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Early Recognition and Treatment of Glucose Abnormalities to Prevent Type 2 Diabetes Mellitus and Coronary Heart Disease

2001; Elsevier BV; Volume: 76; Issue: 11 Linguagem: Inglês

10.4065/76.11.1137

ISSN

1942-5546

Autores

Warren G. Thompson,

Tópico(s)

Metabolism, Diabetes, and Cancer

Resumo

Striking parallels exist in both risk and protective factors between coronary heart disease and type 2 diabetes mellitus. Patients with insulin resistance are more likely to develop diabetes and coronary heart disease. Better treatment of diabetes may result in less coronary heart disease, although this has not yet been established. Reliance on fasting glucose determinations alone will overlook a substantial number of patients at risk for diabetes and subsequent coronary heart disease. Measurement of glycosylated hemoglobin should be a routine part of screening for patients at risk for diabetes. Patients with glycosylated hemoglobin levels in the high-normal range should be treated more aggressively with diet, exercise, and medication because evidence is good that diabetes can be prevented (or its onset delayed). Patients with borderline elevations of low-density lipoprotein cholesterol concentrations and with high-normal glycosylated hemoglobin levels should be considered for statin therapy, and patients with hypertension with high-normal glycosylated hemoglobin levels should be treated with angiotensin-converting enzyme inhibitors as first-line agents. Studies to determine whether metformin is useful in this population are ongoing. Striking parallels exist in both risk and protective factors between coronary heart disease and type 2 diabetes mellitus. Patients with insulin resistance are more likely to develop diabetes and coronary heart disease. Better treatment of diabetes may result in less coronary heart disease, although this has not yet been established. Reliance on fasting glucose determinations alone will overlook a substantial number of patients at risk for diabetes and subsequent coronary heart disease. Measurement of glycosylated hemoglobin should be a routine part of screening for patients at risk for diabetes. Patients with glycosylated hemoglobin levels in the high-normal range should be treated more aggressively with diet, exercise, and medication because evidence is good that diabetes can be prevented (or its onset delayed). Patients with borderline elevations of low-density lipoprotein cholesterol concentrations and with high-normal glycosylated hemoglobin levels should be considered for statin therapy, and patients with hypertension with high-normal glycosylated hemoglobin levels should be treated with angiotensin-converting enzyme inhibitors as first-line agents. Studies to determine whether metformin is useful in this population are ongoing. Coronary heart disease is the leading cause of death both in the United States and in the world. Diabetes triples the risk of coronary heart disease in men1Lotufo PA Gaziano JM Chae CU et al.Diabetes and all-cause and coronary heart disease mortality among US male physicians.Arch Intern Med. 2001; 161: 242-247Crossref PubMed Scopus (193) Google Scholar and increases the risk in women 6-fold (controlling for other risk factors associated with diabetes and coronary heart disease modestly attenuates this figure).2Manson JE Colditz GA Stampfer MJ et al.A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women.Arch Intern Med. 1991; 151: 1141-1147Crossref PubMed Scopus (613) Google Scholar Whether patients with elevated fasting glucose levels (110–125 mg/dL) are at increased risk for coronary heart disease is less clear as the data are conflicting.3Barrett-Connor E Wingard DL “Normal” blood glucose and coronary risk [editorial].BMJ. 2001; 322: 5-6Crossref PubMed Scopus (28) Google Scholar It seems likely, however, that patients at risk for the development of diabetes are also at risk for the development of coronary heart disease. In 1995 Stern4Stern MP Diabetes and cardiovascular disease: the “common soil” hypothesis.Diabetes. 