Researchers who have been able to observe people developing type 2 diabetes say that they have confirmed for the first time that fat overspills from the liver into the pancreas triggering the chronic condition. The study (“Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss”), led by Roy Taylor, MD, professor and director of Newcastle Magnetic Resonance Centre at Newcastle University Institute of Translational and Clinical Research in the U.K., appears in Cell Metabolism.

The research involved a group of people from Tyneside who previously had type 2 diabetes but had lost weight and successfully reversed the condition as part of the DiRECT trial, which was funded by Diabetes UK.  The majority remained nondiabetic for the rest of the two-year study; however, a small group went on to re-gain the weight and re-developed type 2 diabetes.

“The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission,” the investigators wrote.

“Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes.”

“We saw that when a person accumulates too much fat, which should be stored under the skin, then it has to go elsewhere in the body,” said Taylor, explaining what the advanced scanning techniques and blood monitoring revealed. The amount that can be stored under the skin varies from person to person, indicating a “personal fat threshold” above which fat can cause mischief, he added.

“When fat cannot be safely stored under the skin, it is then stored inside the liver, and over-spills to the rest of the body including the pancreas. This ‘clogs up’ the pancreas, switching off the genes which direct how insulin should effectively be produced, and this causes type 2 diabetes,” continued Taylor.

This research by Taylor and his team appears to confirm his Twin Cycle Hypothesis, i.e., type 2 diabetes is caused by excess fat actually within both the liver and pancreas, and especially that this process is reversible.

This latest paper builds on previous Newcastle studies supported by Diabetes UK showing exactly why type 2 diabetes can be reversed back to normal glucose control. Those studies led to the large DiRECT trial which showed that primary care staff can achieve remission of type 2 diabetes by using a low-calorie diet with support to maintain the weight loss.

A quarter of participants achieved a 15 kg or more weight loss, and of these, almost 9 out of 10 people put their type 2 diabetes into remission. After two years, more than one third of the group had been free of diabetes and off all diabetes medication for at least two years.

In 2020, this approach to management of short duration type 2 diabetes is to be piloted in the NHS in up to 5,000 people across England, and a similar program is being rolled out in Scotland.

“This means we can now see type 2 diabetes as a simple condition where the individual has accumulated more fat than they can cope with,” said Taylor. “Importantly this means that through diet and persistence, patients are able to lose the fat and potentially reverse their diabetes. The sooner this is done after diagnosis, the more likely it is that remission can be achieved.”

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