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CMAJ•JAMCCA NA D I A N ME D I CA L AS S O C I AT I O N J O U R NA L • J O U R NA L D E L’ AS S O C I AT I O N M É D I CA L E CA NA D I E N N E

Supplement to CMAJ 1998 ;159(8 Suppl)

1998 clinical practiceguidelines

for the management of diabetes in Canada

CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S1

1998 clinical practice guidelines forthe management of diabetes in Canada

Sara Meltzer, MD; Lawrence Leiter, MD; Denis Daneman, MD;Hertzel C. Gerstein, MD, MSc; David Lau, MD, PhD; Sora Ludwig, MD; Jean-François Yale, MD; Bernard Zinman, MD;Donna Lillie, RN, BA; Steering and Expert Committees*

A b s t ra c t

O b j e c t ive : To revise and expand the 1992 edition of the clinical practice guidelines forthe management of diabetes in Canada incorporating recent advances in diagnosisand outpatient management of diabetes mellitus and to identify and assess the evi-dence supporting these recommendations.

O p t i o n s : All aspects of ambulatory diabetes care, including organization, responsibili-ties, classification, diagnosis, management of metabolic disorders, and methods forscreening, prevention and treatment of complications in all forms of diabetes werereviewed, revised as required and expressed as a set of recommendations.

O u t c o m e s : Reclassification of types of diabetes based on pathogenesis; increased sensi-t ivity of diagnostic criteria; recommendations for screening for diabetes; improve dd e l ivery of care; recommendations for tighter metabolic control; and optimal meth-ods for screening, prevention and treatment of complications of diabetes.

E v i d e n c e : All recommendations were developed using a justifiable and reproducibleprocess involving an explicit method for the citation and evaluation of the supportinge v i d e n c e .

Va l u e s : All recommendations were reviewed by an expert committee that included peo-ple with diabetes, family physicians, dietitians, nurses, diabetologists, as well as othersubspecialists and methodologists from across Canada.

Benefits, harm and costs: More aggressive screening strategies and more sensitive test-ing and diagnostic procedures will allow earlier detection and management of dia-betes. Cost-effectiveness analyses suggest that this will lead to savings in health carecosts relating to diabetes care by reducing the incidence of complications of diabetes.S i m i l a r l y, tighter metabolic control in most people with diabetes, through intensivediabetes management, seeks to reduce the incidence of complications and, hence,their associated social and economic burdens.

R e c o m m e n d a t i o n s : This document contains numerous detailed recommendations per-taining to all aspects of ambulatory diabetes care, ranging from service delivery to pre-vention and treatment of diabetes-related complications. The terms “insulin-dependentdiabetes mellitus” and “non-insulin-dependent diabetes mellitus” should be replacedby the terms “type 1” and “type 2” diabetes. Testing for diabetes using fasting plasmaglucose (FPG) level should be performed every 3 years in those over 45 years of age.More frequent or earlier testing should be considered for people with additional spe-cific risk factors for diabetes. The FPG level at wh i ch diabetes is diagnosed should bereduced from 7.8 to 7.0 mmol/L to improve the sensitivity of the main diagnostic cri-terion and reduce the number of missed diagnoses. Depending on the type of diabetesand the thera py required to ach i e ve euglycemia, people with diabetes should gener-ally strive for close metabolic control to ach i e ve optimal glucose levels. This entailsr e c e iving appropriate diabetes education through a diabetes health care team, diligentself-monitoring of blood glucose, attention to lifestyle and adjustments in diet andp hysical activ i t y, and the appropriate and stepwise use of oral agents and insulin ther-apies needed to maintain glycemic control. Also highlighted is the need for appropri-ate surveillance programs for complications and management options.

Va l i d a t i o n : All recommendations were graded according to the strength of the evidenceand consensus of all relevant stakeholders. Collateral efforts of the American DiabetesAssociation and the World Health Organization and the input of international expertswere also considered throughout the revision process.

S p o n s o r s : These guidelines were developed under the auspices of the Clinical and

Special supplement

D r. Meltzer is at the RoyalVictoria Hospital, Montre a l ,Que.; Dr. Leiter is at St.M i c h a e l ’s Hospital, To ro n t o ,Ont.; Dr. Daneman is at TheHospital for Sick Childre n ,To ronto, Ont.; Dr. Gerstein iswith the Hamilton HealthSciences Corp., Hamilton,Ont.; Dr. Lau is at the OttawaCivic Hospital, Ottawa, Ont.;D r. Ludwig is at St. BonifaceGeneral Hospital, Wi n n i p e g ,Man.; Dr. Yale is at the RoyalVictoria Hospital, Montre a l ,Que.; Dr. Zinman is at MountSinai Hospital, To ronto, Ont.;and Ms. Lillie is with theCanadian DiabetesAssociation, To ronto, Ont.

*Members of the Steering andExpert Committees appear at theend of the article.

These guidelines have been peerreviewed.

CMAJ 1998;159(8 Suppl):S1-29

D iabetes is a common chronic disease. It alsomeets all 3 criteria for a public health disord e r :“a high disease burden, changing burden sug-

gesting pre v e n t a b i l i t y, and fear that things are unknownand out of contro l . ”1 – 3

C u rre n t l y, the diagnosis of diabetes has been made ina p p roximately 5% of Canadians or 1.5 million people.1

This number is expected to reach 2.2 million by the year2000 and 3 million by 2010.2 M o re o v e r, because UnitedStates statistics demonstrate that for every person withknown diabetes there is someone with undiagnosed dia-betes, these numbers most likely underestimate thep revalence of the disease. Assuming that the same situa-tion is true in Canada, up to 10% of Canadian adults mayc u rrently have diabetes.

Diabetes is a serious health problem. It is a majorcause of coro n a ry art e ry disease (CAD), which is theleading cause of death in Canada. It is also a leading causeof new cases of blindness and kidney disease in adults.The disease often disables people in their middle yearsand, as a group, people with diabetes die younger thanthose not affected by it.4

Diabetes is costly both to the affected person and to soci-e t y. In general, people with diabetes have poorer health andspend more on managing their health than people withoutdiabetes. Although the actual cost of diabetes in Canadaremains unknown, data from the United States suggest thatdiabetes and its management consume approximately 1 in7 health care dollars.5 , 6 These high costs, in addition to eco-nomic analyses showing that early interventions are cost-e ffective, emphasize the importance of the appro p r i a t emanagement of diabetes to society as a whole.7 , 8

In 1992, the Canadian Diabetes Advisory Board pro-duced the first Canadian clinical practice guidelines9 t oa d d ress the educational needs of primary care physiciansand other members of diabetes health care teamsinvolved in the management of people with diabetes.New developments since then led the Clinical andScientific Section of the Canadian Diabetes Association(CDA) to develop revised guidelines to provide ongoings u p p o rt and guidance to health care pro f e s s i o n a l s .

These guidelines are presented here as re c o m m e n d a-tions, graded according to the level of supporting evi-dence and accompanied by a brief explanation or descrip-tion of their context. To be concise and to increase theutility of these guidelines for clinicians, only summaries

of the recommendations are presented. More detaileddiscussion will appear in a subsequent series of art i c l e s .Although these guidelines are not meant to be a textbookon diabetes care, they address key issues or areas of con-t roversy related to outpatient diabetes care .

M e t h o d s

After consultation with the Canadian Diabetes AdvisoryB o a rd, the CDA’s Clinical and Scientific Section, under-took the task of revising and updating the “Clinical practiceguidelines for treatment of diabetes mellitus”9 with theintention of ensuring that the recommendations are evi-dence-based whenever possible. A Steering Committee wasassembled and identified 4 broad areas of ambulatory dia-betes care: organization of diabetes care; definition, classifi-cation, diagnosis and screening; management; and compli-cations. It then re c ruited an Expert Committee made up of37 key stakeholders that included people with diabetes,family physicians, dietitians and nurse educators, diabetol-ogists and other subspecialists, and methodologists fro ma c ross Canada. These people evaluated the literature anddeveloped recommendations for each of the 4 broad are a s .

The principles used for developing these guidelines,assigning levels of evidence to the relevant citations andmaking and grading recommendations were drawn fro mthe guidelines literature1 0 – 1 4 and summarized in a series ofdocuments for the Expert Committee. The system chosenfor grading the recommendations is similar to that used tograde recommendations on hypertension and thro m b o-s i s1 0 , 1 1 and diff e red from that used to grade re c o m m e n d a-tions related to the periodic health examination.1 5

Key citations identified within each broad area wereassigned a level of evidence based on the problem addre s s e dand the design of the study (Table 1). Recommendationsw e re developed and graded on the basis of these citations aswell as the consensus opinion of the relevant subcommitteeand the full Expert Committee (Table 2). Some re c o m-mendations were assigned a lower grade than supported bythe evidence when the consensus opinion of the ExpertCommittee was that there was a need for further support-ive evidence; recommendations were assigned a grade of“D” when they were based on the strong consensus opin-ion of the Expert Committee in the absence of clear sup-p o rting evidence or when evidence was weak. Before a finalgrade was assigned, all key citations and re c o m m e n d a t i o n s

Meltzer et al

S2 JAMC • 20 OCT. 1998; 159 (8 Suppl)

Scientific Section of the Canadian Diabetes Association. The process was facilitatedby funding from Bayer Canada, Eli Lilly/Boehringer Mannheim Alliance, Servier,Pa r k e - D avis, Medisense and Novo-Nordisk Canada. None of the funding sourc e shad a role in the collection, analysis or interpretation of the data or in the decisionto publish this report.

w e re reviewed by 3 methodologists, who were not dire c t l yinvolved in the initial assessment of evidence and the grad-ing of the recommendations. Where appropriate, theassigned level of evidence and grade of re c o m m e n d a t i o nw e re modified on the basis of their assessment.

Submissions were reviewed by the SteeringCommittee as they were being developed. In June 1997,a meeting of the full Expert Committee completed aworking draft that was then circulated nationally andi n t e rnationally for input from stakeholders and fro me x p e rts in diabetes and related fields. This input was syn-thesized into a set of draft recommendations that werep resented in a public forum at the 1997 CDAP rofessional Conference; input from this public foru mwas subsequently incorporated into this document.

Detailed discussions re g a rding the development andjustification of each set of recommendations will befound in specific technical documents (in preparation). As u m m a ry of these discussions and recommendations iscontained here.

Organization of diabetes care

Diabetes is a complex chronic disorder with majors h o rt- and long-term health implications. Diabetes carehinges on the daily commitment of the person with dia-betes to self-management, balancing appropriate lifestylechoices and pharmacologic therapy.1 6 , 1 7 To learn and usethe varied, complex skills re q u i red to achieve this bal-ance, people with diabetes need the support of an inter-d i s c i p l i n a ry team of health and other professionals whoa re expert in total care for diabetes. The diabetes healthc a re (DHC) team provides this support .1 8 – 2 0

Central to the DHC team is the person with diabetesand his or her family. Also at the core are the primary carephysician (who may be a diabetes specialist), the diabetesmedical specialist/endocrinologist/internist and diabeteseducators (nurses and dietitians). If re q u i red, other pro-fessional and lay caregivers may be included in an expand-ed DHC team. These may be medical specialists (oph-thalmologists, cardiologists, neurologists, nephro l o g i s t sand obstetricians), other health professionals (other nurs-es and dietitians, social workers, psychologists and othermental health workers, pharmacists, chiropodists, podia-trists and optometrists), community and public healthagencies and other health org a n i z a t i o n s .2 1

The central recommendation for diabetes care is that itbe organized around the DHC team, which is interd i s c i p l i-n a ry and provides comprehensive, shared care. The modelof shared care that entails ongoing communication among,and participation of, all members of the DHC teami n c reases the commitment and participation of the person

Management of diabetes

CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S3

D Any lower level of evidence supported by consensus

*An appropriate level of evidence was necessary but not sufficient to assign a grade to a rec-ommendation; consensus was required in addition.

Grade Criteria

A Need supportive level 1 or 1+ evidence plus consensus*

B Need supportive level 2 or 2+ evidence plus consensus*

C Need supportive level 3 evidence plus consensus

Table 2: Grades of recommendations for clinical practice guidelines

iii. Selection of people suspected (but not known) to havethe disorder

4

iv. Reproducible description of the test and diagnosticstandard

v. At least 50 people with and 50 people without thedisorder

2 Meets 4 of the level 1 criteria

3

Level Criteria

Meets 3 of the level 1 criteria

Meets 1 or 2 of the level 1 criteria

Studies of treatment and prevention

Studies of diagnosis

v. Reproducible description of the outcome measures

1+ Systematic overview or meta-analysis of randomizedcontrolled trials

1 i. Independent interpretation of test results

1 1 randomized controlled trial with adequate power

2+

ii. Independent interpretation of the diagnostic standard

Systematic overview or meta-analysis of level 2randomized controlled trials

2 Randomized controlled trial that does not meet level 1criteria

3 Nonrandomized clinical trial or cohort study

4 Before–after study, cohort study withnoncontemporaneous controls, case–control study

5 Case series without controls

6 Case report or case series of <10 patients

Studies of prognosis

1 i. Inception cohort of patients with the condition ofinterest but free of the outcome of interest

Table 1: Criteria for assigning levels of evidence to the publishedstudies

ii. Reproducible inclusion and exclusion criteria

iii. Follow-up of at least 80% of subjects

iv. Statistical adjustment for confounders

2 Meets criterion i and 3 of the 4 other level 1 criteria



with diabetes.2 2 – 2 4 C a re is most effective when delivered in as t ru c t u red manner2 5 – 3 0 and when it includes ongoing educa-tion and comprehensive care as essential components.1 8 , 3 1

One of the key pro p e rties of the DHC team is flexi-bility in its organization, which will allow for identifica-tion of members of the core and expanded team accord-ing to the characteristics of the community in question.Thus, the DHC team can be stru c t u red to meet thedemands of urban, rural and even remote settings.2 4 , 2 6

Indeed, models of regional DHC teams exist in a numberof Canadian provinces, including Manitoba, Nova Scotiaand nort h e rn Ontario. Incumbent on any DHC team isthe need to maintain current standards of diabetes care .

The primary care physician has an important role asthe first, and at times the principal, medical contact forthe person with diabetes.3 2 , 3 3 In this capacity, primary carephysicians have an obligation to incorporate and evaluateclinical practice guidelines for the care of their patientswith diabetes.2 8 , 3 4

Recommendations

1 . Diabetes care should be organized around an interd i s-c i p l i n a ry diabetes health care (DHC) team. [Grade B,Level 2+1 8 , 1 9 , 2 2]

2 . As an essential member of the DHC team, the prima-ry care physician (who may be a diabetes specialist), inconsultation with the other members of the team, hasthe responsibility toa . incorporate current clinical practice guidelines for

diabetes care into daily management practices2 3 , 2 4

b . c o o rdinate and facilitate the care of the personwith diabetes and use a system of timely re m i n d e r sfor diabetes assessment and management2 3 , 2 4 , 3 5

c . a s s u re communication among all members of theDHC team.2 3 , 2 4 , 3 5 [Grade B, Level 22 3 , 2 4 , 3 5]

3 . Initial and ongoing education of the person with dia-betes should be an integral part of diabetes manage-ment and not merely an adjunct to treatment. [ G r a d eB, Level 2+1 7 , 1 8 , 3 6]

Rights and responsibilities

Diabetes touches all aspects of a person’s life. It maya ffect a person’s ability to function successfully in bothpersonal and work settings.3 7 , 3 8 I m p roved tools and self-management systems now allow many people with dia-betes to function well and to achieve near- n o rmal glucoselevels. There f o re, previous blanket discrimination — inthe workplace, in motor vehicle licensing and in vocation-al training and counselling — should now be re p l a c e dwith a case-by-case re v i e w. Education and advocacy

should focus on awareness of the rights and re s p o n s i b i l i-ties of people with diabetes.3 9 P r i m a ry care physicians andother health professionals should ensure that they areknowledgeable about provincial and national laws re l a t e dto people with diabetes.4 0

Recommendations

4 . The health care system, governments and society as awhole should recognize the rights of people with dia-betes by striving toa . include them in the planning of health care deliveryb . p rovide equitable access to diabetes care and educa-

tion that adheres to the Clinical Practice Guidelinesfor the Management of Diabetes in Canada and theS t a n d a rds for Diabetes Education in Canada

c . eliminate diabetes as an unnecessary cause ofworkplace injury, illness and disability

d . eliminate diabetes as a source of blanket discrimi-nation with respect to health care services, employ-ment, insurance and other related individual rights

e . develop a comprehensive information system tos u p p o rt interd i s c i p l i n a ry delivery of diabetes care .[Grade D, consensus]

5 . F u rt h e r, people with diabetes should strive toa . become full participants in the DHC team, part i c-

ipate actively in planning and take re s p o n s i b i l i t yfor their personal health care delivery

b . a d h e re to recommended guidelines where thepublic interest is at stake (e.g., motor vehiclelicensing). [Grade D, consensus]

Definition, classification, diagnosis and scre e n i n g

In 1995, an international expert committee workingunder the auspices of the American Diabetes Association(ADA) was established to review the National DiabetesData Gro u p ’s (NDDG’s) 1979 classification and diagnos-tic criteria for diabetes4 1 (adapted by the CDA in 1982) inview of more recent re p o rted findings. This review culmi-nated in a new classification and set of diagnostic criteria4 2

that were adopted by the ADA and that are likely to beadopted by the World Health Organization (WHO). Afterreviewing the new classification and all of the relevant pub-lished re p o rts, our Expert Committee concluded that itwas also appropriate for Canada to adopt these changes.

Definition of diabetes

Diabetes mellitus is a metabolic disorder characterizedby the presence of hyperglycemia due to defective insulin

Meltzer et al

S4 JAMC • 20 OCT. 1998; 159 (8 Suppl)

s e c retion, insulin action or both. The chronic hyper-glycemia of diabetes mellitus is associated with significantl o n g - t e rm sequelae, particularly damage, dysfunctionand failure of various organs — especially the kidney, eye,n e rves, heart and blood vessels.

Classification

The major changes from the earlier NDDG classifica-tion and WHO recommendations are summarized as fol-lows (Table 3):• The new classification proposes elimination of the

t e rms “insulin-dependent diabetes mellitus” (IDDM)and “non-insulin-dependent diabetes mellitus”

(NIDDM), but retention of “type 1” and “type 2” dia-betes (using Arabic rather than Roman numerals). TheIDDM–NIDDM terminology was based on tre a t m e n trather than pathogenesis and caused considerable con-fusion. People with any form of diabetes may re q u i reinsulin treatment at some stage of their disease. Suchuse of insulin does not, in itself, classify the patient.

• Type 1 diabetes encompasses diabetes that is primar-ily a result of pancreatic beta-cell destruction and thatis prone to ketoacidosis. This form includes cases dueto an autoimmune process and those for which theetiology of beta-cell destruction is unknown.

• Type 2 diabetes may range from predominant insulinresistance with relative insulin deficiency to a pre-


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S5

Gestational diabetes mellitus (onset or recognition of glucose intolerance in pregnancy)

Infections• Congenital rubella• Cytomegalovirus• Others

Other specific types

Genetic defects of beta-cell function• Chromosome 12, HNF-1α (formerly MODY 3)• Chromosome 7, glucokinase (formerly MODY 2)• Chromosome 20, HNF-4α (formerly MODY 1)• Mitochondrial DNA• Others

Genetic defects in insulin action• Type A insulin resistance• Leprechaunism• Rabson–Mendenhall syndrome• Lipoatrophic diabetes• Others

Diseases of the endocrine pancreas• Pancreatitis • Trauma pancreatectomy • Neoplasia• Cystic fibrosis• Hemochromatosis• Fibrocalculous pancreatopathy• Others

Type 1 diabetes mellitus (beta-cell destruction, usually leading to absolute insulin deficiency)• Immune mediated• Idiopathic

Endocrinopathies• Acromegaly• Cushing’s syndrome• Glucagonoma• Pheochromocytoma• Hyperthyroidism• Somatostatinoma• Aldosteronoma• Others

Uncommon forms of immune-mediated diabetes• “Stiff-man” syndrome• Anti-insulin receptor antibodies• Others

Drug or chemical induced• Vacor• Pentamidine• Nicotine acid• Glucocorticoids• Thyroid hormones• Diazoxide • Beta-adrenergic agonists• Thiazine• Dilantin• Alpha-interferon• Others

Other genetic syndromes sometimes associated with diabetes• Down’s syndrome• Klinfelter’s syndrome• Turner’s syndrome • Wolfram’s syndrome • Friedreich’s ataxia • Huntington’s chorea • Laurence–Biedel syndrome • Myotonic dystrophy• Porphyria • Prader–Willi syndrome• Others

DNA = deoxyribonucleic acid, HNF = hepatocyte nuclear factor, MODY = maturity onset diabetes of the youth.Source: Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.42

Type 2 diabetes mellitus (may range from predominantly insulin resistance with relative insulin deficiency to predominantlysecretory defect with insulin resistance)

Table 3: Etiologic classification of diabetes mellitus

dominant secre t o ry defect with insulin re s i s t a n c e .• A wide variety of relatively uncommon conditions are

listed under “other specific types” (Table 3). Theseconsist mainly of specific genetically defined forms ofdiabetes or diabetes associated with other diseases ord rug use.

• The classification of gestational diabetes mellitus(GDM) remains unchanged. GDM refers to glucoseintolerance with onset during pre g n a n c y.4 3

Diagnostic criteria

P reviously used diagnostic criteria (level of fasting venousplasma glucose ≥7.8 mmol/L) lacked sensitivity; a significantp ro p o rtion of people in whom a diagnosis of diabetes wouldhave been made based on glucose level 2 h after a 75-g glu-cose load never received this test and, thus the diagnosis wasnot made.4 2 , 4 4 The diagnostic threshold of 11.1 mmol/L usedfor the 2-h sample in the oral glucose tolerance test(OGTT) was based on the risk of microvascular diabeticcomplications developing; the arbitrarily chosen fastingplasma glucose (FPG) threshold of 7.8 mmol/L actuallydefined a greater degree of hyperglycemia than did the 2-hplasma glucose (2hPG) threshold of 11.1 mmol/L.4 2

A recent re-evaluation of population studies suggeststhat an FPG level of 7.0 mmol/L correlates most closelywith a 2hPG level of ≥11.1 mmol/L and best predicts thedevelopment of microvascular disease.4 2 , 4 5 , 4 6 The loweringof the FPG diagnostic level from 7.8 to 7.0 mmol/Le n s u res that both the FPG and 2hPG define a similard e g ree of hyperglycemia and risk for microvascular dis-ease. It also permits the diagnosis of diabetes to be madeon the basis of a commonly available test — the FPG.

Although below the diabetic thresholds, FPG levelsbetween 6.1 and 7.0 mmol/L are abnormally high; peo-ple with FPG levels in this range are considered to have“ i m p a i red fasting glucose” (IFG).4 2 Although they do nothave the diabetes-associated risk for microvascular dis-ease, they and people with “impaired glucose tolerance”(IGT) have a higher risk for the development of diabetesmellitus and cardiovascular disease than the general pop-ulation. Preventive strategies involving lifestyle changesand increased frequency of screening for diabetes melli-tus should be a priority for these people.4 4 The long-termoutcome and economic ramifications of identification ofthese new subgroups have yet to be assessed.

