Diabetes resolution and hyperinsulinaemia after metabolic Roux-en-Y gastric bypass

The global prevalence of type 2 diabetes mellitus and impaired glucose metabolism continues to rise in conjunction with the pandemic of obesity. The metabolic Roux-en-Y gastric bypass operation offers the successful resolution of diabetes in addition to sustained weight loss and excellent long-term outcomes in morbidly obese individuals. The procedure consists of the physiological BRAVE effects: (i) Bile flow alteration; (ii) Reduction of gastric size; (iii) Anatomical gut rearrangement and altered flow of nutrients; (iv) Vagal manipulation and (v) Enteric gut hormone modulation. This operation provides anti-diabetic effects through decreasing insulin resistance and increasing the efficiency of insulin secretion. These metabolic outcomes are achieved through weight-independent and weight-dependent mechanisms. These include the foregut, midgut and hindgut mechanisms, decreased inflammation, fat, adipokine and bile metabolism, metabolic modulation, shifts in gut microbial composition and intestinal gluconeogenesis. In a small minority of patients, gastric bypass results in hyperinsulinaemic hypoglycaemia that may lead to nesidioblastosis (pancreatic beta-cell hypertrophy with islet hyperplasia). Elucidating the precise metabolic mechanisms of diabetes resolution and hyperinsulinaemia after surgery can lead to improved operations and disease-specific procedures including 'diabetes surgery'. It can also improve our understanding of diabetes pathogenesis that may provide novel strategies for the management of metabolic syndrome and impaired glucose metabolism.