Type 2 diabetes causes major global health problems and has been believed to be a lifelong condition with inevitable worsening. Steadily increasing numbers of drugs appeared to be required to achieve even modest control. Early type 2 diabetes has now been shown to be reversed by substantial weight loss and this has allowed temporal tracking of the underlying pathophysiological changes. Areas covered: In early type 2 diabetes, negative calorie balance decreases liver fat within days, and allows return of normal control of hepatic glucose production. Over 8 weeks, the negative calorie balance allows the raised levels of intra-pancreatic fat and simultaneously first phase insulin secretion to normalise. These findings are consistent with the 2008 Twin Cycle Hypothesis of the etiology and pathogenesis of type 2 diabetes. Individuals develop type 2 diabetes when they exceed their personal fat threshold for safe storage of fat and there is no difference in pathophysiology between those with BMI above or below 30 kg/m2. Expert commentary: Type 2 diabetes can now be understood as a state of excess fat in liver and pancreas, and remains reversible for at least 10 years in most individuals.
Keywords: Pathogenesis of type 2 diabetes; Twin Cycle Hypothesis; etiology of type 2 diabetes; liver fat; pancreas fat; reversal of type 2 diabetes.