Sex-specific in the nonlinear associations of hemoglobin glycation index and all-cause mortality in the general US adult population: results from NHANES 1999–2018

BACKGROUND: The hemoglobin glycation index (HGI) and its association with mortality risk in the United States adults remain insufficiently understood. This research explores potential links between HGI levels and all-cause mortality using nationally representative data. METHODS: >The relationship between HGI and mortality was investigated using data from National Health and Nutrition Examination Survey (NHANES) (1999-2018) covering 19,287 U.S. adults. HGI was calculated via linear regression of glycated hemoglobin A1c (HbA1c) on fasting plasma glucose (FPG). The National Death Index was utilized to link mortality outcomes, with tracking continuing through December 31, 2019. To explore sex-specific associations, we utilized weighted Cox regression models with multivariable adjustments, along with restricted cubic splines and segmented Cox analyses. Robustness was confirmed through stratified analyses and sensitivity tests. RESULTS: In U.S. males, HGI showed a U-shaped association with mortality (threshold: -0.131). Below this, lower HGI was protective (hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.42-0.66); above it, higher HGI increased risk (HR 1.34; 95% CI 1.16-1.55). In females, an L-shaped pattern emerged, where higher HGI below the threshold correlated with a decreased likelihood of mortality (HR 0.48; 95% CI 0.40-0.59). These sex-specific associations were verified through stratified and sensitivity analyses. CONCLUSIONS: The cohort study observed a U-shaped pattern between HGI and all-cause mortality in U.S. males, whereas an L-shaped association was found in females. These sex-specific patterns warrant further investigation to explore clinical implications.