ARE INSULIN AND PROINSULIN INDEPENDENT RISK MARKERS FOR PREMATURE CORONARY-ARTERY DISEASE

Controversy persists about whether hyperinsulinemia and hyperproinsuli nemia are independent risk markers for coronary atherosclerosis, A com mon limitation of most previous studies has been imprecise categorizat ion of disease status in normal and coronary artery disease (CAD) grou ps, We assessed the relationship of pancreatic P-cen secretory product s and premature CAD in a case-control study of 134 nondiabetic subject s, aged less than or equal to 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies, Case patient s comprised 66 patients with premature CAD, and control subjects (non- CAD group) included 68 patients without CAD but with traditional CAD r isk factors and chest pain and/or abnormal electrocardiograms but norm al catheterization and/or thallium stress studies, In addition to the CAD and non-CAD group comparison, both groups were compared with a ref erence group of 27 mixed lean and obese control volunteers, All CAD an d non-CAD patients had a 3-h 75-g oral glucose tolerance test with mea surement of fasting and post-glucose load immunoreactive insulin (IRI) , specific insulin (INS), proinsulin-like material CPI), and C-peptide , Increased fasting insulin and fasting proinsulin levels both were st atistically significantly associated with higher odds of being in eith er the premature CAD and the non-CAD groups when compared with the ref erence group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory produc t in both comparisons, P < 0.05), However, increased pancreatic beta-c en secretory hormone levels did not show a statistically significant r elative risk for being in the premature CAD group when compared with t he non-CAD group, After adjustment for BMI, all statistically signific ant associations disappeared for IRI, INS, and PI when the odds favori ng being in the CAD and non-CAD groups were compared versus the refere nce group, Furthermore, the odds of being in the premature CAD and non -CAD groups when compared with the reference group were not significan tly associated to the ratio of PI to insulin and C-peptide, Thus, alth ough there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels c ompared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD, Fu rthermore, the association of higher insulin and proinsulin levels wit h the Likelihood of a patient having or not having CAD disappears afte r adjustment for BMI, suggesting that insulin and proinsulin are not i ndependent risk markers but are primarily dependent on obesity.