Abstract
BACKGROUND: While the triglyceride-glucose (TyG) index and related indices have been recognized as markers of insulin resistance and cardiometabolic disorders, few studies have examined their association with all-cause mortality in individuals with depression. This study aimed to investigate the relationship between the TyG index, its related indices, and all-cause mortality among patients with depression in the United States. METHODS: A total of 3,179 patients with depression were identified from the National Health and Nutrition Examination Survey (NHANES, 2005-2018). Participants were categorized into tertiles (T1, T2, T3) based on the TyG index and its derived indices: TyG combined with body mass index (TyG-BMI), waist circumference (TyG-WC), and waist-to-height ratio (TyG-WHtR). Cox regression analysis and Kaplan-Meier curve analysis were used to explore the relationship between the independent variable TyG and its derived indicators and the dependent variable all-cause mortality.Curve fitting and threshold effect analyses were performed to evaluate potential nonlinear or dose-response relationships. Subgroup and sensitivity analyses were conducted to validate the robustness of the results. RESULTS: Over a 13-year follow-up period, both the lowest and highest tertiles of the TyG index and its related indices were associated with significantly increased risks of all-cause mortality compared to the middle tertile. Restricted cubic spline analysis revealed U-shaped nonlinear relationships between these indices and all-cause mortality, with distinct threshold effects. Among the indices, TyG-BMI and TyG-WC demonstrated the strongest associations, though similar trends were observed for the other TyG-related indices. CONCLUSION: This study identified nonlinear associations between the TyG index and its related indices (TyG-BMI, TyG-WC, TyG-WHtR) and all-cause mortality in patients with depression, with clear threshold effects. These findings highlight the potential utility of stratified risk assessment and targeted interventions based on these thresholds.