NF, Pi-Sunyer X, et al.Weight management through lifestylemodification for the prevention andmanagement of type 2 diabetes: rationaleand strategies: a statement of theAmerican Diabetes Association, the NorthAmerican Association for the Study ofObesity, and the American Society forClinical Nutrition. Diabetes Care 2004;27:2067–2073

608. Norris SL, Zhang X, Avenell A, et al. Efficacyof pharmacotherapy for weight loss inadults with type 2 diabetes mellitus:a meta-analysis. Arch Intern Med 2004;164:1395–1404

609. Tricco AC, Ivers NM, Grimshaw JM, et al.Effectiveness of quality improvementstrategies on the management ofdiabetes: a systematic review and meta-analysis. Lancet 2012;379:2252–2261

610. O’Connor PJ, Bodkin NL, Fradkin J, et al.Diabetes performance measures: currentstatus and future directions. DiabetesCare 2011;34:1651–1659

611. Peikes D, Chen A, Schore J, Brown R.Effects of care coordination onhospitalization, quality of care, and healthcare expenditures among Medicarebeneficiaries: 15 randomized trials. JAMA2009;301:603–618

612. Feifer C, Nemeth L, Nietert PJ, et al.Different paths to high-quality care:three archetypes of top-performingpractice sites. Ann FamMed 2007;5:233–241

613. Reed M, Huang J, Graetz I, et al.Outpatient electronic health records andthe clinical care and outcomes of patientswith diabetes mellitus. Ann Intern Med2012;157:482–489

614. Cebul RD, Love TE, Jain AK, Hebert CJ.Electronic health records and quality ofdiabetes care. N Engl J Med 2011;365:825–833

615. BattersbyM, Von KorffM, Schaefer J, et al.Twelve evidence-based principles forimplementing self-management supportin primary care. Jt Comm J Qual Patient Saf2010;36:561–570

616. Grant RW, Wald JS, Schnipper JL, et al.Practice-linked online personal healthrecords for type 2 diabetes mellitus:a randomized controlled trial. Arch InternMed 2008;168:1776–1782

617. Pullen-Smith B, Carter-Edwards L,Leathers KH. Community healthambassadors: a model for engagingcommunity leaders to promote betterhealth in North Carolina. J PublicHealth Manag Pract 2008;14(Suppl.):S73–S81

618. Bojadzievski T, Gabbay RA. Patient-centered medical home and diabetes.Diabetes Care 2011;34:1047–1053

619. Rosenthal MB, Cutler DM, Feder J.The ACO rulesdstriking the balancebetween participation andtransformative potential. N Engl J Med2011;365:e6

620. Washington AE, Lipstein SH. The Patient-Centered Outcomes ResearchInstitutedpromoting better information,decisions, and health. N Engl J Med 2011;365:e31

S80 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014