Sleep duration, plasma metabolites, and obesity and diabetes: a metabolome-wide association study in US women

Josef Fritz; Tianyi Huang; Christopher M Depner; Oana A Zeleznik; Elizabeth M Cespedes Feliciano; Wenjun Li; Katie L Stone; JoAnn E Manson; Clary Clish; Tamar Sofer; Eva Schernhammer; Kathryn Rexrode; Susan Redline; Kenneth P Wright; Céline Vetter

doi:10.1093/sleep/zsac226

Sleep duration, plasma metabolites, and obesity and diabetes: a metabolome-wide association study in US women

Sleep. 2023 Jan 11;46(1):zsac226. doi: 10.1093/sleep/zsac226.

Authors

Josef Fritz^{1

2}, Tianyi Huang³, Christopher M Depner⁴, Oana A Zeleznik³, Elizabeth M Cespedes Feliciano⁵, Wenjun Li⁶, Katie L Stone⁷, JoAnn E Manson^{8

9}, Clary Clish¹⁰, Tamar Sofer¹¹, Eva Schernhammer^{3

12}, Kathryn Rexrode^{9

13}, Susan Redline^{8

14}, Kenneth P Wright¹⁵, Céline Vetter¹

Affiliations

¹ Circadian and Sleep Epidemiology Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
² Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Health and Kinesiology, University of Utah, Salt Lake City, UT, USA.
⁵ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁶ Department of Public Health, School of Health Sciences, University of Massachusetts Lowell, Lowell, MA, USA.
⁷ California Pacific Medical Center Research Institute, San Francisco, CA, USA.
⁸ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
¹¹ Division of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
¹² Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria.
¹³ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁴ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁵ Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.

Abstract

Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and diabetes. We evaluated cross-sectional differences in metabolite levels between women with self-reported habitual short (<7 h), medium (7-8 h), and long (≥9 h) sleep duration to delineate potential underlying biological mechanisms. In total, 210 metabolites were measured via liquid chromatography-mass spectrometry in 9207 women from the Nurses' Health Study (NHS; N = 5027), the NHSII (N = 2368), and the Women's Health Initiative (WHI; N = 2287). Twenty metabolites were consistently (i.e. praw < .05 in ≥2 cohorts) and/or strongly (pFDR < .05 in at least one cohort) associated with short sleep duration after multi-variable adjustment. Specifically, levels of two lysophosphatidylethanolamines, four lysophosphatidylcholines, hydroxyproline and phenylacetylglutamine were higher compared to medium sleep duration, while levels of one diacylglycerol and eleven triacylglycerols (TAGs; all with ≥3 double bonds) were lower. Moreover, enrichment analysis assessing associations of metabolites with short sleep based on biological categories demonstrated significantly increased acylcarnitine levels for short sleep. A metabolite score for short sleep duration based on 12 LASSO-regression selected metabolites was not significantly associated with prevalent and incident obesity and diabetes. Associations of single metabolites with long sleep duration were less robust. However, enrichment analysis demonstrated significant enrichment scores for four lipid classes, all of which (most markedly TAGs) were of opposite sign than the scores for short sleep. Habitual short sleep exhibits a signature on the human plasma metabolome which is different from medium and long sleep. However, we could not detect a direct link of this signature with obesity and diabetes risk.

Keywords: cohort studies; diabetes; epidemiology; habitual sleep duration; long sleep; metabolites; metabolomics; obesity; short sleep; women.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cross-Sectional Studies
Diabetes Mellitus* / epidemiology
Female
Humans
Metabolome
Obesity
Sleep
Sleep Duration
Sleep Wake Disorders*

Abstract

Publication types

MeSH terms

Grants and funding