Previous investigations on incretin pathophysiology have already established the impact of reduced islet sensitivity to incretins in determining the loss of their insulinotropic power in the natural history of T2D: we have demonstrated a reduced incretin effect in nondiabetic people, regardless of circulating GIP and GLP-1 levels, predicting diabetes onset after acute β cell mass reduction by pancreatoduodenectomy. The gene discussed is GIP; the disease is diabetes mellitus.