Why weight loss produces remission of type 2 diabetes in some patients

August 2, 2018, Cell Press
Cross sectional MRI images are displayed with pixels colour-coded for fat content. In this individual, the high liver fat at baseline (30.4 percent) decreased to 1.3 percent after weight loss. The lower panels, at the level of the pancreas (outlined in white), show the decrease in pancreas fat (8.9 to 7.5 percent) associated with the restoration of first phase and maximal insulin secretion. Credit: Taylor et al.

A clinical trial recently showed that nearly half of individuals with type 2 diabetes achieved remission to a non-diabetic state after a weight-loss intervention delivered within 6 years of diagnosis. Now a study published August 2nd 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 finding challenges the previous paradigm that beta-cell function is irreversibly lost in patients with type 2 diabetes.

"This observation carries potentially important implications for the initial clinical approach to management," says senior study author Roy Taylor of Newcastle University. "At present, the early management of type 2 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 at the time of diagnosis is appropriate to rescue the beta ."

According to the World Health Organization, diabetes affects approximately 422 million people worldwide. Approximately 90% 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.

This traditional view was recently challenged by results from the United-Kingdom-based Diabetes Remission Clinical Trial (DiRECT) overseen by Taylor. 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 -management program (). One year later, 46% of the individuals in the intervention group successfully responded to weight loss in that they recovered and maintained control over blood glucose concentrations. Some non-responders simply had not lost enough weight, but in those who had, it was not clear how their response differed from that of responders.

To address this question, Taylor and his collaborators 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 intervention group. They 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). 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.

However, 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, 98% of the participants were white, so additional studies are needed to assess the generalizability of the results. Moreover, the participants were evaluated for only 12 months of weight maintenance, so longer-term studies are underway.

"The knowledge of reversibility of type 2 diabetes, ultimately due to re-differentiation of pancreatic , will lead to further targeted work to improve understanding of this process," Taylor says. "This provides a major focus for cell biologists to make specific advances."

Explore further: New potential target for treatment of diabetes

More information: Cell Metabolism, Taylor et al.: "Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for Beta Cell Recovery" http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30446-7 , DOI: 10.1016/j.cmet.2018.07.003

Related Stories

New potential target for treatment of diabetes

July 25, 2018
Researchers at Karolinska Institutet have discovered that one of the building blocks in the calcium channels in the pancreatic beta cells play an important role in regulating our blood glucose values. Treatments aimed at ...

New study shows vegan diet improves diabetes markers in overweight adults

February 12, 2018
A plant-based diet improves beta-cell function and insulin sensitivity in overweight adults with no history of diabetes, according to a new study published in Nutrients by researchers from the Physicians Committee for Responsible ...

Avoiding type 2 diabetes – there is more than one diet to choose from

April 19, 2018
If you have high blood glucose, but not high enough to be diagnosed with diabetes (so-called prediabetes) you may have been advised by your doctor to lose weight and to eat less fat and more fibre. If this sounds a bit one-size-fits-all, ...

The relevance of GABA for diabetes highlighted in two new studies

April 5, 2018
Dynamic interactions between the nervous system, hormones and the immune system are normally ongoing, but in diabetes the balance is disturbed. Two studies published in EBioMedicine by an international research team from ...

Beta cell-seeded implant restores insulin production in type 1 diabetes mouse model

March 19, 2018
Researchers have successfully created a novel biomaterial that can be seeded with insulin-producing beta cells. Implantation of the beta cell-seeded biomaterial reversed diabetes in a mouse model by effectively normalizing ...

Intra-pancreatic triacylglycerol drops with weight loss in T2DM

December 21, 2015
(HealthDay)—The weight loss-associated decrease in intra-pancreatic triacylglycerol which occurs after gastric bypass is specific to type 2 diabetes mellitus (T2DM), according to a study published online Dec. 1 in Diabetes ...

Recommended for you

Very low calorie diets trialled by NHS to tackle diabetes

December 7, 2018
Hundreds of thousands of people will receive NHS help to battle obesity and type 2 diabetes under radical action set out by Simon Stevens, Chief Executive of NHS England.

New therapeutic avenue for type 2 diabetes

December 6, 2018
Restoring the action of insulin is one of the keys to fighting type 2 diabetes. Researchers from Inserm led by Dominique Langin at the Institute of Cardiovascular and Metabolic Diseases (Inserm/Université de Toulouse) are ...

Subtype of immune B cells can delay type 1 diabetes onset in mice

December 6, 2018
A team of researchers at Baylor College of Medicine and the University of Michigan Medical School reports today in the JCI Insight that a subset of immune B cells, known as CD19+IgM+ B cells, can delay the onset of type 1 ...

Is the pancreas regeneration debate settled? An original theory renewed

December 5, 2018
A contentious debate among diabetes researchers has surrounded the regeneration of pancreatic insulin-producing cells: not if these cells regenerate, but rather how.

One in four patients say they've skimped on insulin because of high cost

December 3, 2018
For patients with diabetes, insulin is a life-saving medicine and an essential component of diabetes management, yet in the past decade alone, the out-of-pocket costs for insulin have doubled in the United States. One-quarter ...

Parsing diabetic skin infections

December 3, 2018
People with diabetes are more susceptible to skin infection. According to a new study by C. Henrique Serezani, Ph.D., Stephanie Brandt, Ph.D., and colleagues, this susceptibility might be due to overabundance of a compound ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.