Diabetes Treatments

(USPSTF) review of the evidence for screening asymptomatic people for type 2 diabetes to to the National Diabetes Surveillance System (NDSS) which …

Feig et al with CTF Type 2 Diabetes

Screening for Type 2 Diabetes to Prevent Vascular Complications: Updated Recommendations from the Canadian Task Force on Preventive Health Care
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Denice S Feig, MD, MSc, FRCPC

Valerie A Palda, MD, MSc, FRCPC and

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Lorraine L Lipscombe, MD, FRCPC with

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Canadian Task Force on Preventive Health Care

1 Assistant Professor, University of Toronto Department of Medicine, Division of Endocrinology Metabolism Mount Sinai Hospital 5027-60 Murray Street Toronto, Ontario M5G 1X5 2

Assistant Professor, University of Toronto, General Internal Medicine St Michaels Hospital Victoria 4-151, 30 Bond Street Toronto, Ontario M5B 1W8
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Clinical Associate, Endocrinology Burton Hall 404, Womens College Campus Sunnybrook and Womens College Health Sciences Centre 60 Grosvenor Street Toronto, Ontario M5S 1B6
4 117-100 Collip Circle London, Ontario N6G 4X8 Tel: 519-858 -5181 Fax: 519-858-5112 address for correspondence

Technical Report November 2003

Running Head: Feig et al with CTF Type 2 Diabetes

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Feig et al with CTF Type 2 Diabetes BACKGROUND Rationale for the Review In 1994, the Canadian Task Force for Preventive Health Care CTFPHC reviewed the
evidence regarding screening for diabetes Given the poor sensitivity of the screening test and the lack of evidence for prevention of microvascular and macrovascular complications in patients with type 2 diabetes, the Task Force recommended against screening for diabetes in the absence of symptoms or risk factors D recommendation Beaulieu, 1994 Since 1994 a number of

studies have been published looking at prevention of diabetes complications in patients with type 2 diabetes, as well as primary prevention of diabetes Therefore, the CTFPHC undertook to 10 update this topic by drawing heavily on the recent United States Preventive Services Task Force USPSTF review of the evidence for screening asymptomatic people for type 2 diabetes to prevent cardiovascular eventsHarris, 2003 That review was enhanced by the Canadian Task Force on Preventive Health Care : new literature on screening was incorporated, and a systematic review of the evidence related to the prevention of diabetes in people with impaired glucose tolerance was undertaken

Burden of Illness According to the National Diabetes Surveillance System NDSS which is based on physician services data and hospitalization data, in
1998-99 the prevalence of diabetes mellitus 20 DM in Canadians aged 20 years and older was 480 or approximately 1,054,100 people The prevalence increases with age, from 104 in Canadians aged 20-29, to 1349 in those 75 years or older An estimated 406 of cases occurred in people aged 20 to 59 years Diabetes in Canada 2002 It is estimated that type 2 diabetes accounts for more than 90 of diagnosed diabetes

Complications and health outcomes Diabetes is characterized by chronic hyperglycaemia and the subsequent development of microvascular complications that can lead to blindness, end-stage renal disease, peripheral neuropathies and sexual dysfunction, as well as macrovascular disease associated with a 2-4 fold

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Feig et al with CTF Type 2 Diabetes increased risk of coronary heart disease, an increased risk of stroke and limb amputations Brownlee 2001; Kannel 1979; Pyorala 1987; Stamler 1993 At the time of clinical diagnosis the prevalence of retinopathy has been estimated to be between 10 and 37 Harris 1992 and UKPDS 30 1998 In a study of newly diagnosed patients, 2 had had a myocardial infarct, 3 had angina and 1 had had a stroke UKPDS 6 1990 Ten years following the diagnosis of
diabetes greater than 20 of patients will have had a major cardiovascular event, less than 5 will have developed blindness, and under 2 will have developed end-stage renal disease or lower extremity amputation Harris 2003 In 1999, 26 of all deaths in Canada were attributed to diabetes This is likely to be an 10 underestimation since diabetes was listed as the cause of death in only 28 of people with diabetes even though they had died of diabetes-related illnesses such as kidney failure, heart disease or stroke Health Canada 1998

Economic Burden In Canada, the economic burden due to diabetes in 1993 was estimated to be 17 billion One quarter of those costs were attributable to the direct values of goods and services, while the remainder were due to lost production from illness, injury, disability or premature death Moore 1997

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Risk Factors for Type 2 Diabetes Diabetes is a chronic disease with multi- factorial causes involving the interaction of genetic susceptibility and environmental factors Some are non- modifiable factors such as ethnicity, family history and age, but others such as overweight, obesity and lack of physical activity are potentially modifiable Among
individuals with self- reported diabetes in 1998, 743 were overweight and 651 reported that they were not physically active compared to 554 of the general population Diabetes in Canada 2002 Type 2 diabetes also occurs more frequently in women with prior gestational diabetes, polycystic ovarian syndrome, and in people with hypertension and dyslipidemia Smoking, excess consumption of alcohol and hypertension exacerbate the risk of complications from DM

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Feig et al with CTF Type 2 Diabetes Special Populations A systematic review of the literature, carried out in 1994, determined that in the United States, nearly all minority groups had higher prevalence rates for DM than the white population Carter 1996 It is widely recognized that type 2 DM has become a serious health problem in various aboriginal groups around the world In Canada, the prevalence of diabetes among First Nations is now at least 3 times the national average The Aboriginal Peoples Survey, conducted across Canada in 1991, determined that 85 of North American Indian peoples on reserves or settlements had diabetes The prevalence rate was lower in those living off reserve 53 Chapter 6, Diabetes in Canada 2002 10 Why
Screen? The idea to screen for diabetes comes from the notion that approximately 50 of people with prevalent diabetes have not been diagnosed Harris 1998 Data from the United Kingdom Diabetes Study suggested that patients are diagnosed either because of symptoms of hyperglycemia ie polydipsia, polyuria, fatigue, blurry vision 537, infections 13, because of a diabetes-related complication 21, or through asymptomatic screening associated with the use of blood chemistry profiles done in other situations ie pre-operative 312 Colagiuri 2002 As depicted in Figure 1, it is believed that diabetes is manifest initially as a mild 20 impairment in glucose tolerance by either impaired fasting glucose IFG or impaired glucose tolerance IGT The impairment in glucose tolerance then progresses to overt diabetes, which is initially asymptomatic point A With a further impairment of glucose tolerance symptoms appear point B and the clinical diagnosis is made The time between point A and point B can be called the preclinical phase and is defined as the period during which the blood sugars are diagnostic of diabetes, however, patients remain asymptomatic and undiagnosed The length of this preclinical
phase has been estimated at 9-12 years Harris 1992 Using this estimate, systematic screening would detect diabetes on average 5-6 years before discovery by clinical diagnosis Harris 2003 One of the difficulties with these estimates comes from the variable way in which diabetes is diagnosed Since most patients are discovered while being assessed for 30 other conditions, the population advantage of systematic screening may be less 4

