Cluster 5 diabetes risk persisted despite long-term weight loss, study finds
Researchers found one high-risk metabolic group kept elevated type 2 diabetes risk after sustained weight loss in the TULIP study.
By Lucas Ferreira · Science & Environment Writer
3 min read
Cluster 5 diabetes risk remained high even after long-term weight loss in a study led by researchers at the German Center for Diabetes Research, University Hospital Tübingen and Helmholtz Munich. The finding matters because it suggests standard lifestyle-based prevention may not protect every person at elevated risk for type 2 diabetes in the same way.
The researchers reported in the journal Diabetes that people in Tübingen’s type 2 diabetes risk cluster 5 had rising blood sugar, declining insulin secretion and a continuing high risk of developing the disease. Those changes appeared despite substantial weight loss that participants maintained for years.
What is cluster 5 diabetes risk?
Tübingen researchers previously divided people at risk of type 2 diabetes into six metabolic risk groups, or clusters. The groups differ in how often diabetes develops and in how diabetes-related complications progress, according to the German Center for Diabetes Research.
Clusters 3 and 5 had already been identified as groups with especially high odds of developing type 2 diabetes. In the new analysis, the research team asked whether people in those clusters responded differently to lifestyle-based prevention than people in other clusters.
The study used data from the Tübingen Lifestyle Intervention Program, known as TULIP. Participants had an increased risk of type 2 diabetes, took part in a two-year lifestyle program and were followed for about nine years afterward.
The analysis focused on people who lost a meaningful amount of weight and kept it off over the long term. According to the German Center for Diabetes Research, people in cluster 5 still showed worse blood sugar regulation and weaker insulin production after losing about 8% of their body weight and sustaining that loss.
Why can diabetes risk stay high after weight loss?
The researchers said insulin resistance appeared to be a central factor in the weaker response seen in cluster 5. Their analysis pointed to severe fatty liver disease as the likely driver of that resistance.
Fat buildup in the liver may also have limited the ability of pancreatic beta cells to release insulin, according to the research team. Insulin is the hormone that helps regulate blood sugar, and reduced insulin secretion can contribute to higher glucose levels.
The findings fit earlier evidence that fatty liver disease and insulin resistance are key disease processes in Tübingen’s cluster 5 group, the researchers said. Those traits may increase vulnerability not only to type 2 diabetes but also to cardiovascular disease.
What the findings could mean for prevention
The study does not overturn the role of diet, exercise and weight loss in lowering type 2 diabetes risk. The German Center for Diabetes Research said a healthy lifestyle can reduce risk for many people.
The results do suggest that some high-risk patients may need prevention plans that address their specific metabolic problems, rather than relying on weight loss alone. The researchers said future prospective studies are needed to confirm whether people with profiles like cluster 5 require more intensive care or targeted treatment.
The journal reference lists the study as “Different Metabolic Responses to Long-term Weight Loss After Lifestyle Intervention Among Type 2 Diabetes Risk Clusters: Results From the TULIP Study,” published in Diabetes in 2026. The paper’s DOI is 10.2337/db25-0757.
This story draws on original reporting from ScienceDaily.