ArticleFrontiers in endocrinology2026
Association of four non-insulin-based insulin resistance surrogate markers with colorectal cancer risk: a large-scale prospective cohort study using the UK Biobank.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Colorectal cancer (CRC) remains a persistent global health challenge, with a rising incidence strongly linked to metabolic dysfunction. Insulin resistance (IR), a hallmark of metabolic dysregulation, is a well-established driver of tumorigenesis and cancer progression. However, the relative predictive value of distinct non-insulin-based surrogate markers of IR for CRC risk assessment remains poorly defined. Methods: This prospective study analyzed data from 385,206 participants in the UK Biobank. Non-insulin-based surrogate markers evaluated included the TyG index, TyG-BMI, the TG/HDL-C ratio, and METS-IR. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC. Restricted cubic splines (RCS) assessed dose-response relationships. Incremental predictive value and clinical utility were evaluated via C-index increments and decision curve analysis (DCA). Robustness was verified through extensive subgroup and sensitivity analyses. Results: Over a median follow-up of 13.8 years, 5,175 incident CRC cases were documented. All four IR surrogates were independently and positively associated with CRC risk (all Conclusions: Elevated non-insulin-based IR surrogates are robust predictors of CRC risk. The BMI-integrated indices, METS-IR and TyG-BMI, demonstrated superior risk stratification performance. These low-cost, readily available tools may facilitate the early identification of high-risk individuals and inform evidence-based primary prevention strategies.
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