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. 2025 Jul 1;15(1):20928.
doi: 10.1038/s41598-025-06439-2.

A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults

Ye Wang  1   2 , Yanping Mao  2 , Tianmei Xu  1 , Lujie Han  3 , Wenxuan Zhang  1 , Wangdi Sun  4 , Jiaxi Xu  5 , Enyan Yu  6
Affiliations

A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults

Ye Wang et al. Sci Rep. .

Abstract

The rising incidence of cognitive disorders has become a significant challenge in global public health. The ratio of Gamma-glutamyl transferase (GGT) to high-density lipoprotein (HDL), associated with insulin resistance, has an unclear relationship with cognitive function. Our cross-sectional study utilized data from the NHANES database, employing the digit symbol substitution test (DSST) to assess cognitive ability. We conducted weighted linear regression, weighted mediation analysis, dose-response relationships, and subgroup analyses to investigate the link between the GGT/HDL ratio and DSST scores, with a particular focus on the mediating role of diabetes. The study included 2750 participants. After adjusting for covariates, we found that a higher GGT/HDL ratio was significantly correlated with lower DSST scores (β = -0.06, 95% CI -0.08 to -0.04, P < 0.001, P for non-linear = 0.169), and diabetes mediated the relationship between the GGT/HDL ratio and DSST scores, accounting for 13.8% of the total effect (P = 0.034). These findings suggest that in the U.S. population aged 60 and above, an increased GGT/HDL ratio is associated with an increased risk of cognitive decline, with diabetes playing a mediating role in this association.

Keywords: Cognitive impairment; Diabetes mellitus; GGT/HDL ratio; Gamma-glutamyl transferase; High-density lipoprotein; NHANES.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Association between GGT/HDL and cognitive performance in DSST. Solid lines and filled ranges indicate predictive values and 95% confidence intervals. Adjusted for age, gender, race, education level, married status, BMI, smoking status, alcohol status, high cholesterol, liver conditions.
Fig. 2
Fig. 2
The mediating effect of diabetes on the relationship between GGT/HDL and DSST in elderly adults.
Fig. 3
Fig. 3
Forest plot showing the subgroup analysis for the association between GGT/HDL and the DSST scores.
Fig. 4
Fig. 4
Flow chart of participant selection.
See this image and copyright information in PMC

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