1995; 44: 369-374Crossref PubMed Scopus (0) Google Scholar called attention to the “common soil” between diabetes and cardiovascular disease. In that review he summarized the evidence for the parallel antecedents of the 2 diseases: low birth weight, obesity, central obesity, hypertension, and low high-density lipoprotein (HDL) cholesterol. He noted that elevated triglyceride, insulin, and glucose levels were risk factors for diabetes and possibly risk factors for cardiovascular disease. Three studies have been published since then confirming that hypertension and a low HDL cholesterol level frequently precede the development of diabetes.5Perry IJ Wannamethee SG Walker MK Thomson AG Whincup PH Shaper AG Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.BMJ. 1995; 310: 560-564Crossref PubMed Scopus (473) Google Scholar, 6Haffner SM Mykkanen L Festa A Burke JP Stern MP Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state.Circulation. 2000; 101: 975-980Crossref PubMed Scopus (406) Google Scholar, 7von Eckardstein A Schulte H Assmann G Risk for diabetes mellitus in middle-aged Caucasian male participants of the PROCAM Study: implications for the definition of impaired fasting glucose by the American Diabetes Association.J Clin Endo-crinol Metab. 2000; 85: 3101-3108Crossref PubMed Google Scholar Fasting triglyceride level was a predictor in 2 of these studies.5Perry IJ Wannamethee SG Walker MK Thomson AG Whincup PH Shaper AG Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.BMJ. 1995; 310: 560-564Crossref PubMed Scopus (473) Google Scholar6Haffner SM Mykkanen L Festa A Burke JP Stern MP Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state.Circulation. 2000; 101: 975-980Crossref PubMed Scopus (406) Google Scholar The Atherosclerosis Risk in Communities study, which included a large number of African American subjects, found that the relative risk of diabetes was nearly 2.5 times greater in hypertensive patients.8Gress TW Nieto FJ Shahar E Wofford MR Brancati FL Atheroslcerosis Risk in Communities Study Hypertension and antihypertensive therapy as risk factors for type 2 diabetes.N Engl J Med. 2000; 342: 905-912Crossref PubMed Scopus (996) Google Scholar Since Stern's review, weight gain in adulthood has also been related to the risk of diabetes and coronary heart disease.9Willett WC Manson JE Stampfer MJ et al.Weight, weight change, and coronary heart disease in women: risk within the “normal” weight range.JAMA. 1995; 273: 461-465Crossref PubMed Scopus (872) Google Scholar, 10Ford ES Williamson DF Liu S Weight change and diabetes incidence: findings from a national cohort of US adults.Am J Epidemiol. 1997; 146: 214-222Crossref PubMed Scopus (467) Google Scholar, 11Rosengren A Wedel H Wilhelmsen L Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality: a prospective population study.Eur Heart J. 1999; 20: 269-277Crossref PubMed Scopus (168) Google Scholar In this review, I discuss several other antecedents that diabetes and coronary heart disease have in common, including alcohol and tobacco use, diet, and exercise (Table 1). The “common soil” shared between diabetes and coronary heart disease suggests that physicians should make an aggressive effort to diagnose and treat patients at risk. The relationship between fasting glucose, insulin, postprandial glucose, and glycosylated hemoglobin levels and coronary heart disease is then discussed to show that relying on the fasting glucose level alone will result in substantial failure to diagnose patients at risk. Finally, I discuss the treatment implications of the risk factor studies as well as the results of some seminal randomized trials that could result in improved treatment.Table 1Common Risk and Protective Factors for Diabetes and Coronary Heart Disease Risk factors Low birth weightHigh body mass indexCentral obesity (waist-to-hip ratio)Weight