Feig et al with CTF Type 2 Diabetes The CTF adopted the analytic framework used by the USPSTF in analyzing the diabetes screening literature In approaching diabetes and its complications, the USPSTF came to regard diabetes as a vascular disease, with both microvascular and macrovascular complications As in the general population, interventions to prevent macrovascular complications such as treatment of hypertension, hyperlipidemia and treatment with aspirin, were reviewed and examined in the context of those with diabetes, as well as the treatments specific to diabetes such as tight glycemic control Similar treatments were looked at for the prevention of microvascular complications, however, the majority of the evidence for such prevention in the
literature focused on the effects of tight glycemic control In their approach to the important health 10 outcomes, cardiovascular events, significant visual loss, end-stage renal disease and amputation were considered Other outcomes such as progression of retinopathy and nephropathy were considered as intermediate outcomes Finally, the USPSTF attempted to discern the added benefit of screening and diagnosing patients earlier than the usual clinical detection time The objective of this review was to answer the following key questions: Key Question 1: Is there direct RCT evidence that screening for diabetes improves health outcomes? Key Question 2: What is the yield of screening, both in terms of the accuracy and reliability of screening tests and the prevalence of undiagnosed diabetes in the population? 20 Key Question 3: What is the added efficacy of initiating treatments tight glycemic control, tight blood pressure control, lipid and aspirin treatment, foot care programs, counseling for lifestyle change at screening detection compared with clinical detection in improving health outcomes? Key Question 4: What is the efficacy of lifestyle intervention for people with impaired
fasting glucose or impaired glucose tolerance in improving health outcomes? Key Question 5: What are the harms of screening or treatment?

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Feig et al with CTF Type 2 Diabetes METHODS Harris et al reviewed the literature from the USPSTF review of the same topic from 1996 and searched MEDLINE and the Cochrane library from January 1, 1994 to July 30 2002 Harris 2003 The CTF updated a similar search of the literature from July 30, 2002 to Dec 31, 2002 No further articles meeting the inclusion criteria were found The evidence was reviewed using the Canadian Task Force methods outlined in the Appendix

RESULTS Conclusions of the USPSTF regarding the Value and Yield of Screening Tools Harris 10 2003 Key Question 1 Is there direct RCT evidence that screening for diabetes improves health outcomes? No studies compared screening for diabetes with an unscreened population or examined health outcomes

Key Question 2 What is the yield of screening, both in terms of the accuracy and reliability of screening tests and the prevalence of undiagnosed diabetes in the population? a Predictive Value of the Screening Tool The historical gold standard for the diagnosis of diabetes is the 2 hr post
glucose load value 2 hr 20 PG of 111 mmol/L or more following a 75g oral glucose tolerance test OGTT In 1997 the American Diabetes Association suggested that a fasting plasma glucose FPG threshold of 70 mmol/L was an acceptable alternative to the 2 hr PG for the diagnosis of diabetes Expert Committee 1997 Both of these criteria were chosen because they have been shown to reflect a threshold separating those subjects who are at substantially increased risk of microvascular complications retinopathy Bennett 1976, McCance 1994, Engelgau 1997, The expert committee 2003 These thresholds do not do as well for prediction of macrovascular disease While the FPG and 2 hr PG in the diabetes range are both strongly associated with coronary artery disease and all-cause mortality rates Charles 1996, values below these levels are also

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Feig et al with CTF Type 2 Diabetes indicative of increased risk for macrovascular disease Persons with impaired glucose tolerance IGT 2 hr PG between 78-110 also have a higher risk of cardiovascular events and mortality, than those with normal glucose tolerance DECODE 1999, Coutinho 1999 In a meta-analysis that assessed the relationship between glucose and
cardiovascular events in 95,783 persons, IGT was associated with a relative risk of 158 and impaired fasting glucose IFG with a risk of 133 for cardiac events Coutinho 1999

b Accuracy and Reliability of the Screening Tool Although the FPG required to diagnose DM has been lowered to 70 mmol/L to improve 10 sensitivity, in studies of good to fair quality the FPG cutpoint of 70 mmol/L or more still had a sensitivity of only 40-87 to detect a 2 hr PG of 111 mmol/L, but a specificity of 96-99 Blunt 1991 Lee 1997 Chang 1998 Wiener 1997 However as mentioned, the FPG of 70 mmol/L has been shown to be strongly associated with the prevalence of retinopathy McCance 1994, Engelgau 1997, The expert committee Lowering the FPG threshold further to 61 mmol/L would improve sensitivity 66-95 at the cost of specificity 90-96 Engelgau 2000 The random postprandial capillary glucose may be comparable to the FPG, depending on the cutpoint used In one study, a random capillary glucose of 67 mmol/L or more had a sensitivity of 75, with a specificity of 88 Harris 2003 20 In terms of reliability, the FPG appears to be more reproducible than the 2 hr- post glucose PG When adults were given the OGTT and it
was repeated at 2 to 6 weeks, the intraindividual coefficients of variation were higher for the 2 hr PG than for the FPG 64 for FPG, 167 for 2 hr PG Mooy 1996 While some studies have shown that frequency distributions for the diagnosis of diabetes using HbA1c are similar to those using FPG, and some studies have defined cutpoints above which microvascular disease is more likely, many different methods still exist for the measurement of HgA1c, making it difficult to assign an appropriate cutpoint The Expert Committee

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Feig et al with CTF Type 2 Diabetes

c Other Screening Tools Three questionnaires have been studied as potential tools for screening asymptomatic people, the ADA questionnaire Take the Test, Know the Score, the NHANES questionnaire, and the Netherlands Hoorn Study questionnaire They were shown to have insufficient sensitivity 49-80 to be used as a screening tool Rolka 2001, Newman 1994

d Prevalence of Undiagnosed Diabetes in the Population Data from the NHANES III in the United States showed that use of the FPG cutoff of 70 10 mmol/L or more yielded a DM prevalence of 435 in individuals 40-74 years of age without a medical history of diabetes The Expert Committee
2003 In summary, the fasting plasma glucose is currently considered the most acceptable test to diagnose diabetes in the asymptomatic patient The cutpoint FPG of 70 mmol/L or more has only 40-87 sensitivity, but good specificity and is strongly associated with retinopathy Macrovascular disease is associated with hyperglycemia, both below and above this cutpoint, with increasing risk associated with increasing values Coutinho 1999 The OGTT, while considered the gold standard, is more costly and time-consuming than the FPG and less reliable

Conclusions of the USPSTF regarding Treatment Options to Prevent Significant Health 20 Outcomes Harris 2003 Key Question 3 What is the added efficacy of initiating treatments tight glycemic control, tight blood pressure control, lipid and aspirin treatment, foot care programs, counseling for lifestyle change at screening detection compared with clinical detection in improving health outcomes? Treatment of DM and Prevention of Significant Health Outcomes The health outcomes considered included death, cardiovascular events, significant visual loss, end -stage renal disease, and amputations Since the largest mortality impact associated with diabetes
is from cardiovascular events, a good deal of importance was placed on prevention of cardiovascular disease

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Feig et al with CTF Type 2 Diabetes a Tight Glucose Control The review found that tight glucose control in the preclinical phase of diabetes was unlikely to lead to a large benefit This conclusion was primarily drawn from the findings of a large RCT of good quality, which found that after 10 years of tight glucose control there was no significant difference in all-cause mortality 187 vs 179 p044, and no significant difference in diabetes-related death death from MI, stroke, PVD, renal disease hyper- or hypoglycemia and sudden death There was a reduction in myocardial infarction RR 084 95 CI 07-10, however this did not reach significance p0052 UKPDS 33 A significant reduction in microvascular endpoints was also found, however this was primarily due to a 10 reduction of retinal photocoagulation, which, given a trial where treatment was not blinded, may have been subject to bias There was a significant reduction in progression of retinopathy, however there was no difference in deterioration of visual acuity or proportion of patients who became blind in both eyes No
significant difference in amputations, stroke, or renal failure was detected Four other RCTs were small and not sufficiently powered to find significant differences in many of the outcomes and found no significant difference in cardiovascular events Only one study, a multifactorial intervention trial, showed a significant reduction in blindness in 1 eye, but no difference in visual acuity between groups Gaede 1999

