INS and obesity due to melanocortin 4 receptor deficiency: One theory suggests that obesity, particularly central obesity, increases insulin resistance and hyperinsulinaemia (Giovannucci, 1995; Kahn and Flier, 2000) via alterations in the signalling of endogenous hormones, particularly not only insulin and insulin-like growth factors, but also steroid hormones, and possibly, adipocyte-derived factors such as leptin and adiponectin (Gunter and Leitzmann, 2006; John et al, 2006).