Weight loss and exercise are widely considered powerful tools for preventing type 2 diabetes, but new research suggests the benefits may not be the same for everyone.
Losing weight and staying active are widely recommended ways to reduce the risk of type 2 diabetes. But new research suggests that for some people, those efforts may not be enough.
Scientists in Germany have identified a high-risk group of people whose blood sugar control continued to worsen despite years of successful weight loss and healthier living. The findings highlight how type 2 diabetes is not a single disease with a one-size-fits-all solution, but a complex condition driven by different biological mechanisms in different people.
The study, published in the journal Diabetes, was conducted by researchers from the German Center for Diabetes Research (DZD), University Hospital Tübingen, and Helmholtz Munich.
Why Some People Stay at High Risk
Several years ago, DZD researchers identified six distinct risk clusters among people predisposed to type 2 diabetes. These groups differ in both diabetes risk and the likelihood of developing related complications.* Clusters 3 and 5 were found to carry the greatest risk of progressing to type 2 diabetes. In the latest study, researchers explored whether long-term weight loss and lifestyle changes were equally effective across these different risk groups.
The analysis used data from the Tübingen Lifestyle Intervention Program (TULIP). Participants with elevated diabetes risk completed a two-year lifestyle intervention program and were monitored for about nine years afterward. Researchers focused on individuals who achieved substantial and lasting weight loss.
Unexpected Results Despite Long-Term Weight Loss
“We were particularly interested in whether individuals in risk clusters 3 and 5 differed from those in other clusters with regard to improvements in blood glucose levels and the prevention of type 2 diabetes,” explains Professor Norbert Stefan, the lead author of the study. “We were very surprised to find that, despite a large and sustained weight loss of 8% and after a very long follow-up period of 9 years, individuals in risk cluster 5 showed increasing blood glucose levels, declining insulin secretion, and a persistently high risk of type 2 diabetes.”
Researchers then investigated why lifestyle intervention appeared to provide less protection for people in cluster 5. Their findings point to insulin resistance as a likely cause, driven in part by severe fatty liver disease and impaired insulin production from pancreatic beta cells linked to liver fat buildup. These factors appeared to contribute to worsening blood sugar control in this group.
Fatty Liver Disease May Play a Central Role
The results support earlier research showing that fatty liver disease and insulin resistance are key biological drivers in people assigned to Tübingen’s type 2 diabetes risk cluster 5. According to the researchers, these underlying conditions may leave individuals especially vulnerable to both type 2 diabetes and cardiovascular disease.
The study also suggests that people in cluster 5 may respond less effectively to lifestyle-based diabetes prevention strategies than those in other risk groups, even after achieving major and sustained weight loss, particularly when it comes to glucose metabolism. Researchers say future studies will be needed to confirm the findings, but the results point toward a need for more personalized diabetes prevention approaches for high-risk groups like cluster 5.
Reference: “Different Metabolic Responses to Long-term Weight Loss After Lifestyle Intervention Among Type 2 Diabetes Risk Clusters: Results From the TULIP Study” by Caroline Z. Meier, Robert Wagner, Marlene Ganslmeier, Konstantinos Kantartzis, Martin Heni, Andreas Peter, Reiner Jumpertz-von Schwartzenberg, Jürgen Machann, Fritz Schick, Andreas L. Birkenfeld, Hans-Ulrich Häring, Andreas Fritsche and Norbert Stefan, 13 April 2026, Diabetes.
DOI: 10.2337/db25-0757
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