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b Tight Blood Pressure Control Aggressive treatment of blood pressure was found to lead to improved outcomes over conventional, less stringent, blood pressure goals in patients with diabetes Earlier detection of diabetes would therefore change the blood pressure treatment target and presumably improve outcomes This evidence was primarily drawn from 2 RCTs of fair quality In a trial of patients with hypertension, subjects were randomized to one of three diastolic blood pressure goals 90, 85,or 80 and ASA or placebo Hansson 1998 After 5 years, there was no significant benefit noted between the three blood pressure groups overall However, in the patients with diabetes there were significantly more major cardiovascular events RR206 124-344 and higher cardiovascular
mortality RR30 128-708 in the 90 mm Hg group compared with

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the 80 mm Hg group 9

Feig et al with CTF Type 2 Diabetes In the UKPDS, patients with hypertension randomized to tight blood pressure control for 10 years had a significant reduction in diabetes related death MI, sudden death, stroke, PVD and renal failure RR 068 95 CI 049-094, as well as a significant reduction in risk of stroke RR 056 035-089, any diabetes related end point 076 062-092, risk of microvascular disease aggregate clinical endpoint, and risk of retinal photocoagulation UKPDS 38 1998 Two other smaller RCTs in diabetic patients given intensive blood pressure therapy showed a significant reduction in all-cause mortality in one Estacio 2002, and a reduction in stroke in the other Schrier 2002

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c Treatment of Hyperlipidemia Lipid-lowering treatment had a substantial benefit on cardiovascular outcomes and mortality in patients with diabetes and hyperlipidemia,, regardless of low-density lipoprotein LDL cho lesterol level in some studies Several randomized controlled trials of primary and secondary cardiac prevention, using HMG-CoA reductase inhibitors statins and fibrates, have shown significant reductions
in cardiovascular events in patients with diabetes and hyperlipidemia relative risk reduction similar in both: 24-42 treated over 5-6 years Pyorala 1997; Koskinen 1992; Frick 1987; LIPID Study Group 1998; Downs 1998; Rubins 1999; Haffner 1999; Pignone 2001; MRC/BHF Heart Protection study 2002; Robins 2001; Goldberg 1998 In one fair study of primary prevention, use of bezafibrate in diabetic patients with mild

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hyperlipidemia reduced the incidence of myocardial infarction or ischemic changes on ECG by 69 p001 Elkeles 1998 Although the relative risk reduction in primary prevention studies was similar in persons with and without diabetes, the absolute risk reduction would be larger in persons with diabetes given their baseline risk of cardiovascular disease is 2-4 times higher than non-diabetic persons Patients with diabetes appear to benefit even at low levels of LDL cholesterol In a large RCT of patients with diabetes and non-diabetic patients considered at high risk for cardiovascular events with or without previous cardiac disease, pa tients treated with simvastatin for 5 years had a significant decrease in overall mortality, primarily due to a decrease in cardiovascular
deaths RR 083 075-091 MRC/BHF Heart Protection Study 2002 All

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patients treated with simvastatin had a similar and significant proportional reduction in CHD

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Feig et al with CTF Type 2 Diabetes events including patients with diabetes and previous heart disease, as well as patients with diabetes but no previous coronary heart disease first major coronary event: 55 on simvastatin vs 84 on placebo, p00001 In a subgroup analysis, among all the 5963 patients with diabetes, the proportional risk reduction was about 25 irrespective of sex, age, or treatment for hypertension MRC/BHF Heart Protection Study 2003 A similar reduction was seen even in patients with diabetes who presented with LDL levels below 30 mmol/L or total cholesterol below 50 mmol/L 27 reduction 13-40, p00007 MRC/BHF Heart Protection Study 2003 Even among the 1343 diabetic patients without known occlusive arterial disease whose pretreatment LDL cholesterol was below 30 mmol/L, there was a marginally significant 30 10 reduction in first major vascular events in patients on simvastatin p005 MRC/BHF Heart Protection Study 2003 In an analysis of two secondary prevention trials, it was noted that in patients with LDL
levels below 32 mmol/L, only the patients with diabetes benefited from statin therapy, whereas nondiabetic persons did not Sacks 2002

d Treatment with ASA The relative risk reduction seen in patients taking aspirin appears to be similar in patients with diabetes and without diabetes, and appears to be related to level of CV risk In a metaanalysis of 145 RCTs using antiplatelet therapy for secondary prevention, diabetic subjects had approximately a 25 reduction in vascular events, a reduction similar to the non-diabetic 20 subjects Antiplatelet 1994 In a study of patients with hypertension, aspirin significantly reduced cardiovascular events by 15 p003 and myocardial infarction by 36 p0002, with a similar RR seen in patients with and without diabetes Similar results were seen in the Early Treatment Diabetic Retinopathy Study of patients with type 1 and type 2 diabetes, where 48 had previous CV disease Aspirin decreased the RR for myocardial infarction to 072 055095 over 5 years The USPSTF summary on aspirin for the primary prevention of cardiovascular events estimated that for 1000 patients with a 5 risk of CHD over 5 years, 6 to 20 myocardial infarctions would be prevented by
aspirin use while 0 to 2 hemorrhagic strokes and 2 to 4 major GI bleeding events would be caused USPSTF 2002 The net benefit of aspirin would increase with increasing cardiovascular risk 30

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Feig et al with CTF Type 2 Diabetes e Counseling for Diet, Physical Activity and Smoking Cessation No studies were found that showed that the diagnosis of diabetes led to more effective outcomes in patients counseled to improve their diet, increase physical activity or stop smoking

f Foot Care Programs Foot care programs given to patients with long-standing diabetes can reduce the risk for amputations McCabe 1998; Litzelman 1993; Patout 2000 however, the risk of amputations in newly diagnosed patients or in patients within the first 10 years after diagnosis is low Resnick 1999 Therefore, the benefit of counseling patients in the preclinical phase is unlikely to confer 10 a large benefit

Overall USPSTF Perspective on Screening and Treatment of Type 2 Diabetes In summary, the USPSTF review concluded that the knowledge of diabetes in patients with hyperlidemia and hypertension would lead to changes in treatment recommendations for blood pressure and lipid control, which in turn would reduce
adverse cardiac outcomes over a 10 year horizon This conclusion was dependent in part on the baseline level of cardiac risk of the patient, and in certain circumstances, it was the diagnosis of DM which increased the CV risk to a level worthy of intervention

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Prevention of Progression from Impaired Glucose Values to Type 2 Diabetes Key Question 4 What is the efficacy of lifestyle intervention for people with impaired fasting glucose or impaired glucose tolerance IFG/IGT in improving health outcomes? Impaired glucose tolerance IGT and impaired fasting glucose IFG are terms used to describe those who have glucose values above the normal range but do not meet the criteria for a diabetes diagnosis Persons with both IGT and IFG have an increased risk of future diabetes Unwin 2002, Edelstein 1997 Rates of progression to diabetes in persons with IGT range from around 4 to 9 per year Edelstein 1997, and the average risk of diabetes with either IFG or IGT is around five times greater than those with normal glucose tolerance Unwin 2002 These

