Different Insulin Resistance Surrogates and Risk of All-Cause and Cardiovascular Mortality among Adults with Metabolic Syndrome-Like Characteristics: Evidence from NHANES 1999–2018 – A Cohort Study

Background: We investigated the predictive effects of four insulin resistance (IR) surrogate indices, namely homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-glucose (TyG), metabolic score of insulin resistance (METS-IR), and estimated glucose disposal rate (eGDR), on the risk of death in adults with metabolic syndrome-like characteristics. Methods: We selected 11,841 individuals with metabolic syndrome-like characteristics from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Tthe relationships between various IR surrogates and mortality were assessed through Cox proportional hazards regression. Results: Over a median follow-up period of 123 months, there were 1,742 cases of all-cause mortality and 479 instances of cardiovascular mortality. Compared with patients with eGDR ≤ 6.30, there was a significantly lower risk of all-cause mortality in the second, third and highest eGDR quartiles (adjusted hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.68–0.95, P = 0.010; adjusted HR: 0.68, 95% CI: 0.55–0.85, P < 0.001; adjusted HR: 0.62, 95% CI: 0.46–0.84, P = 0.002, respectively; P for trend < 0.001). The eGDR showed a stronger correlation with all-cause mortality than HOMA-IR, TyG, and METS-IR, particularly among individuals under 60 years old. Notably, the relationship between eGDR and mortality showed a significant interaction with age ( P for interaction < 0.001). Survival analysis further corroborated this discrepancy. Conclusions: The eGDR exhibited a more pronounced association with all-cause mortality among US adults presenting with metabolic syndrome-like characteristics, in comparison to the other three indices, particularly among individuals younger than 60 years.