Insulin Resistance Modification is a Game Changer for Type 2 Diabetes Treatment Strategy

Abstract

Insulin resistance, appearing years before diabetes main diagnostic sign, hyperglycemia, stands in the origin of type 2 diabetes (T2DM), generated by complex impairment of a spectrum biochemical processes the most important of which is the failure of phosphatidylinositol 3-kinase enzymatic chain responsible for glucose uptake and endothelial nitric oxide (NO) synthase activation. Therefore in conditions with insulin resistance the impairment of glucose uptake is strongly coupled with NO deficit and severe vasodilatory dysfunction. However T2DM conventional treatment even worsens diabetes fundamental pathophysiological mechanisms reflected by aggravated obesity and insulin resistance. These may generate vasodilatory dysfunction, arterial hypertension and dyslipidemia, diminishing intensive glycemic control mainly microvascular benefit. Glucocentric model of T2DM management should be replaced by approach focused primarily to impede insulin resistance rather then manage its cardiometabolic consequences. Antidiabetics should be selected to achieve hypoglycemic goals without increase of body weight and with ability to decrease insulin resistance, the key triggering factor of global vascular impairment and T2DM cardiovascular mortality.