During T2DM progression, obesity and insulin resistance increase insulin secretion to trigger a vicious cycle of hyperinsulinemia and insulin resistance that ultimately results in β-cell failure via β-cell degranulation, trans/dedifferentiation, and, to some extent, apoptosis (Remedi and Emfinger, 2016). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.