Nature Medicine publication: Prevention of type 2 diabetes through prediabetes remission without weight loss

A new Nature Medicine publication co-authored by Prof. Dr. Reiner Jumpertz-von Schwartzenberg and colleagues from the German Center for Diabetes Research (DZD) reveals that prediabetes remission, returning blood glucose to normal levels, can protect against developing type 2 diabetes even without weight loss.

In a post-hoc analysis of the Prediabetes Lifestyle Intervention Study (PLIS) involving more than 1,100 participants, about 22 % of individuals who did not lose weight during a one-year lifestyle intervention achieved remission to normal glucose regulation. Over a follow-up of up to ten years, these participants had a 71 % lower risk of progressing to type 2 diabetes compared with those who remained prediabetic.

The study found that these “responders” and “non-responders” showed similar body-weight trajectories, but differed in fat distribution. Responders gained mostly subcutaneous fat, while non-responders accumulated visceral (abdominal) fat, which is metabolically harmful. Responders also exhibited improved insulin sensitivity, enhanced β-cell function, and greater responsiveness to the hormone GLP-1.

These results challenge the long-standing assumption that weight loss is the only effective way to prevent diabetes. Instead, achieving normal blood glucose regulation, regardless of body weight change, may be a more powerful target for diabetes prevention.

“Our findings show that the protective effects of lifestyle intervention are not limited to weight loss,” says Prof. Jumpertz-von Schwartzenberg. “Focusing on glucose normalization and metabolic health could transform how we approach diabetes prevention.”

The findings were independently replicated in the U.S. Diabetes Prevention Program, confirming their robustness and global relevance.

Reference:
Sandforth A. et al. Prevention of type 2 diabetes through prediabetes remission without weight loss. Nature Medicine (2025). DOI: 10.1038/s41591-025-03944-9

Find the Nature Medicine article here: https://www.nature.com/articles/s41591-025-03944-9