gainHypertensionLow high-density lipoprotein cholesterol levelHigh fasting triglyceride level (controversial for heart disease)Cigarette smokingHigh glycemic load and glycemic index (controversial)High trans fatty acid intake (controversial for diabetes)Elevated high-sensitivity C-reactive protein (more data needed for diabetes)Protective factors Alcohol consumption (in moderation)Exercise (benefit in both physical activity and physical fitness)Whole grain and fiber intakeFish and fish oil intake (controversial for diabetes) Open table in a new tab Alcohol use is inversely related to coronary heart disease in more than 60 prospective studies.12Goldberg IJ Mosca L Piano MR Fisher EA Wine and your heart: a science advisory for healthcare professionals from the Nutrition Committee, Council on Epidemiology and Prevention, and Council on Cardiovascular Nursing of the American Heart Association.Circulation. 2001; 103: 472-475Crossref PubMed Scopus (220) Google Scholar Most studies do not show an added benefit from red wine.12Goldberg IJ Mosca L Piano MR Fisher EA Wine and your heart: a science advisory for healthcare professionals from the Nutrition Committee, Council on Epidemiology and Prevention, and Council on Cardiovascular Nursing of the American Heart Association.Circulation. 2001; 103: 472-475Crossref PubMed Scopus (220) Google Scholar Alcohol in moderation (1 drink daily) has been associated with an approximately 40% lower risk of developing diabetes after controlling for weight, family history, and exercise in 4 prospective studies.13Stampfer MJ Colditz GA Willett WC et al.A prospective study of moderate alcohol drinking and risk of diabetes in women.Am J Epidemiol. 1988; 128: 549-558PubMed Google Scholar, 14Rimm EB Chan J Stampfer MJ Colditz GA Willett WC Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men.BMJ. 1995; 310: 555-559Crossref PubMed Scopus (502) Google Scholar, 15Wei M Gibbons LW Mitchell TL Kampert JB Blair SN Alcohol intake and incidence of type 2 diabetes in men.Diabetes Care. 2000; 23: 18-22Crossref PubMed Scopus (192) Google Scholar, 16Ajani UA Hennekens CH Spelsberg A Manson JE Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians.Arch Intern Med. 2000; 160: 1025-1030Crossref PubMed Scopus (179) Google Scholar Furthermore, alcohol has been associated with a reduced incidence of coronary heart disease in diabetic patients.17Solomon CG Hu FB Stampfer MJ et al.Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus.Circulation. 2000; 102: 494-499Crossref PubMed Scopus (151) Google Scholar, 18Valmadrid CT Klein R Moss SE Klein BE Cruickshanks KJ Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus.JAMA. 1999; 282: 239-246Crossref PubMed Scopus (148) Google Scholar, 19Ajani UA Gaziano JM Lotufo PA et al.Alcohol consumption and risk of coronary heart disease by diabetes status.Circulation. 2000; 102: 500-505Crossref PubMed Scopus (129) Google Scholar Moderate alcohol intake has been associated with improved sensitivity to insulin.20Facchini F Chen YD Reaven GM Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity.Diabetes Care. 1994; 17: 115-119Crossref PubMed Scopus (249) Google Scholar Seven prospective studies have documented a relationship between smoking and type 2 diabetes.14Rimm EB Chan J Stampfer MJ Colditz GA Willett WC Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men.BMJ. 1995; 310: 555-559Crossref PubMed Scopus (502) Google Scholar21Feskens EJ Kromhout D Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men: the Zutphen Study.Am J Epidemiol. 1989; 130: 1101-1108PubMed Google Scholar, 22Rimm EB Manson JE Stampfer MJ et al.Cigarette smoking and the risk of diabetes in women.Am J Public Health. 1993; 83: 211-214Crossref PubMed Scopus (231) Google Scholar, 23Kawakami N Takatsuka N Shimizu H Ishibashi H Effects of smoking on the incidence of non-insulin-dependent diabetes mellitus: replication and extension in a Japanese cohort of male employees.Am J Epidemiol. 