There is overwhelming evidence that obesity management helps mitigate fat-induced metabolic stress in the liver and pancreas and moderately improves insulin secretory capacity of pancreatic β-cells and insulin resistance (Steven et al., 2016; Taylor et al., 2019), thereby leading to a significant improvement in glycemic control and even remission of T2D (Schauer et al., 2016; Lean et al., 2018; Lean et al., 2019). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.