Different Metabolic Responses to Long-term Weight Loss After Lifestyle Intervention Among Type 2 Diabetes Risk Clusters: Results From the TULIP Study

We previously identified six clusters of people at different risks of type 2 diabetes and/or comorbidities, of which cluster 3 (β-cell deficient) and 5 (older age, higher BMI, severe insulin resistance) had a high risk of progression to diabetes. We have now investigated whether cluster 3 and 5 individuals differed from those of the other clusters in changes in insulin sensitivity, insulin secretion, and the development of type 2 diabetes during a long-term reduction of body weight. A total of 190 participants completed a 24-month lifestyle intervention in the Tübingen Lifestyle Intervention Program (TULIP) and were followed up for 8.7 ± 1.6 years. Sixty participants had a weight loss ≥3% (mean reduction of 8%) at the long-term follow-up. Of them, cluster 5 participants (n = 17) had a larger increase of adjusted fasting glycemia compared with the cluster group 1,2,4,6 (n = 33) and cluster 3 (n = 10) and a larger increase of adjusted 2-h glucose levels compared with cluster 3 (all P 0.05). In cluster 5, a larger decrease of adjusted insulin secretion compared with cluster 3 (P = 0.01) and cluster group 1,2,4,6 (P = 0.05) was observed. Forty-one percent of cluster 5 participants (0% in cluster group 1,2,4,6 and 10% in cluster 3) developed type 2 diabetes. In conclusion, despite a sustained and large amount of weight loss, diabetes risk cluster 5 participants had deterioration of glycemia and insulin secretion and a high risk of type 2 diabetes. If this result can be replicated in a prospective study, people of this cluster would need targeted prevention strategies. Article Highlights There may be heterogeneity in the response to a lifestyle intervention to prevent type 2 diabetes. This study investigated whether participants of Tübingen Lifestyle Intervention Program (TULIP) type 2 diabetes risk clusters 3 and 5, who have a very high risk of diabetes, benefit from long-term weight loss following a 2-year lifestyle intervention. Diabetes risk cluster 5 participants had an impaired response regarding improvement of glycemia and insulin secretion and a high risk of developing type 2 diabetes, despite a long-term (9-year) mean weight loss of 8%. Alternative or intensified interventions should be considered for people in Tübingen type 2 diabetes risk cluster 5.