Insulin Resistance–Related Factors, but not Glycemia, Predict Coronary Artery Disease in Type 1 Diabetes

Abstract

OBJECTIVE -To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. RESEARCH DESIGN AND METHODS-This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8 -47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis Ն50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death.RESULTS -A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or Ն50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P Ͻ 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P Ͻ 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P ϭ 0.016), whereas HbA 1 showed no association with subsequent CAD.CONCLUSIONS -These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points. Diabetes Care 26:1374 -1379, 2003B oth type 1 and type 2 diabetes increase the risk of coronary artery disease (CAD) (1). However, the reasons underlying this are largely unknown, although renal disease (2) and the standard CAD risk factors seem important (3). The role of glycemic control is controversial; two studies (3,4) suggest little relationship to CAD, although others report such an association (5).Although it has been an accepted practice to consider all CAD manifestations together, because they are believed to be linked by the same underlying atherosclerosis, important differences have been noted in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of type 1 diabetes. This study suggested somewhat distinct pathophysiologic mechanisms; for example, depressive symptomatology was more related to morbidity than mortality (3).To further address these issues, risk factors, including glycemic control, for angina, ischemic electrocardiogram (ECG), and hard CAD (myocardial infarction [MI], CAD death, or angiographically proven stenosis) were investigated in this prospective study of type 1 diabetes using, for the first time, the ...

Changes in glycaemic control and risk of coronary artery disease in type 1 diabetes mellitus: findings from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC)

“…A 10 year followup of patients at the Hvidore hospital in Denmark also failed to show an independent effect of HbA 1c , though the authors suggested that this might have been due to the small number of events [9]. Finally, in our Pittsburgh Epidemiology of Diabetes Complications Study (EDC) 10 year follow-up analysis, we found no significant relationship between either baseline glycaemia [10] or cumulative exposure [11] and CAD incidence. Overall, in a metaanalysis, Selvin et al reported a nonsignificant odds ratio of 1.15 per 1% change in HbA 1c (95% CI 0.92-1.43) [12].…”

“…Significant univariate CAD predictors previously identified [10] and those from Table 2 were considered for multivariable analyses. In multivariable logistic regression analyses, only diabetes duration, HDL-cholesterol and non-HDL-cholesterol and change in HbA 1c remained significant predictors (Table 3).…”

The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study

“…Independently of diabetes, plasma adiponectin levels inversely predicted cardiovascular outcomes in patients with endstage renal disease and were related to metabolic risk factors such as insulin levels, insulin sensitivity, and triglyceride and HDL cholesterol levels [12]. In recent reports from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC), both insulin resistance and markers of inflammation were important predictors of CAD in type 1 diabetes [13]. Based on these observations, the role of adiponectin as a key underlying factor linking these two causal pathways deserves further investigation.…”

Leptin therapy in insulin-deficient type I diabetes

“…Second, unopposed lipogenic action of insulin may also contribute to glycemic instability by intermittently promoting fatty acid (FA)-mediated insulin resistance (2)(3)(4), which, in the long term, contributes to lipotoxic cardiomyopathy (5). Third, chronic hyperinsulinemia may enhance cholesterologenesis (6) and account for the high incidence of coronary artery disease in patients with T1DM (7,8). Even when plasma lipid and lipoprotein levels are normal in patients with type 1 diabetes, the apoB-lipoproteins are cholesteryl esterenriched and are potentially more atherogenic (9).…”