These studies have shown that in conditions of systemic IR due to multiple etiologies (obesity, impaired glucose tolerance status, carriers of the AKT2-mutation who are genetically predisposed to IR), insulin-stimulated BGU, measured during the hyperinsulinemic euglycemic clamp, is increased when compared to lean, metabolically healthy controls [12,22,99]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.