Karine Spiegel

Impact of sleep debt on metabolic and endocrine function

BACKGROUND Chronic sleep debt is becoming increasingly common and affects millions of people in more-developed countries. Sleep debt is currently believed to have no adverse effect on health. We investigated the effect of sleep debt on metabolic and endocrine functions. METHODS We assessed carbohydrate metabolism, thyrotropic function, activity of the hypothalamo-pituitary-adrenal axis, and sympathovagal balance in 11 young men after time in bed had been restricted to 4 h per night for 6 nights. We compared the sleep-debt condition with measurements taken at the end of a sleep-recovery period when participants were allowed 12 h in bed per night for 6 nights. FINDINGS Glucose tolerance was lower in the sleep-debt condition than in the fully rested condition (p<0.02), as were thyrotropin concentrations (p<0.01). Evening cortisol concentrations were raised (p=0.0001) and activity of the sympathetic nervous system was increased in the sleep-debt condition (p<0.02). INTERPRETATION Sleep debt has a harmful impact on carbohydrate metabolism and endocrine function. The effects are similar to those seen in normal ageing and, therefore, sleep debt may increase the severity of age-related chronic disorders.

Effects of poor and short sleep on glucose metabolism and obesity risk

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.

Metabolic consequences of sleep and sleep loss.

Reduced sleep duration and quality appear to be endemic in modern society. Curtailment of the bedtime period to minimum tolerability is thought to be efficient and harmless by many. It has been known for several decades that sleep is a major modulator of hormonal release, glucose regulation and cardiovascular function. In particular, slow wave sleep (SWS), thought to be the most restorative sleep stage, is associated with decreased heart rate, blood pressure, sympathetic nervous activity and cerebral glucose utilization, compared with wakefulness. During SWS, the anabolic growth hormone is released while the stress hormone cortisol is inhibited. In recent years, laboratory and epidemiologic evidence have converged to indicate that sleep loss may be a novel risk factor for obesity and type 2 diabetes. The increased risk of obesity is possibly linked to the effect of sleep loss on hormones that play a major role in the central control of appetite and energy expenditure, such as leptin and ghrelin. Reduced leptin and increased ghrelin levels correlate with increases in subjective hunger when individuals are sleep restricted rather than well rested. Given the evidence, sleep curtailment appears to be an important, yet modifiable, risk factor for the metabolic syndrome, diabetes and obesity. The marked decrease in average sleep duration in the last 50 years coinciding with the increased prevalence of obesity, together with the observed adverse effects of recurrent partial sleep deprivation on metabolism and hormonal processes, may have important implications for public health.

Impact of Sleep and Sleep Loss on Neuroendocrine and Metabolic Function

Background: Sleep exerts important modulatory effects on neuroendocrine function and glucose regulation. During the past few decades, sleep curtailment has become a very common behavior in industrialized countries. This trend toward shorter sleep times has occurred over the same time period as the dramatic increases in the prevalence of obesity and diabetes. Aims: This article will review rapidly accumulating laboratory and epidemiologic evidence indicating that chronic partial sleep loss could play a role in the current epidemics of obesity and diabetes. Conclusions: Laboratory studies in healthy young volunteers have shown that experimental sleep restriction is associated with a dysregulation of the neuroendocrine control of appetite consistent with increased hunger and with alterations in parameters of glucose tolerance suggestive of an increased risk of diabetes. Epidemiologic findings in both children and adults are consistent with the laboratory data.

Sleep as a Mediator of the Relationship between Socioeconomic Status and Health: A Hypothesis

Abstract: This article discusses the hypothesis that the adverse impact of low socioeconomic status (SES) on health may be partly mediated by decrements in sleep duration and quality. Low SES is frequently associated with a diminished opportunity to obtain sufficient sleep or with environmental conditions that compromise sleep quality. In a recent study, we examined carbohydrate metabolism, endocrine function, and sympatho‐vagal balance in young, healthy adults studied after restricting sleep to four hours per night for six nights as compared to a fully rested condition obtained by extending the bedtime period to 12 hours per night for six nights. The state of sleep debt was associated with decreased glucose tolerance, elevated evening cortisol levels, and increased sympathetic activity. The alterations in glucose tolerance and hypothalamo‐pituitary‐adrenal function were qualitatively and quantitatively similar to those observed in normal aging. These results indicate that sleep loss can increase the “allostatic load” and facilitate the development of chronic conditions, such as obesity, diabetes, and hypertension, which have an increased prevalence in low SES groups.