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Feig et al with CTF Type 2 Diabetes intermediate conditions are not usually associated with diabetic renal, visual or neurologic
complications, but they have been shown to increase ones risk of cardiovascular disease and mortality DECODE 1999, Coutinho 1999, Meigs 1998, Bjornholt 1999, Balkau 1999, Saydah 2002, Khaw 2001, Barzilay 2001, Haffner 1990, McPhillips 1990, Harris 1998-1 Because IGT and IFG are asymptomatic states, persons with these abnormalities can only be identified through screening There is considerable debate regarding the best screening test, particularly since IGT requires a 2-hour OGTT, which is more time-consuming and cumbersome than the FPG However, evidence suggests that the OGTT to detect IGT may be a better test to identify persons at risk for diabetes than the FPG Although both conditions portend similar 10 risks of future diabetes, persons with IGT comprise a larger high- risk group than those with IFG IGT affects around 12-20 of adults, whereas 7-14 of persons have IFG DECODE 1999, Nakagami 2002, Harris 1998-2 In addition prospective studies suggest that IGT is a more sensitive predictor of diabetes risk than is IFG, despite comparable specificities Shaw 1999, McNeely 2003 Finally when the IFG category is compared to IGT, 90-96 of persons with IFG have co-existing IGT, but a
normal fasting glucose misses an additional 57-76 of persons who have isolated IGT Anand 2003, Amoah 2002, Metcalf 2000, Wahl 1998, Gimeno 1998, Devegt 1998 Even when the fasting glucose target is reduced to 53 mmol/L, only 60 of persons with IGT are detected with the FPG Ana nd 2003 Therefore although the FPG may be useful to identify persons with IFG who are at risk for diabetes, a normal test may miss up to 20 40 of individuals with isolated IGT who remain at risk The potential benefit of screening for IFG and IGT depends on the availability of interventions to reduce diabetes outcomes No studies have analyzed the impact of screening for these conditions on diabetes complications However five randomized controlled trials have examined the effect of either intensive lifes tyle or pharmacologic interventions in overweight persons with IGT on the incidence of diabetes Pan 1997, Tuomilehto 2001, Knowler 2002, Chiasson 2002, Buchanan 2002, and one study also evaluated the incidence of cardiovascular events and hypertension as secondary outcomes Chiasson 2003 Lifestyle intervention studies from China, Finland, and the US evaluated the benefits of programs providing regular individual
counselling sessions on dietary and exercise advice, as well as physical activity training when 30 necessary Pan 1997, Tuomilehto 2001, Knowler 2002 Programs from the two larger studies were aimed at reducing and maintaining a 5-7 weight loss, through dietary changes and at least 13

Feig et al with CTF Type 2 Diabetes 20-30 minutes per day of exercise Tuomilehto 2001, Knowler 2002 Despite a weight loss success rate of around 40, these interventions resulted in a 42-58 reduction in progression to diabetes over 3-6 years The US study also assessed the benefit of metformin treatment in subjects with IGT, and they found a 31 reduction in incident diabetes over 3 years, which dropped to 25 after a 1 to 2-week period off the drug Knowler 2003 It is unclear whether the blood glucose levels would have continued to rise if these patients were followed for a longer period Acarbose has also been shown to reduce diabetes incidence by 25 over 3 years in persons with IGT Chiasson 2002 In addition, this study recently reported a 49 reduction in cardiovascular events and a 10 34 reduction in hypertension with acarbose treatment in IGT patients Chiasson 2003 This benefit was found despite the
fact that 31 of the subjects taking acarbose discontinued their treatment early versus 19 of those on placebo, as the outcomes were analyzed on an intention-to-treat basis However, because of the high rate of intolerance to acarbose due to its known gastrointestinal side effects, its use in asymptomatic persons with IGT may be limited Lastly, troglitazone has been shown to decrease progression to diabetes over 2 years by 55 in a group of women with a history of gestational diabetes Buchanan 2002 Two clinical trials examining the effectiveness of other medications to prevent diabetes in IGT patients are currently underway: The DREAM study with rosiglitazone and ramipril, and the NAVIGATOR study using nateglinide and valsaran Unwin 2002 20 These trials provide good evidence that intensive lifestyle interventions, and possibly therapy with metformin and acarbose, can reduce the progression from IGT to diabetes in the short-term There is also fair evidence that acarbose can reduce cardiovascular outcomes and hypertension in persons with IGT Chiasson 2003 Regarding prevention of diabetes with medication, because the primary diabetes outcomes in the acarbose and metformin studies were
evaluated while the subjects were taking the drugs acarbose, or taken off for a very brief period metformin, the ability of these agents to prevent versus simply mask new diabetes is unclear These treatments may therefore have to be continued indefinitely to provide benefit, and the long-term safety of these agents in asymptomatic persons without diabetes is not known Furthermore, the adverse effects of troglitazone and its withdrawal from the market preclude its 30 use

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Feig et al with CTF Type 2 Diabetes

Key Question 5 What are the harms of screening or treatment? While few studies have examined the harmful effects of screening for diabetes, in those studies that looked at patients diagnosed through screening no decrease in quality of life has been found Edleman 2002 Patients who are diagnosed clinically appear to benefit from intensive glycemic control with improved quality of life UKPDS 37; Testa 1998 JAMA; Testa 1998 Diabetes Care No studies were found looking at the distress associated with disease labeling or loss of insurability however, treatment appears to be relatively safe Treatment of hyperglycemia with oral hypoglycemic agents or insulin may lead to
hypoglycemia, although 10 episodes of severe hypoglycemia are infrequent 23 of patients on insulin and 06 of patients on OHAs in the UKPDS ACE inhibitors and statins have low rates of serious adverse effects Bradford 1994; Pierce 1990

INTERPRETATION Canadian Task Force Interpretation of the Current Research Evidence Although there is no direct evidence that screening for type 2 diabetes in the general population improves health outcomes, certain high-risk groups such as those with hyperlipidemia and hypertension, may benefit from screening and treatment Patients with asymptomatic disease in the preclinical phase can be reliably diagnosed through screening Intensive therapy 20 of blood pressure, and hyperlipidemia, as well as treatment with aspirin in patients with diabetes leads to improved health outcomes Of those patients with diabetes discovered clinically, the benefits of tight glycemic control in the first 10 years were seen only in intermediate outcomes ie decrease in progression of retinopathy and nephropathy, with a non-significant trend for lower MI rates Therefore, clinical health outcomes such as death, CV events, blindness, ESRD and amputations were not reduced by 10
years of glucose-lowering treatment With screened patients presumably the gain within the first 15 years would be similar or even less, given that their level of hyperglycemia would be milder in most cases One would expect that the benefit may be translated into improved health outcomes in trials of longer duration It is also possible

