Calorie restriction and reversal of type 2 diabetes

ABSTRACT

Introduction: 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
• reversal of type 2 diabetes
• etiology of type 2 diabetes
• Twin Cycle Hypothesis
• pancreas fat
• liver fat

Acknowledgments

The author is grateful to the noble Newcastle volunteers, who over several decades of research into type 2 diabetes have given time, effort and blood in the name of research. The work would not have been possible without the extraordinary hard work and skill of many research fellows and especially Peter Carey, Balasubramanian Ravikumar, Ee Lin Lim, Sarah Steven, Mavin Macauley, Carl Peters and Ahmad Al-Mrabeh.

Declaration of interest

The Counterpoint study was funded by Diabetes UK, and the Counterbalance study by a Newcastle Biomedical Research Centre grant and a Fellowship from NovoNordisk Foundation. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

No funding to declare.