As no consistent differences exist in the secretion of GIP [32] or GLP-1 [33] between individuals with and without T2D, the reduction of the “incretin effect” is the result of the total loss of the insulinotropic response to GIP and the reduced ability of GLP-1 to induce insulin secretion, likely due to a reduction of functional β-cell mass and receptor activity [1]. This evidence concerns the gene INS and type 2 diabetes mellitus.