Relationship between insulin sensitivity and hyperinsulinemia in early insulin resistance is sex-dependent

Abstract Context Insulin resistance (IR) is a major risk factor for the development of several diseases that have reached epidemic proportions worldwide, including hypertension, obesity and type 2 diabetes. In many diseased states, IR is associated with fasting hyperinsulinemia/excessive glucose-stimulated insulin secretion. However, it is not known whether hyperinsulinemia precedes/leads to the natural development of IR or vice versa. Objective Here, we assess the relationship between hyperinsulinemia and insulin sensitivity in a cohort of healthy young lean men and women, where IR is observed in those who exhibit a low expression of type I skeletal muscle fibers and a high resting heart rate. Methods Biopsies were obtained from the vastus lateralis muscle, followed by an intravenous glucose tolerance test. Insulin secretion and whole-body insulin sensitivity were calculated. Results In this young population of normoglycemic, glucose-tolerant individuals, insulin sensitivity was significantly and negatively associated with fasting levels of plasma insulin, as well as insulin secretion in response to glucose infusion. Surprisingly, however, all the correlations became stronger when calculated in women, but became insignificant when calculated in men. In contrast, insulin sensitivity was significantly correlated with expression of type I skeletal muscle fibers and resting heart rate to similar extents in both sexes. Conclusions In the natural development of IR in men, it appears that hyperinsulinemia is a compensatory adaptation to peripheral IR rather than its cause.