How does weight loss ‘fix’ type 2 diabetes?

A recent clinical trial (the Diabetes Remission Clinical Trial [DiRECT]) — the results of which were published last year in The Lancet — discovered that nearly half of the participants with type 2 diabetes who followed a weight loss program experienced the remission of their condition by the end of the study.

Traditionally, specialists thought of diabetes as a condition to be managed rather than cured, so these new findings offer fresh insight into how type 2 diabetes could be counteracted using a tool within anyone’s reach: diet and lifestyle choices.

Still, after the trial’s results were published, a question remained unanswered: “Why would weight loss lead to diabetes remission in some people?”

Now, researcher Roy Taylor — from Newcastle University in the United Kingdom — who oversaw DiRECT, together with colleagues from various academic institutions, claim that they may have found the answer.

Their observations were published in the journal Cell Metabolism.

Weight loss can normalize blood sugar

For DiRECT, the researchers recruited participants who had been diagnosed with type 2 diabetes within 6 years from the start of the trial.

For the study, the volunteers were randomly split into two groups: some were assigned best-practice care, acting as the control group, while others joined an intensive weight management program while still receiving appropriate care for diabetes.

After 1 year from the start of the trial, 46 percent of those assigned to the weight loss program had managed to recover and maintain normal blood sugar levels.

According to the researchers, the participants in the second group who did not achieve these results had not lost enough weight to do so, but still it remained unclear why their metabolisms had not responded to the regimen in the same way.

Now, Taylor and team suggest that the people who responded well to the weight loss program showed early, sustained improvement in the functioning of a type of pancreatic cell known as beta cells, which are tasked with the production, storage, and release of insulin.

And in this idea lies a new challenge to previously held beliefs; specialists had always thought that, in type 2 diabetes, pancreatic beta cells are destroyed, contributing to the development of the condition.

“This observation carries potentially important implications for the initial clinical approach to management,” notes Taylor.

“At present,” he adds, “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.”

Our data suggest that substantial weight loss at the time of diagnosis is appropriate to rescue the beta cells.”

Roy Taylor

Are pancreatic beta cells involved?

To reach this conclusion, Taylor and team first looked at various metabolic factors — including liver fat content, pancreatic fat content, blood concentration of triglycerides, and beta-cell function — to see whether they played a role in the participants’ response to their weight loss program.

The team examined the contribution of these factors to the metabolic response in a subset of DiRECT participants, of which 64 volunteers had been assigned to the intervention group.

This examination revealed that participants who had not responded to the weight management program had had diabetes for a longer time — namely, about 3.8 years vs. 2.7 years.

But in other respects, both nonresponders and responders proved to be similar: they had lost about the same amount of weight, exhibited a similar reduction of liver and pancreatic fat, and had a similar downregulation of blood triglycerides.

The one difference between responders and nonresponders was this: that the people who regained normal blood glucose levels after the intervention exhibited early, constant improvement in the function of pancreatic beta cells.

When beta cells secrete insulin, they do so in two phases, the first of which amounts to a brief spike in insulin levels and takes about 10 minutes. People with type 2 diabetes typically do not experience it.

In DiRECT, the beta cells of those who responded to the weight management program did go through the first phase of insulin secretion, while the beta cells of nonresponders did not.

Taylor and colleagues’ findings indicate that weight loss can help redress fat metabolism in people with type 2 diabetes. However, those who experience a more precipitated loss of pancreatic beta cell function may not respond.

“The knowledge of reversibility of type 2 diabetes, ultimately due to redifferentiation of pancreatic beta cells, will lead to further targeted work to improve understanding of this process,” explains Taylor.

Nevertheless, the researchers admit that DiRECT should not remain the only source of evidence, as its results were seen in a particular cohort — of which 98 percent of the participants were white — which was only evaluated for a year. Further studies should aim to be more long-term and more diverse.

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