METS-IR, TyG-BMI, and SPISE showed robust nonlinear associations with CKM syndrome risk, with broadly comparable discriminatory performance and SPISE showing a marginal advantage, and associations were stronger in males.
METS-IR and TyG-BMI were positively associated with CKM syndrome risk, while SPISE showed an inverse association at both 1- and 5-year follow-up.
All three insulin resistance indices exhibited nonlinear dose-response relationships with CKM syndrome risk.
Adding each IR index to the base model significantly improved discrimination for both short- and long-term CKM syndrome prediction.
SPISE achieved the highest AUROC at both 1-year and 5-year time points, showing a statistically significant but marginal advantage over the other indices.
Subgroup analyses indicated stronger associations between IR indices and CKM syndrome in males and in participants aged under 40 years for short-term risk.
The study cohort consisted of 12,334 Chinese adults enrolled in a retrospective design spanning 2015 to 2019.
This research suggests that three different measures of insulin resistance — METS-IR, TyG-BMI, and SPISE — are all meaningfully linked to the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome, a cluster of interconnected conditions affecting the heart, kidneys, and metabolism. The study followed over 12,000 Chinese adults for up to five years and found that higher insulin resistance (as measured by METS-IR and TyG-BMI) was associated with greater CKM syndrome risk, while higher SPISE scores — which reflect better insulin sensitivity — were associated with lower risk. Importantly, these relationships were not simple straight-line associations but followed more complex curved patterns. All three indices improved the ability to predict who would develop CKM syndrome beyond standard clinical information alone, with accuracy improving for both one-year and five-year predictions. While their overall predictive performance was similar, SPISE had a slight statistical edge. The associations were notably stronger in men and in adults under 40, suggesting these indices may be especially useful for identifying younger males at elevated risk. This research suggests that simple, calculated indices of insulin resistance — which can be derived from routine blood tests and body measurements without invasive procedures — could serve as practical tools for identifying people at risk of CKM syndrome earlier, particularly in populations where measuring insulin directly is not feasible. The findings also highlight that risk assessment tools may need to be tailored by sex and age to be most effective.
Luo H, Wang X, Zhang C, He J, Sun M, Yang Y, et al.. (2026). Short- and long-term associations of insulin resistance indices with cardiovascular-kidney-metabolic syndrome risk: a retrospective cohort study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1917797