The genetic basis of Insulin resistance. A brief review

Insulin resistance, represents the primary physiologic defect underlying the metabolic syndrome (MS) which includes insulin resistance/hyperinsulinemia, glucose intolerance and/or type 2 diabetes mellitus, visceral obesity, hypertension, and dyslipidemia. This constellation of traits is a major risk factor of cardiovascular mortality and morbidity. Insulin sensitivity varies among individuals. Although environment, physical inactivity and caloric excess, plays an important role in the development of obesity and thus insulin resistance, several studies show that there are also a genetic influence in the development of insulin resistance. Extreme forms of insulin resistance may be caused by mutations in the genes for the insulin receptor and peroxisome proliferator-activated receptor gamma, these forms rare. The genetic basis for common more moderate forms of insulin resistance is likely to be polygenic and heterogeneous. There is evidence that gene variants may have phenotypic influences on more than one MS traits which may explain, in part, the clustering of these traits. We briefly review in this article the evidence that insulin resistance has a genetic basis. The identification of specific gene variants will help understanding the molecular basis of MS and ultimately will help to set up preventive and therapeutic interventio