Recommendations

6 . The specific fasting plasma glucose (FPG) level used todiagnose diabetes should be reduced from 7.8 to 7.0mmol/L. [Grade A, Level 14 2 , 4 5 , 4 6]

7 . The term “impaired glucose tolerance” (IGT) isretained, but now depends only on measurement ofplasma glucose 2 h after a 75-g glucose load (2hPG).[Grade D, consensus]

8 . The term “impaired fasting glucose” (IFG) should beestablished to identify another intermediate stage ofa b n o rmal glucose homeostasis. [Grade D, consensus]

9 . Both IGT and IFG indicate a need for annual testingand attention to associated risk factors and lifestylechanges. [Grade D, consensus]

The diagnostic criteria for diabetes and the glucoset h resholds for other diagnostic categories are summa-rized in Tables 4 and 5. These criteria are based onvenous sample methods in the laboratory. Although thef requency distributions of hemoglobin A1c ( H b A1c) lev-els in some studies have characteristics similar to thoseobtained from FPG and 2hPG tests,4 5 , 4 6 the lack of stan-d a rdization of the HbA1c test precludes its use in thediagnosis of diabetes.

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S6 JAMC • 20 OCT. 1998; 159 (8 Suppl)

Gestational diabetes mellitus* (GDM) ≥5.3

FPG = fasting plasma glucose, PG = plasma glucose, N/A = not applicable.*A diagnosis of gestational diabetes mellitus requires 2 abnormal values among the 3 measurements.

CategoryFPG;

mmol/L

Impaired fasting glucose (IFG) 6.1–6.9

≥10.6

Impaired glucose tolerance (IGT) <7.0

N/A

N/A

Diabetes mellitus (DM) ≥7.0

N/A

PG 1 h after75-g glucose

load;mmol/L

≥8.9

≥11.1

7.8–11.0

N/A

PG 2 h after75-g glucose

load;mmol/L

Table 5: Glucose levels for diagnosis

OR

*The classic symptoms of diabetes include fatigue, polyuria, polydipsia and unexplained weightloss. Casual is defined as any time of the day, without regard to the interval, since the last meal.†Fasting is defined as no caloric intake for at least 8 h.§For details of the test see National Diabetes Data Group article.41 Only FPG and 2hPG valuesare required.

• A plasma glucose value in the 2-h sample (2hPG) of the ora lglucose tolerance test (OGTT) ≥11.1 mmol/L§

A confirmatory test must be done on another day in all cases in the ab -sence of unequivocal hy p e r g lycemia accompanied by acute metabolicd e c o m p e n s a t i o n. This must be based on laboratory measurements ofvenous plasma glucose.

• Symptoms of diabetes plus a casual plasma glucose va l u e ≥1 1 . 1mmol/L*

OR

• A fasting plasma glucose (FPG) ≥7.0 mmol/L†

Table 4: Diagnosis of diabetes mellitus

Screening for gestational diabetes

GDM occurs in 2% to 4% of all pregnancies, and thediagnosis of GDM has implications for both the baby andm o t h e r. The established morbidity for the baby includesm a c rosomia (with the risk of fetal and maternal traumaduring birth) and neonatal hypoglycemia;4 7 other conse-quences are now rare. Although the value of diagnosing andt reating GDM has been questioned,4 8 , 4 9 recent cost–benefita n a l y s e s5 0 , 5 1 have demonstrated the value of treating thiscondition primarily due to decreased costs for care of then e w b o rn. The value of identifying a mother who is at highrisk for later diabetes remains unproven; however, the inci-dence of postpartum diabetes mellitus, IGT and lipida b n o rmalities is elevated. Recognition of those at riskwould allow application of preventive strategies, such aschanges in nutrition and physical activity, that might helpminimize the pro g ression to more significant disease.

Due to its high prevalence and impact and because clin-ical criteria cannot reliably identify those with GDM, allp regnant women should be screened for GDM unless theya re in a very low-risk group. Thus, screening should bec a rried out for all women over 25 years of age, as well asany woman under age 25 who is obese, belongs to an eth-nic group predisposed to diabetes (e.g., Aboriginal peopleand people of Hispanic, Asian and African descent), has afamily history or previous history of diabetes or has a his-t o ry of giving birth to babies with a birthweight over 4k g .4 3 , 5 2 (Low-risk people include lean Caucasian womanunder age 25 years, with no personal or family history ofdiabetes and no history of large babies.) The evidencere g a rding glucose levels for screening remains unclear;5 2

t h e re f o re, no changes were made in this are a .

Recommendations

1 0 . All pregnant women should be screened for gesta-tional diabetes mellitus (GDM) between 24 and 28weeks’ gestation, with the exception of those in a verylow-risk group. [Grade D, consensus]

1 1 . The pre f e rred screening test is measurement of plas-ma glucose level 1 h after a 50-g oral glucose loadgiven at any time of day.• If the level at 1 h is ≥7.8 mmol/L, a glucose toler-

ance test is warr a n t e d .• If the level at 1 h is ≥10.3 mmol/L, then GDM can

be diagnosed. [Grade B, Level 25 3]

Diagnosis of gestational diabetes

The worldwide diversity of criteria for the diagnosis ofGDM continues to be problematic. The NDDG criteria

w e re based on original data (100-g, 3-h oral glucose test)that predicted long-term risk of diabetes in the mother,and these levels of hyperglycemia were then found to cor-relate with neonatal morbidity. WHO criteria (using a 75-g, 2-h test) aim for uniformity with the nonpregnant state,but suggest treating IGT when found in pre g n a n c y.5 4

Two studies5 5 , 5 6 involving over 4000 patients in totalp rovide statistical normative data using a 75-g, 2-h glu-cose test. Given the ease of the 75-g, 2-h test in terms ofless nausea, less time for the patient and cost savings, andin view of the normative data available in support of it, itshould be recommended as the optimum test. The fast-ing level found in the 2 studies was slightly diff e rent, andthat derived by Carpenter and Coustan5 7 by the conver-sion of the original O’Sullivan and Mahan data5 8 l i e sbetween these 2 values. Thus, it was felt that a fastingglucose threshold of 5.3 mmol/L, which best identifies ahigh risk for macro s o m i a ,5 7 , 5 9 should be used.

F i n a l l y, these recommendations are recognized as inter-im ones in the absence of clear evidence. For the next re v i-sion of the Canadian clinical practice guidelines, we hopethat the criteria for the diagnosis of GDM will be based onf i rm outcome data.

Recommendations

1 2 . GDM should be diagnosed by measuring FPG leveland plasma glucose levels at 1 and 2 h after ingesting a75-g glucose load. If 2 of the following 3 values are metor exceeded, a diagnosis of GDM is established. If only1 value is met or exceeded, the diagnosis is impaire dglucose tolerance of pre g n a n c y :F a s t i n g >5.3 mmol/L1 h >10.6 mmol/L2 h >8.9 mmol/L

[Grade D, consensus]In view of the common use of the 100-g OGTT dur-

ing pre g n a n c y, a 100-g glucose load may be used in car-rying out a diagnostic test and measuring following val-ues as recommended by the ADA.6 0

Screening for type 2 diabetes

A p p roximately 3% to 5% of the general adult popula-tion has unrecognized type 2 diabetes.6 1 Tests for hyper-glycemia can identify these people, and this may result insignificant benefit because many of them will have or willbe at risk for preventable diabetic complications.6 2

Routine testing for type 2 diabetes is, there f o re, justifiableas a routine clinical activity in some, but not all, settings.6 3

Thus, although the relatively low prevalence of diabetesin the general population makes it unlikely that mass


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S7

s c reening will be cost–beneficial, testing for diabetes inpeople with risk factors for type 2 diabetes or with dia-betes-associated conditions is likely to result in more goodthan harm and will lead to overall cost savings.8

Several widely available tests for hyperglycemia havebeen assessed in the context of diabetes screening. Theseinclude FPG and casual plasma glucose levels, 2hPG levelduring an OGTT, glycated hemoglobin level and glyco-suria assessment.6 2 , 6 3 The FPG is the most reliable of thesetests, although each has advantages and disadvantages int e rms of convenience, cost, assay standardization and re l i-able identification of people for whom further evaluationand treatment are worthwhile. Thus, routine use ofO G T Ts or measurement of insulin levels to identify peo-ple at high risk for type 2 diabetes is not necessary.

Recommendations

1 3 . Mass screening for type 2 diabetes in the general pop-ulation is not recommended. [Grade D, consensus]

1 4 . Testing for diabetes using a FPG test should be per-f o rmed every 3 years in those over 45 years of age.[Grade D, consensus]

1 5 .M o re frequent or earlier testing (or both) should bec o n s i d e red in those with additional risk factors for dia-betes, i.e.,• a first-degree relative with diabetes• member of high-risk population (e.g. Aboriginal

people, Hispanic, Asian and African descent)• o b e s i t y• a low level of high-density lipoprotein (HDL) cho-

l e s t e rol (≤0.9 mmol/L) or an elevated fasting levelof trigylcerides (>2.8 mmol/L). [Grade D, consensus]

1 6 . Annual testing should be considered in those withone or more of the following more predictive risk fac-tors (irrespective of the above factors), such as• h i s t o ry of IGT or IFG• p resence of complications associated with diabetes

m e l l i t u s• h i s t o ry of GDM or baby with birthweight over 4 kg• p resence of hypert e n s i o n• p resence of coro n a ry art e ry disease (CAD). [ G r a d e

D, consensus]

Preventing type 2 diabetes

P rospective cohort studies have identified historical,physical and biochemical variables that are associatedwith subsequent type 2 diabetes. These variables includeolder age, certain ethnic backgrounds, obesity (especiallycentral obesity), physical inactivity, a history of GDM,o v e rt coro n a ry art e ry disease, high fasting insulin levels

and IGT.6 4 – 6 6 Randomized studies testing behaviouralmodification and sulfonylureas in the prevention of type2 diabetes in people with IGT have followed these obser-v a t i o n s .6 7 – 7 0 To date, no effective treatments have beenidentified, with the exception of a program of diet ande x e rcise that yielded a clinically significant absolute riskreduction (about 25%) in the rate of diabetes over 6 yearsin a trial conducted in Da Qing, China.6 9

A large, randomized trial of behaviour modification(Diabetes Prevention Trial) being carried out by theNational Institutes of Health should confirm and extendthe generalizability of the Da Qing study.6 9 In the mean-time, in view of the promising results of that study and theaccepted value of weight control, diet and exercise in re d u c-ing cardiovascular risk, these activities should be pro m o t e d .This recommendation can be made irrespective of one’srisk for type 2 diabetes, including risk according to labora-t o ry parameters. Ongoing preventive trials will also assessthe efficacy and safety of other interventions includingintensified lifestyle change, metformin, troglitazone anda c a r b o s e .6 5 , 6 6 , 7 1 , 7 2 H o w e v e r, until these trials are completed,the use of pharmacologic treatments to prevent type 2 dia-betes remains experimental.

Recommendation

1 7 . In those at increased risk, a program of weight contro lt h rough diet and regular exercise is recommended andmay prevent type 2 diabetes. [Grade B, Level 16 9]

Preventing type 1 diabetes

The common form of type 1 diabetes is marked byimmune-mediated loss of pancreatic beta-cells. Thisp rocess is incited by an interaction between genetic ande n v i ronmental factors. During the asymptomatic phase,ongoing autoimmune destruction of the pancreatic beta-cells occurs. This can be identified reliably in first-degre erelatives by screening for immune abnormalities, such asislet-cell antibodies, and later by metabolic abnorm a l i t i e s ,namely reduced first-phase insulin secretion measured byan intravenous glucose tolerance test.

Two strategies to p re v e n tthe disease are, there f o re, pos-sible: altering environmental factors in people who aregenetically at risk (primary pre v e n t i o n )7 3 or modifying theimmune process in people with subclinical beta-cell lossidentified by positive screening tests (secondary pre v e n-t i o n ) .7 4 , 7 5 Randomized trials of primary prevention (i.e.,removal of cow’s milk protein from infant feeds) and sec-o n d a ry prevention (i.e., nicotinamide, oral insulin and par-enteral insulin) have been initiated. However, at present nop reventive measures for the disease are known to be eff e c-

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S8 JAMC • 20 OCT. 1998; 159 (8 Suppl)

tive and safe. In the case of primary prevention, thes t rength of evidence for a causal link between early expo-s u re to cow’s milk protein and subsequent type 1 diabetes isnot adequate to recommend that cow’s milk be ro u t i n e l yp roscribed from infant feeds (although breast feeding canbe recommended given its other benefits).

Clinically important benefits of screening for pro d ro-mal type 1 diabetes are not established, and such scre e n-ing carries the potential for negative psychosocial eff e c t s( s p e c i f i c a l l y, informing otherwise well people that they areat increased risk for a debilitating chronic disease may dom o re harm than good).

Recommendation

1 8 . Attempts to prevent type 1 diabetes — either bymanipulating environmental factors or by treating peo-ple at high risk — are experimental and should be con-fined to formal re s e a rch projects. [Grade D, consensus]

M a n a g e m e n t

The primary goal of therapy is to maintain the person’shealth in the broad sense of the word. Clearly, avoidanceof acute and long-term complications is a major concern .In addition, the person’s quality of life and overall sense ofwell-being are an integral part of management. Becausev i rtually every aspect of daily life may be affected by man-agement, it must always be re m e m b e red that the personwith diabetes is the key member of the DHC team. Formost people with diabetes, improving metabolic contro lwill prevent the onset or delay the pro g ression of long-t e rm complications. Depending on the type of diabetesand the therapy re q u i red, this objective may be more orless difficult to achieve without acute adverse effects. Themetabolic goals of treatment must, there f o re, be tailore dto the individual person and include consideration of thefamily and other psychosocial factors.

Examination and assessment

At the first visit of a person with newly or previously diag-nosed diabetes, the primary care physician should conduct ac o m p rehensive medical interv i e w, focusing on the natureand extent of diabetes symptoms. A complete medical histo-ry should be obtained with special emphasis on potential riskfactors for chronic disease. The information outlined inTables 6 to 10 may have to be obtained in stages, but it isessential for comprehensive diabetes management. If dia-betes has been diagnosed pre v i o u s l y, information should besought on a number of items, as indicated in Table 7.

A comprehensive physical examination should be per-

f o rmed, with special attention to systems affected by dia-betes. Laboratory investigations, in addition to glycatedhemoglobin and plasma glucose levels (to verify the accu-racy of self-monitoring and assess immediate glycemicstatus), should be carried out (Tables 9 and 10). Thisi n f o rmation forms the basis for a long-term care plan.

Diabetes is a chronic disease, and those with diabetesre q u i re regular medical assessment and laboratory testingto ensure optimal health. Some newly diagnosed peoplewith diabetes may re q u i re daily visits, whereas others couldre q u i re weekly or monthly visits until target goals formetabolic control are achieved. There a f t e r, all people withdiabetes should be followed every 2 to 4 months, althoughm o re frequent visits should be scheduled if indicated.

Targets for metabolic control

T h e re is strong evidence that decreasing blood glucose


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S9

Risk factors • Hypertension, dyslipidemia, central obesity andcigarette smoking

Social factors • Family dynamics, education, employment,lifestyle, coping skills

Drug history • Current medications, ethanol and possible druginteractions

*Hirsutism, obesity and fertility are statistically associated with increased risk for diabetes.

Symptoms • Onset and progression of symptoms ofhyperglycemia

• Symptoms of acute and long-termcomplications of diabetes (e.g., ophthalmologic,renal, cardiovascular, neurologic, skin and footproblems)

Past history • Endocrine disorders• Infections• Cardiovascular disease• Surgery (e.g., pancreatic)• Obstetric (if relevant)

Familyhistory

• Diabetes mellitus• Cardiovascular disease• Dyslipidemia• Hypertension, renal disease• Syndrome of insulin resistance (metabolic

syndrome)• Infertility, hirsutism*• Autoimmune diseases

Functionalinquiry

• Status of organ systems to determine othermedical disorders

• Eating habits (e.g., food choices, meal plans,meal timing, ethnic and cultural influences)

• Weight history, especially recent changes• Level of physical activity and limiting factors

(i.e., type, duration, intensity, frequency andtime of day of exercise)

• Risk factors for diabetes (e.g., family history,obesity, previous gestational diabetes)

Table 6: History to be taken during initial visits

levels toward the normal range reduces the frequency ofm i c rovascular complications7 6 , 7 7 and that improving lipidlevels reduces the frequency of CAD.7 8 N e v e rtheless, thelevels re q u i red to maximize these benefits, while keepingside effects to a minimum, remain subject to debate.

Glucose levels

The target glucose levels defined in Table 11 apply to

most adults and adolescents with diabetes mellitus. “Ideallevels” are levels within the normal range for people with-out diabetes. This level of glucose control may be attainableearly after diabetes onset in those managed with diet ther-apy but rarely in those requiring pharmacologic therapy(attained in less than 5% of the intensive therapy group ofthe Diabetes Control and Complications Trial [DCCT]7 7) .

“Optimal levels” are those that approach the norm a lrange and are associated with a low risk of developingc h ronic complications of diabetes. However, these levelsmay be impossible to attain in some people withouts e v e re side effects (e.g., hypoglycemia, decreased qualityof life) and difficult to obtain in many (in the DCCT,they were attained in fewer than 50% of people in theintensive therapy gro u p7 7) .

“Suboptimal glucose levels” attainable in the majorityof people with diabetes (90% of subjects in the intensivetherapy group in the DCCT7 7), range between 7.1 and 10mmol/L before a meal and between 11.1 and 14 mmol/Lafter a meal. However, most people with diabetes shouldstrive to lower glucose levels further toward optimal lev-els. For certain people (e.g., those under age 5, those withhypoglycemic unawareness or those with a short lifeexpectancy), this “suboptimal” level of glucose contro lmay be the best that is safely attainable.

“Inadequate glucose levels” are associated with acutesymptoms of hyperglycemia and a markedly incre a s e drisk of chronic complications and re q u i re re a s s e s s m e n tand readjustment of therapy.

Lipid levels

The relation between lipid levels and CAD is dis-cussed in the complications section. Ta rget lipid levels forthe prevention of CAD in people with diabetes are simi-lar to those for people without diabetes. Table 12 shows

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S1 0 JAMC • 20 OCT. 1998; 159 (8 Suppl)

Cardiovascular system Signs of congestive heart failure, pulses, bruits

Abdomen Organomegaly

General Height, weight, waist circumference (central obesity), BMI,* blood pressure (lying and standing), pulse

Genitourinary system Rule out fungal infections

Head and neck Eyes (pupillary reactions, extraocular movements, lens opacities and fundi), oral cavity (hygiene and caries), thyroidassessment

Musculoskeletal system Foot inspections, signs of limited joint mobility and arthropathy of the hands, colour and temperature

Central nervous system Routine evaluation for dysesthesias, change in proprioception, vibration, light touch (monofilament) and reflexes.Evaluation for autonomic neuropathy, if appropriate

Skin Inspection for cutaneous infections, problems with injection sites and signs of dyslipidemias

Chest Routine

*BMI = body mass index (body weight in kg divided by height in m2).

Table 8: Initial and follow-up physical examination

Hypoglycemia • Awareness, symptoms, frequency, time ofoccurrence, severity, precipitating causes,treatment and prevention

Social andpsychologicalfactors

• Support of family and friends• Economic abilities• Medical insurance• Medic alert

Lifestyle • Details of nutrition counselling, mealplans, adherence to prescribed mealplans, ethnic and cultural influences andweight changes

• Diabetes education received in the past(location and level of program), currentunderstanding of diabetes and itsmanagement

• Level of physical activity (i.e., type,duration, intensity, frequency and time ofday of exercise)

Monitoring • Method used and technique• Frequency, timing in relation to meals,

records• Quality control of meter (correlation with

laboratory)

Antihyperglycemicmedications

• Oral agents (type, dose, compliance), anyadjustment in response to monitoring

• Insulin (type, source, dose, injectionsites), understanding of dose adjustmentsin response to food, activity

Table 7: Directed history for diabetes to be obtained at initial andfollow-up visits

these targets and also acknowledges the fact that diabetesitself is a potent risk factor for CAD in both men andwomen after age 30. Thus, a 35-year-old man with dia-betes already has 2 key risk factors and an associated 10-year risk of CAD of 10% to 20%.7 9

Monitoring blood glucose control

The ability of people with diabetes to monitor dailychanges in blood glucose has markedly improved the abil-ity to control glucose levels. It permits recognition of lowlevels of blood sugars before major problems occur8 0 , 8 1 a n dallows people to assess the effects of diet, exercise andchanges in treatment regimens. The person with diabetes,in consultation with health professionals, should decideon the frequency of blood glucose measurements, takinginto account the benefits of monitoring and the cost andpain associated with the pro c e d u re .8 2 Many people tre a t e dt h rough diet or with oral agents benefit from the assess-ment of fasting and postmeal testing. People with type 1

diabetes often use premeal and bedtime tests, as well asi n t e rmittent postmeal testing to adjust their insulin doses.

Optimal use of blood glucose self-monitoring re q u i re sa periodic (at least annually) verification of accuracy. Thelevel measured in capillary blood using a meter should dif-fer by less than 15% from a simultaneous laboratory mea-s u rement of a fasting venous blood sample.8 3 Testing forglycated hemoglobin should be perf o rmed periodically toassess overall glucose control, as it reflects glucose contro lover the preceding 2 to 4 months. If discordance in theassessment of the glucose control is apparent betweenself-monitoring of blood glucose at home and the HbA1cm e a s u rement, despite verified accuracy of the meter, theuse of memory-equipped meters should be considere d .Supplemental checking of urine for ketones and moref requent monitoring of glucose level may be re q u i red inc e rtain situations, such as during pregnancy and in peoplewith type 1 diabetes during interc u rrent illness or whenthe blood glucose level is consistently over 15 mmol/L.8 2

Recommendations

1 9 . Glycated hemoglobin should be measured every 3 to4 months in all patients taking insulin and at leaste v e ry 6 months in people on nutrition therapy or oralhypoglycemic agents. [Grade D, consensus]

2 0 . Self-monitoring of blood glucose level is an e s s e n t i a lcomponent of the therapeutic plan of• all people with type 1 diabetes [Grade B, Level 28 4]• all pregnant women with pre-existing diabetes or

GDM [Grade B, Level 18 5]• all insulin-treated people with type 2 diabetes.

[Grade D, consensus]2 1 . Self-monitoring of blood glucose level is an i n t e g r a l

component of the therapeutic plan for the majority ofpeople with type 2 diabetes treated with oral hypo-glycemic agents. It may be useful for people with type


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S1 1

ECG = electrocardiogram, FPG = fasting plasma glucose, HDL = high-density lipoproteins, LDL = low-density lipoproteins, TG = triglyceride.

