The U-shaped association between the metabolic score for insulin resistance and incident gallstone disease: a population-based cohort study

Background The association between the Metabolic Score for Insulin Resistance (METS-IR) index and incident gallstone disease remains unclear. This study investigated this association using cohort data. Methods A total of 52,723 participants without gallstone disease at baseline were included. Participants were stratified into five groups according to METS-IR quintiles. Multivariable Cox proportional hazards regression models were used to assess the association between METS-IR and the risk of developing gallstone disease. Restricted cubic spline (RCS) was employed to examine the dose-response relationship. Threshold effect analysis was subsequently conducted to identify potential inflection points. Additionally, subgroup and sensitivity analyses were performed to evaluate the robustness and reliability of the findings. Results Over a mean follow-up of 3.13 years, 1,407 incident cases of gallstone disease occurred. Compared to the Q2 group, the risk was significantly higher in Q3 (hazard ratio (HR)=1.29, 95% confidence interval (CI): 1.08–1.54), Q4 (HR = 1.50, 95% CI: 1.25–1.80), and Q5 (HR = 1.85, 95% CI: 1.53–2.25), but not in Q1 (HR = 1.12, 95% CI: 0.93–1.35). A nonlinear U-shaped association was identified, with an inflection point at a METS-IR of 29.83. Below this point, each unit increase in METS-IR was associated with a 2.7% lower risk (HR = 0.973, 95% CI: 0.956–0.991). Above it, each unit increase was associated with a 4.1% higher risk (HR = 1.041, 95% CI: 1.031–1.051). Subgroup and sensitivity analyses confirmed robustness. Conclusions The METS-IR exhibits a nonlinear U-shaped association with the risk of incident gallstone disease. Both lower and higher METS-IR levels, relative to the identified inflection point, are associated with an elevated risk of incident gallstone disease.