Insulin Resistance Markers Predict New-Onset Diabetes in Middle-Aged and Elderly Adults with Cardiovascular-Kidney-Metabolic Syndrome

Abstract

Objective

Insulin resistance (IR) is central to cardiovascular–kidney–metabolic (CKM) syndrome, but the best IR-related marker for identifying CKM patients at high risk of diabetes remains uncertain. This study examined associations between IR-related markers and new-onset diabetes and compared their predictive performance.

Methods

We analyzed 6,307 CKM participants from the China Health and Retirement Longitudinal Study (CHARLS) and 6,388 from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and restricted cubic spline analyses were used to assess associations of triglyceride-glucose (TyG), TyG-body mass index (TyG-BMI), TyG-waist-to-height ratio (TyG-WHtR), metabolic score for IR (METS-IR), and estimated glucose disposal rate (eGDR) with diabetes. Subgroup analyses and receiver operating characteristic curves were employed to evaluate robustness and discrimination.

Results

Over 7 years, diabetes developed in 736 CHARLS participants (11.67%) and 1,451 NHANES participants (22.71%). Five IR-related markers were significantly associated with the risk of diabetes and demonstrated good predictive performance. Elevated levels of TyG, TyG-BMI, TyG-WHtR, and METS-IR, as well as lower levels of eGDR, were associated with increased diabetes risk (all P < 0.001). Most associations remained robust across subgroup analyses. Among the five markers, eGDR demonstrated the highest predictive performance in the NHANES cohort (AUC: 0.789; 95% CI: 0.776–0.802) and showed favorable predictive ability in the CHARLS cohort.

Conclusion

IR-related markers are significantly associated with the risk of diabetes in individuals with CKM syndrome and serve as reliable predictors of new-onset diabetes. Among these indicators, eGDR and TyG-WHtR were relatively reliable predictors, highlighting their potential as valuable tools for early diabetes screening.

Keywords

Insulin resistance / Estimated glucose disposal rate (eGDR) / Cardiovascular-Kidney-Metabolic syndrome / China Health and Retirement Longitudinal Study (CHARLS) / National Health and Nutrition Examination Survey (NHANES) / Predictive performance

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Funding

Medical Research Fund of Shenzhen Medical Academy of Research and Translation(C2301004)

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The Author(s), under exclusive licence to the Huazhong University of Science and Technology