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Sandforth, L. ; Raverdy, V.* ; Sandforth, A. ; Bauvin, P.* ; Chatelain, E.* ; Verkindt, H.* ; Mingrone, G.* ; Guidone, C.* ; Verrastro, O.* ; Zhou, K. ; Archid, R.* ; Mihaljevic, A.L.* ; Caiazzo, R.* ; Baud, G.* ; Marciniak, C.* ; Chetboun, M.* ; Ganslmeier, M. ; Minelli Faiao, V. ; Heni, M.* ; Fritsche, L. ; Moller, A. ; Kantartzis, K. ; Peter, A. ; Lehmann, R. ; Wagner, R. ; Prystupa, K. ; Fritsche, A. ; Stefan, N. ; Preissl, H. ; Birkenfeld, A.L. ; Jumpertz von Schwartzenberg, R. ; Pattou, F.*

Subphenotype-dependent benefits of bariatric surgery for individuals at risk for type 2 diabetes.

Diabetes Care, DOI: 10.2337/dc25-0160 (2025)
DOI PMC
OBJECTIVE: Bariatric surgery is an effective treatment option for individuals with obesity and type 2 diabetes (T2D). However, whether outcomes in subtypes of individuals at risk for T2D and/or comorbidities (Tübingen Clusters) differ, is unknown. Of these, cluster 5 (C5) and cluster 6 (C6) are high-risk clusters for developing T2D and/or comorbidities, while cluster 4 (C4) is a low-risk cluster. We investigated bariatric surgery outcomes, hypothesizing that high-risk clusters benefit most due to great potential for metabolic improvement. RESEARCH DESIGN AND METHODS: We allocated participants without T2D but at risk for T2D, defined by elevated BMI, to the Tübingen Clusters. Participants had normal glucose regulation or prediabetes according to American Diabetes Association criteria. Two cohorts underwent bariatric surgery: a discovery (Lille, France) and a replication cohort (Rome, Italy). A control cohort (Tübingen, Germany) received behavioral modification counseling. Main outcomes included alteration of glucose regulation parameters and prediabetes remission. RESULTS: In the discovery cohort, 15.0% of participants (n = 121) were allocated to C4, 22.3% (n = 180) to C5, and 62.4% (n = 503) to C6. Relative body weight loss was similar among all clusters; however, reduction of insulin resistance and improvement of β-cell function were strongest in C5. Prediabetes remission rate was lowest in low-risk C4 and highest in high-risk C5. Individuals from high-risk clusters changed to low-risk clusters in both bariatric surgery cohorts but not in the control cohort. CONCLUSIONS: Participants in C5 had the highest benefit from bariatric surgery in terms of improvement in insulin resistance, β-cell function, and prediabetes remission. This novel classification might help identify individuals who will benefit specifically from bariatric surgery.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Grants Type 1 Diabetes Exchange
Helmholtz Munich
Federal Ministry of Education and Research
German Research Association
EFPIA
Helmholtz Society
Obesity Action Coalition
Juvenile Diabetes Research Foundation
The European Federation of Pharmaceutical Industries and Associations (EFPIA)
EU Horizon 2020 research and innovation program