*Geek Box: The ‘Twin Cycle Hypothesis’

*Geek Box: The ‘Twin Cycle Hypothesis’

The earliest detectable characteristic of deteriorating glucose tolerance is insulin resistance in skeletal muscle tissue, which is followed by a progressive decline in pancreatic beta-cell function as the pancreas attempts to secrete more insulin to keep blood glucose levels in range. This view of diabetes has been considered, however, to be glucose-centric, particularly as evidence for the substantial accumulation of excess intracellular triglycerides in both skeletal muscle, and the liver.

In view of this evidence, in 2008 Professor Roy Taylor at Newcastle University developed the ’twin cycle hypothesis’, which focused more on chronic energy excess and the effects on visceral fat accumulation, than simply glucose alone. The hypothesis stated that during conditions of energy excess, surplus carbohydrate is converted into fat [triglycerides] in the liver [de novo lipogenesis], while excess dietary fat also accumulates in the liver.

This increase in liver fat inhibits the ability of insulin to suppress glucose production in the liver, resulting in liver insulin resistance and elevated blood glucose levels. The liver attempts to clear fat by upregulating very-low-density lipoprotein [VLDL] production, which transports TGs from the liver and results in elevated circulating TGs. However, these VLDL-TGs need to go somewhere, and if subcutaneous fat storage is at capacity, VLDL deposits its TGs into other visceral areas, in particular the pancreatic cells that secrete insulin.

This build up of fat in the pancreas impairs the capacity of beta-cells, which ultimately results in complete loss of function of beta-cells. Type-2 diabetes is characterised by this twin cycle of excess fat accumulation in the liver spilling over the pancreas, and this is central to the progressive loss of beta-cell function that characterises diabetes progression.

To date, the only dietary intervention which appears to reverse this is the diet Taylor and his colleagues implemented in a number of interventions, using liquid-based extreme energy deficit diets consisting of ~800kcal/d, which reduce these hepatic and pancreatic fat depots, restoring beta-cell function in individuals who still retain a degree of functionality [i.e., patients who long ago lost beta-cell function may not reverse the condition].