For instance, betatrophin levels were variable in type 2 diabetes mellitus (T2DM), either increased [11–14, 23] or decreased [15, 22], and similar patterns were observed in obesity [13, 15, 17–20] and IR [10–12, 15, 21, 22]. Here, ANGPTL8 is linked to obesity due to melanocortin 4 receptor deficiency.