Routine clinical care • Routine visit at 2–4 mo with directed history for diabetes (Table 7)• Blood pressure, foot examination at each visit• Evaluation of progress toward reduction of risks of long-term complications• Adjustment of treatment plans

Glycemic control • Glycated hemoglobin every 2–4 mo• Laboratory–meter glucose correlation at least annually• FPG level (preferred for correlation), as needed

Complication and risk evaluation • Fasting lipid profile including total, HDL, calculated LDL cholesterol and TG levels annually• Dipstick urinalysis to screen for gross proteinuria:

—if negative, microalbuminuria screening with a random daytime urinary albumin: creatinine ratioyearly in type 2 and yearly after 5 yr of postpubertal type 1 diabetes

—if positive, a 24-h urine test for endogenous creatinine clearance rate and microalbuminuria every6–12 mo

• Resting or exercise ECG if appropriate (age >35 yr)

Table 10: Clinical aspects to be determined during follow-up visits

Diabetes knowledge • Knowledge of value of glucose control• Hypoglycemia (prevention, recognition

and treatment)• Determination of individual target goals• Appreciation of lifestyle considerations• Recognition of further educational or

motivational needs

Nutritional andphysical activitycounselling

• Dietitian visits• Goals for lifestyle change

Monitoring • Frequency of testing• Meter knowledge and laboratory

correlation

Medicationcounselling (oralagents and/or insulin)

• Method of administration• Dosage adjustments

Table 9: Management plan to be discussed during initial visits

2 diabetes controlled by diet therapy alone. [Grade D,c o n s e n s u s ]

2 2 . To ensure optimal self-monitoring of blood glucoselevel, the person with diabetes must be educated onthe use of the glucose meter [Grade A, Level 18 6], inter-p retation of the results and (where possible) how tomodify treatment according to blood glucose levels.[Grade D, Level 58 7]

Metabolic thera py for type 1 and type 2 diabetes

In people with type 1 diabetes, glucose control willdepend on coordination of insulin doses, food intake andphysical activity. In those with type 2 diabetes, deteriorationof control over the disease over time is common and is asso-ciated with pro g ressive deterioration of beta-cell functionthat occurs independently of the initial therapeutica p p roach chosen.8 8 , 8 9 T h e re f o re, it can be expected thattherapy for people with diabetes will have to be pro g re s-sively augmented over time. If the individually determ i n e dt a rget levels for people with type 2 diabetes have not been attainedwithin 2 to 4 months, the next level of therapy should be intro -duced, as indicated in the stepwise approach outlined in Figure 1.

Nutritional approaches

Nutrition is often said to be the cornerstone of diabetesc a re, but it is a controversial and complex topic. The fol-lowing is not intended to be a complete discussion of themany issues involved, but merely to highlight some of thegeneral principles and recommendations of the CDA. Adetailed review of the nutritional management of diabetes isbeing pre p a red by CDA’s National Nutrition Committee.

E v e ryone with diabetes should receive individualadvice on nutrition and, whenever and wherever possible,they should be re f e rred to re g i s t e red dietitians who willassess their current intake and individual nutritionalneeds. In nutrition counselling, a number of factors mustbe considered to empower people with diabetes to achievet reatment goals. These factors are type of diabetes,lifestyle, socioeconomic issues, presence of obesity, pro-g ression of beta-cell dysfunction, type of treatment, per-sonal pre f e rences and the nature of any complications.

The dietitian, in cooperation with the DHC team, willp rovide education and development of skills to pro m o t ehealthy eating habits, as well as continuing support asn e c e s s a ry through follow-up appointments. Nutrition

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S1 2 JAMC • 20 OCT. 1998; 159 (8 Suppl)

Diabetes and 1 other risk factor 10–20

Diabetes and no other risk factor 0–10

CAD = coronary artery disease, HDL = high-density lipoprotein, LDL = low-density lipoprotein, TG = triglycerides.*Major risk factors: family history of premature CAD, smoking, hypertension, low HDL (≤0.9 mmol/L) and age over 30 yr in both men and women†All 3 target values must be achieved.Source: Adapted from the 1998 Canadian guidelines by the Working Group on Hypercholesterolemia and Other Dyslipidemias, 79 by including the presence of diabetes as arisk factor.

<3.0

<2.0

<2.0

<2.0

TG;mmol/LRisk factors*

10-yr risk;%

<5

<4.0

Diabetes and either CAD or 3 or more other risk factors >40

<3.5

<2.5

Diabetes and 2 other risk factors 20–40

LDL cholesterol;mmol/L

Target lipid levels†

<7

<6

<5

<4

Total:HDLcholesterol ratio

Table 12: Evaluation of plasma lipid levels in people with diabetes

Glucose level 1–2 h after meal(mmol/L)

4.4–7

Hb = hemoglobin.*These levels are likely related to minimal long-term complications but may be impossible to achieve in most patients with type 1 diabetes with current therapies. †Attainable in the majority of people with diabetes but may not be adequate to prevent complications.‡These levels are related to a markedly increased risk of long-term complications, requiring a reassessment and readjustment of therapy (see specific recommendations).

Level

Ideal (normal nondiabetic)

5.0–11

Glycated Hb (% of upper limit) e.g., HbA1c assay

≤100 (0.04–0.06)

4–7

≤115 (< 0.07)

Fasting or premeal glucose level(mmol/L)

3.8–6.1

Optimal*(target goal)

11.1–14

7.1–10

116–140 (0.07–0.084)

Suboptimal† (action may be required)

Table 11: Levels of glucose control for adults and adolescents with diabetes mellitus

>14

>10

>140 (> 0.084)

Inadequate‡(action required)

counselling should be an ongoing process, with a step-wise increase in the complexity of the information givento the patient. Other members of the DHC team should

discuss and re i n f o rce dietary strategies with the personwith diabetes.

In type 2 diabetes, nutritional approaches are oriented


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S1 3

Fig. 1: A stepwise approach to type 2 diabetes. *As of September 1998, troglitazone was not yet marketed in Canada.

Nonpharmacologictherapy

Lifestyle modifications:Nutrition therapy (consultation with a dietitian)Physical activityAvoidance of smoking

Education:Teach diabetes self-care, including self-monitoring

of blood glucose level

Oral agent monotherapy(alpha-glucosidase inhibitor,biguanides, sulfonylurea)

Choice of agent should be tailored to the inidividual: If FPG >10 mmol/L, use sulfonylurea or

biguanides. Biguanides are associated with less weight gain

and lower frequency of hypoglycemia thansulfonylurea, but gastrointestinal side effectsmay be a limiting factor.

In the elderly, initiate at a lower dose, and choiceof agent may differ.

If there is renal or hepatic failure biguanides arecontraindicated.

Oral combinationtherapy

Agent or agents from other classes may be addeduntil the maximum dose of an agent of each class isreached.

Bedtime insulin± oral agents*

When insulin therapy is initiated, theconcomitant use of oral agents is anacceptable option. When insulintherapy is added to oral agents, it maybe in the form of a single injection ofintermediate-acting insulin at bedtime.This approach may result in betterglucose control with a smaller insulindose and may induce less weight gainthan the use of insulin alone.

Insulininjections, 1–4/day

Once other modes of therapy nolonger work, insulin doses(frequently high) and the number ofinjections (2-4) should be adjustedto achieve target glucose levels. Onoccasion, oral agents may be addedto the insulin regimen: acarbose,metformin or troglitazone.

If, at any point, thepatient becomesmetabolicallydecompensated(symptomatichyperglycemia andketosis)

If individualized goals for glucoseare not ach i e ved within 2–4

months, reassess lifestylei n t e r ventions to maximize benefits.

A dvance to next level of thera py.







Stepwise Approach to Type 2 Diabetes

t o w a rd improving glucose and lipid levels through dietmodification and weight loss when appro p r i a t e .9 0 If weightreduction is needed, it should be attempted gradually (0.25to 1.0 kg/wk). In type 1 diabetes, the major eff o rts are dire c t-ed toward coordination of food intake (particularly carbo-hydrates) and insulin dosages to improve glycemic contro l .

Recommendations

2 3 . All people with diabetes should receive individualadvice on nutrition from a re g i s t e red dietitian. [ G r a d eD, consensus]

2 4 . In obese people with type 2 diabetes, diet therapy aswell as lifestyle changes incorporating increased phys-ical activity should be the initial therapy, as this canresult in improved metabolic control and weight loss.[Grade B, Level 19 1]

2 5 . Nutritional recommendations for people with diabetesa re the same as those of Health and We l f a re Canadafor the general population. This includes choosing avariety of foods from the 4 food groups (grain pro d-ucts, vegetables and fruits, milk products and meat anda l t e rnatives), attaining a healthy body weight, decre a s-ing saturated fat intake to less than 10% of calories andhaving an adequate intake of carbohydrate, pro t e i n ,vitamins and minerals. The distribution of nutrientsmay be tailored to the individual patient depending onneeds and personal pre f e rences. Meal-planning, usinga p p roximately 55% carbohydrate and 30% fat contentoften serves as a starting point in the development ofspecific recommendations. [Grade D, consensus]

2 6 .S u c rose and sucrose-containing foods can be substi-tuted for other carbohydrates as part of mixed meals,up to a maximum of 10% of calories, provided ade-quate control of blood glucose and lipids is main-t a i n e d .9 2 [Grade B, Level 29 3]

Physical activity and exercise

An active lifestyle promotes cardiovascular fitness andw e l l - b e i n g ,9 4 i n c reased insulin sensitivity, lower bloodp re s s u re and a healthy lipoprotein profile in all peoplewith diabetes. A consistent, stepwise increase in physicalactivity may also improve glycemic control and re d u c ethe need for medications in people with type 2 diabetes.9 5

Knowledge of the acute effects of exercise is mandatoryfor any person treated with insulin. Unless considerableh y p e rglycemia (i.e., >15 mmol/L) is present, low to moder-ate intensity exercise lowers glucose levels both during andafter the activity, increasing the risk of a hypoglycemicepisode. Conversely, intense exercise systematically raisesglucose levels, both during the activity and for variable dura-

tions afterw a rd, and can lead to pro g ressive hyperg l y c e m i a(and even ketosis in people with type 1 diabetes), part i c u l a r-ly in those who are hyperglycemic before exerc i s i n g .

These effects on glucose levels can be moderated byaltering diet, insulin and the type and timing of exerc i s e .Systematic self-monitoring of glucose level before, dur-ing and e s p e c i a l l yfor many hours after exercise is, there-f o re, important for establishing the patient’s response toe x e rcise and guiding the appropriate management ofe x e rcise. In patients with type 1 diabetes, the use of inten-sive diabetes management regimens with either multipledaily injections or continuous subcutaneous insulin infu-sion (CSII) provides additional flexibility in appro p r i a t e-ly modifying the insulin dose for exerc i s e .9 6 , 9 7

F i n a l l y, the advantages of increased activity levels mustbe balanced against the risks.9 8 For example, patients withm a c roangiopathy are susceptible to cardiac or otherischemic events and to cardiac arrhythmias; patients withp roliferative retinopathy are at risk for vitreous hemor-rhage; and patients with neuropathy are susceptible tolower extremity (particularly foot) injuries.

Recommendations

2 7 . A stepwise increase in physical activity that is integrat-ed into the person’s lifestyle should be part of the ther-apeutic plan for everyone with type 2 diabetes who isable to increase activity. It should be prescribed withspecific modifications for people with known occlusivevascular disease (or at high risk of subclinical disease),significant sensory polyneuropathy or advancedm i c rovascular complications. [Grade D, consensus]

2 8 . In anyone treated with insulin, re c o m m e n d a t i o n sre g a rding alterations of diet, insulin regimen, injec-tion sites and self-monitoring should be appro p r i a t efor the general level of physical activity or specifictypes of exercise undertaken. Oral agent doses mayneed to be decreased. [Grade D, consensus]

2 9 . The initiation of a vigorous exercise program re q u i re san appropriate, detailed history and physical examina-tion and specific laboratory investigations (e.g., exer-c i s e - s t ress cardiography in those over 35 years of age).[Grade D, consensus]

30 . General advice re g a rding physical activity for every-one with diabetes includes:• use proper footwear, inspect both feet daily and

after each exercise session, if indicated, and useadequate protective devices

• avoid exercising during any period of poor meta-bolic contro l

• ingest rapidly absorbed carbohydrate if pre - e x e r-cise glucose level is under 5 mmol/L

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S1 4 JAMC • 20 OCT. 1998; 159 (8 Suppl)

• avoid exercise in extreme hot or cold conditions.• administer insulin into a site away from the most

actively exercising extremities. [Grade D, consensus]

Oral antihyperglycemic agents

C u rrent approved categories of oral agents include sul-f o n y l u reas, biguanides, alpha-glucosidase inhibitors andthiazolidinediones. (As of September 1998, thiazolidine-diones had been approved but not yet marketed in Canada.)S u l f o n y l u reas (acetohexamide, chlorpropamide, glyburide,gliclazide, tolbutamide, tolazamide) stimulate pancre a t i cinsulin release. Biguanides (metformin) primarily decre a s ehepatic glucose production and may also delay glucoseabsorption and enhance insulin-mediated glucose uptake.Alpha-glucosidase inhibitors (acarbose) slow absorption ofs t a rch and sucrose in the gut. Thiazolidinediones (tro g l i t a-zone) potentiate insulin action, although the full range ofmechanisms is not fully understood. Sulfonylureas mayi n c rease the risk of hypoglycemia; this effect is not seenwith metformin, acarbose or troglitazone unless they arecombined with insulin or a sulfonylurea. Specific detailsre g a rding the actions, metabolism and side effects of thesed rugs can be found in a number of review art i c l e s .9 9 – 1 0 9

All people with type 1 diabetes re q u i re insulin therapyto prevent hyperglycemia and life-threatening ketoacido-sis. Although type 1 diabetes is usually acute, some adultswith newly developed type 1 diabetes may present with aslowly pro g ressive disease that could be misdiagnosed astype 2 diabetes; indeed it may even respond initially tooral agents. However, if these patients are started on oralagents instead of insulin, they will be at risk of decom-pensating relatively rapidly and developing ketoacidosisas their pancreas stops producing insulin. There f o re, thepossibility that an adult with new-onset diabetes has type1 diabetes (particularly if that person is not obese) and,thus, re q u i res insulin must be carefully considere d .

Recommendations

3 1 . When changes in lifestyle fail to result in achievementof target glucose levels in 2 to 4 months or if symp-toms or severe hyperglycemia persist, oral hypo-glycemic agents should be initiated. If lifestylechanges and oral agents are unsuccessful or in thep resence of signs of deterioration with significantsymptoms of hyperglycemia, the person must begininsulin therapy dire c t l y. [Grade A, Level 11 1 0]

3 2 . The initial oral agent used can be (in alphabeticalo rder) an alpha-glucosidase inhibitor, a biguanide ora sulfonylurea; the choice depends on the individual,taking into consideration the following points.

• For those with a high degree of hyperg l y c e m i a(FPG >10 mmol/L), metformin or a sulfonylure amay be chosen as a first agent. [Grade A, Level 11 1 0]

• M e t f o rmin is associated with less weight gain andless hypoglycemia than sulfonylureas [Grade B,Level 11 1 0 , 1 1 1], but gastrointestinal side effects maybe a limiting factor.

• M e t f o rmin is contraindicated in the presence ofsignificant renal or hepatic insuff i c i e n c y, as it maycause lactic acidosis. [Grade D, consensus]

• Acarbose may be added to diet, metformin or sul-f o n y l u rea therapy to improve glucose contro l[Grade A, Level 11 1 2], but gastrointestinal sidee ffects may be a limiting factor.

3 3 . If target glucose levels are not attainable with a singleagent, an agents or agents from other classes may beadded, until the maximum dose of an agent of each classis reached. [Grade A, Level 11 1 2 for the addition of acar-bose to other oral agents; Grade A, Level 11 1 1 for theaddition of metformin to sulfonylurea; Grade D, Level48 8 , 1 0 5 for the addition of sulfonylurea to other agents]

Insulin therapy

Insulin is available in human, analogue and animal for-mulations. Human insulin is associated with less anti-insulin antibody formation than animal insulin1 1 3 a n dshould be used for people initiating insulin therapy. Insulinregimens should be adapted to an individual’s tre a t m e n tgoals, lifestyle, diet, age, general health, motivation, capac-ity for hypoglycemia awareness and self-management, andsocial and financial circumstances. Anyone beginninginsulin therapy must receive initial and ongoing educationthat includes comprehensive information on its care anduse, recognition and treatment of hypoglycemia, manage-ment of sick days, and adjustments for food intake andphysical activity. If the person with diabetes is not alre a d yself-monitoring blood glucose, he or she should learn orreview the pro c e d u re s .

Insulin preparations can be classified according totheir time of onset and duration; in ascending order theseinclude lispro, re g u l a r, NPH, lente and ultralente insulin.A variety of protocols using combinations of theseinsulins can successfully control glucose levels. The mostf requently used protocols include

• multiple daily injections (basal-bolus pro t o c o l :regular or lispro insulin before each meal, NPHor ultralente as the basal type)

• 2 injections per day (split-mixed protocol: mixtureof regular and NPH administered before bre a k f a s tand dinner)

• a single injection of NPH insulin at bedtime with


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S1 5

oral agents during the day (for patients with type2 diabetes only)

P remixed insulin preparations (mixtures of re g u l a rand NPH insulins in various pro p o rtions) are availableand may facilitate the use of the split-mixed pro t o c o l ,p a rticularly in the elderly. Insulin pen devices are gainingin popularity because of their greater ease of use.Intensive insulin therapy using a subcutaneous pump(CSII) is an alternative to multiple daily injections, pri-marily in patients with type 1 diabetes.1 1 4

Insulin use in type 1 diabetes

Insulin is essential for life in people with type 1 dia-betes. The associated significant beta-cell destru c t i o noccurs very quickly in the young and more slowly whenthe disease presents later in life.

As already noted, insulin is available in a number off o rmulations defined by their absorption rate, peak activ-ity and duration of action. Long-acting (ultralente) andi n t e rmediate-acting (NPH and lente) insulins are bestused as a background (basal) insulin, but may be used atmealtime. Short-acting insulins (regular and lispro) arerapidly absorbed and best used as mealtime (bolus)insulins. Combinations of these insulins and adjustmentof the time of their administration are re q u i red for opti-mal blood glucose contro l .

L i s p ro is a new insulin analogue that is absorbed morerapidly than regular insulin after subcutaneous injection.It results in lower postprandial glucose levels, fewer noc-t u rnal hypoglycemic events and improved quality of lifein some people.1 1 5 , 1 1 6 T h e re is no strong evidence that itcan result in lower HbA1c c o m p a red with regular insulin,except in those using pump therapy.1 1 7 It should be usedwith caution in the presence of gastro p a resis and shouldnot be combined with acarbose. At present, lispro insulinis not recommended during pre g n a n c y, as there arei n s u fficient data to support its safety.1 1 5 , 1 1 6

Recommendations

3 4 . Most people with type 1 diabetes should aim for opti-mal glucose levels to prevent or delay micro v a s c u l a rcomplications of diabetes. [Grade A, Level 17 7]

3 5 . To achieve target glucose levels, multiple daily injec-tions (3 or 4 per day) or the use of continuous subcu-taneous insulin infusion (CSII) as part of an intensi-fied diabetes management regimen are usuallyre q u i red. [Grade A, Level 17 7]

3 6 . Regular or lispro insulin, or both, can be used beforemeals in intensified therapy (multiple daily injectionsand CSII). Lispro has been associated with lower post-

prandial glucose levels and lower rates of hypoglycemiathan regular insulin. [Grade A, Level 17 7 , 1 1 5 , 1 1 6] Lispro isthe pre f e rred insulin for use in CSII. [Grade B, Level 21 1 7]

Insulin use in type 2 diabetes

Most people with type 2 diabetes will initially attainacceptable glucose control through diet and use of oralagents. Insulin therapy may be re q u i red temporarily dur-ing periods of illness or stress. Many others will becomere f r a c t o ry to diet and oral agents and will re q u i re insulinfor metabolic control. In these people, insulin doses (fre-quently high) and the number of injections (1–4) shouldbe adjusted to achieve target glucose levels.8 8 A combina-tion of insulin and oral agents may effectively contro lglucose levels.

Recommendations

3 7 . Intensive insulin therapy may prevent micro v a s c u l a rcomplications in people with type 2 diabetes. [ G r a d eB, Level 17 6]

3 8 . If individual treatment goals have not been re a c h e don a regimen that includes appropriate use of diet,e x e rcise and oral agents, then insulin therapy shouldbe initiated to improve glycemic control. [Grade A,Level 11 1 8]

3 9 . When insulin therapy is initiated, the concomitantuse of oral agents is an acceptable option. Wheninsulin therapy is added to oral agents, a single injec-tion of intermediate-acting insulin may be added atbedtime. [Grade B, Level 11 1 9] This approach mayresult in better glucose control with a smaller insulindose [Grade A, Level 1+1 2 0] and may induce less weightgain than with the use of insulin alone.

4 0 . Poor glucose control despite insulin therapy can bei m p roved by the addition of one of the following orala g e n t s :• acarbose [Grade A, Level 11 2 1]• m e t f o rmin [Grade B, Level 11 2 2]• t roglitazone [Grade A, Level 11 2 3]

On initiating troglitazone therapy, liver enzymesshould be evaluated due to potential, severe hepatic dys-function; evaluation should occur before therapy, month-ly for the first 8 months, bimonthly for the next 4 monthsand periodically there a f t e r. [Grade D, Level 51 2 4]

Diabetes in children and adolescents

Specific recommendations have been developed forc h i l d ren and adolescents because of considerations thata re relevant for this age gro u p .

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Type 1 diabetes

The insulin regimen and distribution of carbohy-drates in the meal plan must be flexible in children andadolescents to allow for normal growth and develop-ment while balancing the need for reasonable glycemicc o n t rol. Ongoing education of the child or adolescent isessential, to achieve age-appropriate knowledge andskills and eventual self-suff i c i e n c y. Intensive education,with ongoing re i n f o rcement re g a rding sick-day manage-ment and prevention of diabetic ketoacidosis, must bep rovided for all families.1 2 5 , 1 2 6 All parents must be taughtthe use of glucagon for severe hypoglycemia.1 2 7

Adolescents must receive ongoing counselling re g a rd i n gd i s o rd e red eating pattern s ,1 2 8 smoking, contraception,alcohol and drug abuse, and driving, as these activitiesrelate to diabetes care .

All children should be screened for associated autoim-mune diseases, such as hypothyroidism, by determ i n i n gt h y roid-stimulating hormone (TSH) level. Selected chil-d ren with poor growth, poor glycemic control or unpre-dictable, frequent hypoglycemia should be tested for celi-ac disease using antigliadin antibodies1 2 9 and forAddison`s disease by determining adenocort i c o t ro p i ch o rmone (ACTH) level.

