[Methods for the measurement of insulin resistance. Hyperinsulinemic euglycemic clamp]

Insulin resistance is defined as the decrease of the biological action of insulin, and it mainly presents as an hyperinsulinaemia. The clinical investigation of the states of insulin resistance requires expertise in sophisticated in vivo and in vitro methods. The hyperinsulinaemic euglycemic clamp is the reference method for quantifying insulin resistance. The clamp technique consists in infusing insulin at constant rate and, to prevent any decrease in the plasma glucose level, by infusing dextrose. The rate of dextrose infused to maintain euglycaemia is an estimate of the amount of glucose which is taken up by the tissues under the effect of a defined plasma insulin concentration. Using several rates of insulin infusion allows to establish the relationship between the whole body glucose disposal and plasma insulin levels, and to discriminate between the states of decreased insulin sensitivity and/or altered maximal capacity to dispose of glucose. The measurement of glucose fluxes, using the constant infusion of stable isotope labelled glucose, allows to differentiate the hepatic and the peripheral components of insulin resistance. Insulin sensitivity may be estimated using other methods, such as the minimal model which consists in a mathematical analysis of the intravenous glucose tolerance test. In vitro studies include the search for anti-insulin antibodies and anti-insulin-receptor antibodies, the study of insulin receptors (insulin binding, tyrosine-kinase activity and gene structure) and of the post-receptor glucose metabolism. Genetic syndromes of extreme insulin resistance, the pathophysiology of which is poorly known, are the main applications of these investigations. However, insulin resistance plays an important role in non-insulin-dependent diabetes mellitus, and also in insulin-dependent diabetes and various pathological or physiological endocrine disorders.