Weight Loss Alone May Not Prevent Diabetes Progression in High-Risk Prediabetes, Finds Study
Germany: A study published in the journal Diabetes found that weight loss alone may not be sufficient to prevent progression from prediabetes to type 2 diabetes in certain high-risk individuals.
Researchers followed participants in the Tübingen Lifestyle Intervention Program for nearly nine years and observed that people with a high-risk phenotype — characterized by severe insulin resistance, higher BMI, older age, and metabolic dysfunction-associated steatotic liver disease (MASLD) — experienced worsening blood sugar control and declining beta-cell function despite achieving substantial and sustained weight loss.
Experts emphasized that although lifestyle modification and weight reduction remain the cornerstone of diabetes prevention and management, some patients may require earlier and more intensive interventions. These may include liver-targeted medications, advanced pharmacologic therapy, or metabolic/bariatric surgery rather than relying on lifestyle measures alone.
The findings are from the Tübingen Lifestyle Intervention Program (TULIP), where investigators had previously classified individuals into six distinct clusters based on their metabolic profiles and risk of developing type 2 diabetes and related complications. Among these, cluster 3 (marked by impaired insulin secretion) and cluster 5 (characterized by older age, higher body mass index, and pronounced insulin resistance) were identified as having particularly high risk.
To better understand how these high-risk groups respond to long-term weight loss, researchers analyzed 190 participants who completed a structured 24-month lifestyle intervention. These individuals were followed for an average of nearly 9 years.
The study led to the following findings:
- At long-term follow-up, 60 participants achieved at least 3% weight loss, with an average reduction of around 8%.
- Despite sustained weight loss, metabolic outcomes differed significantly across clusters.
- Participants in cluster 5 showed worsening glycemic control compared to other groups.
- Cluster 5 individuals experienced greater increases in fasting glucose and 2-hour post-load glucose levels.
- A significant decline in insulin secretion was observed in cluster 5 participants.
- In contrast, cluster 3 participants demonstrated more favorable metabolic responses.
- Cluster 3 individuals showed improved insulin sensitivity along with preservation of insulin secretion, despite baseline impairment.
- Progression to type 2 diabetes was highest in cluster 5, with approximately 41% developing the condition during follow-up.
- No cases of diabetes were reported in lower-risk clusters (1, 2, 4, and 6).
- About 10% of participants in cluster 3 progressed to type 2 diabetes.
- The findings indicate that substantial and sustained weight loss does not confer equal metabolic benefits across all risk groups.
The study highlights that metabolic responses to lifestyle interventions vary across individuals. Although weight loss is generally beneficial, it may not sufficiently address underlying disease mechanisms in high-risk groups, particularly those with severe insulin resistance and liver-related dysfunction.
The researchers noted that, if validated in future prospective studies, these findings could influence clinical practice. High-risk individuals, such as those in cluster 5, may require more personalized prevention strategies beyond standard lifestyle measures, supporting a shift toward precision-based diabetes care.
Reference:
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, Norbert Stefan; Different Metabolic Responses to Long-term Weight Loss After Lifestyle Intervention Among Type 2 Diabetes Risk Clusters: Results From the TULIP Study. Diabetes 20 May 2026; 75 (6): 965–973. https://doi.org/10.2337/db25-0757
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