Planning the transition from pediatric to adult dia-betes care must be undertaken with sensitivity to theneeds of the adolescent and recognition of the factorsthat predict noncompliance with medical follow-up.1 3 0 , 1 3 1

Recommendations

4 1 . The metabolic goals and therapeutic strategies foradolescents over 12 years of age are the same as thosefor adults. [Grade A, Level 17 7 , 1 3 2] The target HbA1c f o rp re p u b e rtal children is 120% to 140% of the upperlimit of normal with targets for glucose and HbA1cgraduated according to the child’s age. [Grade D, con -sensus] E x t reme caution is re q u i red to avoid hypo-glycemia in children under 5 years of age, because of thep e rmanent cognitive deficit that may occur in this ageg roup. [Grade D, Level 41 3 3 , 1 3 4]

4 2 . All children with diabetes should have access to anexperienced DHC team. The complex physical,developmental and emotional needs of children andtheir families re q u i re specialized care to ensure thebest long-term outcome. [Grade D, Level 41 2 6]

4 3 . In children and adolescents with new-onset diabetes,initial outpatient education and management shouldbe considered if appropriate personnel and a 24-htelephone consultation service are available in thec o m m u n i t y. [Grade C, Level 31 3 5]

Type 2 diabetes

Type 2 diabetes (as distinct from genetic maturity-onsetdiabetes of the young or MODY forms), occurs in specialg roups of children. Curre n t l y, it occurs in 1% to 2% ofc h i l d ren of Aboriginal, Hispanic or black origin and up to4% of adolescent girls. In Canada, type 2 diabetes has beenre p o rted in Aboriginal children aged 7 and older. Mostc h i l d ren are not symptomatic and are currently identifiedby screening programs in high-risk populations.

Due to the relatively low frequency and short history ofthis problem, which was recognized only in the 1980s, themost appropriate screening guidelines have not been devel-oped. However, owing to the devastating consequences ofearly-onset complications, it is prudent to consider scre e n-ing in Aboriginal children. The best management strategyfor this age group is unknown. Intensive programs toi n c rease physical activity and nutritional interventions havep roven beneficial in the summer camp setting and must beencouraged in the home and community. There are noc o n t rolled trials of safety or efficacy of oral agents or insulinfor type 2 diabetes in this age group (see “Diabetes inAboriginal people” for further discussion).

Diabetes in the elderly

Because the renal threshold for glucose increases withage, elderly people frequently do not have classic symp-toms of hyperglycemia (polyuria, polydypsia) until bloodglucose values are markedly elevated. When symptomsa re present, they are generally nonspecific (fatigue,d e p ression, failure to thrive).

A wide variety of factors affect the ability of elderlypeople to follow treatment regimens. Management plansmust account for limited abilities, comorbidities andpotentially limited lifespans.1 3 6 – 1 3 8 Although the interpre-tation of biologic status must be considered, “elderly” inthe present context refers to people over 70 years of age.

Recommendations

4 4 . The same glucose targets apply to otherwise healthyelderly as to younger people with diabetes. In peoplewith multiple comorbidity, the goal should be to avoidsymptoms of hyperglycemia and prevent hypoglycemia.[Grade D, consensus]Closer to normal glucose levels areassociated with a lower risk of complications in elderlypeople with type 2 diabetes. [Grade A, Level 11 3 6 , 1 3 8]

4 5 . Elderly people with diabetes should be re f e rred to aDHC team. Interd i s c i p l i n a ry interventions have beenshown to improve glycemic control in the elderly.[Grade B, Level 21 3 9 – 1 4 1]


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4 6 . In chronic care institutions, specific dietary re s t r i c-tions may not be useful in improving glycemic contro l .[Grade D, Level 41 4 2] The recommended distribution ofnutrients is as suggested for the general aging popula-tion. [Grade D, consensus]

4 7 . Moderate exercise is beneficial for elderly people withtype 2 diabetes; however, comorbid conditions mayp revent aerobic physical training [Grade D, Level 41 4 3] ,and any increase in activity levels may be difficult toachieve. [Grade D, consensus]

4 8 . In elderly people, sulfonylureas should be used withcaution because the risk of hypoglycemia incre a s e sexponentially with age. [Grade D, Level 51 4 4] In gener-al, initial doses should be half those for younger peo-ple, and doses should be increased more slowly.[Grade D, consensus]Gliclazide may be the pre f e rre ds u l f o n y l u rea, as it is associated with a reduced fre-quency of hypoglycemic events compared with gly-buride. [Grade A, Level 11 4 5]

4 9 . In elderly people, the use of premixed insulins as ana l t e rnative to mixing insulins may minimize dosagee rrors. [Grade B, Level 21 4 6]

Diabetes and pregnancy

C u rre n t l y, the major problems associated with excess glu-cose crossing the placenta in pregnancy include teratogenic-ity and metabolic and growth abnormalities in the fetus.L o n g - t e rm metabolic sequelae for women with GDM andthe offspring of women with any form of diabetes in pre g-nancy may also occur.1 4 7 , 1 4 8

Pre-existing diabetes

In the absence of pre p regnancy planning and care f u lfollow-up, maternal diabetes may be associated with ani n c reased risk of spontaneous abortion, perinatal mort a l-ity and perinatal morbidity. Congenital malform a t i o n scontinue to be the major cause of perinatal mortality indiabetic women and are 2 to 7 times more common thanin nondiabetic women.1 4 9

Both retinal and renal disease may become more severeduring pregnancy. Because significant backgroundretinopathy may lead to deterioration of vision, aff e c t e dwomen must have their eyes carefully monitored beforeand during pre g n a n c y. Similarly, women with significantp roteinuria before pregnancy are at risk for hypert e n s i o nduring pregnancy (with or without eclampsia), as well asworsened renal function after pre g n a n c y.

Thus, any woman planning a pregnancy should workwith a specialized DHC team to assess the level of glycemicc o n t rol and the status of microvascular complications,1 5 0

and to plan appropriate ongoing monitoring of glucose,blood pre s s u re and maternal and fetal status until delivery.Women taking oral hypoglycemic agents should discontin-ue them and initiate use of insulin before conception.

Recommendations

Before pregnancy

5 0 .P regnancy in women with diabetes should be care f u l-ly planned, preferably in consultation with a high-riskp re p regnancy clinic. [Grade C, Level 31 5 0]

5 1 . All women with diabetes should attempt to attain“ideal” blood glucose control (see Table 11). Glycatedhemoglobin (HbA1c) levels greater than 140% of theupper limit of normal nonpregnant values should beavoided as they are clearly associated with incre a s e drisk of spontaneous abortion and malform a t i o n s .[Grade B, Level 21 5 1]

5 2 . Both diabetic nephropathy and diabetic re t i n o p a t h ymay pro g ress during pregnancy and should be evaluat-ed and followed care f u l l y. [Grade B, Level 21 5 2 , 1 5 3] Wo m e nshould also be assessed for CAD. [Grade D, consensus]

During pregnancy

5 3 . All women with diabetes should aim for ideal glucoselevels without significant hypoglycemia. [Grade D,Level 51 5 4]

5 4 . Any woman on diet therapy alone who does notachieve target values should be started on insulin. Useof oral agents is not recommended. [Grade D, consensus]

5 5 . Ketosis should be avoided, especially during the thirdt r i m e s t e r. [Grade B, Level 21 5 5] Weight gain should bem o n i t o red, normal weight gain should be the goaland weight-reducing diets should be avoided. [ G r a d eD, consensus]

5 6 . Retinal examination should be perf o rmed re g u l a r l y, atleast once in the first trimester with subsequent fre-quency adjusted to the severity of the re t i n o p a t h y.[Grade B, Level 21 5 2]

Gestational diabetes mellitus

Gestational diabetes is glucose intolerance of vary i n gseverity detected or first recognized during pre g n a n c y. Itsp revalence varies widely according to the population stud-ied and criteria used for diagnosis; it often reflects thep revalence of diabetes in a given population. It is associat-ed with an increased risk of fetal macrosomia, neonatalhypoglycemia, hyperbilirubinemia, hypocalcemia andpolycythemia. Perinatal mortality is rare today in women

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with diagnosed GDM. The children of mothers withGDM may have an increased risk of childhood obesity anddiabetes as young adults.1 4 7 , 1 4 8 , 1 5 5 The recognition of GDMindicates an increased risk of future diabetes in the moth-er (primarily type 2). The basis for therapy is diet adjust-ment, monitoring of maternal and fetal well-being andglucose control. Use of insulin is appropriate if glucosec o n t rol is not attained with diet alone.1 5 6

Recommendations

5 7 . Women with GDM should receive dietary counsellingand carry out frequent FPG and postprandial glucosemonitoring. [Grade C, Level 35 9] The goals associatedwith the best neonatal outcome are an FPG level <5 . 3mmol/L [Grade C, Level 31 5 7], a 1-h postprandial glu-cose level <7.8 mmol/L [Grade A, Level 11 5 8] and a2hPG level <6.7 mmol/L. [Grade D, Level 35 9]

5 8 .D i e t a ry counselling should be provided to ensure awell-balanced diet, with a goal of achieving norm a lm a t e rnal glucose levels and normal weight gain in themother and the fetus. Because of the risk of ketone-mia, weight-reducing diets are not re c o m m e n d e d .[Grade D, consensus]

5 9 . FPG and postprandial glucose levels should be mon-i t o red. [Grade A, Level 11 5 8] If diet therapy does notresult in achievement of glucose target values, insulintherapy should be initiated. [Grade D, consensus]

6 0 . Regular and moderate exercise, particularly of theupper body, should be encouraged. [Grade A, Level 11 5 9]

6 1 . Women who have had GDM should be advised toachieve a healthy body weight and exercise re g u l a r l yp o s t p a rtum to reduce the risk of subsequent diabetes.[Grade D, consensus]

6 2 . Women who have had GDM are at high risk for sub-sequent diabetes or glucose intolerance. [Grade C,Level 31 6 0 , 1 6 1] An OGTT (75-g, 2-h) should be per-f o rmed 6 weeks to 6 months postpartum to rule outthe presence of glucose intolerance or diabetes.[Grade D, consensus]

Diabetes in Aboriginal people

Over the past 50 years, dramatic changes in lifestyle inAboriginal communities across North America have hada profound impact on the social, environmental andhealth status of this population. Although morbidityassociated with infectious diseases and starvation hasd e c reased, chronic diseases such as obesity, diabetes andc a rdiovascular disease have emerged. Type 2 diabetesmellitus is now recognized as a major health pro b l e mamong Aboriginal people. Indeed, recent population-

based epidemiologic surveys in Canada have re v e a l e dage-adjusted prevalence rates of 19% to 26%, which areamong the highest re p o rted rates in the world.1 6 2 , 1 6 3

Due to the relatively recent onset of this epidemic inAboriginal populations, complications associated withdiabetes are only beginning to emerge as significanthealth problems. There f o re, aggressive screening forCAD, neuro p a t h y, nephropathy and retinopathy shouldaccompany visits to physicians by Aboriginal peoplea c c o rding to the recommended practice guidelines.

Most Aboriginal communities are aware of diabetesand its many complications; the establishment of theNational Aboriginal Diabetes Association (NADA) in1996 reflects this. However, diabetes is often not a prior-ity for communities in which other important politicaland health issues predominate. According to some, dia-betes is a social disease or, more appro p r i a t e l y, a result ofsocial conditions. Geographic isolation, poor eating pat-t e rns, minimal physical activity, substance abuse, psy-chosocial issues and even absence of basic health care inisolated communities may be significant barriers to therecognition of diabetes as a priority.

Much of the responsibility for diabetes care in commu-nities lies with community health re p resentatives, who areusually overburdened with other duties. In some cases,community health re p resentatives are able to provide bet-ter care with more training, and a number of initiativesa c ross Canada are addressing this need. Expanded com-munity-based prevention programs are also re q u i re d .

Major challenges face health care professionals and pol-icymakers in terms of providing appropriate and practicaldiabetes screening and treatment programs to Aboriginalpopulations. Culturally appropriate community-basedi n t e rvention strategies must be developed by support i n gcommunity initiatives and providing technical and finan-cial re s o u rces. Cooperation and partnership with politicalleaders in grassroots organizations are essential elementsin the support of innovative strategies. Local input com-bined with the knowledge and experience of multidiscipli-n a ry teams is re q u i re d .

The major focus of this strategy should be primary pre-vention, and a number of such initiatives are under way1 6 4

(e.g., in Kahnawake, Que., and Sandy Lake, Ont.).P rograms aimed at schoolchildren and their parents arecritical for the prevention of diabetes in future genera-tions. In addition to prevention strategies, eff o rts toi m p rove metabolic control and assure regular surv e i l l a n c efor complications, are also needed. High-risk groups suchas children and women in the childbearing ages re q u i rep a rticular attention.1 6 5 – 1 6 8 Despite the significant chal-lenges that accompany the institution of such pro g r a m s ,the management and prevention of diabetes and associat-


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S1 9

ed complications in Aboriginal populations should be ahigh priority in health care planning and delivery.

At present there is no evidence that therapeutic strate-gies should differ from those used for the general popu-l a t i o n .

Recommendations

6 3 . Community-based screening programs based onmeasuring blood glucose levels should be establishedin Aboriginal communities. Urban people ofAboriginal origin should be screened for diabetes inp r i m a ry care settings. [Grade D, consensus]

6 4 .P r i m a ry prevention programs initiated by Aboriginalcommunities should be encouraged. [Grade D, consensus]

6 5 .T h e re must be recognition of, respect for and sensi-tivity re g a rding the unique language, culture and geo-graphic issues as they relate to diabetes care inAboriginal communities across Canada. [Grade D,c o n s e n s u s ]

C o m p l i c a t i o n s

Major acute complications of diabetes are hypo-glycemia and hyperglycemic crises including ketoacidosisand hyperg l y c e m i c - h y p e rosmolar states. A person withdiabetes experiencing an acute complication may bet reated in an ambulatory setting or re q u i re emerg e n c yadmission to a hospital ward or an intensive care unit.Once a patient has re c o v e red from such an episode,a p p ropriate education by the DHC team is necessary top revent re c u rre n c e s .

L o n g - t e rm complications may occur in both type 1 andtype 2 diabetes. These include macrovascular complica-tions (CAD, cere b rovascular disease, and peripheral vascu-lar disease) and microvascular complications (re t i n o p a t h y,n e p h ro p a t h y, neuropathy and foot pro b l e m s ) .

R e g u l a r, systematic surveillance for these acute andl o n g - t e rm complications is an integral component of com-p rehensive diabetes care. An organized and coord i n a t e da p p roach should be implemented for follow-up visits.

Retinopathy

Diabetic retinopathy is the major cause of adult blind-ness in North America and likely the most feared of thel o n g - t e rm complications. Diabetes is the sole or con-tributing cause of blindness in about 86% of the eyes ofpeople with type 1 diabetes, and in 33% of the eyes ofpeople with type 2 diabetes.1 6 9 P roliferative re t i n o p a t h yoccurs in 23% of patients with type 1 diabetes, 14% ofpeople with type 2 diabetes taking insulin and 3% of peo-

ple with type 2 diabetes not taking insulin;1 7 0 m a c u l a redema occurs in 11%, 15% and 4% of these gro u p s ,re s p e c t i v e l y.1 7 1 Patients with diabetes are also at incre a s e drisk of developing cataracts.1 7 2 Evidence for increased riskof primary open-angle glaucoma is conflicting.1 7 3 , 1 7 4

S c reening strategies for sight-threatening re t i n o p a t h y(i.e., proliferative retinopathy or macular edema) mustreflect diff e rences in the incidence and prevalence ofretinopathy in type 1 and type 2 diabetes.1 7 5 – 1 7 8

Development of diabetic retinopathy in children under10 years of age with type 1 diabetes is rare re g a rdless ofthe duration of diabetes.1 7 7 The prevalence rate incre a s e ssharply after 5 years duration of diabetes in postpubert a lpeople with type 1 diabetes.1 7 7 C o n v e r s e l y, re t i n o p a t h ymay be present in 21% of people soon after clinical diag-nosis of type 2 diabetes, but is vision-threatening in onlyabout 3%.1 7 1 , 1 7 3 – 1 7 6 I m p o rtant predictors of the pro g re s s i o nof retinopathy are longer duration of diabetes, higherlevel of glycated hemoglobin, more severe re t i n o p a t h y,higher blood pre s s u re, higher lipid levels and, in type 1diabetes, pre g n a n c y.1 5 2 , 1 7 5 – 1 8 0

The “gold standard” for assessing diabetic re t i n o p a t h yis 7-standard field, stereoscopic-colour fundus photogra-p h y.1 8 1 Seventy-nine per cent agreement in the detection ofp roliferative retinopathy can be achieved by fundus exam-ination by direct ophthalmoscopy through dilated pupilsc a rried out by highly trained personnel (re g a rdless of pro-fessional designation).1 8 2 Examinations by inexperiencedo b s e rvers or examinations through undilated pupils fail todetect proliferative retinopathy in about 50% of patientsand macular edema in all cases.1 8 3 , 1 8 4 Contact lens fundusb i o m i c roscopy by retinal specialists results in 81% agre e-ment in the detection of clinically significant maculare d e m a .1 8 5 The Early Treatment Diabetic RetinopathyS t u d y ’s final scale is the best means of categorizing theseverity of retinopathy and provides important pro g n o s t i ci n f o rm a t i o n .1 8 6

In type 1 diabetes, the onset of retinopathy can bedelayed or its pro g ression slowed by intensive insulint h e r a p y, with achievement of improved contro l .7 7 In type2 diabetes, epidemiologic studies show that hyper-glycemia is an independent risk factor for the incidenceand pro g ression of retinopathy; however, the risks andbenefits of insulin therapy have not been completelye s t a b l i s h e d .4 , 1 8 7

In both types of diabetes, elevated diastolic blood pre s-s u re is a risk factor for the development of maculare d e m a ,1 8 0 , 1 8 8 and elevated systolic blood pre s s u re is a riskfactor for loss of vision.1 8 9 People with elevated serum cho-l e s t e rol, low-density lipoprotein (LDL) cholesterol ortriglyceride levels are more likely to have or develop re t i-nal hard exudate, which can be associated with risk of loss

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of vision independent of the extent of macular edema.1 7 9

Retinopathy can become worse during pre g n a n c y, inde-pendent of higher levels of glycated hemoglobin.1 5 2

Focal/grid laser treatment for clinically significantmacular edema reduces loss of vision by 50%.1 9 0 F u l limplementation of scatter laser treatment and vitre c t o m yreduces legal blindness by 90% in patients with severen o n p roliferative or proliferative re t i n o p a t h y.1 9 1 – 1 9 3 In type1 diabetes, early vitrectomy perf o rmed for nonclearing,s e v e re vitreous hemorrhage provides a better chance ofvisual re c o v e ry than if treatment is deferred. In type 2diabetes, early vitrectomy has no such benefit and carr i e sa 2-fold higher overall risk of serious untoward eventsthan if deferred for 1 year.1 9 4 In people with type 1 or type2 diabetes, early vitrectomy for advanced active pro l i f e r-ative retinopathy unresponsive to laser tre a t m e n tachieves significant re c o v e ry of visual acuity compare dwith conventional management.1 9 5

Recommendations

6 6 . The development and pro g ression of re t i n o p a t h ymay be prevented through intensive diabetes man-agement achieving optimal metabolic control [ G r a d eA Level 17 6 , 7 7] and treatment of elevated blood pre s s u reor lipid levels. [Grade D, Level 41 7 9 , 1 8 8 , 1 8 9]

6 7 . In people with diabetes, screening for sight-thre a t e n i n gretinopathy should be perf o rmed by experienced pro-fessionals highly trained in direct ophthalmoscopyt h rough dilated pupils or by retinal specialists. [Grade A,Level 1,1 8 2 , 1 8 3 , 1 8 5 Level 21 8 4]

6 8 .S c reening and evaluation for retinopathy should bep e rf o rmed annually 5 years after the onset of diabetesin postpubertal patients (age 15 years or over) withtype 1 diabetes and in everyone with type 2 diabetesat the time of diagnosis. [Grade A, Level 11 7 5] Thei n t e rval for follow-up assessments should be tailore dto the severity of the re t i n o p a t h y. In those with type 2diabetes who have no or minimal re t i n o p a t h y, therecommended interval is 2 years and should notexceed 4 years. [Grade A, Level 11 7 6 , 1 7 8]

6 9 . Women with type 1 diabetes should have an oph-thalmic assessment before conception in a plannedp regnancy and in the first trimester of pregnancy andbe followed up as needed during pre g n a n c y. [Grade A,Level 11 5 2]

7 0 .P roliferative or severe nonproliferative re t i n o p a t h ynecessitates re f e rral to an ophthalmologist or re t i n a lspecialist with access to surgical facilities. [Grade A,Level 11 9 0 – 1 9 5]

7 1 . Visually disabled people should undergo low-visionevaluation and rehabilitation. [Grade D, consensus]

Nephropathy

Diabetic nephropathy is the number one cause of end-stage renal failure in Canada and the western world.1 9 6 – 1 9 8

The costs of dialysis and renal transplantation are high.In addition, people with diabetes and end-stage renal fail-u re have high morbidity and mortality rates due to car-diovascular disease.1 9 6 – 2 0 3

The focus of treatment of diabetic nephropathy is onp revention through early screening and detection. Elevatedm i c roalbuminuria is the earliest reliable and clinicallydetectable sign of pro g ressive nephropathy in both type 1and 2 diabetes.1 9 7 , 2 0 4 – 2 1 0 S c reening for increased micro a l b u-minuria is necessary 5 years after the onset of diabetes forpeople over 15 years of age with type 1 diabetes and at thetime of diagnosis for everyone with type 2 diabetes to detectp ro g ressive nephropathy at the earliest stage.2 1 1 – 2 1 5 O n c en e p h ropathy is diagnosed, intensive glucose con-t ro l ,7 6 , 7 7 , 2 1 6 – 2 2 4 inhibition of angiotensin-converting enzyme( A C E ) ,2 2 5 – 2 2 9 n o rmalization of blood pre s s u re2 3 0 – 2 4 1 and elim-ination of all cardiovascular risk factors2 4 2 – 2 4 4 will help pre-vent its pro g ression. If overt nephropathy is evident (i.e.,m o re than 300 mg/d of albumin in urine), all those withtype 1 diabetes should receive ACE inhibitors. ACEinhibitors should also be considered for those with type 2diabetes and overt nephro p a t h y. Data suggest that dietaryreduction of protein intake may delay pro g ression of re n a lf a i l u re .2 4 5 Follow-up should include monitoring of seru mc reatinine and potassium, a 24-h creatinine clearance testand quantitation of proteinuria at least twice a year.

