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      Analysis of the relationship between sleep-related disorders and cadmium in the US population

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          Abstract

          Background

          Cadmium is a heavy metal that accumulates in the body due to environmental and occupational exposure. The neurotoxicity of cadmium received increasingly attention in recent years. Sleeping is regulated and coordinated by nervous system, however, little is known about the relationship between cadmium and sleep. This study aimed to examine the relationship between blood cadmium concentrations and sleep-related disorders in US adults.

          Methods

          This cross-sectional study used data on blood cadmium and sleep from the 2005–2008 and 2015–2020 National Health and Nutrition Examination Survey (NHANES). Weighted multiple regression, generalized weighted modeling, and weighted restricted cubic splines (RCS) were utilized to investigate the association between blood cadmium and sleep outcomes (sleep duration, trouble sleeping, symptoms of obstructive sleep apnea (OSA) and daytime sleepiness). Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, gender, ethnicity, education level, marital status, smoking status, alcohol consumption, diabetes mellitus (DM), cardiovascular disease (CVD) and hypertension groups.

          Results

          In 19,152 participants, the median blood cadmium concentration was 0.48 (IQR: 0.28, 0.82)μg/L. Compared with the lowest reference quartile, participants in the higher quartile had a significantly higher risk of insufficient sleeping (<7 h/night) in crude model (OR 1.53, 95% CI 1.33–1.74), Model 1 (OR 1.57, 95% CI 1.38–1.80) and Model 2 (OR 1.45, 95% CI 1.27–1.65). In the unadjusted model, individuals in the highest quartile of cadmium level had a significantly increased risk of OSA symptoms of 53% (OR = 1.53, 95% CI: 1.42, 1.65) compared with participants in the bottom quartile, and this risk increased by 35% (OR = 1.35, 95% CI: 1.23, 1.48) after adjusting for all covariates. Individuals in the highest quartile of cadmium level were 76% more likely to have a trouble sleeping than individuals in the lowest quartile in the unadjusted model (OR = 1.76, 95% CI: 1.31, 1.93), whereas in the fully adjusted model, this likelihood was 86% higher (OR = 1.86, 95% CI: 1.51, 1.96). A similar positive correlation was also observed for cadmium level and daytime sleepiness. However, no relationship was noted between cadmium and excessive sleep duration (≥9 h). A linear dose–response relationship was found between cadmium concentration and the risk of insufficient sleeping (P non-linearity = 0.321), OSA symptoms (P non-linearity = 0.176), trouble sleeping (P non-linearity = 0.682) and daytime sleepiness (P non-linearity = 0.565). Additionally, no significant interactions between cadmium concentrations and subgroup variables were identified (P for interaction>0.05).

          Conclusion

          Insufficient sleep, symptoms of OSA, trouble sleeping and daytime sleepiness were found to have a positive association with the blood cadmium concentration in US adults. However, further prospective studies are necessary to establish whether there is a causal relationship between these factors.

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          Most cited references41

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          National Sleep Foundation’s updated sleep duration recommendations: final report

          To make scientifically sound and practical recommendations for daily sleep duration across the life span.
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            A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment.

            The rational for the study was to review the literature on the toxicity and corresponding mechanisms associated with lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As), individually and as mixtures, in the environment. Heavy metals are ubiquitous and generally persist in the environment, enabling them to biomagnify in the food chain. Living systems most often interact with a cocktail of heavy metals in the environment. Heavy metal exposure to biological systems may lead to oxidation stress which may induce DNA damage, protein modification, lipid peroxidation, and others. In this review, the major mechanism associated with toxicities of individual metals was the generation of reactive oxygen species (ROS). Additionally, toxicities were expressed through depletion of glutathione and bonding to sulfhydryl groups of proteins. Interestingly, a metal like Pb becomes toxic to organisms through the depletion of antioxidants while Cd indirectly generates ROS by its ability to replace iron and copper. ROS generated through exposure to arsenic were associated with many modes of action, and heavy metal mixtures were found to have varied effects on organisms. Many models based on concentration addition (CA) and independent action (IA) have been introduced to help predict toxicities and mechanisms associated with metal mixtures. An integrated model which combines CA and IA was further proposed for evaluating toxicities of non-interactive mixtures. In cases where there are molecular interactions, the toxicogenomic approach was used to predict toxicities. The high-throughput toxicogenomics combines studies in genetics, genome-scale expression, cell and tissue expression, metabolite profiling, and bioinformatics.
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              Cadmium, Environmental Exposure, and Health Outcomes

              Objectives We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food. Data sources We reviewed epidemiologic studies published between 2004 and 2009 concerning the bioavailability of cadmium in food, assessment of exposure, and body burden estimate, along with exposure-related effects in nonoccupationally exposed populations. Data extraction and synthesis Bioavailability of ingested cadmium has been confirmed in studies of persons with elevated dietary exposure, and the findings have been strengthened by the substantial amounts of cadmium accumulated in kidneys, eyes, and other tissues and organs of environmentally exposed individuals. We hypothesized that such accumulation results from the efficient absorption and systemic transport of cadmium, employing multiple transporters that are used for the body’s acquisition of calcium, iron, zinc, and manganese. Adverse effects of cadmium on kidney and bone have been observed in environmentally exposed populations at frequencies higher than those predicted from models of exposure. Increasing evidence implicates cadmium in the risk of diseases that involve other tissues and organ systems at cadmium concentrations that do not produce effects on bone or renal function. Conclusions Population data raise concerns about the validity of the current safe intake level that uses the kidney as the sole target in assessing the health risk from ingested cadmium. The data also question the validity of incorporating the default 5% absorption rate in the threshold-type risk assessment model, known as the provisional tolerable weekly intake (PTWI), to derive a safe intake level for cadmium.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2796774/overviewRole: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2829788/overviewRole: Role: Role: Role: Role: Role:
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                25 October 2024
                2024
                : 12
                : 1476383
                Affiliations
                Key Laboratory of Respiratory Disease of Ningbo, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University , Zhejiang, China
                Author notes

                Edited by: Fabrizio Bianchi, National Research Council (CNR), Italy

                Reviewed by: Natasa Krsto Rancic, University of Nis, Serbia

                Nadia Mahmoud Tawfiq Jebril, University of Babylon, Iraq

                *Correspondence: Chao Cao, dyyycaochao@ 123456163.com
                Article
                10.3389/fpubh.2024.1476383
                11544537
                ae82eb7c-a9a3-42a9-9b6a-1d54f5efbff2
                Copyright © 2024 Luo, Zhu, Xiong, Qiu and Cao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 August 2024
                : 17 October 2024
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 42, Pages: 12, Words: 7762
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Zhejiang Pronvincial Medical and Health Science and Technology Plan (Grant No. 2024KY1537) and the fourth Ningbo health youth technical backbone personnel training program.
                Categories
                Public Health
                Original Research
                Custom metadata
                Environmental Health and Exposome

                cadmium,sleep-related disorder,obstructive sleep apnea,daytime sleepiness,trouble sleeping,sleep duration,nhanes

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