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Feig et al with CTF Type 2 Diabetes that improved health outcomes would be demonstrated if treatment were started sooner, however there is no evidence indicating this currently There is good evidence that patients with diabetes, hypertension, and/or hyperlipidemia treated for 5 years with intensive blood pressure control, lipid lowering agents, and aspirin have a reduction in cardiovascular events and mortality Because of the significant benefit to CV events within 5 years of treatment, it is assumed that screened patients who would be diagnosed on average 5-6 years earlier, would also benefit This is because knowledge of their diagnosis of diabetes would lead to tighter blood pressure control and more aggressive lipid therapy There is fair evidence that patients with diabetes including those with previous cardiac 10 disease and normal lipids
benefited from statin therapy, however, this benefit is likely related to overall level of cardiac risk Although there are studies suggesting a benefit of treating persons in the pre-diabetes stage of IGT to decrease diabetes progression and possibly cardiovascular disease, the evidence is still inadequate to recommend screening for IFG or IGT However, screening for diabetes in certain contexts may nonetheless identify a number of persons with IGT These patients should be treated with lifestyle interventions aimed at lowering weight and increasing exercise, as it may lower the incidence of diabetes Furthermore, acarbose treatment can also be considered for these patients, as it has been shown to reduce cardiovascular outcomes and hypertension It should be noted that the prevention trials were all between 3 and 6 years, and it is unclear 20 whether the effects of lifestyle or pharmacologic interventions persist beyond that period Furthermore, it is still uncertain whether diabetes can truly be prevented or whether these strategies simply delay its onset The impact of delaying diabetes for a few years on preventing end-organ complications would likely be small, as complication risks
are low in the first 15 years after diabetes diagnosis The beneficial effects of lifestyle modification on cardiovascular events in persons with IGT also remain to be demonstrated Finally, the cost-effectiveness of screening for IGT and offering lifestyle interventions only to those with a positive test, versus offering these programs to all persons with diabetes risk factors, has not been examined

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Feig et al with CTF Type 2 Diabetes Canadian Task Force Recommendations Table 1 There is fair evidence to recommend screening adults with hypertension for type 2 diabetes to reduce the incidence of CV events and mortality Grade B recommendation 2 There is fair evidence to recommend screening adults with hyperlipidemia for type 2 diabetes to reduce the incidence of CV events and mortality Grade B recommendation 3 There is good evidence to recommend treatment of overweight individuals with IGT with lifestyle interventions to reduce the incidence of diabetes progression Grade B recommendation 4 There is insufficient evidence to recommend treatment of overweight individuals with IGT 10 with metformin or acarbose to reduce the incidence of diabetes progression Grade I recommendation 5
There is fair evidence to recommend treatment of overweight individuals with IGT with acarbose to prevent cardiovascular outcomes and hypertension Grade B recommendation
Body mass index BMI, kg/m2 25 or 22 in individuals of Asian descent

Clinical Considerations In patients who do not meet the above criteria, the decision to screen for diabetes or impaired glucose tolerance may be made on an individual basis The decision to screen should hinge on an estimate of patients overall cardiovascular risk Patients whose overall risk would 20 be raised by the diagnosis of diabetes to the extent that treatment would be changed, ie overall CVD risk is raised over 10/year, may merit screening Patients with other cardiac risk factors such as smoking, which put them at increased risk for cardiovascular disease, may benefit from screening for type 2 diabetes Screening involves only patients who are asymptomatic Individuals who exhibit symptoms or signs of diabetes, or those who have potential complications associated with diabetes, should receive diagnostic testing Screening is best accomplished with a fasting glucose The fasting glucose is more reliable and less cumbersome than the 75g OGTT,
and has similar predictive value for the development of retinopathy as the 2 hr PG, but may miss some cases of diabetes The diagnosis

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Feig et al with CTF Type 2 Diabetes can be made if the fasting glucose is 70 mmol/L, or the 2 hr PG is 111 mmol/L Expert Committee for the diagnosis2003 The test should be done on two occasions before a diagnosis can be made The diagnosis of impaired fasting glucose is made if the fasting glucose is 61-69 mmol/L, and the diagnosis of impaired glucose tolerance is made if the 2 hr PG is 78110 mmol/L following a 75g oral glucose tolerance test There is no information regarding the optimal screening frequency

Recommendations of Others In its 2003 clinical practice guidelines the Canadian Diabetes Association recommends 10 screening for diabetes using a fasting plasma glucose every 3 years in those 40 years of age and older grade consensus Canadian Diabetes Association, 2003 It recommends that screening be considered at an earlier age or be performed more frequently, or both, using a fasting glucose or 2-hour OGTT in people with additional risk factors for diabetes grade D, consensus The American Diabetes Association recommends patients,
particularly those with a BMI 25kg/m2 , should be screened at 3- year intervals beginning at age 45, using a fasting glucose They too suggest testing should be considered at an earlier age or be carried out more frequently in those who are overweight if additional diabetes risk factors are present The USPSTF found the evidence insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired 20 fasting glucose Grade I recommendation They did, however, recommend screening for type 2 diabetes in adults with hypertension or hyperlipidemia Grade B recommendation USPSTF recommendations and rationale 2003

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Members of the Canadian Task Force on Preventive Health Care Chair: Dr John W Feightner, Professor, Department of Family Medicine, The University of Western Ontario, London, Ont Vice-Chair: Dr Harriet MacMillan, Professor, Departments of Psychiatry and Behavioural Neurosciences and Pediatrics, Offord Centre for Child Studies, McMaster University, Hamilton, Ont Members : Drs Paul Bessette, Professeur titulaire, Département dobstétrique-gynécologie, Université de Sherbrooke, Sherbrooke, Que; R Wayne Elford,
Professor Emeritus, Department of Family Medicine, University of Calgary, Calgary, Alta; Denice Feig, Associate Professor, Departments of Medicine, of Obstetrics Gynecology, and of Health Policy Management and Evaluation, University of Toronto, Toronto, Ont; Joanne Langley, Associate Professor, Departments of Pediatrics and of Community Health and Epidemiology, Dalhousie University, Halifax, NS; Valerie Palda, Assistant Professor, Departments of Medicine and of Health Policy Management and Evaluation, University of

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Feig et al with CTF Type 2 Diabetes Toronto, Toronto, On Christopher Patterson, Professor, Division of Geriatric Medicine, t; Department of Medicine, McMaster University, Hamilton, Ont; Bruce A Reeder, Professor, Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Sask Resource staff: Ruth Walton, Research Associate, Canadian Task Force on Preventive Health Care, Department of Family Medicine, The University of Western Ontario, London, Ont Acknowledgements The Task Force thanks the following independent experts for reviewing a draft form of this report: Dr Paul S Frame, Dept of Family Medicine, University of Rochester,
Rochester, New York; Dr Janet Hux, Dept of Medicine, University of Toronto, Ontario The views expressed in this report are those of the authors and the Canadian Task Force and do not necessarily reflect the positions of the independent reviewers The authors would like to thank Dr Russell Harris for his valuable input, and Ruth Walton for her helpful assistance in preparing this manuscript