1997; 145: 103-109Crossref PubMed Scopus (100) Google Scholar, 24Uchimoto S Tsumura K Hayashi T et al.Impact of cigarette smoking on the incidence of type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey.Diabet Med. 1999; 16: 951-955Crossref PubMed Scopus (79) Google Scholar, 25Nakanishi N Nakamura K Matsuo Y Suzuki K Tatara K Cigarette smoking and risk for impaired fasting glucose and type 2 diabetes in middle-aged Japanese men.Ann Intern Med. 2000; 133: 183-191Crossref PubMed Scopus (123) Google Scholar, 26Manson JE Ajani UA Liu S Nathan DM Hennekens CH A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians.Am J Med. 2000; 109: 538-542Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar The risk is especially prominent in men with normal body mass index. Heavy cigarette smoking approximately doubles the risk of developing diabetes. One large study failed to find a relationship in multivariate analysis; however, unlike the positive studies, family history was not evaluated as a possible confounder.5Perry IJ Wannamethee SG Walker MK Thomson AG Whincup PH Shaper AG Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.BMJ. 1995; 310: 560-564Crossref PubMed Scopus (473) Google Scholar Only one of the positive studies was performed in women. Smoking is associated with lower body mass index and might be thought to reduce the risk of diabetes. However, smoking is positively related to central obesity,27Seidell JC Cigolini M Deslypere JP Charzewska J Ellsinger BM Cruz A Body fat distribution in relation to physical activity and smoking habits in 38-year-old European men: the European Fat Distribution Study.Am J Epidemiol. 1991; 133: 257-265PubMed Google Scholar and it may increase insulin resistance.28Facchini FS Hollenbeck CB Jeppesen J Chen YD Reaven GM Insulin resistance and cigarette smoking [published correction appears in Lancet. 1992;339:1492].Lancet. 1992; 339: 1128-1130Abstract PubMed Scopus (605) Google Scholar Thus, patients at risk for the development of diabetes should be especially counseled not to smoke. The Nurses’ Health Study followed 75,521 nurses for 10 years.29Liu S Stampfer MJ Hu FB et al.Whole-grain consumption and risk of coronary heart disease: results from the Nurses’ Health Study.Am J Clin Nutr. 1999; 70: 412-419PubMed Google Scholar, 30Liu S Manson JE Stampfer MJ et al.Whole grain consumption and risk of ischemic stroke in women: a prospective study.JAMA. 2000; 284: 1534-1540Crossref PubMed Scopus (271) Google Scholar, 31Liu S Manson JE Stampfer MJ et al.A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women.Am J Public Health. 2000; 90: 1409-1415Crossref PubMed Scopus (373) Google Scholar Coronary heart disease developed in 761, is-chemic stroke in 352, and diabetes in 1879 subjects. The highest quintile of whole grain consumption was associated with a 25% reduction in coronary heart disease, a 30% reduction in ischemic stroke, and a 40% reduction in diabetes. The Iowa Women's Health Study followed approximately 35,000 women older than 55 years for 6 to 9 years and documented 438 coronary deaths and 1141 cases of diabetes.32Jacobs Jr, DR Meyer KA Kushi LH Folsom AR Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: the Iowa Women's Health Study.Am J Clin Nutr. 1998; 68: 248-257PubMed Google Scholar33Meyer KA Kushi LH Jacobs Jr, DR Slavin J Sellers TA Folsom AR Carbohydrates, dietary fiber, and incident type 2 diabetes in older women.Am J Clin Nutr. 2000; 71: 921-930PubMed Google Scholar There was a 30% reduction in coronary death and a 20% reduction in diabetes in the highest quintile group. Refined grains were not protective in either of these studies. Multiple prospective studies have shown a reduced incidence of coronary heart disease with increased fiber intake.34Morris JN Marr JW Clayton DG Diet and heart: a postscript.BMJ. 1977; 2: 1307-1314Crossref PubMed Scopus (272) Google Scholar, 35Kromhout D Bosschieter EB de Lezenne Coulander C Dietary fibre and 10-year mortality from coronary heart disease, cancer, and all causes: the Zutphen Study.Lancet. 