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Remission of type-2 diabetes with weight loss
August 15, 2018, 3:26 pm

A clinical trial conducted in the United Kingdom as part of the Diabetes Remission Clinical Trial (DiRECT) has shown that nearly half of individuals with type 2 diabetes achieved remission to a non-diabetic state after a weight-loss intervention delivered within six years of diagnosis.

According to the World Health Organization, diabetes affects approximately 422 million people worldwide. Approximately 90 percent of cases are type 2 diabetes, a condition in which the body does not produce enough or respond properly to insulin. This hormone, produced by beta cells in the pancreas, helps a sugar called glucose in the blood enter cells in muscle, fat, and liver to be used for energy. Type 2 diabetes has long been considered a lifelong condition that worsens over time.

The new study also revealed that the successful response to weight loss is associated with the early and sustained improvement in the functioning of pancreatic beta cells. This finding challenges the previous paradigm that beta-cell function is irreversibly lost in patients with type 2 diabetes.

At present, the early management of type 2 diabetes tends to involve a period of adjusting to the diagnosis plus pharmacotherapy with lifestyle changes, which in practice are modest. The new data suggests that substantial weight loss at the time of diagnosis is appropriate to rescue the beta cells.

In the study, the participants, who were diagnosed with type 2 diabetes within 6 years of the start of the study, were randomly assigned to best-practice care (control group) or an intensive primary-care-led weight-management program (intervention group). One year later, 46 percent of the individuals in the intervention group successfully responded to weight loss in that they recovered and maintained control over blood glucose concentrations.

The researchers also found that responders to the weight loss program were similar to non-responders before the intervention but had a shorter duration of diabetes (2.7 years vs. 3.8 years). In addition, although both responders and non-responders had lost comparable amounts of weight, leading to similar reductions in liver fat content, pancreatic fat content, and blood concentrations of triglycerides, only the responders demonstrated early and sustained improvement in beta-cell function.

In particular, the most striking difference between responders and non-responders was the first-phase insulin response. Pancreatic beta cells secrete insulin in two phases in response to an increase in blood glucose concentration. The first phase, which consists of a brief spike lasting approximately 10 minutes, is typically absent in patients with type 2 diabetes. First-phase insulin secretion increased in responders after weight loss but did not change in non-responders.

Taken together, the findings suggest that weight loss normalizes fat metabolism in all individuals with type 2 diabetes, but the more rapid loss of the capacity of beta cells to recover prevents some individuals from returning to a non-diabetic state.

However, the researchers cautioned that the reversibility of type 2 diabetes, ultimately due to re-differentiation of pancreatic beta cells, means that we will need to undertake further targeted work to improve understanding of this process.

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