Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes

BackgroundType 2 diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Zinc deficiency contributes to T2DM development, while copper may exacerbate diabetes through prooxidant mechanisms. Higher zinc levels may protect against copper toxicity. This study investigates the as...

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Main Authors: Yang Jiao, Xing Zhang, Lian Duan, Ruijie Cheng, Ning Yang, Zhao Peng, Ben Li, Lu Xu, Wenwen Chen, Jingrong Chen, Yanchao Liu, Hong Yan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2025.1532080/full
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author Yang Jiao
Xing Zhang
Lian Duan
Ruijie Cheng
Ning Yang
Zhao Peng
Ben Li
Ben Li
Lu Xu
Wenwen Chen
Jingrong Chen
Yanchao Liu
Hong Yan
author_facet Yang Jiao
Xing Zhang
Lian Duan
Ruijie Cheng
Ning Yang
Zhao Peng
Ben Li
Ben Li
Lu Xu
Wenwen Chen
Jingrong Chen
Yanchao Liu
Hong Yan
author_sort Yang Jiao
collection DOAJ
description BackgroundType 2 diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Zinc deficiency contributes to T2DM development, while copper may exacerbate diabetes through prooxidant mechanisms. Higher zinc levels may protect against copper toxicity. This study investigates the association of plasma zinc and copper levels with mild cognitive impairment (MCI) in T2DM patients.MethodsT2DM patients admitted to Tongji Hospital from 2012 to 2018 were classified into MCI (n = 136) and control (n = 136) groups, matched by age (± 3 years) and gender. Conditional logistic regression was used to assess the associations between plasma zinc, copper levels and MCI. A generalized additive model (GAM) evaluated the dose–response relationship between plasma zinc, copper levels and Mini-Mental State Examination (MMSE) scores.ResultsThe median of plasma metal levels in MCI and control groups were 831.31 μg/L and 936.29 μg/L for zinc, 932.07 μg/L and 860.47 μg/L for copper, and 0.91 and 1.11 for the zinc-to-copper (Zn/Cu) ratio. Compared to participants in the lowest tertile, the multivariable-adjusted odds ratios with 95% confidence intervals (CI) for MCI in the highest tertile were 0.33 (0.13, 0.79) for zinc, 3.56 (1.42, 8.94) for copper, and 0.37 (0.15, 0.93) for the Zn/Cu ratio. Plasma Aβ40 levels were significantly lower (p = 0.009) and plasma Aβ42/40 levels were significantly higher (p = 0.008) in MCI group compared with those in control group. Zinc concentration was positively associated with Aβ42. For per SD (327.71 μg/L) increase in plasma zinc levels, the percent change (95% CI) of Aβ42 were 2.90 (0.85, 4.99).ConclusionHigher plasma zinc levels and higher Zn/Cu ratio were associated with lower odds of MCI in T2DM patients, while higher copper levels increased the risk of MCI. This study provides insights on plasma zinc, copper, and Zn/Cu ratio and Aβ of MCI, further studies are needed to clarify the underlying mechanisms for novel therapies that could prevent or cure multiple T2DM-related cognitive impairments.
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spelling doaj-art-5484ed89f44841e89be159c5a02aae702025-08-20T02:47:37ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-03-011210.3389/fnut.2025.15320801532080Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetesYang Jiao0Xing Zhang1Lian Duan2Ruijie Cheng3Ning Yang4Zhao Peng5Ben Li6Ben Li7Lu Xu8Wenwen Chen9Jingrong Chen10Yanchao Liu11Hong Yan12Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaChangsha Institute for Food and Drug Control, Changsha, ChinaXiangyang Public Inspection and Testing Center, Xiangyang, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackgroundType 2 diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Zinc deficiency contributes to T2DM development, while copper may exacerbate diabetes through prooxidant mechanisms. Higher zinc levels may protect against copper toxicity. This study investigates the association of plasma zinc and copper levels with mild cognitive impairment (MCI) in T2DM patients.MethodsT2DM patients admitted to Tongji Hospital from 2012 to 2018 were classified into MCI (n = 136) and control (n = 136) groups, matched by age (± 3 years) and gender. Conditional logistic regression was used to assess the associations between plasma zinc, copper levels and MCI. A generalized additive model (GAM) evaluated the dose–response relationship between plasma zinc, copper levels and Mini-Mental State Examination (MMSE) scores.ResultsThe median of plasma metal levels in MCI and control groups were 831.31 μg/L and 936.29 μg/L for zinc, 932.07 μg/L and 860.47 μg/L for copper, and 0.91 and 1.11 for the zinc-to-copper (Zn/Cu) ratio. Compared to participants in the lowest tertile, the multivariable-adjusted odds ratios with 95% confidence intervals (CI) for MCI in the highest tertile were 0.33 (0.13, 0.79) for zinc, 3.56 (1.42, 8.94) for copper, and 0.37 (0.15, 0.93) for the Zn/Cu ratio. Plasma Aβ40 levels were significantly lower (p = 0.009) and plasma Aβ42/40 levels were significantly higher (p = 0.008) in MCI group compared with those in control group. Zinc concentration was positively associated with Aβ42. For per SD (327.71 μg/L) increase in plasma zinc levels, the percent change (95% CI) of Aβ42 were 2.90 (0.85, 4.99).ConclusionHigher plasma zinc levels and higher Zn/Cu ratio were associated with lower odds of MCI in T2DM patients, while higher copper levels increased the risk of MCI. This study provides insights on plasma zinc, copper, and Zn/Cu ratio and Aβ of MCI, further studies are needed to clarify the underlying mechanisms for novel therapies that could prevent or cure multiple T2DM-related cognitive impairments.https://www.frontiersin.org/articles/10.3389/fnut.2025.1532080/fulltype 2 diabetes mellituszinccoppermild cognitive impairmentcase-control study
spellingShingle Yang Jiao
Xing Zhang
Lian Duan
Ruijie Cheng
Ning Yang
Zhao Peng
Ben Li
Ben Li
Lu Xu
Wenwen Chen
Jingrong Chen
Yanchao Liu
Hong Yan
Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
Frontiers in Nutrition
type 2 diabetes mellitus
zinc
copper
mild cognitive impairment
case-control study
title Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
title_full Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
title_fullStr Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
title_full_unstemmed Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
title_short Association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
title_sort association of plasma zinc and copper levels with mild cognitive impairment in patients with type 2 diabetes
topic type 2 diabetes mellitus
zinc
copper
mild cognitive impairment
case-control study
url https://www.frontiersin.org/articles/10.3389/fnut.2025.1532080/full
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