Objective: Diabetes presenting at younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes (T2DM) onset with subsequent cancer incidence.

Research Design and Methods: The prospective population-based longitudinal cohort included 428,568 new-onset T2DM patients from 2011 to 2018. Participants were divided into four groups according to their T2DM onset age: 20-54, 55-64, 65-74, ≥75. The incidence of overall and 14 site-specific cancers was compared to the general population (100,649,346 person-years). A two-sample Mendelian randomization (MR) based on data from the UK Biobank, Pan-Cancer and FinnGen was used to explore the potential causality from age of diabetes onset to 13 cancers.

Results: A total of 18,853 and 582,643 cancer cases were reported in the cohort and general population. The age-standardized rate of overall cancer was 500.93/100,000 person-years and standardized incidence ratio (SIR) was 1.10 (95% CI: 1.09-1.12) in T2DM patients. With T2DM onset age from <55 to ≥75, the SIRs of overall cancer were 1.48 (95% CI: 1.41-1.54) to 0.86 (95% CI: 0.84-0.89). Similar trends were detected in site-specific cancers and both males and females. The meta-analysis of MR results from Pan-Cancer and FinnGen showed a putative causal effect of earlier age of diabetes onset on increased overall cancer risk (OR: 0.93, 95% CI: 0.86-0.99), lymphoma, and liver cancer.

Conclusions: Our findings showed the earlier age of T2DM onset was associated with higher risk of subsequent cancers, which highlighted the necessity of stratifying management for T2DM according to the onset age.

Key words: Type 2 diabetes mellitus, Age of diabetes onset, Cancer incidence, Mendelian Randomization Analysis

Disclosure

J. Tian: None. T. Hou: None. J. Chalmers: None.

Funding

Shanghai Foundation of National Facility for Translational Medicine (TMSK-2021-506); Three-Year Action Plan of Shanghai Public Health (GWV-7)

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