Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

Aim: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes.
Methods: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model.
Results: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI.
Conclusions: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.
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