A lifestyle program that helped participants lose and maintain about 8% of their body weight over roughly nine years did not yield the same metabolic benefits for everyone, according to researchers in Germany. People classified in a high-risk category known as “cluster 5” continued to show worsening blood sugar control and declining insulin secretion despite sustained weight loss.
Scientists at the German Center for Diabetes Research (DZD), University Hospital Tübingen and Helmholtz Munich analyzed data from the Tübingen Lifestyle Intervention Program (TULIP), a study that enrolled people at elevated risk of type 2 diabetes. Participants completed a two-year lifestyle program and were then followed for about nine years.
In the analysis, the researchers focused on people who achieved substantial weight loss and maintained it long term—about 8% of body weight—and assessed whether outcomes differed across previously defined type 2 diabetes risk “clusters.”
The team reported that participants assigned to “cluster 5” showed rising blood glucose levels over time along with declining insulin secretion, indicating a persistently high risk of developing type 2 diabetes even after sustained weight loss. In the ScienceDaily report, lead author Professor Norbert Stefan said the researchers were “very surprised” to see these adverse changes after a long follow-up despite the magnitude and durability of weight reduction.
The study, published in the journal Diabetes, suggests insulin resistance is a major contributor to the ongoing risk in cluster 5 and may be linked to severe fatty liver disease. The researchers said fat accumulation in the liver could also impair pancreatic beta-cell function, reducing the body’s ability to secrete insulin and helping drive higher blood sugar.
The findings add to earlier work indicating that fatty liver disease and insulin resistance are central features of this high-risk subgroup. The authors said that if future prospective research confirms the results, diabetes prevention approaches may need to be more personalized for people with biological profiles like cluster 5, potentially requiring more intensive or targeted strategies than standard lifestyle advice alone.
