ASSESSMENT OF INSULIN RESISTANCE INVIVO - APPLICATION TO THE STUDY OFTYPE-2 DIABETES

Besides insulin secretion, insulin sensitivity plays a key role in the feedback glucose-insulin closed loop. It can be altered in numerous p hysiological, pathological and pharmacological conditions. It can be e stimated in vivo using methods that open the feedback loop (insulin su ppression test, glucose clamp) or that analyze the closed loop by empl oying mathematical models of glucose kinetics. The most popular method is the euglycemic hyperinsulinemic glucose clamp. This test should be ideally coupled with a priming-constant infusion of a glucose tracer together with indirect calorimetry. This combination allows to study t he glucose kinetics (R(a) and R(d), and thus endogenous - mainly hepat ic - glucose production) and its metabolism (oxidation or storage as g lycogen), respectively. One alternative approach is the frequently sam pled intravenous glucose tolerance test where the dynamic changes in p lasma insulin and glucose levels are analyzed using the so-called 'min imal model' method. Noninsulin-dependent or type 2 diabetes is charact erized by a significant defect in both insulin secretion and action. T he insulin resistance is located at the liver site (increased glucose production) and at the peripheral tissues (decreased oxidation and, ev en more, defective storage of glucose in the muscles). This insulin re sistance, which predominates at the postreceptor level, seems to be ge netically determined but is worsened by weight excess and by hyperglyc emia itself. This contributes to a vicious circle which aggravates pro gressively the severity of the disease.