Sex differences in the association between insulin resistance and myocardial infarction across glycaemic states

Abstract Background : Females are generally less prone to cardiovascular (CV) events than males, but this protection in trumped by the presence of diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim at investigating differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index – VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first myocardial infarction (MI) across different glycaemic states. Methods : In this post-hoc analysis of the PAROKRANK study, IR indexes were calculated in a population with (n=696) and without (n=707) a first MI, free from known diabetes. MI patients were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. Results : Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p=0.06). Females were less insulin resistant than males. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9 and 1.9, 1.1-3.4 respectively). Conclusions : These results support the assumption that IR is of special importance as a CV risk factor in females and IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor in females than in males.