INS and obesity due to melanocortin 4 receptor deficiency: Thus, although cross-sectional studies have postulated that insulin secretion follows an inverted U-pattern (also termed Starling’s curve of the pancreas) during natural progression from normal glucose tolerance to impaired glucose tolerance and type 2 diabetes [72], it has been repeatedly reported that a large part of individuals with normal glucose tolerance already show hyperinsulinemia before the development of impaired glucose tolerance/obesity.