Estimated Glucose Disposal Rate and Mortality in Cardiovascular Kidney Metabolic Syndrome: Nonlinear Associations and Stratified Prognostic Significance by Glycometabolic Phenotypes

Background The correlation between estimated glucose disposal rate (eGDR), a novel metric for assessing the body's glucose handling capacity, and the prognosis of patients with cardiovascular kidney metabolic syndrome (CKM) has not yet been clarified, and its clinical relevance in different glucose metabolic states still needs to be validated. Methods This is a cohort study based on data from participants diagnosed with CKM in the National Health and Nutrition Examination Survey (NHANES 1999–2018). A weighted Cox proportional risk model combined with restricted cubic spline (RCS) analysis was used to systematically assess the association between eGDR levels and the prognosis of patients with CKM and to explore the dose-response relationship. The pattern of association between eGDR level and mortality among different subgroups was clarified by stratified analysis. The subject Receiver Operating Characteristic (ROC) curve was further applied to compare the predictive efficacy of eGDR with traditional insulin resistance indices (Triglyceride Glucose Index TyG, Homeostasis Modelling Assessment of Insulin Resistance Index HOMA-IR) for mortality risk. Results Cox regression analysis demonstrated that in the overall CKM population, eGDR levels showed significant associations with both all-cause mortality and cause-specific mortality (all p  < 0.05). RCS analysis further revealed nonlinear associations between eGDR and all-cause mortality ( p for non-linear = 0.041) as well as diabetes-specific mortality ( p for non-linear = 0.003), while a linear relationship was observed with cardiovascular-specific mortality ( p for non-linear = 0.278), all demonstrating overall significance ( p  < 0.001). Stratified analysis indicated: in the diabetes mellitus (DM) subgroup, eGDR was significantly associated with all-cause mortality; in the Pre-diabetes mellitus (Pre-DM) subgroup, eGDR correlated with cardiovascular-specific mortality risk; and in the normal glucose regulation (NGR) subgroup, eGDR exhibited concurrent associations with all-cause, cardiovascular, and diabetes-specific mortality (all p  < 0.05). Notably, ROC curve analysis suggested superior predictive performance of eGDR for mortality risk compared to TyG index and HOMA-IR in both the overall CKM population and the normal glucose tolerance subgroup. Conclusion In the CKM patient population, eGDR levels were significantly and negatively associated with the risk of all-cause and cause-specific mortality (all p  < 0.05), and the protective effect of high eGDR was consistent across subgroups of glucose metabolic status (DM, Pre-DM, and NGR).