RELATION OF ANGIOGRAPHICALLY DEFINED CORONARY-ARTERY DISEASE AND PLASMA-CONCENTRATIONS OF INSULIN, LIPID, AND APOLIPROTEIN IN NORMOLIPIDEMIC SUBJECTS WITH VARYING DEGREES OF GLUCOSE-TOLERANCE

We investigated the association between hyperinsulinemia and changes in lipid, lipoprotein, and apolipoprotein that would increase the risk of coronary artery disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded in 127 male subjects, including 41 with normal glucose tolerance, 41 glucose tolerance, and 45 with nondiabetes mellitus (NIDDM). Subjects were divided into 2 groups according to results: the group with CAD (n = 94) and the group with normal coronary arteries (n = 33), All subjects were normolipidemic (total cholesterol <230 mg/dl and triglycerides <150 mg/dl). The CAD group had a significantly lower plasma level of high-densi)ty lipoprotein (HDL) cholesterol and apolipoprotein A-I (ape A-I) and a higher level of apolipoprotein B (ape B) than the normal group with normal glucose tolerance. In considering subjects with impaired glucose tolerance or NIDDM, the CAD group had a significantly lower plasma level of HDL cholesterol and apo A-I and a significantly higher plasma level of total cholesterol, triglycerides, and apo normal and impaired glucose tolerance, and NIDDM, the elevation of plasma insulin concentration during both the complete test period and the early phase of an oral glucose challenge was significantly higher in the CAD than in the normal group. In all subjects, graded reductions in HDL cholesterol and apo A-I and graded increases in plasma total cholesterol, triglycerides, and apo B were observed with increasing tertiles of the postglucose challenge measurements of insulinemia. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. Thus, hyperinsulinemia appeared to be associated with changes In lipid and apolipoprotein that predisposed toward coronary atherosclerosis not only in nondiabetic subjects, but also in those with impaired glucose tolerance and NIDDM. The plasma levels of both apo A-I and apo B, both nontraditional risk factors, were better predictors of CAD than were plasma levels of lipids in normolipidemic men.