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      Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men

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          Abstract

          Background

          Sleep restriction is associated with development of metabolic ill-health, and hormonal mechanisms may underlie these effects. The aim of this study was to determine the impact of short term sleep restriction on male health, particularly glucose metabolism, by examining adrenocorticotropic hormone (ACTH), cortisol, glucose, insulin, triglycerides, leptin, testosterone, and sex hormone binding globulin (SHBG).

          Methodology/Principal Findings

          N = 14 healthy men (aged 27.4±3.8, BMI 23.5±2.9) underwent a laboratory-based sleep restriction protocol consisting of 2 baseline nights of 10 h time in bed (TIB) (B1, B2; 22:00–08:00), followed by 5 nights of 4 h TIB (SR1–SR5; 04:00–08:00) and a recovery night of 10 h TIB (R1; 22:00–08:00). Subjects were allowed to move freely inside the laboratory; no strenuous activity was permitted during the study. Food intake was controlled, with subjects consuming an average 2000 kcal/day. Blood was sampled through an indwelling catheter on B1 and SR5, at 09:00 (fasting) and then every 2 hours from 10:00–20:00. On SR5 relative to B1, glucose ( F 1,168 = 25.3, p<0.001) and insulin ( F 1,168 = 12.2, p<0.001) were increased, triglycerides ( F 1,168 = 7.5, p = 0.007) fell and there was no significant change in fasting homeostatic model assessment (HOMA) determined insulin resistance ( F 1,168 = 1.3, p = 0.18). Also, cortisol ( F 1,168 = 10.2, p = 0.002) and leptin ( F 1,168 = 10.7, p = 0.001) increased, sex hormone binding globulin ( F 1,167 = 12.1, p<0.001) fell and there were no significant changes in ACTH ( F 1,168 = 0.3, p = 0.59) or total testosterone ( F 1,168 = 2.8, p = 0.089).

          Conclusions/Significance

          Sleep restriction impaired glucose, but improved lipid metabolism. This was associated with an increase in afternoon cortisol, without significant changes in ACTH, suggesting enhanced adrenal reactivity. Increased cortisol and reduced sex hormone binding globulin (SHBG) are both consistent with development of insulin resistance, although hepatic insulin resistance calculated from fasting HOMA did not change significantly. Short term sleep curtailment leads to changes in glucose metabolism and adrenal reactivity, which when experienced repeatedly may increase the risk for type 2 diabetes.

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          Most cited references63

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          Disruption of the Clock Components CLOCK and BMAL1 Leads to Hypoinsulinemia and Diabetes

          The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night1–3. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and while rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes4, it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism, and insulin signaling is delayed in circadian mutant mice, and both Clock 5,6 and Bmal1 7 mutants exhibit impaired glucose tolerance, reduced insulin secretion, and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival, and synaptic vesicle assembly. Remarkably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective β-cell function at the very latest stage of stimulus-secretion coupling. These results demonstrate a role for the β-cell clock in coordinating insulin secretion with the sleep-wake cycle, and reveal that ablation of the pancreatic clock can trigger onset of diabetes mellitus.
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            Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines.

            Total sleep restriction in humans is associated with increased daytime sleepiness, decreased performance, and hormonal/metabolic disturbances. The effects of mild chronic sleep restriction that mimic real life are not known. To assess the effects of modest sleep restriction from 8 to 6 h/night for 1 wk, 25 young, healthy, normal sleepers (12 men and 13 women) were studied for 12 consecutive nights in the sleep laboratory. After 1 wk of sleep restriction, although subjects' nighttime sleep was deeper, subjects were significantly sleepier (multiple sleep latency test) and performed worse in four primary variables of psychomotor vigilance test (both P < 0.01). Furthermore, 24-h secretion of IL-6 was increased by 0.8 +/- 0.3 pg/ml (P < 0.05) in both sexes, whereas TNFalpha was increased only in men. Also, the peak cortisol secretion was lower after sleep restriction than at baseline, and this difference was stronger in men (55.18 +/- 24.83 nmol/liter; P < 0.05) than in women (35.87 +/- 24.83 nmol/liter; P < 0.16). We conclude that in young men and women, modest sleep loss is associated with significant sleepiness, impairment of psychomotor performance, and increased secretion of proinflammatory cytokines. Given the potential association of these behavioral and physical alterations with health, well-being, and public safety, the idea that sleep or parts of it are optional should be regarded with caution.
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              Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin.

              Sleep plays an important role in energy homeostasis. The present study tests the hypothesis that circulating levels of leptin, a hormone that signals energy balance to the brain, are influenced by sleep duration. We also analyzed associations between leptin and sympathovagal balance, cortisol, TSH, glucose, and insulin under different bedtime conditions. Twenty-four-hour hormonal and glucose profiles were sampled at frequent intervals, and sympathovagal balance was estimated from heart rate variability in 11 subjects studied after 6 d of 4-h bedtimes (mean +/- sem of sleep duration during last 2 d: 3 h and 49 +/- 2 min) and after 6 d of 12-h bedtimes (sleep: 9 h and 03 +/- 15 min). A study with 8-h bedtimes was performed 1 yr later (sleep: 6 h and 52 +/- 10 min). Caloric intake and activity levels were carefully controlled in all studies. Mean levels, maximal levels, and rhythm amplitude of leptin were decreased (-19%, -26%, and -20%, respectively) during sleep restriction compared with sleep extension. The decrease in leptin levels was concomitant with an elevation of sympathovagal balance. The effects of sleep duration on leptin were quantitatively associated with alterations of the cortisol and TSH profiles and were accompanied by an elevation of postbreakfast homeostasis model assessment values. Measures of perceived stress were not increased during sleep restriction. During the study with 8-h bedtimes, hormonal and metabolic parameters were intermediate between those observed with 4-h and 12-h bedtimes. In conclusion, sleep modulates a major component of the neuroendocrine control of appetite.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                23 July 2012
                : 7
                : 7
                : e41218
                Affiliations
                [1 ]Centre for Sleep Research, University of South Australia, Adelaide, South Australia, Australia
                [2 ]Los Angeles Biomedical Research Institute at Harbor-University of Los Angeles Medical Center, Torrance, California, United States of America
                [3 ]Sleep and Performance Research Center, Washington State University, Spokane, Washington, United States of America
                [4 ]Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia
                [5 ]Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, South Australia, Australia
                Simon Fraser University, Canada
                Author notes

                Conceived and designed the experiments: SB HPAVD ACR. Performed the experiments: ACR SB LJH. Analyzed the data: ACR JD HPAVD. Contributed reagents/materials/analysis tools: SB ACR JD HPAVD. Wrote the paper: ACR PYL HPAVD GAW SB.

                Article
                PONE-D-12-10655
                10.1371/journal.pone.0041218
                3402517
                22844441
                bf0aa8a4-cc09-4b80-af7d-10aee37d16ea
                Reynolds et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 9 April 2012
                : 18 June 2012
                Page count
                Pages: 10
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Hormones
                Diabetic Endocrinology
                Physiological Processes
                Energy Metabolism
                Sleep
                Biochemistry
                Lipids
                Lipid Metabolism
                Metabolism
                Medicine
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Hormones
                Diabetic Endocrinology
                Physiological Processes
                Energy Metabolism
                Sleep
                Endocrinology
                Endocrine Physiology
                Hormones
                Diabetic Endocrinology

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                Uncategorized

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