Short- and long-term associations of insulin resistance indices with cardiovascular–kidney–metabolic syndrome risk: a retrospective cohort study
TL;DR
The METS-IR, TyG-BMI, and SPISE showed robust nonlinear associations with CKM syndrome risk and were stronger in males, supporting their potential value in sex-tailored risk assessment.
Abstract
Background Insulin resistance (IR) is a key driver of cardiovascular–kidney–metabolic (CKM) syndrome. This study evaluated the independent associations of three novel IR surrogate indices—the Metabolic Score for Insulin Resistance (METS–IR), Triglyceride–Glucose–Body Mass Index (TyG–BMI), and Single Point Insulin Sensitivity Estimator (SPISE)—with CKM syndrome risk and compared their predictive performance for short- and long-term outcomes. Methods This retrospective cohort study included 12,334 Chinese adults aged ≥20 years enrolled between 2015 and 2019. Multivariable logistic regression and restricted cubic splines were used for association assessment, while area under the receiver operating characteristic curve (AUROC) analysis was used to evaluate predictive accuracy. Subgroup analyses were performed for age, sex, and BMI. Results Analysis of 1- and 5-year follow-up outcomes revealed that the METS–IR and TyG–BMI were positively associated with CKM syndrome, whereas SPISE showed an inverse association (all p < 0.001). All indices exhibited nonlinear dose–response relationships. Adding each IR index separately to the base model improved discrimination: 1-year AUROC increased from 0.681 to 0.710–0.712 and 5-year AUROC from 0.719 to 0.737–0.741 (all p < 0.001). SPISE achieved the highest AUROC at both time points, pairwise comparisons with the other indices showed statistically significant differences of 0.002–0.003 (all p ≤ 0.033). Subgroup analyses indicated stronger associations in males and participants aged <40 years for short-term risk, with sex-specific effect modification for long-term outcomes. Conclusion The METS-IR, TyG-BMI, and SPISE showed robust nonlinear associations with CKM syndrome risk. Their overall discriminatory performance was broadly comparable, with SPISE showing a marginal advantage. The associations were stronger in males, supporting their potential value in sex-tailored risk assessment.