1982; 2: 518-522Abstract PubMed Scopus (149) Google Scholar, 36Kushi LH Lew RA Stare FJ et al.Diet and 20-year mortality from coronary heart disease: the Ireland-Boston Diet-Heart Study.N Engl J Med. 1985; 312: 811-818Crossref PubMed Scopus (384) Google Scholar, 37Khaw KT Barrett-Connor E Dietary fiber and reduced ischemic heart disease mortality rates in men and women: a 12-year prospective study.Am J Epidemiol. 1987; 126: 1093-1102PubMed Google Scholar, 38Rimm EB Ascherio A Giovannucci E Spiegelman D Stampfer MJ Willett WC Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men.JAMA. 1996; 275: 447-451Crossref PubMed Google Scholar, 39Pietinen P Rimm EB Korhonen P et al.Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.Circulation. 1996; 94: 2720-2727Crossref PubMed Scopus (301) Google Scholar, 40Wolk A Manson JE Stampfer MJ et al.Long-term intake of dietary fiber and decreased risk of coronary heart disease among women.JAMA. 1999; 281: 1998-2004Crossref PubMed Scopus (356) Google Scholar Three prospective studies have shown a decreased risk of diabetes in subjects consuming more fiber.33Meyer KA Kushi LH Jacobs Jr, DR Slavin J Sellers TA Folsom AR Carbohydrates, dietary fiber, and incident type 2 diabetes in older women.Am J Clin Nutr. 2000; 71: 921-930PubMed Google Scholar41Salmerón J Ascherio A Rimm EB et al.Dietary fiber, glycemic load, and risk of NIDDM in men.Diabetes Care. 1997; 20: 545-550Crossref PubMed Scopus (1175) Google Scholar42Salmerón J Manson JE Stampfer MJ Colditz GA Wing AL Willett WC Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.JAMA. 1997; 277: 472-477Crossref PubMed Google Scholar One randomized trial of cereal fiber43Burr ML Fehily AM Gilbert JF et al.Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART).Lancet. 1989; 2: 757-761Abstract PubMed Scopus (2320) Google Scholar failed to show a reduced incidence of coronary death and myocardial infarction, but 2 other randomized trials showed significant reductions in coronary heart disease with altered diet (including increased fiber).44de Lorgeril M Salen P Martin JL Monjaud I Delaye J Mamelle N Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.Circulation. 1999; 99: 779-785Crossref PubMed Scopus (2325) Google Scholar45Singh RB Rastogi SS Verma R Bolaki L Singh R An Indian experiment with nutritional modulation in acute myocardial infarction.Am J Cardiol. 1992; 69: 879-885Abstract Full Text PDF PubMed Scopus (99) Google Scholar One randomized trial of glucose-intolerant Chinese subjects showed that diet (which included increased fiber) lowered the incidence of diabetes.46Pan 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: 537-544Crossref PubMed Scopus (3314) Google Scholar Patients at risk for coronary heart disease and diabetes should be advised to increase their intake of whole grains and fiber. Foods with a high glycemic index cause a greater increase in blood glucose and insulin levels than foods with a low glycemic index.47Jenkins DJ Wolever TM Taylor RH et al.Glycemic index of foods: a physiological basis for carbohydrate exchange.Am J Clin Nutr. 1981; 34: 362-366PubMed Google Scholar White bread has a higher glycemic index than whole grain bread, potatoes have a higher glycemic index than broccoli, and orange juice has a higher glycemic index than an orange. Experimental studies suggest that low glycemic index diets may result in improved diabetic control.48Järvi AE Karlström BE Granfeldt YE Björck IE Asp N-GL Vessby BOH Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients.Diabetes Care. 1999; 22: 10-18Crossref PubMed Scopus (360) Google Scholar49Chandalia M Garg A Lutjohann D von Bergmann K Grundy SM Brinkley LJ Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus.N Engl J Med. 2000; 342: 1392-1398Crossref PubMed Scopus (786) Google Scholar The Nurses’ Health Study followed 65,173 women and the Health Professionals Study followed 42,759 men for 