In the absence of familial diabetes, only overweight or obesity are responsible for the peripheral defect in insulin sensitivity, thus inducing a compensatory greater insulin (and C-peptide) production; however, when familial diabetes is present, the impaired function/ synthesis of epimerase and LASY is additional to the defect in hepatic clearance, due to a defect of insulin-degrading enzyme function/expression. This evidence concerns the gene INS and Obesity.