Abstract

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment.

Details

Title
Hyperfructosemia in sleep disordered breathing: metabolome analysis of Nagahama study
Author
Nakatsuka, Yoshinari 1 ; Murase, Kimihiko 1 ; Sonomura, Kazuhiro 2 ; Tabara, Yasuharu 3 ; Nagasaki, Tadao 1 ; Hamada, Satoshi 4 ; Matsumoto, Takeshi 5 ; Minami, Takuma 6 ; Kanai, Osamu 7 ; Takeyama, Hirofumi 1 ; Sunadome, Hironobu 1 ; Takahashi, Naomi 1 ; Nakamoto, Isuzu 8 ; Tanizawa, Kiminobu 9 ; Handa, Tomohiro 4 ; Sato, Taka-Aki 10 ; Komenami, Naoko 11 ; Wakamura, Tomoko 8 ; Morita, Satoshi 12 ; Takeuchi, Osamu 13 ; Nakayama, Takeo 14 ; Hirai, Toyohiro 9 ; Kamatani, Yoichiro 2 ; Matsuda, Fumihiko 2 ; Chin, Kazuo 15 

 Kyoto University, Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 Kyoto University, Center for Genomic Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 Kyoto University, Center for Genomic Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Shizuoka Graduate University of Public Health, Graduate School of Public Health, Shizuoka, Japan (GRID:grid.518453.e) (ISNI:0000 0004 9216 2874) 
 Kyoto University, Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 Kyoto University, Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Saiseikai Noe Hospital, Department of Respiratory Medicine, Osaka, Japan (GRID:grid.258799.8) 
 Kyoto University, Department of Primary Care and Emergency Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 National Hospital Organization Kyoto Medical Center, Division of Respiratory Medicine, Center for Respiratory Diseases, Kyoto, Japan (GRID:grid.410835.b) 
 Kyoto University, Nursing Science, Human Health Sciences, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
 Kyoto University, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
10  Shimadzu Corporation, Life Science Research Center, Technology Research Laboratory, Kyoto, Japan (GRID:grid.274249.e) (ISNI:0000 0004 0571 0853) 
11  Kyoto Women’s University, Department of Food and Nutrition, Kyoto, Japan (GRID:grid.411223.7) (ISNI:0000 0001 0666 1238) 
12  Kyoto University, Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
13  Kyoto University, Department of Medical Chemistry, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
14  Kyoto University School of Public Health, Department of Health Informatics, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
15  Nihon University of Medicine, Department of Sleep Medicine and Respiratory Care, Division of Respiratory Medicine, Tokyo, Japan (GRID:grid.260969.2) (ISNI:0000 0001 2149 8846); Kyoto University, Center for Genomic Medicine, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
Pages
12735
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2846402875
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.