Prediabetes Remission Without Weight Loss Prevents Type 2 Diabetes via Visceral Fat Redistribution
This post hoc analysis of the PLIS trial demonstrates that prediabetes remission to normal glucose regulation prevents type 2 diabetes even without weight loss. Responders showed improved insulin sensitivity, beta-cell function, and GLP-1 sensitivity, with adipose tissue redistributing from visceral to subcutaneous depots. For diagnostic laboratories, the findings support using glycaemic biomarkers rather than weight alone to monitor diabetes prevention programmes.
The original study
Prevention of type 2 diabetes through prediabetes remission without weight loss.
- Authors
- Sandforth A, Arreola EV, Hanson RL, Wewer Albrechtsen NJ, Holst JJ, Ahrends R, et al.
- Journal
- Nature medicine
- Type
- Journal Article, Randomized Controlled Trial, Multicenter Study
- PMID
- 41023486
Original abstract
Clinical practice guidelines recommend defined weight loss goals for the prevention of type 2 diabetes (T2D) in those individuals with increased risk, such as prediabetes. However, achieving prediabetes remission, that is, reaching normal glucose regulation according to American Diabetes Association criteria, is more efficient in preventing T2D than solely reaching weight loss goals. Here we present a post hoc analysis of the large, multicenter, randomized, controlled Prediabetes Lifestyle Intervention Study (PLIS), demonstrating that prediabetes remission is achievable without weight loss or even weight gain, and that it also protects against incident T2D. The underlying mechanisms include improved insulin sensitivity, β-cell function and increments in β-cell-GLP-1 sensitivity. Weight gain was similar in those achieving prediabetes remission (responders) compared with nonresponders; however, adipose tissue was differentially redistributed in responders and nonresponders when compared against each other-while nonresponders increased visceral adipose tissue mass, responders increased adipose tissue in subcutaneous depots. The findings were reproduced in the US Diabetes Prevention Program. These data uncover essential pathways for prediabetes remission without weight loss and emphasize the need to include glycemic targets in current clinical practice guidelines to improve T2D prevention.