Conversely, many studies demonstrated a reduced GIP and GLP-1 islet sensitivity in T2D natural history, including our recent research demonstrating that defects in the insulinotropic effect of incretins can be observed even in nondiabetic subjects during the early phases of the disease, with no major changes in the overall circulating incretin levels (9). The gene discussed is GCG; the disease is type 2 diabetes mellitus.