Association of the glucose-to-lymphocyte ratio with all-cause and cardiovascular disease mortality in U.S. adults: A population-based cohort study.

BACKGROUND: The Glucose-to-Lymphocyte Ratio (GLR) reflects metabolic-immune status, but its association with mortality in the general population remains unclear. METHODS: We analyzed 22,120 adults from NHANES (1999-2016) with complete data on glucose, lymphocytes and mortality. Associations between log₂-transformed GLR and all-cause or Cardiovascular Disease (CVD) mortality were evaluated using multivariable Cox models. Nonlinear dose-response relationships were assessed with restricted cubic splines, and survival differences visualized with Kaplan-Meier curves. Model performance was compared using ROC curves and DCA for inflammatory markers, while NRI and IDI were calculated based on the Framingham risk model. RESULTS: Higher GLR was associated with older age, comorbidities, and increased mortality over a median follow-up of 122-months. Fully adjusted models showed associations with all-cause (HR = 1.33, 95% CI 1.25-1.42) and CVD mortality (HR = 1.51, 95% CI 1.36-1.66). Dose-response analyses indicated J-shaped curves with exploratory, cohort-specific inflection points at GLR ≈46 (all-cause) and ≈49 (CVD). GLR showed comparable or slightly better discrimination (AUC 67.5%‒67.7%) than individual inflammatory markers. When added to the Framingham model, GLR provided modest improvements in reclassification indices (NRI and IDI). E-values, subgroup and sensitivity analyses, and competing risks models showed the model was robust. CONCLUSION: In this study, elevated GLR was associated with higher all-cause and CVD mortality in a J-shaped manner. While these findings suggest GLR may be a composite metabolic-immune marker worthy of further investigation, its clinical utility remains uncertain and requires external validation.