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Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com38

SCREENING FOR TYPE 2 DIABETES MELLITUS

For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.

COMMENTARY

From the Department of Medicine (A.M.S., D.B.C.) and Department of Anes-thesiology (D.B.C.), University of Wisconsin School of Medicine and PublicHealth, Madison; and Penn State Diabetes and Obesity Institute, Penn StateCollege of Medicine, Hershey, PA (R.A.G.).

Individual reprints of this article are not available. Address correspondence toAnn M. Sheehy, MD, MS, University of Wisconsin School of Medicine and PublicHealth, 600 Highland Ave, H6/169, Madison, WI 53792 ([email protected]).

2009 Mayo Foundation for Medical Education and Research

The US Preventive Services Task Force (USPSTF) op-erates under the Agency for Healthcare Research andQuality, one of 11 divisions of the US Department ofHealth and Human Services. A panel of preventive medi-cine and health care experts, the USPSTF reviews existingliterature and evidence to make recommendations regard-ing preventive care measures.1 Primary care practitionersrely on such guidelines to make medical decisions, andinsurance companies and government agencies use thisinformation to determine payment for services renderedand for credentialing of institutions.

Recently, the USPSTF updated its guidelines on screen-ing adults for type 2 diabetes mellitus2,3 (Table 1).4 Thisreport was based on a literature review of the existing datain both MEDLINE and the Cochrane Library databases.Members of the USPSTF concluded that screening for dia-betes in asymptomatic individuals with hypertension (bloodpressure >135/80 mm Hg) was merited. Unfortunately, theydid not recommend or highlight the importance of screeningother at-risk populations who would be screened under theAmerican Diabetes Association (ADA) guidelines, citinglack of direct or indirect evidence supporting populationscreening.2 However, the authors acknowledge that directevidence, such as a randomized trial that compared treatedvs untreated persons in whom screening detected diabetes,will not be available because withholding treatment frompersons with known diabetes is unethical. The ADAalso concluded that a study of this type is unlikely to occurand developed guidelines based on existing data and expertopinion that recommend screening for diabetes mellitus ina much wider population because of the epidemic in theUnited States.4

In addition, the criteria used to develop these newUSPSTF recommendations have been a subject of interest.Although USPSTF states its guidelines are based on ex-plicit criteria,1 experts have questioned its more restrictivescreening criteria used to develop its diabetes screening

Back to Wilson and Jungner:10 Good Reasons to Screen for Type 2 Diabetes Mellitus

ANN M. SHEEHY, MD, MS; DOUGLAS B. COURSIN, MD; AND ROBERT A. GABBAY, MD, PHD

guidelines compared with that used for another chronicdisease, obesity.5 This query has merit considering theimpact USPSTF guidelines have on population health.

Clearly, screening for disease must meet certain criteriato be medically and financially acceptable. Perhaps themost recognized criteria were determined by Wilson andJungner6 in 1968. These principles (Table 2), which theWorld Health Organization follows, define the basis ofpreventive medicine 40 years later and are largely consid-ered the standards by which screening tests are judged anddetermined.

Because of the potential far-reaching implications of thenew USPSTF guidelines, it is important to examine themerits of diabetes screening using the 10 criteria of Wilsonand Jungner since national screening recommendationsprofoundly affect health care delivery and outcomes.

IMPORTANT HEALTH PROBLEMDiabetes mellitus has reached epidemic proportions, andthe number of people with this condition continues to in-crease. The 1999-2002 National Health and Nutrition Ex-amination Survey identified 9.3% of the US population 20years or older (19.3 million people) as having diabetes,with approximately two-thirds diagnosed as having diabe-tes and one-third not diagnosed. An additional 26.0% of thepopulation had impaired fasting glucose (IFG), making theburden of disease estimate at 73.3 million people.7 A pre-dicted 48.3 million people in the United States will havediabetes by 2050,8 with a lifetime risk of disease being32.8% and 38.5%, respectively, for US males and femalesborn in 2000.9 Estimated quality-adjusted life years lost inmen and women diagnosed as having diabetes at age 50years is 14.5 and 18.0 years, respectively, with greater yearslost at younger age of diagnosis because such individualshave more years of life to lose.9

