The core underlying risk factors include: (1) obesity (central or visceral obesity), systemic insulin resistance (IR) with hyperinsulinemia, hyperamylinemia, hyperleptinemia, and leptin resistance (LR); (2) hyperlipidemia with atherogenic dyslipidemia typified by elevated very-low-density lipoproteins or triglycerides, elevated small dense low-density lipoproteins-cholesterol, and decreased high-density lipoproteins-cholesterol; (3) essential hypertension (HTN); and (4) hyperglycemia with or without manifest T2DM [1,2]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.