Recommendations

7 2 . The best possible glucose control — if necessaryintensive diabetes management — should be institut-ed in people with type 1 diabetes for the prevention ofonset and delay in pro g ression of early nephro p a t h y.[Grade A, Level 17 7 , 2 2 4]

7 3 . In people with either type 1 or type 2 diabetes, scre e n-ing for microalbuminuria is recommended in those withdipstick-negative or trace proteinuria. Frequency ofs c reening is annual for people over 15 years of age witha 5-year history of type 1 diabetes and for all people afterdiagnosis of type 2 diabetes. [Grade D, consensus]T h erecommended screening method is measurement of ana l b u m i n : c reatinine ratio in a random, daytime urinesample. If values are greater than 2.8 for females and 2.0for males, the test should be repeated (and confirmed in2 out of 3 measurements over 3 months); if uncert a i n t yabout elevation still exists, it should be confirmed with atimed urine collection to measure the rate of micro a l b u-minuria. [Grade A, Level 12 1 2 , 2 1 5]


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S2 1

7 4 . In type 1 diabetes, elevated microalbuminuria (30–299mg albumin in 24 h or 20–200 µg/min) should bet reated with an ACE inhibitor to decrease albumin-uria, even in the absence of hypertension. [Grade A,Level 12 2 5 , 2 2 6 , 2 2 9]

7 5 . People with type 2 diabetes and elevated micro a l b u-minuria (30–299 mg albumin in 24 h) may benefit fro mACE inhibitor therapy to decrease albuminuria. [ G r a d eB, Level 12 2 7 , 2 2 8]

7 6 . People with type 1 diabetes and overt nephro p a t h y(>300 mg albumin in urine in 24 h) should be tre a t e dwith an ACE inhibitor. (Blood pre s s u re goals shouldbe the same as for people with hypertension.) [ G r a d eA, Level 12 3 3]

7 7 . A greater than 50% decrease in creatinine clearancerate necessitates re f e rral to a nephrologist or intern i s tassociated with a dialysis and renal transplantationc e n t re for adequate, well-planned long-term manage-ment. [Grade D, consensus (best practice of the CanadianSociety of Nephro l o g y ) ]

Neuropathy

Detectable neuropathy will develop within 10 years ofthe onset of diabetes in 40% to 50% of people with type1 and type 2 diabetes. Although fewer than 50% of thesepeople are symptomatic,7 7 , 2 4 6 n e u ropathic pain is fre-quently bothersome.2 4 7 – 2 4 9 People with type 2 diabetesmay have neuropathy at the time of diagnosis, whereas itis uncommon in people with type 1 diabetes within thefirst 5 years after onset of diabetes. Increased risk of footulceration, which depends on the degree of foot insensi-t i v i t y,2 5 0 and amputation are serious sequelae of diabeticn e u ro p a t h y. Both somatic and autonomic neuro p a t h ymay occur and may re q u i re re f e rral to a specialist experi-enced in managing the affected body system.

N e u ropathy is most easily detected by examining thepatient for loss of ankle reflexes and perception of 128 Hzvibration in the great toe,7 7 or by using a 10-gS e m m e s – Weinstein monofilament.2 5 1 In people with sig-nificant symptoms of neuro p a t h y, re f e rral for additionaln e u rologic evaluation and to other specialists (e.g., neu-rologist, podiatrist, chiropodist) may be helpful.

Intensive diabetes management is effective for the pri-m a ry or secondary prevention of neuropathy in patientswith type 1 diabetes.7 7 , 2 2 2 , 2 5 2 In patients with type 2 dia-betes, lower glucose levels are associated with re d u c e df requency of neuro p a t h y2 4 6 and intensified therapy mayalso be helpful.7 6

Tricyclic antidepre s s a n t s ,2 4 7 – 2 4 9 , 2 5 3 c a r b a m a z e p i n e ,2 5 4 o rm e x i l e t i n e2 5 5 a re often effective in controlling neuro p a t h i cpain. Adverse effects of these medications, especially mex-

iletine, must be considered before use. The effect of topi-cal capsaicin is less cert a i n .2 5 6 , 2 5 7 Nonaddictive analgesicsmay be used to alleviate pain.

Recommendations

7 8 .S c reening for peripheral neuropathy should be car-ried out annually to identify those at high risk ofdeveloping foot ulcers. [Grade A, Level 12 5 0]

7 9 . Detection of peripheral neuropathy can be donet h rough assessment for• d e c rease or loss of ability to sense vibration or loss

of sensitivity to a 10-g monofilament at the great toe• absent or decreased ankle reflexes. [Grade D,

Level 42 5 1]8 0 . People with type 1 diabetes should be treated for

peripheral neuropathy with intensive managementfor primary prevention or secondary interv e n t i o n .[Grade A, Level 17 7 , 2 2 2]

8 1 . Intensified diabetes management should be consid-e red for people with type 2 diabetes to prevent onsetand pro g ression of neuro p a t h y. [Grade B, Level 17 6]

8 2 . Tricyclic antidepressants and carbamazepine [ G r a d eA, Level 12 4 9 , 2 5 4] should be considered for symptomaticrelief of painful peripheral neuro p a t h y. Topical cap-saicin should be considered as a nonsystemic tre a t-ment for painful neuro p a t h y. [Grade B, Level 12 5 7]

8 3 . People with clinically significant autonomic dysfunc-tion should be appropriately assessed and re f e rred to aspecialist experienced in managing the affected bodysystem. Because sexual dysfunction is common, specif-ic inquiries should be made as people may be re l u c t a n tto volunteer such information. [Grade D, consensus]

Foot care

Foot problems are a major cause of morbidity and mor-tality in people with diabetes and contribute to incre a s e dhealth care costs.2 5 8 , 2 5 9 The sequence of events leading tol o w e r- e x t remity amputation is well known: in people withn e u ro p a t h y2 6 0 or peripheral vascular disease (PVD),2 6 1

minor trauma to the foot leads to skin ulceration, infectionand gangrene, resulting in amputation.2 6 2 – 2 6 6 Foot complica-tions are a major reason for admission to hospital of peoplewith diabetes and account for approximately 20% of alladmissions in the North American population.2 6 4 , 2 6 5 , 2 6 7 , 2 6 8

After amputation of one limb, the prognosis for the con-tralateral limb is poor.2 6 9 , 2 7 0 Of all lower- e x t remity amputa-tions, 45% occur in people with diabetes; the age-adjustedrate of amputation is 11 times higher in those with diabetesthan in people without diabetes.2 7 0 M o re recent data indi-cate that one-half to two-thirds of all lower- e x t re m i t y

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S2 2 JAMC • 20 OCT. 1998; 159 (8 Suppl)

amputations perf o rmed in the United States are in peoplewith diabetes, and these account for more than 50 0 0 0a m p u t a t i o n s .2 5 9 , 2 6 6 , 2 6 8 In the United States, the direct costs forthis common complication of diabetes, including re h a b i l i-tation, are in excess of $500 million a year.2 6 7 , 2 7 1

A p p ropriate management can prevent or heal diabeticfoot ulcers, thereby greatly reducing the amputationr a t e .2 6 3 , 2 6 6 , 2 6 7 , 2 7 2 , 2 7 3 P revention of amputations calls for theuse of various measures, including regular foot examina-tion and evaluation of amputation risk, patient education,early detection and treatment of diabetic foot ulcers and,if necessary, vascular surg e ry.2 6 7 , 2 7 1 – 2 7 4 Characteristics thathave been demonstrated to confer high risk of amputa-tion include previous ulceration, increased age, PVD,n e u ro p a t h y, structural deform i t y, renal transplantation,poor socioeconomic status and smoking.

Recommendations

8 4 . Foot examination in adults should be an integralcomponent of diabetes management and decre a s e srisk of foot ulcers and amputation. [Grade A, Level12 7 3 , 2 7 4] Foot examination should include assessmentof structural abnormalities, neuro p a t h y, vascular dis-ease, ulcerations and evidence of infection. [Grade D,Level 42 6 6] Foot examinations should be perf o rmed atleast annually in all people with diabetes who are over15 years of age and at more frequent intervals forthose at high risk. [Grade D, consensus]

8 5 . P revention of foot ulceration and amputationre q u i res foot care education, proper footwear, avoid-ance of foot trauma, smoking cessation and earlyre f e rral if problems occur. People at high risk of footulceration should receive re i n f o rcement of foot careeducation. [Grade A, Level 12 7 3 , 2 7 4]

8 6 . A person with diabetes who develops a foot ulcerre q u i res therapy by experienced health care pro f e s s i o n-als who have expertise in diabetes foot care. Any infec-tion must be treated aggre s s i v e l y. [Grade D, consensus]

Cardiovascular disease and hypertension

C a rdiovascular disease is a major cause of morbidityand mortality in both type 1 and 2 diabetes; morbidity andm o rtality rates are 2- to 4-fold higher than in age- andsex-matched groups in the nondiabetic population.2 7 5 – 2 7 9

The risk of CAD and stroke is increased 2-fold amongmen with diabetes and 3- to 4-fold among women withd i a b e t e s .2 7 8 – 2 8 2 Silent ischemia and myocardial infarc t i o na re more common and the outcome of an infarction isworse than in nondiabetic people.2 8 3 – 2 8 5 In fact, after anacute myocardial infarction, men and women with dia-

betes are at greater risk for congestive heart failure, havea 4-fold greater risk of re c u rrent infarction, a 2-foldg reater risk of arrhythmias and higher short- and long-t e rm mortality rates than nondiabetic people.2 8 6 , 2 8 7 T h e yalso have a lower overall survival rate.2 8 6 In addition to therisk of CAD and stroke, diabetes is associated withi n c reased risk of PVD, which contributes to the high rateof gangrene and lower-limb amputations.2 7 6 , 2 8 1

The benefits of reducing CAD by modifying themajor risk factors for cardiovascular disease, such ashyperlipidemia, have not been clearly assessed in peoplewith diabetes.2 8 8 N e v e rtheless, subgroup analyses of peo-ple with diabetes who were enrolled in both primary2 8 9

and secondary7 8 p revention trials of lipid-lowering dru g ssuggest that reduction of LDL cholesterol can signifi-cantly decrease morbid events.

As CAD may be asymptomatic in people with diabetes,a g g ressive treatment including the use of acetylsalicylictherapy as a primary prevention strategy should be consid-e red in high-risk people (over the age of 30); acetylsalicylicacid may also be effective for secondary pre v e n t i o n .2 9 0

T h e re is no contraindication to acetylsalicylic acid therapy,even in people with severe stages of diabetic re t i n o p a t h ywho are at risk for (or who have) vitreous hemorrh a g e .2 9 1 , 2 9 2

H y p e rtension complicates diabetes in all populationsand is more frequent with advancing age.2 8 0 In type 1 dia-betes, blood pre s s u re is usually normal at pre s e n t a t i o n .H y p e rtension typically develops with the onset ofn e p h ropathy and is characterized by elevation of systolicand diastolic blood pre s s u re. About half of people with type1 diabetes with 30 or more years of diabetes have hyper-t e n s i o n .2 7 9 People with type 2 diabetes are frequently hyper-tensive at the time of diagnosis, and the increase in bloodp re s s u re is generally correlated with obesity, decre a s e dphysical activity and older age. Isolated systolic hypert e n-sion is particularly common in type 2 diabetes.2 9 3 , 2 9 4

Because hypertension is a major contributor to thedramatically increased morbidity and mortality of bothtype 1 and 2 diabetes,2 0 3 , 2 7 9 it should be recognized andt reated early and aggre s s i v e l y. Although treatment ofh y p e rtension with any known antihypertensive agentmay improve cardiovascular disease outcomes,2 4 1 , 2 9 3 , 2 9 4 t h euse of low-dose diuretics and beta-blockers may be par-ticularly effective in the elderly.2 9 5 ACE inhibitors mayalso decrease cardiovascular events more than calciumchannel antagonists in those at high risk.2 9 6 , 2 9 7 A C Einhibitors have additional advantages in the presence ofdiabetic renal disease. (See N e p h ro p a t h ys e c t i o n . )

Recommendations

8 7 . People with type 1 or 2 diabetes should be encouraged


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S2 3

to adopt a healthy lifestyle to lower their risk of CAD:this means achieving and maintaining healthy eatinghabits and a desirable weight, engaging in regular phys-ical activity and stopping smoking. [Grade D, consensus]

8 8 . A fasting lipid profile (total cholesterol, triglycerides,HDL cholesterol and calculated LDL cholestero l )should be carried out in adults with diabetes andrepeated every 1 to 3 years as clinically indicated.[Grade D, consensus]

8 9 .A p p ropriate treatment of dyslipidemia to achieve tar-get levels (as noted in Table 12) should be institutedfor primary prevention of CAD [Grade D, consensus]and secondary prevention of CAD. [Grade C, Level 37 8]

9 0 .H y p e rtension in people with diabetes (i.e., blood pre s-s u re ≥140/90 mmHg) should be treated to attain targ e tblood pre s s u re <130/85 mmHg. [Grade D, consensus]

9 1 . First-line drug therapies for hypertension in peoplewith diabetes and without overt nephropathy caninclude (in alphabetical order): ACE inhibitors,alpha-blockade agents, angiotensin II receptor antag-onists and calcium channel antagonists. The choice ofa n t i h y p e rtensive agents should be tailored to the indi-vidual and take into account the effects of these agentson card i o v a s c u l a r, metabolic and renal outcomes.[Grade D, consensus]

9 2 .H y p e rtension treatment goals for the elderly should bet a i l o red to the individual. [Grade D, consensus]L o w -dose diuretics and beta-blockers should be considere din the elderly to prevent cardiovascular disease. [ G r a d eA, Level 12 9 5]

9 3 . Low-dose acetylsalicylic therapy (81–325 mg/d)should be considered as primary prevention therapyin high-risk patients (over the age of 30 years) withdiabetes and as a secondary prevention strategy inpeople with diabetes and large vessel disease. [ G r a d eC, Level 32 9 0]

S u m m a ry

These are the first evidence-based clinical practiceguidelines for diabetes to be published in the Americas.The method used to develop them included the re v i e wand grading of the scientific evidence for many of therecommendations, but it also revealed specific are a sw h e re evidence to support clinical practices was lacking.

Outpatient management of diabetes using a share d -c a re team approach is addressed in a comprehensive man-n e r. Unsettled issues relating to such controversial areas asthe treatment of GDM and the management of diabetesin Aboriginal Canadians are explicitly acknowledged andidentified as targets for further investigation or strategyd e v e l o p m e n t .

T h e re has been an overwhelming commitment bymany key stakeholders in this process. Their desire toi m p rove the health of Canadians with diabetes and tocontinue the eff o rt begun with publication of the firstguidelines in 19929 was evident from the intensity of theire ff o rts and the amount of time they committed to theirtasks. They are confident that the recommendations con-tained in these revised clinical guidelines will lay theg roundwork for significant improvement in diabetesc a re, and they trust that publication of these guidelineswill enhance the quality of life of Canadians with dia-betes. Before this can happen, the critical challenge willbe to implement these guidelines in a scientific way sothat the information can be used to further enhancehealth policies for diabetes.

This document is an executive summary of all the re c-ommendations of the 1998 revision of the clinical prac-tice guidelines for management of diabetes mellitus. Itwill be followed by in-depth assessment of each area inthe form of technical review articles that will be pub-lished subsequently.

In addition to those who contributed to the development of this docu-ment, the process benefited from the valuable insights and comments ofnumerous national and international experts who reviewed these guide-lines in detail. The members of the Clinical and Scientific Section andthe Diabetes Educator Section of the Canadian Diabetes Association(CDA) and attendees at the CDA Professional Sections Conference,London, Ont., October 1997, provided valuable insight as part of theconsensus process. Their contributions in enhancing the quality of thisinformation are gratefully acknowledged. An enormous amount of workwas done by the staff of the CDA; particularly important support camefrom Donna Lillie, director of research and professional education. Theexpert secretarial assistance of Shirley Grundy and Mary Richardson,the fundraising support of Nowshad Ali and the administrative detailscarried out by numerous other CDA staff, as well as the medical writingassistance of Arthur Tan are much appreciated. It was also of great ben-efit to have the funding support of our sponsors to pursue this processwith the intensity required.

Note added in pro o f : The benefits of improved glucose and blood pre s-s u re control for the prevention of long-term complications in thosewith type 2 diabetes have been confirmed by recent re p o rts of theresults of the United Kingdom Prospective Diabetes Study.2 9 8 - 3 0 2 T h i slandmark study of over 5000 people with type 2 diabetes over 20 yearsc o n f i rmed the prevention of microvascular complications thro u g hi m p roved glucose control and highlighted the major effects of bloodp re s s u re control on micro- and macrovascular complications of dia-betes. After further evaluation, a position statement will developed bythe CDA on the implications of this study, which may include re v i s i o nof the grading of some of the recommendations in these guidelines.

R e f e re n c e s

1 . Tan H, MacLean DR. Epidemiology of diabetes mellitus in Canada. Clin InvestM e d1 9 9 5 ; 1 8 : 2 4 0 - 6 .

2 . Tan MH, Daneman D, Lau DCW, et al. Diabetes in Canada: strategies toward s2 0 0 0. To ronto: Canadian Diabetes Advisory Board; 1997. p. 3.

3 . Vinicor F. Is diabetes a public health disorder? Diabetes Care1 9 9 4 ; 1 7 : 2 2 - 7 .4 . Diabetes in America. 2nd ed. Washington: National Diabetes Data Gro u p ,

National Institute of Diabetes and Digestive and Kidney Diseases, National

Meltzer et al

S2 4 JAMC • 20 OCT. 1998; 159 (8 Suppl)

Institutes of Health; 1995.5 . Ray NF, Wills S, Thamer M. D i rect and indirect costs of diabetes in the United

S t a t e s. Alexandria (VA): American Diabetes Association; 1993.6 . Rubin RJ, Altman WM, Mendelson DN. Health care expenditures for people

with diabetes, 1992. J Clin Endocrinol Metab1 9 9 4 ; 7 8 : 8 0 9 A - F.7 . Diabetes Control and Complications Trial Research Group. Lifetime benefits

and costs of intensive therapy as practiced in the Diabetes Control andComplications Trial. J A M A 1 9 9 6 ; 2 7 6 : 1 4 0 9 - 1 5 .

8 . Eastman RC, Javitt JJ, Herman WS, et al. Prevention strategies for noninsulindependent diabetes mellitus: an economic perspective. In: Taylor RD, OlefskySI, editors. Diabetes mellitus: a fundamental and clinical text. New Yo r k :Lippincott Raven; 1996. p. 621.

9 . E x p e rt Committee of the Canadian Diabetes Advisory Board. Clinical practiceguidelines for treatment of diabetes mellitus. C M A J 1 9 9 2 ; 1 4 7 : 6 9 7 - 7 1 2 .

1 0 . C a rruthers SG, Larochelle P, Haynes RB, et al. Report of the CanadianH y p e rtension Society Consensus Conference: 1. Introduction. C M A J1 9 9 3 ; 1 4 9 : 2 8 9 - 9 3 .

1 1 . Cook DJ, Guyatt GH, Laupacis A, et al. Clinical recommendations using levelsof evidence for antithrombotic agents. C h e s t1 9 9 5 ; 1 0 8 : 2 2 7 s - 2 3 0 s .

1 2 . H a y w a rd RS, Wilson MC, Tunis SR, et al. Users’ guides to the medical litera-t u re. VIII. How to use clinical practice guidelines. A. Are the re c o m m e n d a t i o n svalid? J A M A 1 9 9 5 ; 2 7 4 : 5 7 0 - 4 .

1 3 . H a y w a rd RS, Laupacis A. Initiating, conducting and maintaining guidelinesdevelopment programs. C M A J 1 9 9 3 ; 1 4 8 : 5 0 7 - 1 2 .

1 4 . Wilson MC, Hayward RS, Tunis SR, et al. Users’ guides to the medical litera-t u re. VIII. How to use clinical practice guidelines. B. What are the re c o m m e n-dations and will they help you in caring for your patients? J A M A1 9 9 5 ; 2 7 4 : 1 6 3 0 - 2 .

1 5 . Goldbloom R, Battista RN. The periodic health examination: intro d u c t i o n .C M A J 1 9 8 6 ; 1 3 4 : 7 2 1 - 3 .

1 6 . B rown SA. Meta-analysis of diabetes patient education re s e a rch: variations ini n t e rvention effects across studies. Res Nurs Health1 9 9 2 ; 1 5 : 4 0 9 - 1 9 .

1 7 . B rown SA. Effects of educational interventions in diabetes care: a meta-analy-sis of findings. Nurs Res1 9 8 8 ; 3 7 : 2 2 3 - 3 0 .

1 8 . Clement S. Diabetes self-management education. Diabetes Care1 9 9 5 ; 1 8 : 1 2 0 4 -1 4 .

1 9 . Dunn SM, Hoskins PL, Constantino M, et al. Diabetic management: the ro l eof the diabetes center. Diabetes Rev1 9 9 4 ; 2 : 3 8 9 - 4 0 2 .

2 0 . Keen H. Management of non-insulin-dependent diabetes mellitus: the UnitedKingdom experience. Ann Intern Med1 9 9 6 ; 1 2 4 : 1 5 6 - 9 .

2 1 . Funnell M. Integrated approaches to the management of NIDDM patients.Diabetes Spectru m 1 9 9 6 ; 9 : 5 5 - 9 .

2 2 . G reenhalgh PM. Shared care for diabetes. A systematic re v i e w. Br J Gen Pract1 9 9 4 ; 6 7 : 1 - 3 5 .

2 3 . Hoskins PL, Fowler PM, Constantino M, et al. Sharing the care of diabeticpatients between hospital and general practitioners: Does it work? Diabetic Med1 9 9 3 ; 1 0 : 8 1 - 6 .

2 4 . H u rwitz B, Goodman C, Yudkin J. Prompting the clinical care of non-insulindependent (type II) diabetic patients in an inner city area: one model of com-munity care. B M J 1 9 9 3 ; 3 0 6 : 6 2 4 - 3 0 .

2 5 . McGill M, Molyneaux LM, Yue DK, et al. A single visit diabetes complicationassessment service: a complement to diabetes management at the primary carelevel. Diabet Med1 9 9 3 ; 1 0 : 3 6 6 - 7 0 .

2 6 . We i n b e rger M, Kirkman MS, Samsa GP, et al. A nurse-coordinated interv e n-tion for primary care patients with non-insulin dependent diabetes mellitus:impact on glycemic control and health-related quality of life. J Gen Intern Med1 9 9 5 ; 1 0 : 5 9 - 6 6 .

2 7 . H a rris MI. Medical care for patients with diabetes: epidemiologic aspects. A n nI n t e rn Med1 9 9 6 ; 1 2 4 : 1 1 7 - 2 2 .

2 8 . Hiss RG. Barriers to care in non-insulin-dependent diabetes mellitus: theMichigan experience. Ann Intern Med1 9 9 6 ; 1 2 4 : 1 4 6 - 8 .

2 9 . Hiss RG, Anderson RM, Hess GE, et al. Community diabetes care: a 10-yearperspective. Diabetes Care1 9 9 4 ; 1 7 : 1 1 2 4 - 3 4 .

3 0 . Weiner JP, Parente ST, Garnick DW, et al. Variation in office-based quality: aclaims-based profile of care provided to Medicare patients with diabetes. J A M A1 9 9 5 ; 2 7 3 : 1 5 0 3 - 8 .

3 1 . D’Eramo-Melkus GA, Wylie-Rosett J, Hagan JA. Metabolic impact of educa-tion in NIDDM. Diabetes Care1 9 9 2 ; 1 5 : 8 6 4 - 9 .

