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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.

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.

There is convincing evidence that, in humans, discrete sleep stages are important for daytime brain function, but whether any particular sleep stage has functional significance for the rest of the body is not known. Deep non-rapid eye movement (NREM) sleep, also known as slow-wave sleep (SWS), is thought to be the most ''restorative'' sleep stage, but beneficial effects of SWS for physical well being have not been demonstrated. The initiation of SWS coincides with hormonal changes that affect glucose regulation, suggesting that SWS may be important for normal glucose tolerance. If this were so, selective suppression of SWS should adversely affect glucose homeostasis and increase the risk of type 2 diabetes. Here we show that, in young healthy adults, all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. SWS suppression reduced delta spectral power, the dominant EEG frequency range in SWS, and left other EEG frequency bands unchanged. Importantly, the magnitude of the decrease in insulin sensitivity was strongly correlated with the magnitude of the reduction in SWS. These findings demonstrate a clear role for SWS in the maintenance of normal glucose homeostasis. Furthermore, our data suggest that reduced sleep quality with low levels of SWS, as occurs in aging and in many obese individuals, may contribute to increase the risk of type 2 diabetes.aging ͉ sleep quality ͉ sleep disordered breathing ͉ delta waves ͉ insulin resistance H uman sleep is composed of rapid-eye-movement (REM) sleep and stages 1, 2, 3, and 4 of non-REM (NREM) sleep. The deeper stages of NREM sleep, i.e., stages 3 and 4, also known as slow-wave sleep (SWS), are thought to be the most ''restorative.'' There is indeed evidence that SWS plays a role in waking neurobehavioral function (1), particularly in memory consolidation (2, 3), but whether SWS is also important for peripheral physiological function is not known. The initiation of SWS is temporally associated with transient metabolic, hormonal, and neurophysiologic changes, all of which could potentially affect glucose homeostasis. These include decreased brain glucose utilization, stimulation of growth hormone release, inhibition of corticotropic activity, decreased sympathetic nervous activity, and increased vagal tone. We therefore hypothesized that SWS plays a role in glucose regulation and that suppression of SWS may adversely affect glucose homeostasis.To test this hypothesis, we developed an experimental model in young healthy lean individuals that was designed to selectively suppress SWS and assessed the impact of this intervention on glucose homeostasis. The EEG was continuously monitored, and SWS was suppressed by delivering acoustic stimuli of varying frequencies and intensities. The intervention was designed to substitute deep NREM sleep, i.e., stages 3 and 4, with shallow NREM slee...

The importance of sleep to hormones and glucose metabolism was first documented more than four decades ago. Since then, sleep curtailment has become an endemic behavior in modern society. In addition, the prevalence of sleep disorders, particularly obstructive sleep apnea (OSA), has increased. OSA is very common in endocrine and metabolic disorders, but often remains undiagnosed. This Review summarizes the laboratory and epidemiologic evidence that suggests how sleep loss, either behavioral or disease-related, and poor quality of sleep might promote the development of obesity and diabetes mellitus, and exacerbate existing endocrine conditions. Treatment of sleep disorders has the potential to improve glucose metabolism and energy balance. Screening for habitual sleep patterns and OSA might be critically important for patients with endocrine and metabolic disorders.