345-OR: Beyond Size Matters—The Impact of Pancreatic Volume and Pancreatic Fat on Type 2 Diabetes

Introduction & Objective: Individuals with type 2 diabetes (T2D) are thought to have a smaller pancreas; however, whether this is cause or consequence of T2D is unclear. We investigated the association between pancreas volume and T2D risk and whether this association was modified by pancreatic fat. Methods: Using magnetic resonance imaging from the UK Biobank, 25,389 individuals were classified into four groups based on the median values of pancreas volume (60 cm3) and pancreatic fat (8%). Odds ratios (ORs) for prevalent T2D were estimated using logistic regression. Additionally, we conducted a 6-year case-cohort study in an independent Japanese cohort using computed tomography during health examinations. Hazard ratios (HRs) for incident T2D were estimated using weighted-Cox regression in 658 randomly-selected individuals and 146 incident T2D cases among 2,168 individuals without diabetes. The regression models in both studies were adjusted for age, sex, body mass index, daily alcohol intake, current smoking, liver fat, and visceral fat. Results: In the UK Biobank, individuals who had fat accumulation in a smaller pancreas exhibited the highest likelihood of T2D. Compared with large/low-fat pancreas, the adjusted ORs (95%CI) of T2D were 1.63 (1.36-1.97) in small/high-fat pancreas, 1.09 (0.89-1.33) in large/high-fat pancreas, and 1.08 (0.85-1.37) in small/low-fat pancreas. This finding was prospectively validated in the Japanese cohort with 6.27-year median follow-up. The adjusted HRs (95%CI) of incident T2D were 3.12 (1.40-6.96) in small/high-fat pancreas, 1.00 (0.59-1.69) in large/high-fat pancreas, and 0.74 (0.26-2.14) in small/low-fat pancreas. Conclusion: Fat accumulation in an already smaller pancreas appears to be a key determinant of elevated T2D risk and might therefore be a novel target for preventive interventions. Disclosure H. Yamazaki: Other Relationship; AstraZeneca, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Kyorin Pharmaceutical Co. Ltd, Takeda Pharmaceutical Company Limited, Takeda Pharmaceutical Company Limited, Magmitt Pharmaceutical Co. S. Tauchi: None. M. Dohke: None. N. Hanawa: None. Y. Kodama: None. A. Katanuma: None. S. Fukuhara: None. K. Prystupa: None. J. Hummel: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. M. Heni: Research Support; Boehringer-Ingelheim. Advisory Panel; Amryt Pharma Plc. Speaker's Bureau; Amryt Pharma Plc. Advisory Panel; Boehringer-Ingelheim, Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. Funding Japan Society for the Promotion of Science KAKENHI grants (JP22K15685); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation: 518749683)