ADM and obesity due to melanocortin 4 receptor deficiency: Some of the mediators include: (1) hyperglycemia and obesity causing insulin resistance, hyperinsulinemia promoting cell proliferation; (2) upregulated adrenomedullin mediating insulin resistance in β-cells; (3) cytokines from activated pancreatic stellate cells causing islet fibrosis and destruction; (4) pro-inflammatory adipokines mediating enhanced insulin resistance; and (5) increased lipolysis from excessive fat accumulation in the metabolic syndrome and obesity leading to generation of non-esterified fatty acids, development of insulin resistance and β-cells dysfunction [21, 23].