Coronary Artery Calcification in Type 2 Diabetes and Insulin Resistance: The Framingham Offspring Study

JAMES B. MEIGS MARTIN G. LARSON SCD RALPH B. D'AGOSTINO PHD DANIEL LEVY MELVIN E. CLOUSE DAVID M. NATHAN PETER W. F. WILSON CHRISTOPHER J. O'DONNELL E p i d e m i o l o g y / H e a l t h S e r v i c e s / P s y c h o s o c i a l R e s e a r c h OBJECTIVE - To assess risk for subclinical coronary atherosclerosis using electron beamcomputed tomography in subjects with or without insulin resistance and with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT/impaired fasting glucose [IFG]) or type 2 diabetes. RESEARCH DESIGN AND METHODS - We categorized glucose tolerance by type 2 diabetes therapy (diagnosed diabetes) or with an oral glucose tolerance test (OGTT) (IFG, IGT, and OGTT-detected diabetes) and insulin resistance as an elevated fasting insulin level, in subjects attending the fifth examination (1991-1995) of the Framingham Offspring Study. A representative subset of subjects without clinical atherosclerosis was selected for electron beam computed tomography in 1998 -1999 from age- and sex-stratified quintiles of the Framingham risk score. The presence of subclinical atherosclerosis was defined as the upper quartile of the Agatston score distribution (score 170). We assessed risk for subclinical atherosclerosis using multivariable logistic regression. RESULTS - Of 325 subjects aged 31-73 years, 51% were men, 11.2% had IFG/IGT, and 9.9% had diabetes (2.8% with diagnosed diabetes); 14.5% had insulin resistance. Compared with NGT, subjects with IFG/IGT tended to be more likely (adjusted odds ratio 1.5, 95% CI 0.7-3.4) and those with diabetes were significantly more likely (2.7, 1.2- 6.1) to have subclinical coronary atherosclerosis. In age- and sex-adjusted models, subjects with insulin resistance were more likely to have subclinical atherosclerosis than those without insulin resistance (2.1, 1.01- 4.2), but further risk factor adjustment weakened this association. In adjusted models including insulin resistance, diabetes remained associated with risk for subclinical atherosclerosis (2.8, 1.2- 6.7); diagnosed diabetes (6.0, 1.4 -25.2) had a larger effect than OGTT-detected diabetes (2.1, 0.8 -5.5). CONCLUSIONS - Individuals with diabetes have an elevated burden of subclinical coronary atherosclerosis. Aggressive clinical atherosclerosis prevention is warranted, especially in diagnosed diabetes. - T for cardiovascular disease (CVD), ype 2 diabetes is a potent risk factor including myocardial infarction, stroke, and intermittent claudication. However, the basis for excess risk for CVD in patients with diabetes remains incompletely defined. A greater prevalence of elevated established CVD risk factors (e.g., hypertension and low HDL cholesterol levels) as well as a greater prevalence of novel CVD risk factors, including insulin resistance and insulin resistance syndromerelated features (e.g., central obesity, microalbuminuria, impaired fibrinolysis, and subclinical inflammation), are all likely to contribute to excess risk (1). However, elevated CVD risk factors may be present many years before diagnosis of diabetes, and clinical CVD is often present at the time of diagnosis of diabetes (2 4). These observations suggest that subclinical atherosclerosis develops as a consequence of the prediabetic metabolic milieu or that diabetes, insulin resistance, and CVD are all a mutual expression of a common pathogenic precursor state (5,6). If type 2 diabetes and CVD arise from a common antecedent, there should be subclinical atherosclerosis in subjects with clinically undetected diabetes and subdiabetic glucose intolerance or with insulin resistance. It is reasonably well established that patients with diagnosed diabetes have a higher prevalence of subclinical atherosclerosis as assessed by carotid artery ultrasonography (4,79). However, data are inconsistent regarding the relationship between subclinical carotid atherosclerosis and subdiabetic or clinically undetected glucose intolerance (7,10 13) or measures of insulin resistance, including fasting hyperinsulinemia (7,14 16). Furthermore, data are scant on associations between glucose intolerance and subclinical atherosclerosis in other vascular beds, particularly the coronary arteries; few studies have focused only on subjects with diagnosed diabetes (1720). In this study, we assessed subclinical atherosclerosis of the coronary arteries using electron beam computed tomography (EBCT) in a representative sample from a community-based cohort. Subjects had no CVD, were with or without insulin resistance, and were with or without impaired glucose tolerance (IGT) or type 2 diabetes. RESEARCH DESIGN AND METHODS Study subjects Study subjects were participants in the Framingham Offspring Study, a community-based observational study of risk factors for CVD (21). From January 1991 through June 1995 (examination cycle 5), a total of 3,799 participants fasted overnight, provided written informed consent, (...truncated)