Josiane L. Broussard, PhD; David A. Ehrmann, MD; Eve Van Cauter, PhD; Esra Tasali, MD; Matthew J. Brady, PhD
Acknowledgment: The authors thank the nursing and dietary staff of the University of Chicago General Clinical Research Center for their expert assistance and the volunteers for participating in this study. The authors also thank Theodore Karrison, PhD, and Kristen Knutson, PhD, for their expertise and assistance in the statistical analysis of this study.
Grant Support: This research was supported by National Institutes of Health grants R01-HL086459, 5T32-HL07909, CTSA UL1-RR024999, P60-DK020595, and P50 HD-057796 and P01-AG11412 and Society in Science—The Branco Weiss Fellowship awarded to Dr. Broussard.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0056.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Tasali (e-mail, etasali@medicine.bsd.uchicago.edu) or Dr. Brady (e-mail, mbrady@medicine.bsd.uchicago.edu).
Requests for Single Reprints: Matthew J. Brady, PhD, Department of Medicine, University of Chicago, 900 East 57th Street, KCBD 8124, Chicago, IL 60637; e-mail, mbrady@medicine.bsd.uchicago.edu.
Current Author Addresses: Dr. Broussard: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, 8700 West Beverly Boulevard, THAE107, Los Angeles, CA 90048.
Drs. Ehrmann and Van Cauter: Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 1027, Chicago, IL 60637. Dr. Tasali: Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 6026, Chicago, IL 60637.
Dr. Brady: Department of Medicine, University of Chicago, 900 East 57th Street, KCBD 8124, Chicago, IL 60637.
Author Contributions: Conception and design: J.L. Broussard, D.A. Ehrmann, E. Van Cauter, E. Tasali, M.J. Brady.
Analysis and interpretation of the data: J.L. Broussard, E. Van Cauter, E. Tasali, M.J. Brady.
Drafting of the article: J.L. Broussard, E. Van Cauter, E. Tasali, M.J. Brady.
Critical revision of the article for important intellectual content: J.L. Broussard, D.A. Ehrmann, E. Van Cauter, E. Tasali, M.J. Brady.
Final approval of the article: J.L. Broussard, D.A. Ehrmann, E. Van Cauter, E. Tasali, M.J. Brady.
Provision of study materials or patients: D.A. Ehrmann, E. Tasali.
Statistical expertise: E. Van Cauter, E. Tasali.
Obtaining of funding: J.L. Broussard, D.A. Ehrmann, E. Van Cauter, E. Tasali, M.J. Brady.
Administrative, technical, or logistic support: J.L. Broussard, D.A. Ehrmann, E. Van Cauter, E. Tasali, M. Brady.
Collection and assembly of data: J.L. Broussard, D.A. Ehrmann, E. Tasali.
Chinese translation
Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown.
To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance.
Randomized, 2-period, 2-condition, crossover clinical study.
University of Chicago Clinical Resource Center.
Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m2 (SD, 1.6).
Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity.
Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt–tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test.
The insulin concentration for the half-maximal pAkt–tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt–tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity.
This was a single-center study with a small sample size.
Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues.
National Institutes of Health.
Broussard JL, Ehrmann DA, Van Cauter E, Tasali E, Brady MJ. Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study. Ann Intern Med. 2012;157:549–557. doi: 10.7326/0003-4819-157-8-201210160-00005
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© 2019
Published: Ann Intern Med. 2012;157(8):549-557.
DOI: 10.7326/0003-4819-157-8-201210160-00005
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, Pulmonary/Critical Care.
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