Introduction and Objective: Increasing evidence suggests that prediabetes may be associated with an increased cancer risk. We determined whether distinct prediabetes subphenotypes differ in their tumor profiles. Methods: A total of 2,260 participants without diabetes from the Malmö Diet and Cancer cohort study, aged 61-85 years, were assigned to the six established Tübingen prediabetes clusters and followed up for a median duration of 10.6 years. Overall survival and diabetes incidence were analyzed using Cox proportional hazards models, overall and site-specific tumor prevalence and incidence using log-binomial regression models. Cluster 2 served as the reference and adjustments were made for age and sex. Results: Cluster assignment was associated with differential risks for tumor outcomes, mortality, and diabetes incidence. Cluster 4 (overweight, metabolically healthy) showed an increased risk of uterine tumors including cervix and endometrium (RR 5.17, 95% CI 1.32-20.29, p-value 0.02). Cluster 5 (obese, insulin-resistant with fatty liver) was associated with elevated pancreatic cancer risk (RR 16.23, 2.8-94.12, 0.002, median time-to-event 6.1 years, range 2.2-8.7 years), increased mortality (HR 1.47, 1.09-1.98, 0.01), and higher incidence of diabetes (HR 13.48 7.29-24.9, 0.001). Cluster 6 (obese, insulin-resistant with kidney disease) showed higher overall tumor prevalence (RR 1.45, 1.07-1.91, 0.01), particularly for uterine (RR 2.59, 1.58-4.02, 0.001) and kidney tumors (RR 6.25, 1.17-33.46, 0.03) and diabetes incidence (HR 5.84, 2.78-12.28, 0.001). Conclusion: Distinct prediabetes subphenotypes show different risk profiles for diabetes, tumors and mortality. Specifically, clusters 4, 5, and 6 show an increased risk for uterine, pancreatic, and renal tumors. The clustering of individuals with prediabetes may allow targeted tumor screening and earlier intervention, potentially improving long-term outcomes. Disclosure J. Seigner: None. S. Hülskämper: None. C. Hoffmann: Other - External Research Fellow in a Graduate Program; Ended; Boehringer Ingelheim International GmbH. R. Wagner: Advisory Panel; Current; Sanofi. Speaker's Bureau; Ended; Daiichi Sankyo, Novo Nordisk. K. Prystupa: None. O. Melander: None. A. Fritsche: None. A.L. Birkenfeld: None.
Seigner et al. (Fri,) studied this question.