ACCEPTED TREATMENT FOR RECOGNIZED DISEASEMany treatment options are available for diabetes that im-prove glycemic control and reduce risks of complications,particularly microvascular disease. Numerous studieshave shown that treatment is effective. The UK Prospec-tive Diabetes Study (UKPDS) found improved microvas-cular outcomes for patients with a hemoglobin A1c (HbA1c)value of 7.0% compared with the group that had a meanHbA1c value of 7.9%.

10 The recently published 10-year

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follow-up data from the UKPDS reported reduction in bothmicrovascular and macrovascular complications in the in-tensive treatment arm.11 A meta-analysis by Selvin et al12found better macrovascular outcomes in patients with type 2diabetes mellitus who achieve tighter glycemic control.These and other studies suggest improved outcomes withtreatment that results in moderate reduction in HbA1cvalues.

Recently, the glucose arm of the Action to ControlCardiovascular Risk in Diabetes Study Group (ACCORD)13(a randomized controlled study that evaluated multiple car-diovascular risk factors simultaneously) was terminatedearly because of increased mortality in the tightly controlledgroup. However, the absolute HbA1c value achieved (6.4%vs 7.5%) may be less important than the rate of change (1.4%in 4 months in the intensive group) or overall magnitude ofchange (61.9% vs 60.8%). Additionally, hypoglycemia inthe intensive treatment arm may have contributed to ad-verse outcomes, as well as the number and/or types ofmedication used and amount of weight gain (27.8% vs14.1% in the intensive vs standard therapy groups, respec-tively, had >10-kg weight gain). The Action in Diabetesand Vascular Disease: Preterax and Diamicron ModifiedRelease Controlled Evaluation (ADVANCE),14 publishedin parallel to ACCORD, achieved a similar HbA1c value(6.5%) but did so more gradually and from a lower startingpoint (7.5%-6.5%; 61.0). In contrast to ACCORD, AD-VANCE showed an improved combined end point of mi-crovascular and macrovascular events in the intensivetherapy arm. Given these findings, ADVANCE, as well asprevious studies such as the UKPDS, still confirms benefitin reducing HbA1c values from the higher ranges, such asfrom 8%, indicating mean glucose value of 183 mg/dL (toconvert to mmol/L, multipy by 0.0555), to 7%, mean glu-cose level of 154 mg/dL.4,15,16 Although primary care practi-tioners who treat patients with cardiovascular disease orthose with several risk factors for cardiovascular diseaseshould use judgment in achieving glycemic targets in lightof the ACCORD data, this study should not in generaldiscourage practitioners from recommending the currentADA target of an HbA1c of 7.0%, as compelling data existto support this glycemic goal.10

AVAILABILITY OF FACILITIES FOR DIAGNOSIS AND TREATMENTGeneral practitioners in nearly any clinic can diagnose andmanage diabetes. Although access to health care and medi-cal insurance in the United States is a problem for certainpatient populations, it is not a problem specific or unique topatients with diabetes mellitus.17

RECOGNIZABLE LATENT OR EARLY SYMPTOMATIC STAGEDiabetes is the classic disease model for screening becauseclinical disease is typically preceded by a lengthy asymp-

tomatic phase.4 Several studies support the importance ofidentifying the preclinical phase. For example, the NursesHealth Study showed that women who eventually developeddiabetes had a higher risk of myocardial infarction (relativerisk, 3.75; 95% confidence interval, 3.10-4.53) even beforetheir diagnosis of diabetes compared with women whonever developed diabetes, with an increased risk likelybeginning as many as 15 years before actual diagnosis ofdiabetes.18 In a Wisconsin cohort, Harris et al19 found a