3 2 . Keen H, Hall M. Saint Vincent: a new responsibility for general practitioners?Br J Gen Pract1 9 9 5 ; 4 6 : 4 4 7 - 8 .

3 3 . S t a rfield B. Primary care: Participants or gatekeepers? Diabetes Care1994;17(Suppl 1):12-7.

3 4 . Bennett IJ, Lambert C, Hinds G, et al. Emerging standards for diabetes caref rom a city-wide primary care audit. Diabet Med1 9 9 4 ; 1 1 : 4 8 9 - 9 2 .

3 5 . Diabetes Integrated Care Evaluation Team. Integrated care for diabetes: clini-cal, psychosocial and economic evaluation. B M J 1 9 9 4 ; 3 0 8 : 1 2 0 8 - 1 2 .

3 6 . B rown SA. Studies of educational interventions and outcomes in diabetic adults:a meta-analysis revisited. Patient Educ Couns1 9 9 0 ; 1 6 : 1 8 9 - 2 1 5 .

3 7 . Robinson N, Bush L, Protopapa LE, Yateman NA. Employers’ attitudes to dia-betes. Diabetic Med1 9 8 9 ; 6 : 6 9 2 - 7 .

3 8 . Robinson N, Bush L, Protopapa LE, Yateman NA. Employment problems and

diabetes. Diabetic Med1 9 9 0 ; 7 : 1 6 - 2 2 .3 9 . Petrides P, Petermann F, Heinrichs HR, et al. Coping with employment dis-

crimination against diabetics: trends in social medicine and social psychology.Patient Educ Couns1 9 9 5 ; 2 6 ( 1 - 3 ) : 2 0 3 - 8 .

4 0 . Diamond Project Group on Social Issues. Global regulations on diabetes tre a t-ed with insulin and their operation of motor vehicles. B M J 1 9 9 3 ; 3 0 7 : 2 5 0 - 3 .

4 1 . National Diabetes Data Group. Classification and diagnosis of diabetes melli-tus and other categories of glucose intolerance. D i a b e t e s1 9 7 9 ; 2 8 : 1 0 3 9 - 5 7 .

4 2 . R e p o rt of the Expert Committee on the Diagnosis and Classification ofDiabetes Mellitus. Diabetes Care1 9 9 7 ; 2 0 : 1 - 1 5 .

4 3 . American Diabetes Association. Gestational diabetes. Diabetes Care1 9 9 8 ;21(Suppl 1):S60-1.

4 4 . Roman SH, Harris MI. Management of diabetes mellitus from a public healthperspective. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 4 4 3 - 7 4 .

4 5 . McCance DR, Hanson RL, Charles MA, et al. Comparison of tests for glycat-ed haemoglobin and fasting and two hour plasma glucose concentrations asdiagnostic methods for diabetes. B M J 1 9 9 4 ; 3 0 8 : 1 3 2 3 - 8 .

4 6 . Engelgau MM, Thompson TJ, Herman WH, et al. Comparison of fasting and2-hour glucose and HbA1c levels for diagnosing diabetes: diagnostic criteriaand perf o rmance revisited. Diabetes Care1 9 9 7 ; 2 0 : 7 8 5 - 9 1 .

4 7 . Langer O, Levy J, Brustman L, et al. Glycemic control in gestational diabetesmellitus: how tight is tight enough: small for gestational age versus large forgestational age? Am J Obstet Gynecol1 9 8 9 ; 1 6 1 : 6 4 6 - 5 3 .

4 8 . Canadian Task Force on the Periodic Health Examination. Periodic healthexamination, 1992 update: 1. Screening for gestational diabetes mellitus. C M A J1 9 9 2 ; 1 4 7 : 4 3 5 - 4 3 .

4 9 . Naylor CD. Diagnosing gestational diabetes mellitus: Is the gold standardvalid? Diabetes Care1 9 8 9 ; 1 2 : 5 6 5 - 7 2 .

5 0 . Elixhauser A, Kitzmiller JL, Weschler JM. Short - t e rm cost benefit of pre - c o n-ception care for diabetes [letter]. Diabetes Care1 9 9 6 : 1 9 : 3 8 4 .

5 1 . Kitzmiller JL, Elixhauser A, Carr S. et al. Assessment of costs and benefits ofmanagement of gestational diabetes mellitus. Diabetes Care1 9 9 8 ; 2 1 ( S u p p l2 ) : B 1 2 3 - 3 0 .

5 2 . Naylor CD, Sermer M, Chen E, Farine D. Selective screening for gestationaldiabetes mellitus. To ronto Trihospital Gestational Diabetes Pro j e c tInvestigators. N Engl J Med1 9 9 7 ; 3 3 7 : 1 5 9 1 - 6 .

5 3 . Landy HJ, Gomez-Marin O, O’Sullivan MJ. Diagnosing gestational diabetesmellitus: use of a glucose screen without administering the glucose tolerancetest. Obstet Gynecol1 9 9 6 ; 8 7 : 3 9 5 - 4 0 0 .

5 4 . World Health Organisation. Diabetes mellitus: re p o rt of a WHO study gro u p.Geneva: The Organisation; Technical Report 727.

5 5 . Sacks DA, Greenspoon JS, Abu-Fadil S, et al. To w a rd universal criteria for ges-tational diabetes: the 75-gram glucose tolerance test in pre g n a n c y. Am J ObstetG y n e c o l1 9 9 5 ; 1 7 2 : 6 0 7 - 1 4 .

5 6 . Lind T, Sutherland HW, Molsted-Pedersen L, et al. A prospective multicentrestudy to determine influence of pregnancy upon the 75-g oral glucose tolerancetest (OGTT). In: Sutherland HW, Stowers JM, Pearson JM, editors.Carbohydrate metabolism in pregnancy and the newborn. London (UK): SpringerVerlag; 1989. p. 206-26.

5 7 . Carpenter MW, Coustan DR. Criteria for screening tests for gestational dia-betes. Am J Obstet Gynecol1 9 8 2 ; 1 4 4 : 7 6 8 - 7 3 .

5 8 . O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pre g-n a n c y. D i a b e t e s1 9 6 4 ; 1 3 : 2 7 8 - 8 5 .

5 9 . Langer O, Rodriguez DA, Xenakis EM, et al. Intensified versus conventionalmanagement of gestational diabetes. Am J Obstet Gynecol1 9 9 4 ; 1 7 0 : 1 0 3 6 - 4 7 .

6 0 . Metzger BE, Coustan DR, Organizing Committee, et al. Summary and re c o m-mendations of the fourth internal workshop-conference on gestational diabetes.Diabetes Care1998;21(Suppl 2):B161-7.

6 1 . H a rris MI, Hadden WC, Knowler WC, et al. Prevalence of diabetes andi m p a i red glucose tolerance and plasma glucose levels in US population aged20–74 years. D i a b e t e s1 9 8 7 ; 3 6 : 5 2 3 - 3 4 .

6 2 . H a rris MI, Modan M. Screening for NIDDM. Why is there no national pro-gram? Diabetes Care1 9 9 4 ; 1 7 : 4 4 0 - 4 .

6 3 . Knowler WC. Screening for NIDDM: opportunities for detection, tre a t m e n t ,and prevention. Diabetes Care1 9 9 4 ; 1 7 : 4 4 5 - 5 0 .

6 4 . Charles MA, Fontbonne A, Thibult N, et al. Risk factors for NIDDM in whitepopulation. Paris prospective study. D i a b e t e s1 9 9 1 ; 4 0 : 7 9 6 - 9 .

6 5 . Eastman RC, Cowie CC, Harris MI. Undiagnosed diabetes or impaired glucosetolerance and cardiovascular risk. Diabetes Care1 9 9 7 ; 2 0 : 1 2 7 - 8 .

6 6 . Tuomilehto J, Knowler WC, Zimmet P. Primary prevention of non-insulin-dependent diabetes mellitus. Diabetes Metab Rev1 9 9 2 ; 8 : 3 3 9 - 5 3 .

6 7 . J a rrett RJ, Keen H, Fuller JH, et al. Worsening to diabetes in men withi m p a i red glucose tolerance (“borderline diabetes”). D i a b e t o l o g i a1 9 7 9 ; 1 6 : 2 5 - 3 0 .

6 8 . Keen H, Jarrett RJ, McCartney P. The ten-year follow-up of the Bedford sur-vey (1962–1972): glucose tolerance and diabetes. D i a b e t o l o g i a1 9 8 2 ; 2 2 : 7 3 - 8 .

6 9 . Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in pre v e n t i n gNIDDM in people with impaired glucose tolerance: the Da Qing IGT andDiabetes Study. Diabetes Care1 9 9 7 ; 2 0 : 5 3 7 - 4 4 .

7 0 . S a rtor G, Schersten B, Carlstrom S, et al. Ten-year follow-up of subjects withi m p a i red glucose tolerance: prevention of diabetes by tolbutamide and diet re g-ulation. D i a b e t e s1 9 8 0 ; 2 9 : 4 1 - 9 .


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S2 5

7 1 . Chiasson JL. The effect of acarbose on insulin sensitivity in subjects withi m p a i red glucose tolerance. Diabet Med1 9 9 6 ; 1 3 : S 2 3 - 4 .

7 2 . Nolan JJ, Ludvik B, Beerdsen P, et al. Improvement in glucose tolerance andinsulin resistance in obese subjects treated with troglitazone. N Engl J Med1 9 9 4 ; 3 3 1 : 1 1 8 8 - 9 3 .

7 3 . N o rris JM, Scott FW. A meta-analysis of infant diet and insulin-dependent dia-betes mellitus: do biases play a role? E p i d e m i o l o g y1 9 9 6 ; 7 : 8 7 - 9 2 .

7 4 . Elliott RB, Pilcher CC, Fergusson DM, et al. A population based strategy top revent insulin-dependent diabetes using nicotinamide. J Pediatr EndocrinolM e t a b1 9 9 6 ; 9 : 5 0 1 - 9 .

7 5 . Keller RJ, Eisenbarth GS, Jackson RA. Insulin prophylaxis in individuals at highrisk of type 1 diabetes. L a n c e t1 9 9 3 ; 3 4 1 : 9 2 7 - 8 .

7 6 . Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents thep ro g ression of diabetic microvascular complications in Japanese patients withnon-insulin-dependent diabetes mellitus: a randomized prospective 6-years t u d y. Diabetes Res Clin Pract1 9 9 5 ; 2 8 : 1 0 3 - 1 7 .

7 7 . Diabetes Control and Complications Trial Research Group (DCCT). Thee ffect of intensive treatment of diabetes on the development and pro g ression ofl o n g - t e rm complications in insulin-dependent diabetes mellitus. N Engl J Med1 9 9 3 ; 3 2 9 : 9 7 7 - 8 6 .

7 8 . Pyorala K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvas-tatin improves prognosis of diabetic patients with coro n a ry heart disease: a sub-g roup analysis of the Scandinavian Simvastatin Survival Study (4S). D i a b e t e sC a re 1 9 9 7 ; 2 0 : 6 1 4 - 2 0 .

7 9 . F rohlich MD, Fodor G, McPherson R, et al. Rationale for and outline of therecommendations of the Working Group on Hyperc h o l e s t e rolemia and OtherDyslipidemias: interim re p o rt. Dyslipidemia Working Group of HealthCanada. Can J Card i o l1998;14(Suppl A):17A-21A.

8 0 . Cox DJ, Kovatchev BP, Julian DM, et al. Frequency of severe hypoglycemia ininsulin-dependent diabetes mellitus can be predicted from self-monitoringblood glucose data. J Clin Endocrinol Metab1 9 9 4 ; 7 9 : 1 6 5 9 - 6 2 .

8 1 . S c h i ffrin A, Suissa S. Predicting nocturnal hypoglycemia in patients with type 1diabetes treated with continuous subcutaneous insulin infusion. Am J Med1 9 8 7 ; 8 2 : 1 1 2 7 - 3 2 .

8 2 . Goldstein DE, Little RR. Monitoring glycemia in diabetes: short - t e rm assess-ment. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 4 7 5 - 8 6 .

8 3 . B e rtrand S, Aris-Jilwan N, Reddy S, et al. Recommendations for the use of self-monitoring of blood glucose in diabetes mellitus. Can J Diabetes Care1 9 9 6 ; 2 0 : 1 4 - 6 .

8 4 . Te rent A, Hagfall O, Cederholm U. The effect of education and self-monitor-ing of blood glucose on glycosylated hemoglobin in type I diabetes: a contro l l e d18-month trial in a re p resentative population. Acta Med Scand1 9 8 5 ; 2 1 7 : 4 7 - 5 3 .

8 5 . Va rner MW. Efficacy of home blood glucose monitoring in diabetic pre g n a n c y.Am J Med 1 9 8 3 ; 7 5 : 5 9 2 - 6 .

8 6 . Wa rd WK, Haas LB, Beard JC. A randomized, controlled comparison ofi n s t ruction by a diabetes educator versus self-instruction in self-monitoring ofblood glucose. Diabetes Care1 9 8 5 ; 8 : 2 8 4 - 6 .

8 7 . Ziegher O, Kolopp M, Louis J, et al. Self-monitoring of blood glucose andinsulin dose alteration in type 1 diabetes mellitus. Diabetes Res Clin Pract1 9 9 3 ; 2 1 : 5 1 - 9 .

8 8 . Abraira C, Colwell JA, Nuttall FQ, et al. Veterans Affairs Cooperative Study onglycemic control and complications in type II diabetes (VA CSDM): Results ofthe feasibility trial. Veterans Affairs Cooperative Study in Type II Diabetes.Diabetes Care1 9 9 5 ; 1 8 : 1 1 1 3 - 2 3 .

8 9 . Tu rner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17:a 9-year update of a randomized, controlled trial on the effect of impro v e dmetabolic control on complications in non-insulin-dependent diabetes mellitus.Ann Intern Med1 9 9 6 ; 1 2 4 ( 1 p t 2 ) : 1 3 6 - 4 5 .

9 0 . B rown SA, Upchurch S, Anding R, et al. Promoting weight loss in type II dia-betes. Diabetes Care1 9 9 6 ; 1 9 : 6 1 3 - 2 4 .

9 1 . Wing RR, Marcus MD, Salata R, et al. Effects of a very-low-calorie diet onl o n g - t e rm glycemic control in obese type 2 diabetic subjects. A rch Intern Med1 9 9 1 ; 1 5 1 : 1 3 3 4 - 4 0 .

9 2 . Chantelau EA, Gosseringer G, Sonnenberg GE, et al. Moderate intake ofs u c rose does not impair metabolic control in pump-treated diabetic out-patients. D i a b e t o l o g i a1 9 8 5 : 2 : 2 0 4 - 7 .

9 3 . Bantle JP, Swanson JE, Thomas W, et al. Metabolic effects of dietary sucrose intype II diabetic subjects. Diabetes Care1 9 9 3 ; 1 6 : 1 3 0 1 - 5 .

9 4 . Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a re c o m-mendation from the Centers for Disease Control and Prevention and theAmerican College of Sports Medicine. J A M A 1 9 9 5 ; 2 7 3 : 4 0 2 - 7 .

9 5 . Schneider SH, Khachadurian AK, Amorosa LF, et al. Ten-year experience withe x e rcise-based outpatient life-style modification program in the treatment ofdiabetes mellitus. Diabetes Care1 9 9 2 ; 1 5 : 1 8 0 0 - 1 0 .

9 6 . American Diabetes Association. Diabetes mellitus and exercise. Diabetes Care1998;21(Suppl 1):S40-4.

9 7 . Wa s s e rman DH, Zinman B. Exercise in individuals with IDDM. Diabetes Care1 9 9 4 ; 1 7 : 9 2 4 - 3 7 .

9 8 . Tsui E, Zinman B. Exercise and diabetes — new insights and therapeutic goals.E n d o c r i n o l o g i s t1 9 9 7 ; 5 : 2 6 3 - 7 1 .

9 9 . Balfour JA, McTavish D. Acarbose: an update of its pharmacology and thera-peutic use in diabetes mellitus. D ru g s1 9 9 3 ; 4 6 : 1 0 2 5 - 5 4 .

1 0 0 . Bell PM, Hadden DR. Metformin. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 5 2 3 - 3 7 .

1 0 1 . Davidson MB, Peters AL. An overview of metformin in the treatment of type 2diabetes mellitus. Am J Med 1 9 9 7 ; 1 0 2 : 9 9 - 1 1 0 .

1 0 2 . Gerich JE. Oral hypoglycemic agents. N Engl J Med1 9 8 9 ; 3 2 1 : 1 2 3 1 - 4 5 .1 0 3 . G roop LC. Sulfonylureas in NIDDM. Diabetes Care1 9 9 2 ; 1 5 : 7 3 7 - 5 4 .1 0 4 . H e n ry RR. Thiazolidinediones. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 5 5 3 -

7 3 .1 0 5 . H e rmann LS, Schersten B, Melander A. Antihyperglycaemic eff i c a c y, re s p o n s e

p rediction and dose-response relations of treatment with metformin ands u l p h o n y l u rea, alone and in primary combination. Diabet Med1 9 9 4 ; 1 1 : 9 5 3 - 6 0 .

1 0 6 . Iwamoto Y, Kosaka K, Kuzuya T, et al. Effects of troglitazone: a new hypo-glycemic agent in patients with NIDDM poorly controlled by diet therapy.Diabetes Care1 9 9 6 ; 1 9 : 1 5 1 - 6 .

1 0 7 . Lebovitz HE. Alpha-glucosidase inhibitors. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 5 3 9 - 5 1 .

1 0 8 . Lebovitz HE. Acarbose, an alpha-glucosidase inhibitor, in the treatment ofnon-insulin-dependent diabetes mellitus (NIDDM). Todays Ther Tre n d s1 9 9 6 ; 1 3 : 2 0 7 - 1 8 .

1 0 9 . Z i m m e rman BR. Sulfonylureas. Endocrinol Metab Clin North Am1 9 9 7 ; 2 6 : 5 1 1 -2 2 .

1 1 0 . United Kingdom Prospective Diabetes Study Group (UKPDS). 13: Relativee fficacy of randomly allocated diet, sulphonylurea, insulin, or metformin inpatients with newly diagnosed non-insulin dependent diabetes followed fort h ree years. B M J 1 9 9 5 ; 3 1 0 : 8 3 - 8 .

1 1 1 . D e F ronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Group. NEngl J Med1 9 9 5 ; 3 3 3 : 5 4 1 - 9 .

1 1 2 . Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the tre a t m e n tof patients with non-insulin dependent diabetes mellitus. Ann Intern Med1 9 9 4 : 1 2 1 : 9 2 8 - 3 5 .

1 1 3 . Heding LG, Marshall MO, Persson B, et al. Immunogenicity of monocompo-nent human and porcine insulin in newly diagnosed type 1 (insulin-dependent)diabetic children. D i a b e t o l o g i a1 9 8 4 ; 2 7 : 9 6 - 8 .

1 1 4 . Diabetes Control and Complications Trial Research Group. Implementation oft reatment protocols in the Diabetes Control and Complications Trial. D i a b e t e sC a re 1 9 9 5 ; 1 8 : 3 6 1 - 7 6 .

1 1 5 . G a rg SK, Carmain JA, Braddy KC, et al. Pre-meal insulin analogue insulinl i s p ro vs Humulin R insulin treatment in young subjects with type 1 diabetes.Diabet Med1 9 9 6 ; 1 3 : 4 7 - 5 2 .

1 1 6 . Pfutzner A, Kustner E, Forst T, et al. Intensive insulin therapy with insulinl i s p ro in patients with type 1 diabetes reduces the frequency of hypoglycemicepisodes. Exp Clin Endocrinol Diabetes1 9 9 6 ; 1 0 4 : 2 5 - 3 0 .

1 1 7 . Zinman B, Tildesley H, Chiasson JL, Tsui E, Strack T. Insulin lispro in CSII:results of a double-blind crossover study. D i a b e t e s1 9 9 7 ; 4 6 : 4 4 0 - 3 .

1 1 8 . Shank ML, Del Prato S, DeFronzo RA. Bedtime insulin/daytime glipizide:e ffective therapy for sulfonylurea failures in NIDDM. D i a b e t e s1 9 9 5 ; 4 4 : 1 6 5 - 7 2 .

1 1 9 . Y k i - J a rvinen H, Kauppila M, Kujansuu E, et al. Comparison of insulin re g i-mens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med1 9 9 2 ; 3 2 7 : 1 4 2 6 - 3 3 .

1 2 0 . Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes: a meta-analysis of the randomizedp l a c e b o - c o n t rolled trials. A rch Intern Med1 9 9 6 ; 1 5 6 : 2 5 9 - 6 4 .

1 2 1 . C o n i ff RF, Shapiro JA, Seaton TB, et al. A double-blind placebo-controlled trialevaluating the safety and efficacy of acarbose for the treatment of patients withi n s u l i n - requiring type II diabetes. Diabetes Care1 9 9 5 ; 1 8 : 9 2 8 - 3 2 .

1 2 2 . Giugliano D, Quatraro A, Consoli G, et al. Metformin for obese, insulin-tre a t-ed diabetic patients: improvement in glycaemic control and reduction of meta-bolic risk factors. Eur J Clin Pharm a c o l1 9 9 3 ; 4 4 : 1 0 7 - 1 2 .

1 2 3 . S c h w a rtz S, Raskin P, Fonseca V, Graveline JF. Efficacy of troglitazone ini n s u l i n - t reated patients with type II diabetes mellitus. Troglitazone andExogenous Insulin Study Group. N Engl J Med1 9 9 8 ; 3 3 8 ( 1 3 ) : 8 6 1 - 6 .

1 2 4 . Watkins PB, Whitcomb RW. Hepatic dysfunction associated with tro g l i t a z o n e .N Engl J Med1 9 9 8 ; 3 8 : 9 1 6 - 7 .

1 2 5 . G e ffken G, Johnson SB, Silverstein J, et al. The death of a child with diabetesf rom neglect: a case study. Clin Pediatr1 9 9 2 ; 3 1 : 3 2 5 - 3 0 .

1 2 6 . Glasgow AM, We i s s b e rg-Benchell J, Tynan WD, et al. Readmissions of chil-d ren with diabetes mellitus to a childre n ’s hospital. P e d i a t r i c s1 9 9 1 ; 8 8 : 9 8 - 1 0 4 .

1 2 7 . S i n g e r-Granick C, Hoffman RP, Kerensky K, et al. Glucagon responses tohypoglycemia in children and adolescents with IDDM. Diabetes Care1 9 8 8 ; 1 1 : 6 4 3 - 9 .

1 2 8 . F a i r b u rn CG, Beglin SJ. Studies of the epidemiology of bulimia nervosa. Am JP s y c h i a t ry 1 9 9 0 ; 1 4 7 : 4 0 1 - 8 .

1 2 9 . Koletzko S, Burg i n - Wo l ff A, Koletzko B, et al. Prevalence of coeliac disease indiabetic children and adolescents: a multicentre study. Eur J Pediatr1 9 8 8 ; 1 4 8 : 1 1 3 - 7 .

