Posted on Aug 03, 2018, 10 p.m.
Nearly half of subjects in a recent clinical trial with type 2 diabetes achieved remission to non-diabetic state after weight loss intervention was delivered within 6 years of diagnosis, study shows successful response to weight loss association with early and sustained improvement in functioning of pancreatic beta cells, as published in the journal Cell Metabolism.
Findings of this study challenge previous paradigm that beta cell function is irreversibly lost within patients with type 2 diabetes, carrying potentially important implication for clinical approaches to management, data suggests substantial weight loss at time of diagnosis is appropriate to rescue beta cells.
Diabetes affects approximately 422 million people around the globe according to W.H.O, 90% being cases of type 2 diabetes, and is long thought to be a lifelong condition that worsens over time. In patients with type 2 diabetes the body does not produce enough or respond properly to insulin, this hormone produced by beta cells in the pancreas helps glucose in the blood enter fat, liver, and muscles to be used as energy.
UK based Diabetes Remission Clinical Trial challenging traditional views included participants diagnosed with type 2 diabetes within 6 years of the beginning of the study, who were randomly assigned to a control group of best practice care, or intensive primary care led weight management intervention program. After 1 year 46% of participants in the intervention group successfully responded to weight loss in that participants recovered and maintained control over glucose concentrations; some nonresponders did not lose enough weight it was not clear as to why participants who did lose weight had differed responses from that of nonresponders.
To address question of differed responses researchers examined potentially relevant metabolic factors such as pancreatic fat content, liver fat, beta cell function, and triglycerides, in a subset of DiRECT participants which included 64 individuals in the intervention group. It was found that weight loss program responders were similar to nonresponders before intervention but had shorter duration of diabetes. Nonresponders and responders lost comparable amounts of weight leading to similar reductions of fat content in all areas looked at. Only responders had demonstrated early and sustained improvement in beta cell function, particularly the first phase insulin response. Pancreatic beta cells secrete insulin in 2 phases in response to increases in blood glucose concentration: first phase being a brief spike typically absent in type 2 diabetes patients; first phase insulin secretion increased in responders after weight loss but didn’t change in nonresponders.
According to the researchers findings suggest weight loss normalizes fat metabolism in type 2 diabetes patients, rapid loss of beta cell capacity to recover prevents some from returning to nondiabetic state. Additional studies are needed due to limitations such as 98% of the participants being caucasian to assess generalizability of results, and evaluation was only 12 months of weight maintenance longer term studies are underway.
Reversibility of type 2 diabetes due to redifferentiation of pancreatic beta cells could lead to further targeted work to improve understandings of the process providing focus for cell biologists to make advances.
Materials provided by Cell Press.
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Roy Taylor, Ahmad Al-Mrabeh, Sviatlana Zhyzhneuskaya, Carl Peters, Alison C. Barnes, Benjamin S. Aribisala, Kieren G. Hollingsworth, John C. Mathers, Naveed Sattar, Michael E.J. Lean. Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for β Cell Recovery. Cell Metabolism, 2018; DOI: 10.1016/j.cmet.2018.07.003