Insulin resistance: sex matters

Abstract

This review summarizes recent advances in our understanding of the differences between the sexes in relation to insulin resistance. Alterations in the body's sensitivity to insulin cause a series of metabolic abnormalities representing essentially the metabolic syndrome (i.e. high fasting plasma triglyceride and glucose and low HDL-cholesterol concentrations, hypertension, abdominal obesity) and type 2 diabetes. Although our knowledge of the causes and consequences of impairments in the insulin signaling pathway at the metabolic, cellular and molecular level has progressed rapidly and continues to do so, serious attempts to discover whether and how sex affects the metabolic control by insulin has only recently started to evolve. The most significant recent findings include data that suggest that females are intrinsically more insulin resistant than males, possibly because of specific sex-linked gene expression and the resulting differences in metabolic control elements (e.g. signaling pathway and substrate shuttling elements, receptors). Sex hormones, environmental and life-style factors augment or improve the female 'genetic' disadvantage, in ways that are possibly also genetically predetermined. Women are distinctly different to men with regard to the actions of insulin, the susceptibility to develop insulin resistance, and the response to stimuli that are known to enhance or impair sensitivity to the effects of insulin. Therefore, sex has to be considered when investigating insulin action, metabolic pathways known to be affected by the actions of insulin and diseases that result from abnormalities in insulin action and their treatment.