Reduced Sleep Duration or Quality: Relationships With Insulin Resistance and Type 2 Diabetes

T ype 2 diabetes mellitus is a chronic condition that is increasing at alarming ratesworldwide. Type 2 diabetes mellitus occurs when insulin resistance (ie, reduced insulin action) is accompanied by impaired insulin secretion. Insulin resistance and type 2 diabetes mellitus are both associated with an increased risk of cardiovascular disease. Obesity, family history of diabetes, decreased physical activity, and aging are among the most common factors known to contribute to the development of diabetes. An improved understanding of the pathogenesis could lead to better preventive and therapeutic strategies. Rapidly accumulating evidence suggests that sleep loss resulting from either behavioral sleep curtailment or sleep disorders may be a novel risk factor for the development of insulin resistance and type 2 diabetes mellitus. In this article, we will first review the current epidemiologic evidence that links reduced sleep duration and/or quality to diabetes. We will then summarize the laboratory studies on the effects of manipulations of sleep duration and quality on glucose metabolism in healthy subjects with a brief discussion of potential mechanisms. In the last section, we will review the studies examining the association between insulin resistance, diabetes, and obstructive sleep apnea (OSA), an increasingly common sleep disorder associated with both sleep loss and poor sleep quality.

Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep

CONTEXT The acylation of ghrelin is essential for its stimulatory effects on GH release and appetite. Most of the physiology of ghrelin has been defined based on the assay of total ghrelin (TG), which mainly reflects levels of unacylated ghrelin. Whether levels of acylated ghrelin (AG) are influenced by circadian time and sleep and impact glucose regulation under physiologic conditions is not known. METHODS Blood was sampled at 10- to 30-min intervals for 24 h in 14 healthy young lean men under controlled conditions of activity, light-dark cycle, and sleep-wake schedule. The subjects ingested three identical carbohydrate-rich meals at 5-h intervals. Sleep was polygraphically monitored. Levels of TG and AG were measured by RIA. The 24-h profiles of glucose and insulin levels were assessed simultaneously. RESULTS Postprandial glucose concentrations were positively correlated with mean levels of AG but not TG, independently of insulin. Postprandial suppression and rebound of AG and TG occurred in parallel and were not impacted by time of day. The nocturnal elevation of AG and TG reflects the postdinner rebound curbed by an inhibitory effect of sleep. The ratio of AG to TG was lower during sleep than during wake, consistent with a reduction of orexigenic signal. CONCLUSIONS Individual differences in AG levels may be an important predictor of overall glucose control under physiological conditions. Sleep, but not time of day, impacts postprandial TG and AG responses. The inhibitory effect of sleep on ghrelin release and acylation is consistent with the association between sleeping and fasting.

Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

CONTEXT Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. OBJECTIVE Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. METHODS Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. RESULTS Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. CONCLUSION The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

The important role of sleep in metabolism.

Both reduction in total sleep duration with slow-wave sleep (SWS) largely preserved and alterations of sleep quality (especially marked reduction of SWS) with preservation of total sleep duration are associated with insulin resistance without compensatory increase in insulin secretion, resulting in impaired glucose tolerance and increased risk of type 2 diabetes. When performed under rigorously controlled conditions of energy intake and physical activity, sleep restriction is also associated with a decrease in circulating levels of leptin (an anorexigenic hormone) and an increase in circulating levels of ghrelin (an orexigenic hormone), hunger and appetite. Furthermore, sleep restriction is also associated with a stimulation of brain regions sensitive to food stimuli, indicating that sleep loss may lead to obesity through the selection of high-calorie food. There is also evidence that sleep restriction could provide a permissive environment for the activation of genes that promote obesity. Indeed, the heritability of body mass index is increased in short sleepers. Thus, chronic sleep curtailment, which is on the rise in modern society, including in children, is likely to contribute to the current epidemics of type 2 diabetes and obesity.

Genetic and environmental influences on prolactin secretion during wake and during sleep

To delineate the contributions of genetic and environmental factors in the regulation of human prolactin (PRL) secretion, the 24-h profile of plasma PRL was obtained at 15-min intervals in 10 pairs of monozygotic and 10 pairs of dizygotic twins. Sleep was monitored polygraphically. PRL secretory rates were derived from plasma concentrations by deconvolution. Diurnal (24-h) variations were quantified by a regression curve to define nadir, acrophase, and amplitude. Pulses of PRL secretion were identified using a computerized algorithm. A procedure specifically developed for twin studies was used to partition the variance into genetic and environmental contributions. Significant genetic effects were identified for daytime PRL concentrations, rhythm amplitude, and overall waveshape of the daily PRL profile. In contrast, environmental effects were dominant for mean concentrations during sleep, total secretory output during sleep, overall 24-h concentrations, and total 24-h secretion. However, when interindividual variations in sleep fragmentation were taken into account, the estimates of genetic variance for PRL concentrations and secretion during sleep approached statistical significance. Significant genetic influences were identified for slow-wave sleep (SWS). Because SWS is associated with increased nocturnal PRL secretion, it is possible that genetic effects on PRL secretion during sleep reflect genetic influences on SWS. In conclusion, genetic factors determine partially both the basal daytime concentrations of PRL and the temporal organization of PRL secretion over the 24-h cycle in normal young men.