Insulin, Intact and Split Proinsulin, and Coronary Artery Disease in Young Men

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Abstract
Background Glucose intolerance and hyperinsulinemia are common disturbances in nondiabetic men with premature coronary artery disease (CAD). To investigate the relation between insulin-like molecules and severity of coronary atherosclerosis, 62 consecutive nondiabetic men presenting with a first myocardial infarction before the age of 45 were studied along with 41 healthy, age-matched, male, population-based control subjects. Methods and Results Specific two-site immunoradiometric assays were used to distinguish intact proinsulin, (des 31,32)proinsulin, and “true” insulin in fasting plasma and during an oral glucose tolerance test (OGTT). Global coronary atherosclerosis and number and severity of distinct stenoses were determined in the patients in 15 proximal coronary arterial segments by use of separate semiquantitative classification systems. The patients had a two- to threefold increase in insulin and insulin propeptide concentrations in the fasting state as well as during the OGTT. Severity of coronary atherosclerosis correlated significantly ( P <.05 to P <.01) with basal proinsulin ( r =.40) and the proinsulin area under the curve (AUC) ( r =.34), basal insulin ( r =.31), basal C peptide ( r =.30), and the glucose AUC ( r =.30). In multiple stepwise regression analysis including insulin-like molecules, major plasma lipoproteins, and lipoprotein subfractions, basal proinsulin (increase in R 2 =.09) and dense LDL triglycerides (increase in R 2 =.10) predicted 19% of the variation of the global coronary atherosclerosis score after adjustment for age, body mass index, fasting insulin concentration, and VLDL triglycerides. Conclusions This study shows that young, nondiabetic, male survivors of myocardial infarction are truly hyperinsulinemic during an OGTT and suggests a close association between proinsulin and coronary atherosclerosis.