TABLE 1. ADA and USPSTF Criteria to Screenfor Diabetes Mellitusa

ADA1. Testing should be considered in all adults who are overweight

(BMI *25 kg/m2) and have the following additional risk factorsPhysical inactivityFirst-degree relative with diabetesMember of high-risk ethnic populationsWomen who were delivered of a baby weighing >4.1 kg or were

diagnosed as having gestational diabetes mellitusHypertensionHDL cholesterol level 250 mg/dLbWomen with polycystic ovarian syndromeImpaired glucose tolerance or impaired fasting glucose on

previous testingOther clinical conditions associated with insulin resistanceHistory of cardiovascular disease

2. In the absence of the above criteria, testing for diabetes andprediabetes should begin at age 45 y

3. If results for diabetes or prediabetes are normal, testing should berepeated at least at 3-y intervals, with consideration of morefrequent testing depending on initial results and risk status

USPSTF1. Screening is recommended for asymptomatic adults with sustained

blood pressure >135/80 mm Hg2. No recommendation for asymptomatic adults with blood pressure

)135/80 mm Hga ADA = American Diabetes Association; BMI = body mass index; HDL =

high-density lipoprotein; USPSTF = US Preventive Services Task Force.b SI conversion factors: To convert cholesterol values to mmol/L, multiply

by 0.0259; to convert triglyceride values to mmol/L, multiply by 0.0114.Adapted from Ann Intern Med3 and Diabetes Care,4 with permission.

TABLE 2. Wilson and Jungner Criteria for Disease Screening(Adopted by the World Health Organization)

1. The condition sought should be an important health problem2. There should be an accepted treatment for patients with recognized

disease3. Facilities for diagnosis and treatment should be available4. There should be a latent or early symptomatic stage5. There should be a suitable test or examination6. The test should be acceptable to the population7. The natural history of the condition, including development from

latent to declared disease, should be adequately understood8. There should be an agreed policy on who to treat as patients9. The cost of case finding (including diagnosis and treatment of

patients diagnosed) should be economically balanced in relationto possible expenditure on medical care as a whole

10. Case finding should be a continuing process and not a once and forall project

From World Health Organization.6




20.8% incidence of retinopathy at the time diabetes wasdiagnosed. Using linear regression and statistical model-ing, onset of diabetes was estimated at 4 to 7 years beforeclinical diagnosis. Taken together, these studies suggestthat both microvascular and macrovascular disease areoccurring before clinically apparent disease and formaldiagnosis.

Formal definitions exist for the prediabetic states IFGand impaired glucose tolerance (IGT). These states aredetected with the same screening test as for diabetes.4Recognition of patients with prediabetes in and of itself isimportant because of evidence of preclinical vascular dis-ease (as aforementioned) and also because of the potentialto prevent or delay onset of actual diabetes mellitus withlifestyle and pharmacological intervention.

SUITABLE TEST OR EXAMINATIONThe fasting plasma glucose (FPG) is a simple, inexpensivetest with essentially no adverse effects or risk.2 Althoughthe FPG is the recommended screening test, patients mayalso be screened with a 75-g oral glucose tolerance test orwith a glucose value obtained randomly when patients aresymptomatic (Table 3).4 In most cases, an abnormal testresult should be confirmed on a subsequent day.

Hemoglobin A1c is used as a marker of long-term glyce-mic control and therefore is used to assess efficacy oftherapy, but it is not currently endorsed by the ADA,American College of Endocrinology, or World Health Or-ganization to diagnose diabetes. However, 1999-2004 datafrom the National Health and Nutrition Examination Sur-vey revealed that an HbA1c value of 5.8% had optimalsensitivity (86%) and specificity (92%) for detecting undiag-nosed diabetes. The authors suggest that this value couldbe used as a trigger to formally screen with FPG.20 Othershave independently recommended using an HbA1c value of6.0% as a trigger to screen and have suggested that valuesgreater than 6.5% could be used in certain diagnostic crite-ria.21 This value, if standardized, could also be useful to furthercharacterize and stratify risk in certain populations, such ashospitalized patients, in whom the prevalence of undiagnoseddiabetes is high; however, FPG values, elevated by counter-regulatory hormone surge, cannot typically be used for dia-betes screening and diagnosis.22

ACCEPTABLE TEST TO THE POPULATIONAs described in the USPSTF position statement, no datasuggest serious adverse outcomes to screening.2 The ADArecommends a FPG (with abnormal result confirmed on asubsequent day) as the screening method of choice, anintervention that is less invasive and less time-consumingthan other readily acceptable screening tests such as mam-mography and colonoscopy.

NATURAL HISTORY OF THE CONDITION UNDERSTOODNot every person at risk will develop diabetes, and noteveryone who develops diabetes will have progressivecomplications. The direct mechanism by which dys-glycemia translates to vascular disease is an area of activeresearch23 and is most likely multifactorial and polygenic.

Screening for disease is beneficial only if discoveringearlier or preclinical disease improves outcome. In bothtype 1 and type 2 diabetes mellitus, periods of hyperglyce-mic exposure can cause long-term adverse effects, the so-called legacy effect.24 Because glycemic control cannot beachieved in patients in whom diabetes has not been diag-nosed, screening plays an important role in preventinglong-term complications. In patients with type 1 diabetes,the Diabetes Control and Complications Trial/Epidemiol-ogy of Diabetes Interventions and Complications (DCCT/EDIC) study group showed that the benefit of tighter glyce-mic control (HbA1c, 7.4% vs 9.1%) for an average of 6.5years was still apparent 11 years later even though glyce-mic control had equalized (7.9% vs 7.8%) during the 11-year follow-up.25 Patients with diabetes whose glycemiawas more tightly controlled during the 6.5 years of studyhad significantly fewer cardiovascular events after the 11years of follow-up. Importantly, 10-year follow-up datafrom the UKPDS cohort, originally a group of 4209 per-sons with newly diagnosed type 2 diabetes mellitus, wererecently published.11 Like the DCCT/EDIC study, lastingbenefits of tighter glycemic control during the interventionperiod were seen despite equalization of HbA1c values inthe follow-up period (8.0% vs 8.1%). These benefits wereapparent for both microvascular and macrovascular endpoints. These studies suggest that glycemic effects arelasting and irreversible and therefore advocate for earlydiagnosis via screening so early and consistent glycemiccontrol can be achieved.

CONSENUS FOR TREATMENTAll patients with prediabetes and diabetes should betreated. The ADA recommends that people with IFG orIGT modify their lifestyle (5%-10% weight loss and 30minutes of exercise daily).4 For individuals with both IGF

TABLE 3. Criteria for Diagnosis of Diabetes Mellitusa,b

1. Fasting plasma glucose level *126 mg/dL OR2. Symptoms of hyperglycemia and a casual plasma glucose level

*200 mg/dL OR3. 2-h plasma glucose level *200 mg/dL during a 75-g oral glucose

tolerance testa In the absence of unequivocal hyperglycemia, these criteria should be

confirmed by repeated testing on a different day.b SI conversion factors: To convert glucose values to mmol/L, multiply by

0.0555.Adapted from Diabetes Care,4 with permission.

Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com 41



and IGT and an additional risk factor (in particular, bodymass index >35 kg/m2 or age




8. Narayan KM, Boyle JP, Geiss LS, Saaddine JB, Thompson TJ. Impact ofrecent increase in incidence on future diabetes burden: U.S., 2005-2050. Dia-betes Care. 2006;29(9):2114-2116.

9. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF.Lifetime risk for diabetes mellitus in the United States. JAMA. 2003;290(14):1884-1890.

10. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glu-cose control with sulphonylureas or insulin compared with conventional treat-ment and risk of complications in patients with type 2 diabetes (UKPDS 33)[published correction appears in Lancet. 1999;354(9178):602]. Lancet. 1998;352(9131):837-853.

11. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-Yearfollow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008Oct 9;359(15):1577-1589. Epub 2008 Sep 10.

12. Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glyco-sylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann InternMed. 2004;141(6):421-431.

13. Action to Control Cardiovascular Risk in Diabetes Study Group. Effectsof intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun12;358(24):2545-2559. Epub 2008 Jun 6.

14. ADVANCE Collaborative Group. Intensive blood glucose control andvascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun12;358(24):2560-2572. Epub 2008 Jun 6.

15. US Department of Health and Human Services, Centers for DiseaseControl and Prevention. National diabetes fact sheet: general information andnational estimates on diabetes in the United States, 2005. www.diabetes.org/uedocuments/NationalDiabetesFactSheetRev.pdf. Accessed November 10,2008.

16. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ; A1c-Derived Average Glucose (ADAG) Study Group. Translating the A1C assayinto estimated average glucose values. Diabetes Care. 2008 Aug;31(8):1473-1478. Epub 2008 Jun 7.

17. Harris MI. Racial and ethnic differences in health insurance coverage foradults with diabetes. Diabetes Care. 1999;22(10):1679-1682.

18. Hu FB, Stampfer MJ, Haffner SM, Solomon CG, Willett WC, MansonJE. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2diabetes. Diabetes Care. 2002;25(7):1129-1134.

19. Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occursat least 4-7 yr before clinical diagnosis. Diabetes Care.1992;15(7):815-819.

20. Buell C, Kermah D, Davidson MB. Utility of A1c for diabetes screeningin the 1999-2004 NHANES population. Diabetes Care. 2007 Sep;30(9):2233-2235. Epub 2007 Jun 11.

21. Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D,Davidson MB. A new look at screening and diagnosing diabetes mellitus. JClin Endocrinol Metab. 2008 Jul;93(7):2447-2453. Epub 2008 May 6.

22. Clement S, Braithwaite SS, Magee MF, et al; Diabetes in HospitalsWriting Committee. Management of diabetes and hyperglycemia in hospitals[published corrections appear in Diabetes Care. 2004;27(3);856 and 2004;27(5):1255]. Diabetes Care. 2004;27(2):553-591.

23. Basta G, Schmidt AM, De Caterina R. Advanced glycation end productsand vascular inflammation: implications for accelerated atherosclerosis indiabetes. Cardiovasc Res. 2004;63(4):582-592.

24. Chalmers J, Cooper ME. UKPDS and the legacy effect [editorial]. NEngl J Med. 2008;359(15):1618-1620.

25. Nathan DM, Cleary PA, Backlund JY, et al; Diabetes Control andComplications Trial/Epidemiology of Diabetes Interventions and Complica-tions (DCCT/EDIC) Study Research Group. Intensive diabetes treatment andcardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643-2653.

26. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glu-cose and impaired glucose tolerance: implications for care. Diabetes Care.2007;30(3):753-759.

27. Diabetes Prevention Program Research Group. Reduction in the inci-dence of type 2 diabetes with lifestyle intervention or metformin. N Engl JMed. 2002;346(6):393-403.

28. Zhang P, Engelgau MM, Valdez R, Benjamin SM, Cadwell B, NarayanKM. Costs of screening for pre-diabetes among US adults: a comparison ofdifferent screening strategies. Diabetes Care. 2003;26(9):2536-2542.

Back to Wilson and Jungner: 10 Good Reasons to Screen for Type 2 Diabetes MellitusIMPORTANT HEALTH PROBLEMACCEPTED TREATMENT FOR RECOGNIZED DISEASEAVAILABILITY OF FACILITIES FOR DIAGNOSIS AND TREATMENTRECOGNIZABLE LATENT OR EARLY SYMPTOMATIC STAGESUITABLE TEST OR EXAMINATIONACCEPTABLE TEST TO THE POPULATIONNATURAL HISTORY OF THE CONDITION UNDERSTOODCONSENUS FOR TREATMENTCOST OF CASE FINDINGPROCESS OF DETERMINING CASES OF DIABETESCONCLUSIONREFERENCES

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