1 3 0 . Frank M. Factors associated with non-compliance with a medical follow-upregimen after discharge from a pediatric diabetes clinic. Can J Diabetes Care1 9 9 6 ; 2 0 : 1 3 - 2 0 .

1 3 1 . Pacaud D, McConnell B, Huot C, et al. Transition from pediatric care to adultc a re for insulin-dependent diabetes patients. Can J Diabetes Care1 9 9 6 ; 2 0 : 1 4 - 2 0 .

1 3 2 . B o u g n e res PF, Landais P, Mairesse AM, et al. Improvement of diabetic contro l

Meltzer et al

S2 6 JAMC • 20 OCT. 1998; 159 (8 Suppl)

and acceptability of a three-injection insulin regime in diabetic adolescents. Amulticenter controlled study. Diabetes Care1 9 9 3 ; 1 6 : 9 4 - 1 0 2 .

1 3 3 . Rovet JF, Ehrlich RM, Hoppe M. Intellectual deficits associated with earlyonset of insulin-dependent diabetes mellitus in children. Diabetes Care1 9 8 7 ; 1 0 : 5 1 0 - 5 .

1 3 4 . Ryan C, Vega A, Drash AL. Cognitive deficits in adolescents who developeddiabetes early in life. P e d i a t r i c s1 9 8 5 ; 7 5 : 9 2 1 - 7 .

1 3 5 . Chase HP, Crews KR, Garg S, et al. Outpatient management vs in-hospitalmanagement of children with new-onset diabetes. Clin Pediatr (Phila)1 9 9 2 ; 3 1 : 4 5 0 - 6 .

1 3 6 . Kuusisto J, Mykkanen L, Pyorala K, et al. NIDDM and its metabolic contro lp redict coro n a ry heart disease in elderly subjects. D i a b e t e s1 9 9 4 ; 4 3 : 9 6 0 - 7 .

1 3 7 . Beks PJ, Mackay AJ, de Neeling JN, et al. Peripheral arterial disease in re l a t i o nto glycaemic level in an elderly Caucasian population: the Hoorn Study.D i a b e t o l o g i a1 9 9 5 ; 3 8 : 8 6 - 9 6 .

1 3 8 . Morisaki N, Watanabe S, Kobayashi J, et al. Diabetic control and pro g re s s i o nof in elderly patients: five-year follow-up study. J Am Geriatr Soc1 9 9 4 ; 4 2 : 1 4 2 -5 .

1 3 9 . K ronsbein P, Jorgens V, Muhlhauser I, et al. Evaluation of a stru c t u red tre a t-ment and teaching programme on non-insulin-dependent diabetes. L a n c e t1 9 8 8 ; 2 : 1 4 0 7 - 1 1 .

1 4 0 . Reaven GM. Beneficial effect of moderate weight loss in older patients withnon-insulin-dependent diabetes mellitus poorly controlled with insulin. J AmGeriatr Soc1 9 8 5 ; 3 3 : 9 3 - 5 .

1 4 1 . Wilson W, Pratt C. The impact of diabetes education and peer support uponweight and glycemic control of elderly persons with noninsulin dependent dia-betes mellitus (NIDDM). Am J Public Health1 9 8 7 ; 7 7 : 6 3 4 - 5 .

1 4 2 . Coulston AM, Mandelbaum D, Reaven GM. Dietary management of nursinghome residents with non-insulin-dependent diabetes mellitus. Am J Clin Nutr1 9 9 0 ; 5 1 : 6 7 - 7 1 .

1 4 3 . S k a rfors ET, Wegener TA, Lithell H, et al. Physical training as treatment fortype 2 (non-insulin-dependent) diabetes in elderly men: a feasibility study over2 years. D i a b e t o l o g i a1 9 8 7 ; 3 0 : 9 3 0 - 3 .

1 4 4 . Asplund K, Wiholm BE, Lithner F. Glibenclamide-associated hypoglycaemia: are p o rt on 57 cases. D i a b e t o l o g i a1 9 8 3 ; 2 4 : 4 1 2 - 7 .

1 4 5 . Tessier D, Dawson KG, Tetrault JP, et al. Glibenclamide vs gliclazide in type 2diabetes of the elderly. Diabet Med1 9 9 4 ; 1 1 : 9 7 4 - 8 0 .

1 4 6 . Coscelli C, Calabrese G, Fedele D, et al. Use of premixed insulin among theelderly: reduction of errors in patient preparation of mixtures. Diabetes Care1 9 9 2 ; 1 5 : 1 6 2 8 - 3 0 .

1 4 7 . S i l v e rman BL, Rizzo TA, Cho NH. Long-term effects of the intrauterine envi-ronment: the Nort h w e s t e rn University Diabetes in Pregnancy Center. D i a b e t e sC a re 1998;(Suppl 2):B142-9.

1 4 8 . Pettit DJ, Knowler WC. Long-term effects of the intrauterine enviro n m e n t :b i rth weight and breast-feeding in Pima Indians. Diabetes Care 1 9 9 8 ; ( S u p p l2 ) : B 1 3 8 - 4 1 .

1 4 9 . Miodovnik M, Mimouni F, Dignan PS, et al. Major malformations in infants ofIDDM women: vasculopathy and early trimester poor gylcemic contro l .Diabetes Care1 9 9 8 ; 2 1 : 7 1 3 - 8 .

1 5 0 . Steel JM, Johnstone FD, Hepburn DA, et al. Can pre p regnancy care of diabet-ic women reduce the risk of abnormal babies? B M J 1 9 9 0 ; 3 0 1 : 1 0 7 0 - 4 .

1 5 1 . Hanson U, Persson B, Thunell S. Relationship between haemoglobin A1c inearly type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spon-taneous abortion and fetal malformation in Sweden. D i a b e t o l o g i a1 9 9 0 ; 3 3 : 1 0 0 -4 .

1 5 2 . Klein BE, Moss SE, Klein R. Effect of pregnancy on pro g ression of diabeticre t i n o p a t h y. Diabetes Care1 9 9 0 ; 1 3 : 3 4 - 4 0 .

1 5 3 . Reece EA, Coustan DR, Hayslett JP, et al. Diabetic nephropathy: pre g n a n c yp e rf o rmance and fetomaternal outcome. Am J Obstet Gynecol1 9 8 8 ; 1 5 9 : 5 6 - 6 6 .

1 5 4 . Small M, Cassidy L, Leiper JM, et al. Outcome of pregnancy in insulin-depen-dent (type 1) diabetic women between 1971 and 1984. Q J Med1 9 8 6 ; 6 1 : 1 1 5 9 -6 9 .

1 5 5 . Pettitt DJ, Baird HR, Aleck KA, et al. Excessive obesity in offspring of PimaIndian women with diabetes during pre g n a n c y. N Engl J Med1 9 8 3 ; 3 0 8 : 2 4 2 - 5 .

1 5 6 . Jovanovic L. American Diabetes Association’s Fourth International Wo r k s h o pC o n f e rence on Gestational Diabetes Mellitus: summary and discussion: thera-peutic interventions. Diabetes Care1 9 9 8 ; 2 1 ( 5 2 ) : B 1 3 1 - 7 .

1 5 7 . Langer O, Berkus M, Brustman L, et al. Rationale for insulin management ingestational diabetes mellitus. D i a b e t e s1 9 9 1 ; 4 0 : 1 8 6 - 9 0 .

1 5 8 . De Veciana M, Major CA, Morgan MA, et al. Postprandial versus pre p r a n d i a lblood glucose monitoring in women with gestational diabetes mellitus re q u i r-ing insulin therapy. N Engl J Med1 9 9 5 ; 3 3 3 : 1 2 3 7 - 4 1 .

1 5 9 . Jovanovic-Peterson L, Durak EP, Peterson CM. Randomized trial of diet ver-sus diet plus cardiovascular conditioning on glucose levels in gestational dia-betes. Am J Obstet Gynecol1 9 8 9 ; 1 6 1 : 4 1 5 - 9 .

1 6 0 . Kaufmann RC, Schleyhahn RC, Huffman DG, et al. Gestational diabetes diag-nostic criteria: long-term maternal follow-up. Am J Obstet Gynecol1 9 9 5 ; 1 7 2 : 6 2 1 - 5 .

1 6 1 . O’Sullivan JB, Mahan CM. Diabetes subsequent to the birth of a large baby: a16-year prospective study. J Chronic Dis1 9 8 0 ; 3 3 : 3 7 - 4 5 .

1 6 2 . Delisle HF, Ekoe JM. Prevalence of non-insulin-dependent diabetes mellitusand impaired glucose tolerance in two Algonquin communities in Quebec.

C M A J 1 9 9 3 ; 1 4 8 : 4 1 - 7 .1 6 3 . H a rris SB, Gittelsohn J, Hanley A, et al. The prevalence of NIDDM and asso-

ciated risk factors in Native Canadians. Diabetes Care1 9 9 7 ; 2 0 : 1 8 5 - 7 .1 6 4 . Macauley AC, Paradia G, Potvin L, et al. The Kahnawake Schools Diabetes

P revention Project: intervention, evaluation, and baseline results of a diabetesp r i m a ry prevention program with a native community in Canada. P rev Med1 9 9 7 ; 2 8 : 7 7 9 - 9 0 .

1 6 5 . Dean HJ, Mundy RL, Moffat M. Non-insulin-dependent diabetes mellitus inIndian children in Manitoba. C M A J 1 9 9 2 ; 1 4 7 : 5 2 - 7 .

1 6 6 . Dean HJ. NIDDM-Y in First Nations children in Canada. Clin Pediatr (Phila)1 9 9 8 ; 3 7 : 8 9 - 9 6 .

1 6 7 . Fox C, Harris SB, Whalen-Brough E. Diabetes among Native Canadians inN o rt h w e s t e rn Ontario: 10 years later. C h ronic Dis Can1 9 9 4 ; 1 5 : 9 2 - 6 .

1 6 8 . H a rris SB, Caulfield LE, Sugamori ME, et al. The epidemiology of diabetes inp regnant Native Canadians. Diabetes Care1 9 9 7 ; 2 0 : 1 4 2 2 - 5 .

1 6 9 . Klein R, Klein BEK, Moss SE. Visual impairment in diabetes. O p h t h a l m o l o g y1 9 8 4 ; 9 1 : 1 - 9 .

1 7 0 . Klein R, Klein BEK, Moss SE. Epidemiology of proliferative diabetic re t i n o p a-t h y. Diabetes Care1 9 9 2 ; 1 5 : 1 8 7 5 - 9 1 .

1 7 1 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study ofDiabetic Retinopathy. IV. Diabetic macular edema. O p h t h a l m o l o g y1 9 8 4 ; 9 1 : 1 4 6 4 - 7 4 .

1 7 2 . Klein BEK, Klein R, Wang Q, et al. Older-onset diabetes and lens opacities.The Beaver Dam Eye Study. Ophthalmic Epidemiol1 9 9 5 ; 2 : 4 9 - 5 5 .

1 7 3 . Klein BEK, Klein R, Jensen SC. Open-angle glaucoma and older-onset dia-betes: the Beaver Dam Eye Study. O p h t h a l m o l o g y1 9 9 4 ; 1 0 1 : 1 1 7 3 - 7 .

1 7 4 . Tielsch JT, Katz J, Quigley HA. Diabetes, intraocular pre s s u re, and primaryopen-angle glaucoma in the Baltimore Eye Study. O p h t h a l m o l o g y1 9 9 5 ; 1 0 2 : 4 8 -5 3 .

1 7 5 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study ofDiabetic Retinopathy. IX. Four-year incidence and pro g ression of diabeticretinopathy when age at diagnosis is less than 30 years. A rch Ophthalmol1 9 8 9 ; 1 0 7 : 2 3 7 - 4 3 .

1 7 6 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study ofDiabetic Retinopathy. X. Four-year incidence and pro g ression of diabeticretinopathy when age at diagnosis is 30 years or more. A rch Ophthalmol1 9 8 9 ; 1 0 7 : 2 4 4 - 9 .

1 7 7 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiology Study ofDiabetic Retinopathy. II. Prevalence and risk of diabetic retinopathy when ageat diagnosis is less than 30 years. A rch Ophthalmol1 9 8 4 ; 1 0 2 : 5 2 0 - 6 .

1 7 8 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiology Study ofDiabetic Retinopathy. III. Prevalence and risk of diabetic retinopathy when ageat diagnosis is 30 or more years. A rch Ophthalmol1 9 8 4 ; 1 0 2 : 5 2 7 - 3 2 .

1 7 9 . Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levelswith retinal hard exudate in diabetic re t i n o p a t h y. Early Treatment DiabeticRetinopathy Study re p o rt 22. A rch Ophthalmol1 9 9 6 ; 1 1 4 : 1 0 7 9 - 8 4 .

1 8 0 . Klein R, Moss SE, Klein BEK, et al. The Wisconsin Epidemiologic Study ofDiabetic Retinopathy. XI. The incidence of macular edema. O p h t h a l m o l o g y1 9 8 9 ; 9 6 : 1 5 0 1 - 1 0 .

1 8 1 . Early Treatment Diabetic Retinopathy Study Research Group. Grading diabet-ic retinopathy from stereoscopic color fundus photographs — an extension ofthe modified Airlie House classification. ETDRS re p o rt 10. O p h t h a l m o l o g y1 9 9 1 ; 9 8 : 7 8 6 - 8 0 6 .

1 8 2 . Moss SE, Klein R, Kessler SD, et al. Comparison between ophthalmoscopy andfundus photography in determining severity of diabetic re t i n o p a t h y.O p h t h a l m o l o g y1 9 8 5 ; 9 2 : 6 2 - 7 .

1 8 3 . Nathan DM, Fogel HA, Godine JE, et al. Role of diabetologist in evaluatingdiabetic re t i n o p a t h y. Diabetes Care1 9 9 1 ; 1 4 : 2 6 - 3 3 .

1 8 4 . Sussman EJ, Tsiaras WG, Soper KA. Diagnosis of diabetic eye disease. J A M A1 9 8 2 ; 2 4 7 : 3 2 3 1 - 4 .

1 8 5 . Kinyoun J, Barton F, Fisher M, et al. Detection of diabetic macular edema: oph-thalmoscopy versus photography. Early Treatment Diabetic Retinopathy Studyre p o rt 5. O p h t h a l m o l o g y1 9 8 9 ; 9 6 : 7 4 6 - 5 1 .

1 8 6 . Early Treatment Diabetic Retinopathy Study Research Group. Fundus photo-graphic risk factors for pro g ression of diabetic re t i n o p a t h y. ETDRS re p o rt 12.O p h t h a l m o l o g y1 9 9 1 ; 9 8 : 8 2 3 - 3 3 .

1 8 7 . Klein R, Klein BEK, Moss SE, et al. Relationship of hyperglycemia to the long-t e rm incidence and pro g ression of diabetic re t i n o p a t h y. A rch Intern Med1 9 9 4 ; 1 5 4 : 2 1 6 9 - 7 8 .

1 8 8 . Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study ofDiabetic Retinopathy. XV. The long-term incidence of macular edema.O p h t h a l m o l o g y1 9 9 5 ; 1 0 2 : 7 - 1 6 .

1 8 9 . Moss SE, Klein R, Klein BEK. Ten-year incidence of visual loss in a diabeticpopulation. O p h t h a l m o l o g y1 9 9 4 ; 1 0 1 : 1 0 6 1 - 7 0 .

1 9 0 . Early Treatment Diabetic Retinopathy Study Research Gro u p .Photocoagulation for diabetic macular edema. ETDRS re p o rt 1. A rc hO p h t h a l m o l1 9 8 5 ; 1 0 3 : 1 7 9 6 - 8 0 6 .

1 9 1 . F e rris FL. How effective are treatments for diabetic retinopathy? J A M A1 9 9 3 ; 2 6 9 : 1 2 9 0 - 1 .

1 9 2 . Diabetic Retinopathy Study Research Group. Photocoagulation treatment ofp roliferative diabetic retinopathy: the second re p o rt of Diabetic RetinopathyStudy findings. O p h t h a l m o l o g y1 9 7 8 ; 8 5 : 8 2 - 1 0 6


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S2 7

1 9 3 . F e rris F. Early photocoagulation in patients with either Type 1 or Type 11 dia-betes. Trans Am Ophthalmol Soc1 9 9 6 ; 9 4 : 5 0 5 - 3 7 .

1 9 4 . Diabetic Retinopathy Vi t rectomy Study Research Group. Early vitrectomy fors e v e re vitreous hemorrhage in diabetic re t i n o p a t h y. Four-year results of a ran-domized trial. Diabetic Retinopathy Vi t rectomy Study re p o rt 5. A rc hO p h t h a l m o l1 9 9 0 ; 1 0 8 : 9 5 8 - 6 4 .

1 9 5 . Diabetic Retinopathy Vi t rectomy Study Research Group. Early vitrectomy fors e v e re proliferative diabetic retinopathy in eyes with useful vision: results of arandomized trial. Diabetic Retinopathy Vi t rectomy Study re p o rt 3.O p h t h a l m o l o g y1 9 8 8 ; 9 5 : 1 3 0 7 - 2 0 .

1 9 6 . Canadian Organ Replacement Registry. Annual re p o rt 1996. Ottawa: CanadianInstitute for Health Information; 1996. Abstract.

1 9 7 . K rolewski AS, Wa rram JH, Fre i re MB. Epidemiology of late diabetic complica-tions. A basis for the development and evaluation of preventive pro g r a m s .Endocrinol Metab Clin North Am1 9 9 6 ; 2 5 : 2 1 7 - 4 2 .

1 9 8 . Incidence and causes of treated ESRD [abstract]. In: Annual re p o rt. Bethesda(Md): United States Renal Data System; 1995. p. 25-37.

1 9 9 . B o rch-Johnsen K, Kreiner S. Proteinuria: value as predictor of card i o v a s c u l a rm o rtality in insulin dependent diabetes mellitus. B M J 1 9 8 7 ; 2 9 4 : 1 6 5 1 - 4 .

2 0 0 . Earle K, Walker J, Hill C, et al. Familial clustering of cardiovascular disease inpatients with insulin-dependent diabetes and nephro p a t h y. N Engl J Med1 9 9 2 ; 3 2 6 : 6 7 3 - 7 .

2 0 1 . K rolewski AS, Wa rram JH, Christlieb AR, et al. The changing natural history ofn e p h ropathy in type I diabetes. Am J Med 1 9 8 5 ; 7 8 : 7 8 5 - 9 4 .

2 0 2 . Selby JV, Fitzsimmons SC, Newman JM, et al. The natural history and epi-demiology of diabetic nephro p a t h y. Implications for prevention and contro l .J A M A 1 9 9 0 ; 2 6 3 : 1 9 5 4 - 6 0 .

2 0 3 . Wang SL, Head J, Stevens L, et al. Excess mortality and its relation to hyper-tension and proteinuria in diabetic patients: the WHO multinational study ofvascular disease in diabetes. Diabetes Care1 9 9 6 ; 1 9 : 3 0 5 - 1 2 .

2 0 4 . Almdal T, Norg a a rd K, Feldt-Rasmussen B, et al. The predictive value ofm i c roalbuminuria in IDDM. A five-year follow-up study. Diabetes Care1 9 9 4 ; 1 7 : 1 2 0 - 5 .

2 0 5 . Forsblom CM, Groop PH, Ekstrand A, et al. Predictive value of micro a l b u m i n-uria in patients with insulin-dependent diabetes of long duration. B M J1 9 9 2 ; 3 0 5 : 1 0 5 1 - 3 .

2 0 6 . Mathiesen ER, Ronn B, Storm B, et al. The natural course of micro a l b u m i n u r i ain insulin-dependent diabetes: a 10-year prospective study. Diabet Med1 9 9 5 ; 1 2 : 4 8 2 - 7 .

2 0 7 . Messent JW, Elliott TG, Hill RD, et al. Prognostic significance of micro a l b u-minuria in insulin-dependent diabetes mellitus: a twenty-three year follow-ups t u d y. Kidney Int1 9 9 2 ; 4 1 : 8 3 6 - 9 .

2 0 8 . Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med1 9 8 4 ; 3 1 1 : 8 9 - 9 3 .

2 0 9 . Ravid M, Savin H, Jutrin I, et al. Long-term stabilizing effect of angiotensin-c o n v e rting enzyme inhibition on plasma creatinine and on proteinuria in nor-motensive type II diabetic patients. Ann Intern Med1 9 9 3 ; 1 1 8 : 5 7 7 - 8 1 .

2 1 0 . Vi b e rti GC, Hill RD, Jarrett RJ, et al. Microalbuminuria as a predictor of clini-cal nephropathy in insulin-dependent diabetes mellitus. L a n c e t1 9 8 2 ; 1 : 1 4 3 0 - 2 .

2 1 1 . K rolewski AS, Laffel LM, Krolewski M, et al. Glycosolated hemoglobin and therisk of microalbuminuria in patients with insulin-dependent diabetes mellitus. NEngl J Med1 9 9 5 ; 3 3 2 : 1 2 5 1 - 5 .

2 1 2 . Nelson RG, Knowler WC, Pettitt DJ, et al. Assessment of risk of overtn e p h ropathy in diabetic patients from albumin excretion in untimed urine spec-imens. A rch Intern Med1 9 9 1 ; 1 5 1 : 1 7 6 1 - 5 .

2 1 3 . Poulsen PL, Hansen B, Amby T, et al. Evaluation of a dipstick test for micro a l-buminuria in three diff e rent clinical settings, including the correlation with uri-n a ry albumin excretion rate. Diabetes Metab1 9 9 2 ; 1 8 : 3 9 5 - 4 0 0 .

2 1 4 . Schwab SJ, Dunn FL, Feinglos MN. Screening for microalbuminuria. A com-parison of single sample methods of collection and techniques of albumin analy-sis. Diabetes Care1 9 9 2 ; 1 5 : 1 5 8 1 - 4 .

2 1 5 . Wa rram JH, Gearin G, Laffel LM, et al. Effect of duration of type I diabetes onthe prevalence of stages of diabetic nephropathy defined by urinary albumin/cre-atinine ratio. J Am Soc Nephro l1 9 9 6 ; 7 : 9 3 0 - 7 .

2 1 6 . Beck-Nielsen H, Richelsen B, Mogensen CE, et al. Effect of insulin pump tre a t-ment for one year on renal function and retinal morphology in patients withIDDM. Diabetes Care1 9 8 5 ; 8 : 5 8 5 - 9 .

2 1 7 . Christensen CK, Christiansen JS, Schmitz A, et al. Effect of continuous subcu-taneous insulin infusion on kidney function and size in IDDM patients: a 2 yearc o n t rolled study. J Diabet Complications1 9 8 7 ; 1 : 9 1 - 5 .

2 1 8 . D a h l - J o rgensen K, Hanssen KF, Kierulf P, et al. Reduction of urinary albumine x c retion after 4 years of continuous subcutaneous insulin-dependent diabetesmellitus. Acta Endocrinol (Copenh)1 9 8 8 ; 1 1 7 : 1 9 - 2 5 .