6 years.41Salmerón J Ascherio A Rimm EB et al.Dietary fiber, glycemic load, and risk of NIDDM in men.Diabetes Care. 1997; 20: 545-550Crossref PubMed Scopus (1175) Google Scholar42Salmerón J Manson JE Stampfer MJ Colditz GA Wing AL Willett WC Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.JAMA. 1997; 277: 472-477Crossref PubMed Google Scholar Both studies found that diets with a high glycemic index were associated with the subsequent development of diabetes (relative risk, 1.37). Glycemic load (the product of glycemic index and carbohydrate intake) was also related to risk of diabetes (relative risk, 1.47). Glycemic index was not related to subsequent development of diabetes in the Iowa Women's Health Study.33Meyer KA Kushi LH Jacobs Jr, DR Slavin J Sellers TA Folsom AR Carbohydrates, dietary fiber, and incident type 2 diabetes in older women.Am J Clin Nutr. 2000; 71: 921-930PubMed Google Scholar All of these studies controlled for age, body mass index, family history of diabetes, physical activity, and other risk factors. Glycemic load was significantly related to coronary heart disease risk in the Nurses’ Health Study.50Liu S Willett WC Stampfer MJ et al.A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women.Am J Clin Nutr. 2000; 71: 1455-1461PubMed Google Scholar The relative risk was doubled in the highest quintile. Glycemic index was also related to coronary heart disease, but the relative risk was 1.3. A much smaller Dutch study found no relation between glycemic index and subsequent coronary heart disease.51van Dam RM Visscher AW Feskens EJ Verhoef P Kromhout D Dietary glycemic index in relation to metabolic risk factors and incidence of coronary heart disease: the Zutphen Elderly Study.Eur J Clin Nutr. 2000; 54: 726-731Crossref PubMed Scopus (174) Google Scholar More studies are needed before glycemic index or glycemic load can be accepted as risk factors for diabetes and coronary heart disease. The evidence that exercise reduces the risk of coronary heart disease is strong.52Thompson WG Exercise and health: fact or hype?.South Med J. 1994; 87: 567-574PubMed Google Scholar Better physical fitness and more physical activity reduce the risk of coronary heart disease.53Lakka TA Venäläinen JM Rauramaa R Salonen R Tuomilehto J Salonen JT Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction in men.N Engl J Med. 1994; 330: 1549-1554Crossref PubMed Scopus (672) Google Scholar There is considerable evidence that increased physical activity is associated with a lower incidence of type 2 diabetes.5Perry IJ Wannamethee SG Walker MK Thomson AG Whincup PH Shaper AG Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.BMJ. 1995; 310: 560-564Crossref PubMed Scopus (473) Google Scholar54Helmrich SP Ragland DR Leung RW Paffenbarger Jr, RS Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus.N Engl J Med. 1991; 325: 147-152Crossref PubMed Scopus (1343) Google Scholar, 55Manson JE Nathan DM Krolewski AS Stampfer MJ Willett WC Hennekens CH A prospective study of exercise and incidence of diabetes among US male physicians.JAMA. 1992; 268: 63-67Crossref PubMed Scopus (618) Google Scholar, 56Hu FB Sigal RJ Rich-Edwards JW et al.Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.JAMA. 1999; 282: 1433-1439Crossref PubMed Scopus (687) Google Scholar, 57Folsom AR Kushi LH Hong CP Physical activity and incident diabetes mellitus in postmenopausal women.Am J Public Health. 2000; 90: 134-138Crossref PubMed Scopus (97) Google Scholar, 58Okada K Hayashi T Tsumura K Suematsu C Endo G Fujii S Leisure-time physical activity at weekends and the risk of type 2 diabetes mellitus in Japanese men: the Osaka Health Survey.Diabet Med. 2000; 17: 53-58Crossref PubMed Scopus (63) Google Scholar The risk reduction varies between 25% and 40% in these studies. There is also evidence that improved physical fitness is associated with a lower incidence of diabetes.59Lynch J Helmrich SP Lakka TA et al.Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men.Arch Intern Med. 1996; 156: 1307-1314Crossref PubMed Google Scholar60Wei M Gibbons LW Mitchell TL Kampert JB Lee CD Blair SN The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men [published correction appears in Ann Intern Med. 1999;131:394].Ann Intern Med. 1999; 130: 89-96Crossref PubMed Scopus (364) Google Scholar Physically unfit men are 3 to 4 times as likely to develop diabetes. A randomized trial in Chinese men with impaired glucose tolerance demonstrated a 46% reduction in the 5-year incidence of diabetes with exercise.46Pan 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: 537-544Crossref PubMed Scopus (3314) Google Scholar Similarly, the risk of cardiovascular events is reduced in diabetic patients who exercise regularly.61Wei M Gibbons LW Kampert JB Nichaman MZ Blair SN Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes.Ann Intern Med. 2000; 132: 605-611Crossref PubMed Scopus (526) Google Scholar62Hu FB Stampfer MJ Solomon C et al.Physical activity and risk for cardiovascular events in diabetic women.Ann Intern Med. 2001; 134: 96-105Crossref PubMed Scopus (319) Google Scholar Patients at risk for coronary heart disease or diabetes should be advised to exercise regularly. Evidence that other coronary risk factors are predictors for diabetes is insufficient. However, any known risk factor for coronary heart disease should be evaluated as a risk factor for diabetes because of the overlap demonstrated above. Inflammatory markers and hemostatic markers should be further evaluated to see if they are predictive of diabetes.63Schmidt MI Duncan BB Sharrett AR et al.Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.Lancet. 1999; 353: 1649-1652Abstract Full Text Full Text PDF PubMed Scopus (871) Google Scholar64Duncan BB Schmidt MI Offenbacher S Wu KK Savage PJ Heiss G ARIC Investigators Factor VIII and other hemostasis variables are related to incident diabetes in adults: the Atherosclerosis Risk in Communities (ARIC) Study.Diabetes Care. 1999; 22: 767-772Crossref PubMed Scopus (93) Google Scholar High-sensitivity C-reactive protein (relative risk, 4.2) and, to a lesser extent, interleukin 6 were significant predictors of the subsequent development of diabetes in the Women's Health Study.65Pradhan AD Manson JE Rifai N Buring JE Ridker PM C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.JAMA. 2001; 286: 327-334Crossref PubMed Scopus (3372) Google Scholar There is strong evidence that C-reactive protein predicts the development of coronary heart disease66Danesh J Whincup P Walker M et al.Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.BMJ. 2000; 321: 199-204Crossref PubMed Scopus (1432) Google Scholar and some evidence that interleukin 6 does as well.67Ridker PM Rifai N Stampfer MJ Hennekens CH Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.Circulation. 2000; 101: 1767-1772Crossref PubMed Scopus (2019) Google Scholar Increased consumption of fish might also be associated with a lower incidence of diabetes, but further data are needed.68Feskens EJ Virtanen SM Rasanen L et al.Dietary factors determining diabetes and impaired glucose tolerance: a 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study.Diabetes Care. 1995; 18: 1104-1112Crossref PubMed Scopus (424) Google Scholar The Nurses’ Health Study recently reported that omega-6 and omega-3 fatty acids are associated with a reduced incidence of diabetes, while trans fatty acids are associated with an increased incidence (total fat, monounsaturated fat, and saturated fat were not related).69Salmerón J Hu FB Manson JE et al.Dietary fat intake and risk of type 2 diabetes in women.Am J Clin Nutr. 2001; 73: 1019-1026PubMed Google Scholar Because of the possibility of error in assessing trans fats in the diet, these data require confirmation.70Clandinin MT Wilke MS Do trans fatty acids increase the incidence of type 2 diabetes? [editorial].Am J Clin Nutr. 2001; 73:

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