1694-P: Subphenotype-Dependent Benefits of Bariatric Surgery in Data-Driven Clusters of Individuals at Risk for Type 2 Diabetes
Authors: SANDFORTH LEONTINE , RAVERDY VIOLETA , SANDFORTH ARVID , BAUVIN PIERRE , GANSLMEIER MARLENE , CHATELAIN ESTELLE , WAGNER ROBERT , PRYSTUPA KATSIARYNA , FRITSCHE ANDREAS , STEFAN NORBERT , PREISSL HUBERT , BIRKENFELD ANDREAS L. , JUMPERTZ VON SCHWARTZENBERG REINER , PATTOU FRANCOIS 
Published: June 2024

A novel classification of patients at risk for type 2 diabetes (T2D) has identified 6 clusters (Tübingen Clusters) of which 3 are associated with obesity. Cluster 4 (C4) has a lower risk for T2D development and complications, cluster 5 (C5) has high cardiovascular, T2D and mortality risk and cluster 6 (C6) has high nephropathy and mortality but moderate T2D risk. To date it is unknown if these clusters differentially benefit from bariatric surgery in terms of prediabetes remission and cardiovascular risk reduction.
We performed cluster allocation of subjects at risk for T2D from the Atlas Biologique de l’Obésité Sévère (ABOS) cohort in France (n=806) who underwent Roux-en-Y gastric bypass, sleeve gastrectomy or gastric banding. Patients were followed up for 12 months. Prediabetes remission was defined according to ADA criteria. Outcome variables were tested using mixed effects models or chi-squared tests.
Of all participants, 15.0% (n=121) were allocated to C4, 22.3% (180) to C5 and 62.4% (503) to C6. C6 had the highest BMI (47.5±7.56 kg/m2 vs C4: 42.7±5.24 and vs C5: 46.4±6.57, p&lt;0.001), cluster 5 had highest triglycerides (1.90±0.91 mmol/l vs C4 1.14±0.50 vs C6 1.31±0.49, p&lt;0.001) and highest insulin resistance (HOMA-IR: 5.04±2.96 vs C4 1.68±0.61 vs C6 3.8±1.97, p&lt;0.001). However, prediabetes remission rate was lowest in cluster 4 (54%) and highest in clusters 5 (77%, p vs C4 &lt;0.05) and 6 (74%, p=ns). Relative Framingham risk score was highest at baseline in C5 (1.15±0.42 vs C4: 1.00±0.40, p&lt;0.05 vs C6: 1.02±0.39, p&lt;0.01) but reduced to similar values as in C4 and C6 (0.80±0.03 vs 0.77±0.03 vs 0.79±0.02, both p=ns).
These data show that despite pronounced metabolic derangements at baseline in C5, prediabetes remission rates were highest in this cluster and surprisingly low in C4. Data-driven classification might help identify individuals that specifically benefit from bariatric surgery. Future research should investigate methods to improve remission rates in C4.

Disclosure
L. Sandforth: None. V. Raverdy: None. A. Sandforth: None. P. Bauvin: None. M. Ganslmeier: None. E. Chatelain: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. K. Prystupa: None. A. Fritsche: Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH, SYNLAB Holding Deutschland GmbH. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Lilly Diabetes, MSD Life Science Foundation, Novo Nordisk. Advisory Panel; Pfizer Inc. Research Support; Sanofi-Aventis Deutschland GmbH. Advisory Panel; GlaxoSmithKline plc. H. Preissl: None. A.L. Birkenfeld: None. R. Jumpertz von Schwartzenberg: None. F. Pattou: Advisory Panel; Novo Nordisk, Metronics, Lilly Diabetes.

Funding
Programme d’Investissement d’Avenir” (PRECINASH, ANR-16-RHUS-0006; European Genomic Institute for Diabetes, ANR-10-LABX-0046), Lille University (WILL-CHAlRES-23-001), Fondation de la Recherche Médicale (EQU202303016330 PATTOU), EU Horizon 2020 research and innovation program (Innovative Medicines Initiative 2, project SOPHIA 875534)