2 1 9 . D e c k e rt T, Lauritzen T, Parving HH, et al. Effect of two years of strict meta-bolic functions in long term insulin-dependent diabetes. Diabet Nephro p a t h y1 9 8 4 ; 3 : 6 - 1 0 .

2 2 0 . Lauritzen T, Frost-Larsen K, Larsen KF, et al. Two-year experience with con-tinuous subcutaneous insulin infusion in relation to retinopathy and neuro p a t h y.D i a b e t e s1 9 8 5 ; 3 4 : 7 4 - 9 .

2 2 1 . R e i c h a rd P, Nilsson BY, Rosenqvist U. The effect of long-term intensifiedinsulin treatment on the development of microvascular complications of diabetesmellitus. N Engl J Med1 9 9 3 ; 3 2 9 : 3 0 4 - 9 .

2 2 2 . R e i c h a rd P, Berglund B, Britz A, et al. Intensified conventional insulin tre a t m e n tre t a rds the microvascular complications of insulin-dependent diabetes mellitus(IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years. JI n t e rn Med1 9 9 1 ; 2 3 0 : 1 0 1 - 8 .

2 2 3 . K roc Collaborative Study Group. Blood glucose control and the evolution ofdiabetic retinopathy and albuminuria. N Engl J Med1 9 8 4 ; 3 1 1 : 3 6 5 - 7 2 .

2 2 4 . Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glu-cose control on late complications of type I diabetes. L a n c e t1 9 9 3 ; 3 4 1 : 1 3 0 6 - 9 .

2 2 5 . L a ffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensin-convert i n genzyme inhibition with captopril on diabetic nephropathy in norm o t e n s i v eIDDM patients with microalbuminuria. North American Micro a l b u m i n u r i aStudy Group. Am J Med 1 9 9 5 ; 9 9 : 4 9 7 - 5 0 4 .

2 2 6 . Mathiesen ER, Hommel E, Giese J, et al. Efficacy of captopril in postponingn e p h ropathy in normotensive insulin dependent diabetic patients with micro a l-buminuria. B M J 1 9 9 1 ; 3 0 3 : 8 1 - 7 .

2 2 7 . Ravid M, Lang R, Rachmani R, et al. Long-term re n o p rotective effect ofa n g i o t e n s i n - c o n v e rting enzyme inhibition in non-insulin-dependent diabetesmellitus: a 7-year follow-up study. A rch Intern Med1 9 9 6 ; 1 5 6 : 2 8 6 - 9 .

2 2 8 . Sano T, Kawamura T, Matsumae H, et al. Effects of long-term enalapril tre a t-ment on persistent microalbuminuria in well-controlled hypertensive and nor-motensive NIDDM patients. Diabetes Care1 9 9 4 ; 1 7 : 4 2 0 - 4 .

2 2 9 . M i c roalbuminuria Captopril Study Group. Captopril reduces the risk ofn e p h ropathy in IDDM patients with microalbuminuria. D i a b e t o l o g i a1 9 9 6 ; 3 9 : 5 8 7 - 9 3 .

2 3 0 . B j o rck S, Mulec H, Johnsen SA, et al. Renal protective effect of enalapril in dia-betic nephro p a t h y. B M J 1 9 9 2 ; 3 0 4 : 3 3 9 - 4 3 .

2 3 1 . Kasiske BL, Kalil RS, Ma JZ, et al. Effect of antihypertensive therapy on the kid-ney in patients with diabetes: a meta-re g ression analysis. Ann Intern Med1 9 9 3 ; 1 1 8 : 1 2 9 - 3 8 .

2 3 2 . L a c o u rc i e re Y, Nadeau A, Poirer L, et al. Captopril or conventional therapy inh y p e rtensive type II diabetics. Three-year analysis. H y p e rt e n s i o n1 9 9 3 ; 2 1 : 7 8 6 - 9 4 .

2 3 3 . Lewis SB, Hunsicker LG, Bain RP, et al. The effect of angiotensin-convert i n genzyme inhibition on diabetic nephro p a t h y. N Engl J Med1 9 9 3 ; 3 2 9 : 1 4 5 6 - 6 2 .

2 3 4 . Liou HH, Huang TP, Campese VM. Effect of long-term therapy with captoprilon proteinuria and renal function in patients with non-insulin-dependent dia-betes and with non-diabetic renal diseases. N e p h ro n1 9 9 5 ; 6 9 : 4 1 - 8 .

2 3 5 . Mathiesen ER, Borch-Johnsen K, Jensen DV, et al. Improved survival in patientswith diabetic nephro p a t h y. D i a b e t o l o g i a1 9 8 9 ; 3 2 : 8 8 4 - 6 .

2 3 6 . Mogenson CE. Long-term antihypertensive treatment inhibiting pro g ression ofdiabetic nephro p a t h y. B M J 1 9 8 2 ; 2 8 5 : 6 8 5 - 8 .

2 3 7 . Nielsen FS, Rossing P, Gall MA, et al. Impact of lisinopril and atenolol on kid-ney function in hypertensive NIDDM subjects wtih diabetic nephro p a t h y.D i a b e t e s1 9 9 4 ; 4 3 : 1 1 0 8 - 1 3 .

2 3 8 . P a rving HH, Smidt UM, Hommel E, et al. Effective antihypertensive tre a t m e n tpostpones renal insufficiency in diabetic nephro p a t h y. Am J Kidney Dis1 9 9 3 ; 2 2 : 1 8 8 - 9 5 .

2 3 9 . P a rving HH, Hommel E. Prognosis in diabetic nephro p a t h y. B M J1 9 8 9 ; 2 9 9 : 2 3 0 - 3 .

2 4 0 . P a rving HH, Andersen AR, Smidt UM, et al. Early aggressive anti-hypert e n s i v et reatment reduces rate of decline in kidney function in diabetic nephro p a t h y.L a n c e t1 9 8 3 ; 1 : 1 1 7 5 - 9 .

2 4 1 . American Diabetes Association. Treatment of hypertension in diabetes. D i a b e t e sC a re 1 9 9 6 ; 1 9 : S 1 0 7 - 1 7 .

2 4 2 . American Diabetes Association. Standards of medical care for patients with dia-betes mellitus. Diabetes Care1 9 9 4 ; 1 7 : 6 1 6 - 2 3 .

2 4 3 . American Diabetes Association. Role of cardiovascular risk factors in pre v e n t i o nand treatment of macrovascular disease in diabetes. Diabetes Care1 9 9 3 ; 1 6 : S 7 2 - 8 .

2 4 4 . American Diabetes Association. Detection and management of lipid disorders indiabetes. Diabetes Care1 9 9 3 ; 1 6 : S 1 0 6 - 1 2 .

2 4 5 . Pedrini MT, Levey AS, Lau J, et al. The effect of dietary protein restriction onthe pro g ression of diabetic and non-diabetic renal diseases: a meta-anaylsis. A n nI n t e rn Med1 9 9 6 ; 1 2 4 : 6 2 7 - 3 2 .

2 4 6 . P a rtanen J, Niskanen L, Lehtinen J, et al. Natural history of peripheral neu-ropathy in patients with non-insulin-dependent diabetes mellitus. N Engl J Med1 9 9 5 ; 3 3 3 : 8 9 - 9 4 .

2 4 7 . Max MB, Lynch SA, Muir J, et al. Effects of desipramine, amitriptyline and flu-oxetine on pain in diabetic neuro p a t h y. N Engl J Med1 9 9 2 ; 3 2 6 : 1 2 5 0 - 6 .

2 4 8 . Max MB, Kishore-Kumar R, Schafer SC, et al. Efficacy of desipramine in painfuldiabetic neuropathy: a placebo-controlled trial. P a i n 1 9 9 1 ; 4 5 : 1 - 9 .

2 4 9 . Max MB, Culnane M, Schafer SC, et al. Amitriptyline relieves diabetic neu-ropathy pain in patients with normal or depressed mood. N e u ro l o g y1 9 8 7 ; 3 7 : 5 8 9 -9 6 .

2 5 0 . Young MJ, Breddy JL, Veves A, et al. The prediction of diabetic neuropathic footulceration using vibration perception thresholds: a prospective study. D i a b e t e sC a re 1 9 9 4 ; 1 7 : 5 5 7 - 6 0 .

2 5 1 . Vinik AI, Suwanwalaikorn S, Stansberry KB, et al. Quantitative measurement ofcutaneous perception in diabetic neuro p a t h y. Muscle Nerv e 1 9 9 5 ; 1 8 : 5 7 4 - 8 4 .

2 5 2 . Diabetes Control and Complications Trial Research Group (DCCT). The eff e c tof intensive diabetes therapy on the development and pro g ression of neuro p a t h y.Ann Intern Med1 9 9 5 ; 1 2 2 : 5 6 1 - 8 .

2 5 3 . G o m e z - P e rez FJ, Rull JA, Dies H, et al. Nortriptyline and fluphenazine in thesymptomatic treatment of diabetic neuro p a t h y. A double-blind cross-over study.

Meltzer et al

S2 8 JAMC • 20 OCT. 1998; 159 (8 Suppl)

P a i n 1 9 8 5 ; 2 3 : 3 9 5 - 4 0 0 .2 5 4 . McQuay H, Carroll D, Jadad AR, et al. Anticonvulsant drugs for management

of pain: a systematic re v i e w. B M J 1 9 9 5 ; 3 1 1 : 1 0 4 7 - 5 2 .2 5 5 . Stracke H, Meyer UE, Schumacher HE, et al. Mexiletene in the treatment of

diabetic neuro p a t h y. Diabetes Care1 9 9 2 ; 1 5 : 1 5 5 0 - 5 .2 5 6 . Low PA, Opfer-Gehrking TL, Dyck PJ, et al. Double-blind, placebo-contro l l e d

study of the application of capsaicin cream in chronic distal painful polyneu-ro p a t h y. P a i n 1 9 9 5 ; 6 2 : 1 6 3 - 8 .

2 5 7 . Capsaicin Study Group. Treatment of painful diabetic neuropathy with topicalcapsaicin. A multicenter, double-blind, vehicle-controlled study. A rch InternM e d1 9 9 1 ; 1 5 1 : 2 2 2 5 - 9 .

2 5 8 . American Diabetes Association clinical practice recommendations 1997: footc a re in patients with diabetes mellitus. Diabetes Care1997;20(Suppl 1):1-70.

2 5 9 . Reiber GE, Boyko EJ, Smith DG. Lower extremity foot ulcers and amputationsin diabetes. In: Diabetes in America. 2nd ed. Washington: National DiabetesData Group, National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health; 1995. p. 409.

2 6 0 . Eastman RC. Neuropathy in diabetes. In: Diabetes in America. 2nd ed.Washington: National Diabetes Data Group, National Institute of Diabetesand Digestive and Kidney Diseases, National Institutes of Health; 1995. p. 339.

2 6 1 . Palumbo PJ, Melton LJ. Peripheral vascular disease and diabetes. In: Diabetes inA m e r i c a. 2nd ed. Washington: National Diabetes Data Group, NationalInstitute of Diabetes and Digestive and Kidney Diseases, National Institutes ofHealth; 1995. p. 401.

2 6 2 . Boyko EJ, Lipsky BA. Infection and diabetes. In: Diabetes in America. 2nd ed.Washington: National Diabetes Data Group, National Institute of Diabetesand Digestive and Kidney Diseases, National Institutes of Health; 1995. p. 485.

2 6 3 . F ry k b e rg RD. Diabetic foot ulcerations. In: The high risk foot in diabetes mellitus.New York: Churchill Livingstone; 1991. p. 151.

2 6 4 . F ry k b e rg RG, Veves A. Diabetic foot infections. Diabetes Metab Rev1 9 9 6 ; 1 2 : 2 5 5 - 7 0 .

2 6 5 . Gibbons GW, Eliopoulos GM, Kozak GP, et al. Infection of the diabetic foot.In: Kozak GP, Campbell DR, Fry k b e rg RG, et al., editors. Management of dia -betic foot pro b l e m s. Philadelphia: Saunders; 1995. p. 121.

2 6 6 . Reiber GE, Pecoraro RE, Koepsell TD. Risk factors for amputation in patientswith diabetes mellitus: a case control study. Ann Intern Med1 9 9 2 ; 1 1 7 : 9 7 - 1 0 5 .

2 6 7 . Bild DE, Selby JV, Sinnock P, et al. Lower- e x t remity amputation in people withdiabetes: epidemiology and prevention. Diabetes Care1 9 8 9 ; 1 2 : 2 4 - 3 1 .

2 6 8 . Reiber GE. Epidemiology of the diabetic foot. In: Levin ME, O’Neal LW,Bowker JH, editors. The diabetic foot. St. Louis: Mosby; 1993. p. 1.

2 6 9 . Ebskov B, Josephsen P. Incidence of reamputation and death after gangrene ofthe lower extre m i t y. P rosthet Orthot Int1 9 8 0 ; 4 : 7 7 - 8 0 .

2 7 0 . Most RS, Sinnock P. The epidemiology of lower extremity amputations in dia-betic individuals. Diabetes Care1 9 8 3 ; 6 : 8 7 - 9 1 .

2 7 1 . Diabetes surveillance, 1991. Washington: United States Dept of Health andHuman Services; 1991. Abstract.

2 7 2 . Assal JP, Muhlhauser I, Pernet A, et al. Patient education as the basis for dia-betes care in clinical practice and re s e a rch. Diabetologia 1 9 8 5 ; 2 8 : 6 0 2 - 1 3 .

2 7 3 . Litzelman DK, Slemenda CW, Langefeld CD, et al. Reduction of lowere x t remity clinical abnormalities in patients with non-insulin-dependent dia-betes mellitus. A randomized controlled trial. Ann Intern Med1 9 9 3 : 1 1 9 : 3 6 - 4 1 .

2 7 4 . Malone JM, Snyder M, Anderson G, et al. Prevention of amputation by diabet-ic education. Am J Surg 1 9 8 9 ; 1 5 8 : 5 2 0 - 4 .

2 7 5 . Fuller JH, Elford J, Goldblatt P, et al. Diabetes mortality: new light on anu n d e restimated public health problem. D i a b e t o l o g i a1 9 8 3 ; 2 4 : 3 3 6 - 4 1 .

2 7 6 . G a rcia MJ, McNamara PM, Gordon T, et al. Morbidity and mortality in dia-betics in the Framingham population. Sixteen year follow-up study. D i a b e t e s1 9 7 4 ; 2 3 : 1 0 5 - 1 1 .

2 7 7 . J a rrett J. Mortality in diabetes. Q J Med1 9 9 0 ; 7 5 : 4 1 3 - 4 .2 7 8 . Stamler J, Va c c a ro O, Neaton JD, et al. Diabetes, other risk factors, and 12-year

c a rdiovascular mortality for men screened in the Multiple Risk FactorI n t e rvention Trial. Diabetes Care1 9 9 3 ; 1 6 : 4 3 4 - 4 4 .

2 7 9 . K rolewski AS, Kosinski EJ, Wa rram JH, et al. Magnitude and determinants ofc o ro n a ry art e ry disease in juvenile-onset, insulin-dependent diabetes mellitus.Am J Card i o l1 9 8 7 ; 5 9 : 7 5 0 - 5 .

2 8 0 . Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framinghams t u d y. J A M A 1 9 7 9 ; 2 4 1 : 2 0 3 5 - 8 .

2 8 1 . Kessler II. Mortality experience of diabetic patients: a twenty-six year follow-ups t u d y. Am J Med 1 9 7 1 ; 5 1 : 7 1 5 - 2 4 .

2 8 2 . L e rner D, Kannel WB. Patterns of coro n a ry heart disease morbidity and mor-tality in the sexes: a 26-year follow-up of the Framingham population. A mH e a rt J 1 9 8 6 ; 1 1 1 : 3 8 3 - 9 0 .

2 8 3 . Nesto RW, Phillips RT, Kett KG, et al. Angina and exertional myocard i a lischemia in diabetic and nondiabetic patients: assessment by exercise thalliums c i n t i g r a p h y. Ann Intern Med1 9 8 8 ; 1 0 8 : 1 7 0 - 5 .

2 8 4 . Scheidt-Nave C, Barrett-Connor E, Wi n g a rd DL. Resting electro c a rd i o g r a p h-ic abnormalities suggestive of asymptomatic ischemic heart disease associatedwith non-insulin-dependent diabetes mellitus in a defined population.C i rc u l a t i o n1 9 9 0 ; 8 1 : 8 9 9 - 9 0 6 .

2 8 5 . Weiner DA, Ryan TJ, Parsons L, et al. Significance of silent myocard i a l

ischemia during exercise testing in patients with diabetes mellitus: a re p o rt fro mthe Coro n a ry Art e ry Surg e ry Study (CASS) Registry. Am J Card i o l1 9 9 1 ; 6 8 : 7 2 9 - 3 4 .

2 8 6 . Abbott RD, Donahue RP, Kannel WB, et al. The impact of diabetes on surv i v a lfollowing myocardial infarction in men vs. women: the Framingham Study.J A M A 1 9 8 8 ; 2 6 0 : 3 4 5 6 - 6 0 .

2 8 7 . Zuanetti G, Latini R, Maggioni AP, et al. Influence of diabetes on mortality inacute myocardial infarction: data from the GISSI-2 study. J Am Coll Card i o l1 9 9 3 ; 2 2 : 1 7 8 8 - 9 4 .

2 8 8 . Yudkin JS. How can we best prolong life? Benefits of coro n a ry risk factor re d u c-tion in non-diabetic and diabetic subjects. B M J 1 9 9 3 ; 3 0 6 : 1 3 1 3 - 8 .

2 8 9 . Downs JR, Beere PA, Whitney E, et al. Design and rationale of the Air Forc e /Texas Coro n a ry Athero s c l e rosis Prevention Study (AFCAPS/TexCAPS). Am JC a rd i o l1 9 9 7 ; 8 0 ( 3 ) : 2 8 7 - 9 3 .

2 9 0 . Antiplatelets Trialists Collaboration. Collaborative overview of randomized tri-als of antiplatelet therapy: prevention of death, myocardial infarction and stro k eby prolonged antiplatelet therapy in various categories of patients. B M J1994;308:71-72, 81-106.

2 9 1 . Early Treatment Diabetic Retinopathy Study Research Group. Aspirin eff e c t son mortality in patients with diabetes mellitus. J A M A 1 9 9 2 ; 2 6 8 : 1 2 9 2 - 3 0 0 .

2 9 2 . Early Treatment Diabetic Retinopathy Study Research Group. Effects ofaspirin on treatment of retinopathy: ETDRS re p o rt 8. O p h t h a l m o l o g y1 9 9 1 ; 9 8 :7 5 7 - 6 5 .

2 9 3 . Joint National Committee on Detection, Evaluation and Treatment of HighBlood Pre s s u re. The sixth re p o rt of the Joint National Committee onDetection, Evaluation, and Treatment of High Blood Pre s s u re. A rch Intern Med1 9 9 7 ; 1 5 7 : 2 4 1 3 - 4 6 .

2 9 4 . Dawson KG, McKenzie JK, Ross SA, et al. Report of the CanadianH y p e rtension Society Consensus Conference: 5. Hypertension and diabetes.C M A J 1993;149:821-6.

2 9 5 . Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypert e n s i v et reatment on cardiovascular disease risk in older diabeteic patients with isolat-ed systolic hypertension. Systolic hypertension in the elderly program cooper-ative re s e a rch group. J A M A 1 9 9 6 ; 2 7 6 : 1 8 8 6 - 9 2 .

2 9 6 . Estacio OE, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compare dto enalapril on cardiovascular outcomes in patients with non-insulin dependentdiabetes and hypertension. N Engl J Med1 9 9 8 ; 3 3 8 : 6 4 5 - 5 2 .

2 9 7 . Tatti P, Pahor M, Byington RP, et al. Outcome results of the fosinopril versusamlodipine cardiovascular events randomized trial (FACET) in patients withh y p e rtension and NIDDM. Diabetes Care1 9 9 8 ; 2 1 : 5 9 7 - 6 0 3 .

2 9 8 . United Kingdom Prospective Diabetes Study Group. Intensive blood glucosec o n t rol with sulphonylureas or insulin compared with conventional tre a t m e n tand risk of complications in patients with type 2 diabetes. (UKPDS 33). L a n c e t1 9 9 8 ; 3 5 2 : 8 3 7 - 5 3 .

2 9 9 . E ffect of intensive blood glucose control with metformin on complications ino v e rweight patients with type 2 diabetes. (UKPDS 34). L a n c e t1 9 9 8 ; 3 5 2 : 8 5 4 - 6 5 .

3 0 0 . Tight blood pre s s u re control and risk of macrovascular and microvascular com-plications in type 2 diabetes. (UKPDS 38). B M J 1 9 9 8 ; 3 1 7 : 7 0 3 - 1 3 .

3 0 1 . E fficacy of atenolol and captopril in reducing risk of macrovascular andm i c rovascular complications in type 2 diabetes. (UKPDS 39). B M J1 9 9 8 ; 3 1 7 : 7 1 3 - 2 0 .

3 0 2 . Cost effectiveness analysis of improved blood pre s s u re control in hypert e n s i v epatients with type 2 diabetes. (UKPDS 40). B M J 1 9 9 8 ; 3 1 7 : 7 2 0 - 6 .

C o r respondence to: Donna Lillie, Canadian Diabetes A s s o c i a t i o n ,National Office, 15 Toronto St., Toronto ON M 5 C2 E 3

*Steering Committee co-chairs: S a ra Meltzer, MD and Law r e n c eL e i t e r, MD. Subcommittee chairs: Denis Daneman, MD (Definition,Classification and Screening); David Lau, MD, PhD (Complicationsc o - chair); Je a n - François Yale, MD (Management); Hertzel C. Gerstein,M D, MSc (Evidence-Based); Sora Ludwig, MD (Organization of Care);and Bernard Zinman, MD (Complications co-chair). S t e e r i n gCommittee members: Keith Dawson, MD, PhD; Jana Hav ra n k ova ,MD; Beverley Madrick, RD, CDE; Meng-Hee Tan, MD; Stewart Harris,M D, MPH; Donna Lillie, RN, BA; Beryl Schultz, RN, CDE. E x p e r tCommittee members: Irwin N. Antone, MD; Iain Begg, MB; A n d r eB e l a n g e r, MD, MSc; Ti m o t hy Benstead, MDC; Claude Catellier, MD;Keith Dawson, MD, PhD; Heather Dean, MD; Peggy Dunbar, MEd,PDt, CDE; Lynn Edwards, PDt, CDE; Jean-Marie Ekoe, MD; Fra n ç o i sGilbert, MD; Jana Hav ra n k ova, MD; Stewart Harris, MD, MPH; A n n eHolbrook, MD, MSc, PharmD; Dereck Hunt, MD; Carol Joyce, MD;Jeff Mahon, MD; Errol Marliss, MD; James McSherry, MD; Gray d o nM e n e i l l y, MD; Stuart Ross, MD; Edmond A. Ryan, MD; Andrew Steele,MDC; Catharine Whiteside, MD, PhD; Thomas Wo l e ve r, MD, PhD


CMAJ • O C T. 2 0, 1998; 159 (8 Suppl) S2 9

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