Insulin and Cardiovascular Disease: Paris Prospective Study

The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) risk factors in a large population of working men. The baseline cohort included 7028 men, 6093 who had a 75-g oral glucose tolerance test with measurement of plasma insulin and glucose levels (0 and 2 h) and 125 who were known non-insulin-treated diabetic patients. After a mean follow-up of 11 yr, 126 deaths ascribed to CHD were reported. Major independent predictors of CHD death were blood pressure, smoking, plasma cholesterol level, and fasting and 2-h postload plasma insulin level. Impairment of glucose tolerance, including overt diabetes, did not rank as an independent predictor when other baseline variables were accounted for. In the subset of the baseline cohort who presented with impaired glucose tolerance or diabetes (n = 943), 26 died from CHD during the follow-up. The strongest independent predictor of subsequent CHD death in this subsample with abnormal glucose tolerance was plasma triglyceride level. In view of the accumulating evidence that hyperinsulinemia and hypertriglyceridemia generally occur in the same type of subjects, in relation to insulin resistance and central obesity, the epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk.