TyG index is associated with colorectal adenomatous polyps and genetically linked to colon polyps: a cross-sectional and Mendelian randomization study.

Background: The triglyceride-glucose (TyG) index, a simple and validated surrogate marker of insulin resistance, may be clinically relevant to colorectal polyp development because insulin resistance can promote colorectal neoplasia through hyperinsulinemia, chronic inflammation, oxidative stress, and dysregulated insulin-like growth factor signaling. However, the relationship between TyG index and colorectal polyps remains incompletely understood. This study aimed to investigate the association between TyG index and colorectal polyp risk using both observational and genetic approaches. Methods: We conducted a cross-sectional study of 4,263 patients undergoing colonoscopy. Associations between TyG index and colorectal adenomatous polyps were assessed using multivariable logistic regression. A two-sample Mendelian randomization (MR) analysis evaluated potential causal effects, with inverse-variance weighted (IVW) method as primary analysis and multiple sensitivity analyses. Results: Although the crude distribution of colorectal polyps across TyG quartiles did not show a strictly monotonic pattern, participants in different TyG quartiles differed substantially in age, sex distribution, BMI, lifestyle factors, comorbidities, and metabolic profiles. Therefore, multivariable logistic regression was performed to account for potential confounding. Higher TyG index was significantly associated with increased prevalence of colorectal adenomatous polyps after full adjustment (odds ratio [OR] 1.13, 95% CI: 1.01-1.27; P-trend = 0.032). Restricted cubic spline analysis showed no evidence of a nonlinear association between the TyG index and colorectal adenomatous polyp risk (P for nonlinearity = 0.459), supporting the use of a linear model in this dataset. MR analysis supported a observational and potential causal association between genetically predicted TyG index and colon polyps (inverse-variance weighted OR: 1.20, 95% CI: 1.10-1.31; P < 0.001), with consistent results across sensitivity analyses and no evidence of directional pleiotropy (P = 0.884). However, no significant association was found for rectal polyps. Conclusion: Both observational evidence and genetic evidence support a positive association between the TyG index and colon polyps, whereas the MR analysis did not provide evidence for a causal association with rectal polyps. These findings suggest the potential utility of the TyG index in risk stratification and underscore the role of insulin resistance in the pathogenesis of colorectal neoplasia.