1307-OR: Site-Specific Cancer Risk across Type 2 Diabetes Subtypes and Adults without Diabetes in a Real-World Cohort of 1.2 Million Adults

Introduction and Objective: Type 2 diabetes (T2D) is associated with elevated cancer risk, yet whether heterogeneity in T2D identifies individuals at particularly high or low risk relative to individuals without diabetes remains unclear. We evaluated site-specific cancer risk across T2D subtypes compared with adults without diabetes. Methods: We analyzed retrospective electronic health records from Epic Cosmos (2012-2023) of newly diagnosed T2D (n=630,715; mean age 64.3 years; 51.6% female) matched on age, sex, and smoking to adults without diabetes. Individuals with prior cancers were excluded. T2D was classified into severe insulin-deficient (SIDD), mild obesity-related (MOD), mild age-related (MARD), and Mixed subtypes using validated algorithms (AUC 0.81-0.99). Cause-specific Cox models estimated adjusted hazards of first incident colorectal, liver, pancreatic, breast, endometrial, ovarian, and prostate cancers within 10 years. Results: Compared to adults without diabetes (Figure), all subtypes showed elevated hazards (hazard ratios [HRs] ranging from 1.85 to 3.27) of metabolic cancers (liver and pancreatic). MOD and SIDD were associated with higher hazards of endometrial (HRs: 1.29 - 1.85) and ovarian cancers but lower hazards of prostate cancer (HRs: 0.74 - 0.83). Conclusion: T2D subtypes are associated with distinct patterns of site-specific cancer risk relative to adults without diabetes. Disclosure Z. Li: None. J. Guo: None. J. Varghese: None. Funding Winship Invest$ 2024 pilot grant