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

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-section...

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Main Authors: Ye Wang, Yanping Mao, Tianmei Xu, Lujie Han, Wenxuan Zhang, Wangdi Sun, Jiaxi Xu, Enyan Yu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06439-2
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author Ye Wang
Yanping Mao
Tianmei Xu
Lujie Han
Wenxuan Zhang
Wangdi Sun
Jiaxi Xu
Enyan Yu
author_facet Ye Wang
Yanping Mao
Tianmei Xu
Lujie Han
Wenxuan Zhang
Wangdi Sun
Jiaxi Xu
Enyan Yu
author_sort Ye Wang
collection DOAJ
description 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.
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spelling doaj-art-7adb0fa9ee664228b18bdeed1b72f3a92025-08-20T03:03:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-06439-2A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adultsYe Wang0Yanping Mao1Tianmei Xu2Lujie Han3Wenxuan Zhang4Wangdi Sun5Jiaxi Xu6Enyan Yu7The Second Clinical Medical College of Zhejiang Chinese Medical UniversityDepartment of Psychiatry, Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou Institute of Medicine (HIM)The Second Clinical Medical College of Zhejiang Chinese Medical UniversityCenter for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical CollegeThe Second Clinical Medical College of Zhejiang Chinese Medical UniversityDepartment of Psychiatry, Zhejiang HospitalDepartment of Psychiatry, Tongde Hospital of Zhejiang ProvinceDepartment of Psychiatry, Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou Institute of Medicine (HIM)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.https://doi.org/10.1038/s41598-025-06439-2NHANESGamma-glutamyl transferaseHigh-density lipoproteinGGT/HDL ratioCognitive impairmentDiabetes mellitus
spellingShingle Ye Wang
Yanping Mao
Tianmei Xu
Lujie Han
Wenxuan Zhang
Wangdi Sun
Jiaxi Xu
Enyan Yu
A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
Scientific Reports
NHANES
Gamma-glutamyl transferase
High-density lipoprotein
GGT/HDL ratio
Cognitive impairment
Diabetes mellitus
title A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
title_full A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
title_fullStr A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
title_full_unstemmed A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
title_short A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults
title_sort cross sectional study of the diabetes mediated ggt to hdl ratio and cognitive function in older adults
topic NHANES
Gamma-glutamyl transferase
High-density lipoprotein
GGT/HDL ratio
Cognitive impairment
Diabetes mellitus
url https://doi.org/10.1038/s41598-025-06439-2
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