2444-P: Role of Insulin Deficiency and Insulin Resistance in Cancer Incidence

Introduction and Objective: Although insulin resistance (IR) is a known risk factor for cancer incidence and progression in the general population, whether IR and insulin deficiency (ID) among individuals with diabetes are associated with cancer incidence and mortality is less understood. Methods: Among adults (≥18years) with diabetes and no history of cancer in pooled U.S. cohorts (n = 3944; 65.6 years [SD: 10.0], 55% female), we identified the earliest visit where fasting glucose and insulin were measured and studied time to cancer incidence using Cox regression. Homeostatic indices for IR [HOMA-IR] and β-cell function [HOMA-B]) were used to categorize participants into Mild (11.7%), IR dominant (46.7%), ID dominant (19.6%), and IR + ID dominant (22.0%) phenotypes. Findings were validated using NHANES 1999-2018 linked to cause-specific mortality among participants with diabetes (n = 3777) and cancer (n = 2044). Results: In pooled community cohorts, rates of incident cancer were similar across insulin phenotypes relative to the Mild phenotype (Panel A; Panel D): IR dominant (HR 1.16 [95% CI 0.84-1.59]), ID dominant (HR 0.92 [95% CI 0.63-1.33]), and IR + ID dominant (HR 1.13 [95% CI 0.78-1.63]). In NHANES, associations were null for cancer mortality among diabetes cases (Panel B; Panel D). However, cancer mortality among cancer cases was lower among the ID dominant (HR 0.66 [95% CI 0.47-0.94]) (Panel C; Panel D). Conclusion: IR and ID phenotypes did not differ in cancer risk and mortality among individuals with diabetes. Disclosure D. Hua: None. T. Hung: None. R.N. Ekanayake: None. Z. Li: None. J. Guo: None. J. Varghese: None. Funding Winship Invest$ Pilot Program