New onset of type 2 diabetes after colorectal cancer diagnosis: Results from three prospective US cohort studies, systematic review, and meta-analysis

Background Limited data indicate that patients with colorectal cancer (CRC) are at higher risk of developing type 2 diabetes (T2D). We prospectively examined the risk of T2D between individuals with and without CRC in three large cohorts and conducted a meta-analysis.Methods We assessed the diagnosis of CRC and T2D among 111,485 women from the Nurses' Health Study, 112,958 women from the Nurses' Health Study II, and 46,581 men from the Health Professionals Follow-up Study. We used multivariable Cox regression with time-varying covariates to calculate the hazard ratio (HR) of T2D in relation to CRC diagnosis. We further performed a systematic review and meta-analysis of cohort studies.Findings Up to 36 years of follow-up (6.9 million person-years), we documented 3402 incident CRC cases and 26,469 T2D cases. Compared to non-CRC individuals, those with CRC were more likely to develop T2D (multivariable-adjusted HR 1.20, 95% CI 1.05-1.38). The association was most evident for individuals with fewer risk factors for T2D. In the meta-analysis of seven cohort studies (1,061,744 participants), CRC was associated with higher T2D risk (meta-analysis HR 1.21, 95% CI 1.11-1.31, I2 = 57.9%). By CRC duration, a statistically significant association was observed in the first 10 years but not after 10 years of CRC diagnosis (<= 5 years, meta-analysis HR 1.32, 95% CI 1.27-1.36; 5.1-10 years, 1.14 [1.04-1.25]; >10 years, 1.14 [0.91-1.37]).Interpretation CRC was associated with increased T2D risk, especially in the first ten years after CRC diagnosis. Our findings highlight the importance of T2D prevention for CRC survivorship care.Funding NHS cohort infrastructure grant (UM1 CA186107), NHS program project grant that funds cancer research (P01 CA87969), NHS II cohort infrastructure grant (U01 CA176726), HPFS cohort infrastructure grant (U01 CA167552) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-010). Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).