These results demonstrate that the increase in the ISR induced by excess adiposity and the decrease in the ICR associated with insulin resistance and increased plasma insulin concentration were able to sufficiently raise basal and postprandial plasma insulin levels to maintain normoglycermia in individuals with obesity and moderate insulin resistance (Ob-NFG-NGT), but not in those with more severe insulin resistance (Ob-NFG-IGT and Ob-IFG-IGT). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.