In overt beta cell dysfunction, when beta cells are exhausted towards failure, there is reduced insulin biosynthesis and insufficient insulin secretion [66]—i.e., more insulin is required, e.g., exogenously to maintain glucose homeostasis—and there is decreased insulin signaling in peripheral organs i.e., reduced glucose uptake, with prevailing hyperglycemia that progressively exacerbates. The gene discussed is INS; the disease is Hyperglycemia.