2611-P: Serum Metabolite Signatures of Visceral Adipocyte Hypertrophy and Its Association with Diabetes Remission after Bariatric Surgery

Introduction and Objective: To determine whether subcutaneous or visceral adipocyte hypertrophy independently predicts post-surgery diabetes remission, and to develop a less-invasive serum metabolite model for visceral adipocyte hypertrophy quantification. Methods: This study included 150 adults (37 men and 113 women) aged 34.8±7.7 years with type 2 diabetes (T2D) who underwent sleeve gastrectomy. Paired subcutaneous and visceral adipose tissue samples were collected. Glucose tolerance status was classified by American Diabetes Association criteria. Untargeted serum metabolomics was used to predict visceral adipocyte hypertrophy. Diabetes remission was assessed at 1-year follow-up. Results: During 1-year follow-up, 106 participants (70.7%) with baseline T2DM achieved diabetes remission. Baseline visceral adipocyte diameter was significantly larger in the sustained T2D group than in the T2D remission group (108±9.5 μm vs. 102±9.8 μm, P <0.001), whereas subcutaneous adipocyte diameter did not differ significantly (111 [104-119] μm vs. 111 [103-117] μm, P =0.890). Visceral adipocyte diameter was associated with a lower probability of diabetes remission after bariatric surgery (RR 0.92, 95% CI 0.88-0.96). Mechanistically, circulating metabolites linking hypertrophy to remission outcomes were predominantly enriched in phospholipid biosynthesis pathway. Leveraging this, a less-invasive serum metabolite-based model predicting visceral adipocyte hypertrophy was developed and validated in an independent cohort, and was significantly associated with cardiometabolic traits. Conclusion: Visceral adipocyte hypertrophy was an independent predictor of 1-year diabetes remission after bariatric surgery. Serum metabolite signature offers a practical, less-invasive approach to quantify visceral adipocyte hypertrophy and has the potential for preoperative risk stratification.