INS and obesity due to melanocortin 4 receptor deficiency: Over-nutrition, and resulting obesity, both trigger chronic inflammation in metabolic tissues (termed meta-inflammation) and contribute directly or indirectly to β-cell dysfunction, both quantitatively (i.e., the relative decrease in β-cell mass) and qualitatively (impaired β-cell insulin secretion), which result in compromised insulin secretion and T2DM1.