INSULIN, INTACT AND SPLIT PROINSULIN, AND CORONARY-ARTERY DISEASE IN YOUNG MEN

Background Glucose intolerance and hyperinsulinemia are common disturb ances in nondiabetic men with premature coronary artery disease (CAD). To investigate the relation between insulin-like molecules and severi ty of coronary atherosclerosis, 62 consecutive nondiabetic men present ing with a first myocardial infarction before the age of 45 were studi ed along with 41 healthy, age-matched, male, population-based control subjects. Methods and Results Specific two-site immunoradiometric assa ys were used to distinguish intact proinsulin, (des 31,32)proinsulin, and ''true'' insulin in fasting plasma and during an oral glucose tole rance test (OGTT). Global coronary atherosclerosis and number and seve rity of distinct stenoses were determined in the patients in 15 proxim al coronary arterial segments by use of separate semiquantitative clas sification systems. The patients had a two- to threefold increase in i nsulin and insulin propeptide concentrations in the fasting state as w ell as during the OGTT. Severity of coronary atherosclerosis correlate d significantly (P<.05 to P<.01) with basal proinsulin (r=.40) and the proinsulin area under the curve (AUG) (r=.34), basal insulin (r=.31), basal C peptide (r=.30), and the glucose AUC (r =.30). In multiple st epwise regression analysis including insulin-like molecules, major pla sma lipoproteins, and lipoprotein subfractions, basal proinsulin (incr ease in R(2)=.09) and dense LDL triglycerides (increase in R(2)=.10) p redicted 19% of the variation of the global coronary atherosclerosis s core after adjustment for age, body mass index, fasting insulin concen tration, and VLDL triglycerides. Conclusions This study shows that you ng, nondiabetic, male survivors of myocardial infarction are truly hyp erinsulinemic during an OGTT and suggests a close association between proinsulin and coronary atherosclerosis.