INS and obesity due to melanocortin 4 receptor deficiency: During the past decade, T2D-associated variants have been shown to modulate T2D risk through diverse mechanisms: some increase T2D risk through an impact on obesity (e.g., FTO), others reduce insulin sensitivity (e.g., PPARG, IRS1), whereas others compromise insulin secretion, either through direct effects on islet function (e.g., KCNJ11) or development (e.g., HNF1A) or indirectly through impact on incretin signaling (e.g., GLP1R) (82).