A recent clinical trial (Diabetes Remission Clinical Trial - DiRECT), discovered that nearly half of the participants with type-2 diabetes, who followed a weight-loss programme, experienced the remission of their condition within six years of their diagnosis. Now, a study published on 2nd August in the journal Cell Metabolism reveals that this successful response to weight loss is associated with the early and sustained improvement in the functioning of pancreatic beta cells. This contradicts the earlier belief that beta-cell function is irreversibly lost in patients with type-2 diabetes.
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 can be counteracted using a tool within anyone’s reach: diet and lifestyle choices. “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. Our data suggests that substantial weight loss at the time of diagnosis is appropriate to rescue the beta cells,” said senior study author Roy Taylor of Newcastle University.
According to the World Health Organization, diabetes affects approximately 422 million people worldwide; approximately 90% of the cases are of type-2 diabetes. It is a condition in which the body does not produce enough insulin or respond properly to it. Insulin is a hormone produced by beta cells in the pancreas that helps glucose in the blood enter the cells in muscle, fat and liver, to be used for energy. Type-2 diabetes was traditionally viewed as a lifelong condition that worsens over time.
The results of the trials from DiRECT challenge this traditional view. The volunteers were randomly split into two groups: some were assigned best-practice care, acting as the control group; others joined an intensive weight-management programme while still receiving appropriate care for diabetes. A year later, 46% of the individuals assigned to the weight-loss programme 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 metabolism had not responded to the regimen in the same way.
To address this question, Roy Taylor and his team examined potentially relevant metabolic factors, such as liver fat content, pancreatic fat content, blood concentrations of fats called triglycerides, and beta-cell function, in a subset of DiRECT participants, including 64 individuals in the second group. They concluded that responders to the weight-loss programme were similar to non-responders. Both groups had lost comparable amounts of weight, leading to similar reductions in liver fat content, pancreatic fat content and blood concentrations of triglycerides.
The one difference between responders and non-responders was that people who regained normal blood glucose levels after the intervention exhibited early and 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 programme did go through the first phase of insulin secretion, while the beta cells of non-responders did not. The 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 Roy 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% of the participants were white—which was only evaluated for a year. Further studies should aim to be more long-term and more diverse.