Physicians' Academy for Cardiovascular Education

Recovery β cell function important for reversal T2DM after substantial weight loss

Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery

Literature - Taylor R, Al-Mrabeh A, Zhyzhneuskaya S et al. - Cell Metabolism 2018; DOI:

Introduction and methods

The Diabetes Remission Clinical Trial (DiRECT) showed that almost half of those with early (<6 years) of type 2 diabetes (T2DM) can be returned to long-term non-diabetic glucose control by substantial weight loss. Weight loss was achieved and maintained up to 12 months with a very low-calorie diet [1].

It is thought that in the process of development of T2DM, different, but related processes occur in liver and pancreas, involving a major decline in β cell function [2,3]. Metabolic stress can induce β cell de-differentiation and it has been demonstrated that significant weight loss can lead to re-differentiation. This may explain return from T2DM to normal glucose tolerance [4-7].

This pathophysiologic subanalysis of the DiRECT study investigated liver fat content, liver export of triglycerides, pancreas fat content and β cell function in a geographically pre-defined subgroup of participants. Participants with T2DM were randomized to either a low-calorie diet (intervention group, n=64) or usual diabetes management (control group, n=26). The intervention group received liquid formula (825-853 kcal/day) for 12-20 weeks (weight loss phase), followed by a 2-6 week stepped food reintroduction and ongoing support for weight maintenance. Responders were defined as those who returned to non-diabetic glucose control after the weight loss phase.

Main results


Weight loss and return to normal glucose homeostasis were achieved with a structured weight loss intervention in T2DM patients. Those who returned to normal glucose regulation showed sustained recovery of the first-phase insulin response. Irrespective of whether participants showed normalized glucose regulation, liver fat content was reduced, which was maintained up to 12 months. These data suggest that weight loss in early T2DM can lower intra-organ fat content in all, and return to glucose homeostasis appears to be dependent on recovery of β cell function.


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Find this article online at Cell Metabolism Read our summary of the original DiRECT study results

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