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Feig et al with CTF Type 2 Diabetes REFERENCES Alexander CM, Landsman PB, Teutsch SM, Haffner SM NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease NHANES III participants age 50 years and older Diabetes 2003;52:1210-4 Amoah AGB Undiagnosed diabetes and impaired glucose regulation in adult Ghanaians using the ADA and WHO diagnostic criteria Acta Diabetologia 2002;39:7-13 Anand SS, Razak F, Vuksan V, Gerstein HC, Malmberg K, Yi Q, et al Diagnostic strategies to detect glucose intolerance in a multiethnic popula tion Diabetes Care 2003;26:290-6 Antiplatelet Trialists Collaboration Collaborative overview of randomized trials of antiplatelet therapy–I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various
categories of patients BMJ 1994;308:81-106 Balkau B, Bertrais S, Ducimetiere P, Eschwege E Is there a glycemic threshold for mortality risk? Diabetes Care 1999;22:696-9 Barzilay JI, Spiekerman CF, Kuller LH, Burke GL, Bittner V, Gottdiener JS, et al Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study Diabetes Care 2001;24:1233-9 Beaulieu MD Screening for diabetes in the non-pregnant adult In: Canadian Task Force on Preventive Health Care The Canadian Guide to Clinical Preventive Health Care Ottawa: Canada Communication Group; 1994 p 602-9 Bennett PH, Rushforth NB, Miller M, Lecompte PM Epidemiologic studies of diabetes in Pima Indians Recent Prog Horm Res 1976;32:333-76 Bjornholt JV, Erikssen G, Aaser E, Sandvik L, Nitter-Hauge S, Jervell J, et al Fasting blood glucose: an underestimated risk factor for cardiovascular death: results from a 22-year follow-up of healthy nondiabetic men Diabetes Care 1999;22:45-9 Blunt BA, Barrett-Connor E, Wingard DL Evaluation of fasting plasma glucose as a screening test for NIDDM in older adults Ranco bernardo study Diabetes Care 1991;14:989-93 Bradford RH,
Shear CL, Chremos AN, Dujovne CA, Franklin FA, Grillo RB, et al Expanded Clinical Evaluation of Lovastatin Excel study results: two-year efficacy and safety followup Am J Cardiol 1994;74:667-73 Brownlee M Biochemistry and molecular cell biology of diabetic complications Nature 2001;4146865:813-20 Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, et al Preservation of pancreatic -cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women Diabetes 2002;51:2796-803

20

Feig et al with CTF Type 2 Diabetes Canadian Diabetes Association Expert Committee Canadian Diabetes Association 2003 clinical practice guidelines for the prevention and management of diabetes in Canada Screening and prevention Can J Diabetes 2003;27 Suppl 2:S10-3 Carter JS, Pugh JA, Monterossa A Non-insulin dependent diabetes mellitus in minorities in the Unites States Ann Intern Med 1996;125:221-32 Chang CJ, Wu JS, Lu FH, Lee HL, Yang YC, Wen MJ Fasting plasma glucose in screening for diabetes in the Taiwanese population Diabetes Care 1998;21:1856-60 Charles MA, Balkau B, Vauzelle-Kervoeden F, Thibult N, Eschwege E Revision of
diagnostic criteria for diabetes Letter Lancet 1996;348:1657-8 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M STOP-NIDDM Trial Research Group Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial Lancet 2002;359:2072-7 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M STOP-NIDDM Trial Research Group Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial JAMA 2003;290:48694 Colagiuri S, Cull CA, Holman RR for the UKPDS Group Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcome? Diabetes Care 2002;25:1410-7 Colhoun HM, Thomason MJ, Mackness MI, Maton SM, Betteridge DJ, Durrington PN, et al Design of the Collaborative AtoRvastatin Diabetes Study CARDS in patients with type 2 diabetes Diabet Med 2002 193:201-11 Coutinho M, Gerstein HC, Wang Y, Yusuf S The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 124 years Diabetes Care 1999;222:233-40 de Vegt F, Dekker JM, Stehouwer CD,
Nijpels G, Bouter LM, Heine RJ The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance Diabetes Care 1998;21:1686-90 Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS Air Force/Texas Coronary Atherosclerosis Prevention Study JAMA 1998;279:1615-22 Edelman D, Olsen MK, Dudley TK, Harris AC, Oddone EZ Impact of diabetes screening on quality of life Diabete Care 2002;25:1022-6

21

Feig et al with CTF Type 2 Diabetes Edelstein SL, Knowler WC, Bain RP, Andres R, Barrett-Connor EL, Dowse GK, et al Predictors of progression from impaired glucose tolerance to NIDDM: An analysis of six prospective studies Diabetes 1997; 46:701-710 Elkeles RS, Diamond JR, Poulter C, Dhanjil S, Nicolaides AN, Mahmood S, et al Cardiovascular outcomes in type2 diabetes A double-blind placebo-controlled study of bezafibrate: the St Marys, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention SENDCAP Study Diabetes Care 1998;21:641-8 Engelgau M, Narayan
KNV, Herman W Screening for type 2 diabetes Diabetes Care 2000;23:1563-80 Engelgau MM, Thompson TJ, Herman WH, Boyle JP, Aubert RE, Kenny SJ, et al Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes; diagnostic criteria and performance revisited Diabetes Care 1997;20:785-91 Estacio RO, Jeffers BW, Gifford N, Schrier RW Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes Diabetes Care 2000;23 Suppl 2:B54-64 Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia N Engl J Med 1987;317:1237-45 Gaede P, Vedel P, Parving HH, Pedersen O Intensified multifactorial intervention in patients with tyhpe 2 diabetes and microalbunminuria the Steno type 3 randomised trial Lancet 1999;353:617-22 Gimeno SGA, Ferreira SRG, Franco LJ, Iunes M Comparison of glucose tolerance categories according to World Health Organization and American Diabetes Association Diagno stic Criteria in a population-based study in Brazil Diabetes Care 1998;21:1889-92 Goldberg RB, Mellies MJ, Sacks FM, Moy LA,
Howard BV, Howard WJ, et al Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels; subgroup analyses and the Cholesterol and Recurrent Events CARE trial The CARE investigators Circulation 1998;98:2513-9 Haffner SM, Alexander CM, Cook TJ, Boccuzzi SJ, Musliner TA, Pedersen TR, et al Reduced coronary events in simvastatin-treated patents with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analysis in the Scandinavian Simvastatin Survival Study Arch Intern Med 1999;159:2661-7 Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK Cardiovascular risk factors in confirmed prediabetic individuals Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 1990;263:2893-8 Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension:

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Feig et al with CTF Type 2 Diabetes principal results of the Hypertension Optimal Treatment HOT randomized trial Lancet 1998;351:1755-62 Harris MI, Eastman RC Is
there a glycemic threshold for mortality risk? Diabetes Care 1998;21:331-3 Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults: the third national health and nutrition examination survey, 1988-1994 Diabetes Care 1998;21:518-24 Harris MI, Hadden WC, Knowler WC, Bennett PH Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in the US population aged 20-74 yr Diabetes 1987;36:523-34 Harris MI, Klein R, Welborn TA, Knuiman MW Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis Diabetes Care 1992;15:815-9 Harris MI Non- insulin-dependant diabetes mellitus I black and white Americans Diabetes Metab Rev 1990;6:71-90 Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN Screening adults for type 2 diabetes: a review of the evidence for the US Preventive Services Task Force Ann Intern Med 2003;1383:215-29 Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al Current methods of the US Preventive Services Task Force: a review of the process Am J Prev Med 2001;203 Suppl:21-35 Health Canada Diabetes in Canada 2 nd ed
Ottawa: Health Canada; 2002 Available from: URL: http://wwwhc -scgcca/pphb-dgspsp/publicat/dic-dac2/english/01cover_ehtml Health Canada Economic Burden of Illness in Canada, 1998 Catalogue No H21-136/1998 Ottawa: Health Canada; 2002 Available from: URL: http://wwwhc-scgcca/pphbdgspsp/publicat/ebic-femc98/pdf/ebic1998pdf Kannel WB, McGee DL Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framinghan Study Diabetes Care 1979;2:120-6 Khaw KT, Wareham N, Luben R, Bingham S, Oakes S, Welch A, et al Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition EPIC- Norfolk BMJ 2001;322:15-8 Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program Diabetes Care 2003;26:977-80

