DiRECT Study: Putting T2DM in Remission

Can weight loss alone be the key to the reversal of type 2 diabetes? A new study sheds some light. 

References:1. Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;10:541-551.2. Taylor R, Al-Mrabeh A, Zhyzhneuskaya S, et al. Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery. Cell Metab. 2018;pii: S1550-4131:30446-30447.

weight loss, type 2 diabetes, diabetes, recovery, remission

It has long been thought that type 2 diabetes mellitus (T2DM) is a lifelong and progressive disorder, with loss of beta-cell function the most likely underlying mechanism. The Diabetes Remission Clinical Trial (DiRECT) reported return to, and durability of, non-diabetic glucose control in 46% of obese patients who lost weight. A new DiRECT subanalysis sought to understand what factors allowed some DiRECT participants to achieve and maintain T2DM remission while others did not. Was it weight loss alone? Click through the short slideshow above to find out. 

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Putting T2DM in Remission with Weight Loss.1 While T2DM is historically considered a lifelong condition, authors of a new study, DiRECT, suggested weight loss alone may reverse T2DM. The study found that overweight/obese participants with T2DM <6 years duration achieved remission after a mean weight loss of 10 kg and 46% sustained remission. However, what factors enabled only some of the participants to achieve remission while others did not?

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Subanalysis of DiRECT.2 The open-label, randomized controlled trial at 49 primary care clinics in Scotland and England recruited 306 obese/overweight patients who had been diagnosed with T2DM in the last 6 years and who were not on insulin. Participants were randomized to either the intervention or control group. The intervention consisted of withdrawal of antihyperglycemics and antihypertensives, a 825-853 kcal/day formula diet for 3-5 months, a 2-8 week stepped food reintroduction, and support for long-term weight loss and maintenance. 

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Responders Recovered First-phase Insulin Response. Authors of the study found that diabetes duration was shorter in responders, A1c decreased only for responders, liver fat decreased significantly for both groups, pancreatic fat decreased significantly for both groups, first-phase insulin secretion increased significantly only for responders, and an increase in first phase insulin secretion was sustained in responders who maintained wight loss at follow-up.

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Clinical Implications:

  • Study challenges assumptions about irreversibility of beta-cell decline
  • For the first time, the study suggests a difference in T2DM duration is linked to the capacity for beta cell recovery
  • Current management after initial diagnosis may need to change
  • A 24-month follow-up is underway
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Take Home Points:

  • Nearly half of obese/overweight patients with T2DM <6 years duration who had 10 kg weight loss, achieved diabetes remission
  • Recovery of first-phase insulin response defined responders and was sustained at 12 months
  • DiRECT is the first study to suggest that the ability of beta cells to recover persists after diagnosis and is linked to T2DM duration
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