The U-shaped association between the metabolic score for insulin resistance and incident gallstone disease: a...

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.

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.

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.

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.