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Feig et al with CTF Type 2 Diabetes Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin New England Journal of Medicine 2002;346:393-403 Koskinen P, Manttari M, Manninen V,
Huttunen JK, Heinonen OP, Frick MH Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study Diabetes Care 1992;15:820-5 Lee CH, Rook Chong S Evaluation of fasting plasma glucose as a screening test for diabetes mellitus in Singaporean adults Diabet Med 1997;14:119-22 Leiter LA, Barr A, Belanger A, Lubin S, Ross SA, Tildesley HD, et al Diabetes Screening in Canada DIASCAN Study: prevalence of undiagnosed diabetes and glucose intolerance in family physician offices Diabetes Care 2001;24:1038-43 Litzelman DK, Slemenda CW, Langefield CD, Hays LM, Welch MA, Bild DE, et al Reduction of lower extremity clinical abnormalities in patients with non- insulin dependent diabetes mellitus A randomized controlled trial Ann Intern Med 1993;119:36-41 McCabe CJ, Stevenson RC, Dolan AM Evaluation of a diabetic foot screening and protection programme Diabet Med 1998;15:80-4 McCance DR, Hanson RL, Charles MA, Jacobsson LTH, Pettitt DJ, Bennett PH, et al Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes BMJ 1994;21;3086940:1323-8 McNeely MJ, Boyko EJ, Leonetti DL, Kahn SE, Fujimoto WY Comparison of
a clinical model, the oral glucose tolerance test, and fasting glucose for prediction of type 2 diabetes risk in Japanese Americans Diabetes Care 2003;26:758-63 McPhillips JB, Barrett-Connor E, Wingard DL Cardiovascular disease risk factors prior to the diagnosis of impaired glucose tolerance and non- insulin-dependent diabetes mellitus in a community of older adults Am J Epidemiol 1990;131:443-53 Meigs JB, Nathan DM, Wilson PW, Cupples LA, Singer DE Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance The Framingham Offspring Study Ann Intern Med 1998;128:524-33 Metcalf PA, Scragg RKR Comparison of WHO and ADA criteria for diagnosis of glucose status in adults Diabetes Research and Clinical Practice 2000; 49:169-80 Mogensen CE Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas In: Mogensen CE, ed The kidney and hypertension in diabetes mellitus 5th ed Boston: Kluwer; 2000 p 655-706 Moore R, Mao Y, Zhang J, Clarke K Economic Burden of Illness in Canada, 1993 Ottawa: Canadian Public Health Association; 1997 Available from: URL: http://wwwhcscgcca/pphb-dgspsp/publicat/ebic- femc93/indexhtml

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Feig
et al with CTF Type 2 Diabetes Mooy JM, Grootenhuis PA, de Vries H, Kostense PJ, Popp-Snijders C, Bouter LM, et al Intraindividual variation of glucose, specific insulin and proinsulin conctrations measured by two oral glucose tolerance test in a gene ral Caucasian population; the Hoorn Study Diabetologia 1996;39:298-305 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial Lancet 2002;360:7-22 Nakagami T, Qiao Q, Tuomilehto J Cardiovascular risk profile assessment in glucose-intolerant individuals an evaluation of the World Health Organization two-step strategy: the DECODA Study Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia Diabetic Medicine 2002;19:549-57 Newman WP, Nelson R, Scheer K Community screening for diabetes: low detection rate in a low-risk population Diabetes Care 1994;17:363-5 Pan XR, Li GW, Hu YH, et al Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Qing IGT and diabetes study Diabetes Care 1997;20:537-44 Patout CA Jr, Birke JA, Horswell R, Williams D, Cerise FP Effectiveness of a comprehensive
diabetes lower-extremity amputation prevention program in a predominantly low- income African-American population Diabetes Care 2000;23:1339-42 Pierce LR, Wysowski DK, Gross TP Myopathy and rhabdomyolosis associated with lovastatingemfibrozil combination therapy JAMA 1990;264:71-5 Pignone MP, Phillips CJ, Atkins D, Teutsch SM, Mulrow CD, Lohr KN Screening and treating adults for lipid disorders Am J Prev Med 2001:20Suppl 3:77-89 Pyorala K, Laakso M, Uusitupa M Diabetes and atherosclerosis: an epidemiologic view Diabetes Metab Rev 1987;3:463-524 Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease A subgroup analysis of the Scandinavian Simvastatin Survival Study 4S Diabetes Care 1997;20:614-20 Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study 4S Lancet 1994;344:1383-89 Resnick HE, Valsania P, Phillips CL Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans: The National Health and Nutrition Examination Survey Epidemiologic Follow-up Study,
1971-1992 Arch Intern Med 1999;159:2470-5 Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, et al Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial JAMA 2001;285:1585-91

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Feig et al with CTF Type 2 Diabetes Rolka DB, Narayan KM, Thompson TJ, Goldman D, Lindenmayer AJ, Alich K, et al Performance of recommended screening tests for undiagnosed diabetes and dysglycemia Diabetes Care 2001;24:854-65 Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al Gemfibrozil for secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol Veterans Affairs High- Density Lipoprotein Cholesterol Intervention Trial Study Group N Engl J Med 1999;341:410-8 Sacks FM, Tonkin AM, Craven T, Pfeffer MA, Shepherd J, Keech A, et al Coronary heart disease in patients with low LDL-cholesterol: benefit of pravastatin in diabetics and enhanced role for HDL-cholesterol and triglycerides as risk factors Circulation 2002;105:1424-8 Saydah SH, Loria CM, Eberhardt MS, Brancati FL Subclinical states of glucose intolerance and risk of death in the US Diabetes
Care 2001;24:447-53 Schrier RW, Estacio RO, Esler A, Mehler P Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes Kidney Int 2002;61:1086-97 Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid lowering Arm ASCOT-LLA: a multicentre randomized controlled trial Lancet 2003;361:1150-8 Shaw JE, Zimmet PZ, de Courten M, Dowse GK, Chitson P, Gareeboo H, et al Impaired fasting glucose or impaired glucose tolerance: What best predicts future diabetes in Mauritius? Diabetes Care 1999;22:399-402 Stamler J, Vaccaro O, Neaton JD, Wentworth D Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial Diabetes Care 1993;16:434-44 Testa MA, Simonson DC, Turner RR Valuing quality of life and improvements in glycemic control in people with type 2 diabetes mellitus Diabetes Care 1998;21Suppl 3:C44-52 Testa MA, Simonson DC Health economic benefits and quality
of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, doubleblind trial JAMA 1998;280:1490-6 The DECODE study group Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria European Diabetes Epidemiology Group Lancet 1999;354:617-21

