2635-P: Visceral Adiposity and Ectopic Fat Jointly Drive Post-Pancreatitis Diabetes: An Integrated Cohort and Proteomics Study

Introduction and Objective: Visceral and ectopic fat deposition are implicated in post-pancreatitis diabetes mellitus (PPDM-A). This study aimed to identify associated protein biomarkers and develop a novel prediction model by integrating cohort and proteomic data. Methods: We conducted an integrated analysis of clinical, imaging (CT-derived), and proteomic data from a Chinese cohort and the UK Biobank. A Lipid Metabolic Score (LMS) was constructed from several lipid metrics. Model performance was assessed by AUC. Causal inference for the lead protein (STC1) was evaluated via two-sample Mendelian randomization. Results: The LMS and recurrent pancreatitis were independent predictors of PPDM-A in the Chinese cohort. In the UK Biobank, a model combining baseline LMS and HbA1c achieved an AUC of 0.802 for PPDM-A prediction. Incorporating the protein STC1 enhanced the AUC to 0.861. Genetically elevated STC1 levels were causally associated with increased pancreas fat (OR = 1.09; P = 0.011). Conclusion: PPDM-A is driven by recurrent pancreatitis, dysglycemia, and lipid metabolism disorders mediated by visceral and ectopic fat. The proposed clinical-proteomic model, featuring STC1, significantly improves risk stratification and offers a potentially practical tool for early identification of high-risk patients. Disclosure Y. Wang: None. Funding National Natural Science Foundation of China (Grant Nos. 82470935)