Body mass index (BMI) may not play as significant a role in defining type 2 diabetes risk or remission status as previously thought.
A new late-breaking study presented at the American Diabetes Association (ADA) 2022 Scientific Session this week showed that the mechanistic changes behind type 2 diabetes remission among patients considered non-obese by BMI standards were the same as those observed in patients who were considered obese.
In fact, the data—presented by diabetologist and Newcastle professor Roy Taylor, MD—from the ReTUNE trial suggested the Personal Fat Threshold hypothesis may be a more accurate indication for weight-associated type 2 diabetes risk development as well as remission status. Taylor’s threshold hypothesis, in brief detail, suggests individuals have a limit to the rate of fat they may accumulate around their liver and pancreas before issues including insulin resistance and type 2 diabetes may develop.
The new findings contribute more understanding to what Roy said is the “true nature of diabetes,” a definition that experts still grapple with despite the disease’s increasing global presence.
In an interview with HCPLive during ADA 2022, Taylor discussed the motivation of the ReTUNE trial and the clinical takeaways from its outcomes.
“Type 2 diabetes is caused by too much fat inside the liver and inside the pancreas. That prevents a significant function of these organs,” Taylor said. “Take away the fat—bingo, the diabetes disappears in people with short-duration diabetes, by which we mean up to 6 years.”
That said, reversible diabetes—much like the risk of development itself—is nonetheless heterogeneous. Some patients with diabetes over 1 year may struggle to achieve remission despite fat reduction; others with the disease over 2 decades may achieve remission easily by the personal fat threshold protocol.
Though much of this pathophysiological understanding was well established by Taylor and colleagues prior to ReTUNE, the new trial took the hypothesis a step closer to clinical application by comparing diabetes remission capability in both patients with and without BMI-defined obesity.
“The results are really dramatic: most people got rid of their diabetes with just over 6% weight loss—so fairly modest weight loss,” Taylor said. “And we were able to show the liver fat and pancreas fat when down to normal, the liver insulin sensitivity went to completely to normal, with a normal fasting glucose as a result, and the insulin secretion improved—it didn’t normalize, but it improved enough—to allow the HbA1c to be normal in 70% of this group.”
Regarding BMI, Taylor said the new findings would suggest a need to be cautious with the universally-used standard for body weight status when it comes to interpreting diabetes status.
“It was invented to describe populations, and it’s very good at that,” Taylor said. “It can show you the average and spread of BMI in the population. It was never, never, meant to appoint to individuals. And it’s absurd to apply the raw number to individuals to classify them as their likely response to treatment.”
Listen to Taylor explain the clinical utility of the personal fat threshold and the shortcomings of BMI in defining type 2 diabetes status in the video above.
The study, “Remission of Type 2 Diabetes after Weight Loss in ‘Normal’ Weight People—The ReTUNE Study,” was presented at ADA 2022.