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Feig et al with CTF Type 2 Diabetes The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Diabetes Care 1997;20:1183-97 The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the Expert Committee on the Diagnois and Classification of Diabetes Mellitus ADA Position Paper Diabetes Care 2003;261:S5-20 The Long-Term Intervention with Pravastatin in Ischaemic Disease LIPID Study Group Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels N Engl J Med 1998;339:1349-57 Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne -Parikka P, et al Finnish Diabetes Prevention Study Group Prevention of type
2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance New England Journal of Medicine 2001;344:1343-50 US Preventive Services Task Force Aspirin for the primary prevention of cardiovascular events: recommendation and rationale Ann Intern Med 2002;136:157-60 US Preventive Services Task Force Screening for type 2 diabetes mellitus in adults: recommendations and rationale Ann Intern Med 2003;1383:212-4 UK Prospective Diabetes Study Group UKPDS 37 Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control Diabetes Care 1999;22:1125-36 UK Prospective Diabetes Study Group UKPDS 30 Diabetic retinopathy at diagnosis of type 2 diabetes and associated risk factors Arch Ophthalmol 1998;116:297-303 UK Prospective Diabetes Study Group UKPDS 33 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes Lancet 1998;352:837-53 UK Prospective Diabetes Study Group UKPDS 38 Tight blood pressure control and risk fo macrovascular and microvascular complications in type 2
diabetes BMJ 1998;317:703-13 UK Prospective Diabetes Study Group UKPDS 6 Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors Diabetes Research 1990;13:1 -11 Unwin N, Shaw J, Zimmet P, Alberti KGMM Impaired glucose tolerance and impaired fasting glycemia: the current status on definition and intervention Diabetic Medicine 2002;19:70823 Unwin N, Shaw J, Zimmet P, Alberti KGMM Impaired glucose tolerance and impaired fasting glycemia: the current status on definition and intervention Diabetic Medicine 2002; 19:70823

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Feig et al with CTF Type 2 Diabetes Wahl PW, Savage PJ, Psaty BM, Orchard TJ, Robbins JA, Tracy RP Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification Lancet 1998;352:1012-5 Wiener K Fasting plasma glucose as a screening test for diabetes mellitus Diabet Med 1997;14:711-2

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Feig et al with CTF Type 2 Diabetes Figure 1: Natural History of Type 2 Diabetes

Disease Begins

Macrovascular Complications

Microvascular Complications

0

Point A

Point B

IFG / IGT

Screening Detection

Symptoms

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Feig
et al with CTF Type 2 Diabetes Table: Summary of Recommendations
Maneuver Screening patients with hypertension for type 2 diabetes to reduce the incidence of cardiovascular CV events and CV mortality Effectiveness CV events in patients with high blood pressure: RR 206 124344 CV deaths in patients with high blood pressure: RR 30 128708 Decrease in Diabetes Mellitus DM related deaths: RR 068 049-094 Decrease in DM-related strokes: RR 056 035-089 RRR 24-42 in CV events Level I, good Pyorala 1997, Koskinen 1992, Frick 1987, LIPID Study Group 1998, Downs 1998, Rubins 1999, Haffner 1999, Pignone 2001, MRC/BHF Heart Protection study 2002, Robins 2001, Goldberg 1998 Decreased progression to diabetes 42-58 Level I, good Pan 1997, Tuomilehto 2001, Knowler 2002 Level of Evidence Refs Level I, fair Harris 1998, UKPDS 38 1998, Schrier 2002, Estacio 2002 The CTF concludes that there is fair evidence to recommend screening patients with hypertension for type 2 diabetes to reduce the incidence of CV events and CV mortality B Recommendation Recommendations

Screening patients with hyperlipidemia for type 2 diabetes to reduce the incidence of CV events

The CTF concludes that there is fair evidence
to recommend screening patients with hyperlipidemia for type 2 diabetes to reduce the incidence of CV events B Recommendation

Treating overweight people with IGT with lifestyle intervention to reduce the incidence of diabetes progression

The CTF concludes that there is good evidence to recommend treatment of IGT with lifestyle interventions to reduce the incidence of diabetes progression B Recommendation The CTF concludes that there is insufficient evidence to recommend treatment of IGT with metformin or acarbose to reduce the incidence of diabetes progression I Recommendation The CTF concludes that there is fair evidence to recommend treatment of IGT with acarbose to prevent CV events or hypertension B Recommendation

Treating overweight people with IGT with acarbose or metformin to reduce diabetes progression

Metformin 25-31 reduction in diabetes Acarbose 25 reduction in diabetes

Level I, fair Chiasson 2002, Knowler 2002, Knowler 2003

Treating overweight people with IGT with acarbose to reduce CV events and hypertension

49 reduction in CV events 34 reduction in hypertension

Level I, fair Chiasson 2003

Body mass index BMI, kg/m2 25 or 22 in individuals of Asian
descent

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Feig et al with CTF Type 2 Diabetes
Appendix: Methodology of the Canadian Task Force on Preventive Health Care Critical appraisal The Task Force reviewed 1 the initial analytic framework and key questions for the proposed review; 2 the subsequent drafts of the complete manuscript providing critical appraisal of the evidence prepared by the lead authors, including identification and double, independent critical appraisal of key studies or recent systematic reviews, and ratings of the quality of this evidence using the task forces established methodological hierarchy sidebar; and 3 a summary of the evidence and proposed recommendations Consensus development Evidence for this topic was presented by the lead authors and deliberated upon during task force meetings in February, June, and October 2003 Expert panelists addres sed critical issues, clarified ambiguous concepts and analyzed the synthesis of the evidence At the end of this process, the specific clinical recommendations proposed by the lead author were discussed, as were issues related to clarification of the recommendations for clinical application and any gaps in evidence The results of this process are
reflected in the description of the decision criteria presented with the specific recommendations The group and lead authors arrived at final decisions on recommendations unanimously Subsequent to the meetings, the lead authors revised the manuscript accordingly After final revision, the Task Force sent the manuscript to experts in the field identified by Task Force members at the meeting Feedback from these experts was incorporated into a subsequent draft of the manuscript Procedures to achieve adequate documentation, consistency, comprehensiveness, objectivity and adherence to the task force methodology were maintained at all stages during review development, the consensus process and beyond to ensure uniformity and impartiality throughout Levels of evidence A Research design rating: I II-1 II-2 II-3 Evidence from randomized controlled trials Evidence from controlled trials without randomization Evidence from cohort or casecontrol analytic studies, preferably from more than one centre or research group Evidence from comparisons between times or places with or without the intervention; dramatic results from uncontrolled studies could be included here Opinions of respected
authorities, based on clinical experience; descriptive studies or reports of expert committees A study including meta-analyses or systematic reviews that meets all design- specific criteria well A study including meta-analyses or systematic reviews that does not meet or it is not clear that it meets at least one design-specific criterion but has no known fatal flaw A study including meta-analyses or systematic reviews that has at least one design-specific fatal flaw, or an accumulation of lesser flaws to the extent that the results of the study are not deemed able to inform recommendations

III

B Quality internal validity rating see Harris et al, 2001: Good Fair

Poor

General design specific criteria are outlined in Harris et al, 2001 Inclusion/exclusion criteria are detailed in the Methods section Recommendations Grades for Specific Clinical Preventive Actions A B C The CTF concludes that there is good evidence to recommend the clinical preventive action The CTF concludes that there is fair evidence to recommend the clinical preventive action The CTF concludes that the existing evidence is conflicting and does not allow making a recommendation for or against use of the clinical
preventive action, however other factors may influence decision-making The CTF concludes that there is fair evidence to recommend against the clinical preventive action The CTF concludes that there is good evidence to recommend against the clinical preventive action The CTF concludes that there is insufficient evidence in quantity and/or quality to make a recommendation, however other factors may influence decision-making

D E I

The CTF recognizes that in many cases patient specific factors need to be considered and discussed, such as the value the patient places on the clinical preventive action; its possible positive and negative outcomes; and the context and/or personal circumstances of the patient medical and other In certain circumstances where the evidence is complex, conflicting or insufficient, a more detailed discussion may be required

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