Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study

Abstract Background We investigated the association between sleep problems and cardiometabolic risks and the potential linking effect of metabolites and metabolic pathways based on multi-layered research, including observational, mendelian randomization (MR), and metabolomics analysis. Methods A cro...

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Main Authors: Mingcong Chen, Yuzhen Ouyang, Yang Yang, Zihao Liu, Mingyi Zhao
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-024-01505-7
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author Mingcong Chen
Yuzhen Ouyang
Yang Yang
Zihao Liu
Mingyi Zhao
author_facet Mingcong Chen
Yuzhen Ouyang
Yang Yang
Zihao Liu
Mingyi Zhao
author_sort Mingcong Chen
collection DOAJ
description Abstract Background We investigated the association between sleep problems and cardiometabolic risks and the potential linking effect of metabolites and metabolic pathways based on multi-layered research, including observational, mendelian randomization (MR), and metabolomics analysis. Methods A cross-sectional analysis of the 2015–2018 National Health and Nutrition Examination Survey (NHANES) dataset was conducted to identify the association between sleep problems and cardiometabolic risks. A subsequent MR study based on genetic data was performed to explore the causal correlation of significant associations in the NHANES study. The underlying alteration of metabolism was explored by constructing zebrafish models and wide-targeted metabolomics analysis. Results The cross-sectional analysis of the NHANES database revealed a significant association of snoring with obesity [OR = 2.65, 95% confidence intervals (CI): 1.87, 3.74]; sleep apnea with hypertension (OR = 1.68, 95% CI: 1.14, 2.48) and obesity (OR = 1.44, 95% CI: 1.05, 1.96); trouble sleeping with hypertension (OR = 1.84, 95% CI: 1.18, 2.86), obesity (OR = 1.56, 95% CI: 1.07, 2.26), and type 2 diabetes (T2DM) (OR = 1.52, 95% CI: 1.02, 2.25). MR analysis verified the causal relationship between genetically proxied sleep apnea or snoring and obesity. The decreased activity levels and altered expression levels of six circadian genes (bmal1b, cry1aa, cry1ab, clock1a, per1b, per2) were identified in the zebrafish of the sleep disorder group. Multiple metabolites related to disturbed glucose metabolism (e.g., 20-HETE), lipid metabolism (e.g., inosine), and vascular-related metabolites (e.g., riboflavin) were finally identified, indicating the latent effect of metabolism. Conclusions This study identified the chain of sleep-circadian rhythm-metabolism-cardiometabolic risks. These findings can promote improved prevention implementation and therapeutic strategies.
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spelling doaj-art-9a011bb56687485cb7ccea6ae39b20e52024-11-17T12:39:19ZengBMCDiabetology & Metabolic Syndrome1758-59962024-11-0116111310.1186/s13098-024-01505-7Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics studyMingcong Chen0Yuzhen Ouyang1Yang Yang2Zihao Liu3Mingyi Zhao4Department of Pediatrics, The Third Xiangya Hospital, Central South UniversityDepartment of Pediatrics, The Third Xiangya Hospital, Central South UniversityDepartment of Pediatrics, The Third Xiangya Hospital, Central South UniversityDepartment of Pediatrics, The Third Xiangya Hospital, Central South UniversityDepartment of Pediatrics, The Third Xiangya Hospital, Central South UniversityAbstract Background We investigated the association between sleep problems and cardiometabolic risks and the potential linking effect of metabolites and metabolic pathways based on multi-layered research, including observational, mendelian randomization (MR), and metabolomics analysis. Methods A cross-sectional analysis of the 2015–2018 National Health and Nutrition Examination Survey (NHANES) dataset was conducted to identify the association between sleep problems and cardiometabolic risks. A subsequent MR study based on genetic data was performed to explore the causal correlation of significant associations in the NHANES study. The underlying alteration of metabolism was explored by constructing zebrafish models and wide-targeted metabolomics analysis. Results The cross-sectional analysis of the NHANES database revealed a significant association of snoring with obesity [OR = 2.65, 95% confidence intervals (CI): 1.87, 3.74]; sleep apnea with hypertension (OR = 1.68, 95% CI: 1.14, 2.48) and obesity (OR = 1.44, 95% CI: 1.05, 1.96); trouble sleeping with hypertension (OR = 1.84, 95% CI: 1.18, 2.86), obesity (OR = 1.56, 95% CI: 1.07, 2.26), and type 2 diabetes (T2DM) (OR = 1.52, 95% CI: 1.02, 2.25). MR analysis verified the causal relationship between genetically proxied sleep apnea or snoring and obesity. The decreased activity levels and altered expression levels of six circadian genes (bmal1b, cry1aa, cry1ab, clock1a, per1b, per2) were identified in the zebrafish of the sleep disorder group. Multiple metabolites related to disturbed glucose metabolism (e.g., 20-HETE), lipid metabolism (e.g., inosine), and vascular-related metabolites (e.g., riboflavin) were finally identified, indicating the latent effect of metabolism. Conclusions This study identified the chain of sleep-circadian rhythm-metabolism-cardiometabolic risks. These findings can promote improved prevention implementation and therapeutic strategies.https://doi.org/10.1186/s13098-024-01505-7Sleep disorderCardiometabolic risksCircadian rhythmClock genesTargeted metabolomics
spellingShingle Mingcong Chen
Yuzhen Ouyang
Yang Yang
Zihao Liu
Mingyi Zhao
Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
Diabetology & Metabolic Syndrome
Sleep disorder
Cardiometabolic risks
Circadian rhythm
Clock genes
Targeted metabolomics
title Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
title_full Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
title_fullStr Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
title_full_unstemmed Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
title_short Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study
title_sort impact of sleep problems on the cardiometabolic risks an integrated epidemiological and metabolomics study
topic Sleep disorder
Cardiometabolic risks
Circadian rhythm
Clock genes
Targeted metabolomics
url https://doi.org/10.1186/s13098-024-01505-7
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