A weight loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a UK study.
The ReTUNE (Reversal of Type 2 Diabetes Upon Normalisation of Energy Intake in Non-obese People) trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year's duration and a BMI of 27 kg/m2 or lower.
After 1 year, participants had lost 9% of their body weight.
Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.
The research, presented at the Diabetes UK Professional Conference 2022 on April 1, also showed this was accompanied by increases in insulin secretion and reductions in A1c and fasting plasma glucose levels.
Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, UK, said the findings indicate that the "etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised."
This information should make a profound difference in what doctors advise their patients, Taylor added.
"One of the dramatic things about dealing with people in this group," he said, "is they feel very resentful that healthcare professionals tell them not to lose weight."
Based on the current results, Taylor believes this is "inappropriate advice, and it's that personal advice that I think that this study points a way towards."
Weight Loss "First Line of Treatment"
These findings support the theory of a personal fat threshold, above which "type 2 diabetes occurs," said Taylor. "Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI."
Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.
As reported by Medscape Medical News, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.
Inspired by the results of DiRECT and the DROPLET study, the National Health Service (NHS) in England has been rolling out a low calorie-diet treatment program for people who are overweight and living with diabetes.
Asked during the post-presentation discussion whether the current results could have implications for the NHS program, Taylor said it remains, in effect, a study and will not change things for now.
Chris Askew, chief executive of Diabetes UK, said in a release: "This game-changing study...advances our understanding of why type 2 diabetes develops and what can be done to treat it."
"Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer."
Askew continued: "The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn't only possible for people of certain body weights."
Weight and Body Fat Decrease Led to Remission
For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year's duration who had a BMI of 21-27 kg/m2 and compared them with 20 matched controls, with a follow-up of 52 weeks.
Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8 kg/m2, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.
Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight loss program incremented in 5% steps, followed by 6 weeks of weight stability.
Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.
Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.
Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.
Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.
This, Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).
ReTUNE is funded by Diabetes UK. The authors have reported no relevant financial relationships.
Diabetes UK Professional Conference 2022. Abstract A49 (P37). Presented April 1, 2022.