Best Practice & Research Clinical Endocrinology & Metabolism
1Role of sleep duration in the regulation of glucose metabolism and appetite
Introduction
Evidence for a modulatory impact of sleep on many physiological functions, including metabolic regulation and endocrine release, has been reported more than four decades ago. Nighttime hormonal release and glucose control are dependent on the occurrence of specific sleep stages.1, 2, 3 Human sleep is composed of rapid-eye-movement (REM) sleep and stages 1, 2 and 3 of non-REM (NREM) sleep. During the deeper stage of non-REM sleep, i.e. slow wave sleep (SWS) or stage NREM 3, brain glucose utilization and sympathetic nervous activity are decreased and parasympathetic nervous activity is increased, relative to both wake and REM sleep. SWS is also associated with robust elevations of growth hormone (GH) levels, while pituitary–adrenal activity is inhibited.3 Hence SWS is likely to play a major role in total body glucose regulation. More recently, orexin neurons in the lateral hypothalamus have been identified as playing a central role in the maintenance of arousal as well as feeding behavior,*4, 5 suggesting an impact of sleep duration on appetite regulation (reviewed in chapter 12 “Sleep and metabolism: role of hypothalamic neuronal circuitry”).
The first laboratory studies examining the adverse impact of sleep deprivation on metabolic and endocrine functions concluded that the alterations occurring during one or two nights of acute total sleep deprivation were reversed during recovery sleep. Because these results suggested that persistent adverse effects of sleep loss are unlikely, but also because the degree of sleep deprivation in these studies was not commonly occurring on a recurring basis in the general population, little attention was paid to these findings. Since then, recurrent partial sleep deprivation, i.e. the result of a voluntary behavior reflecting the demands and opportunities of modern society, has become increasingly common. The impact of such sleep deprivation, which affects all age groups, was first investigated 10–15 years ago. Fig. 1 summarizes the sleep duration on week nights for US and French adults and adolescents as assessed in years 2005–2008.6, 7, 8, 9 Data from the 2008 “Sleep in America” poll of the National Sleep Foundation indicate that although working adults report a sleep need of an average of 7 h and 18 min to function at best, the average sleep duration is 6 h and 40 min, with 44% of them sleeping less than 7 h on a typical week-night (as opposed to only 15.6% in 196010), and 16% less than 6 h (Fig. 1A right panel6). Sleep times in European countries follow a similar trend; a survey conducted in France among adults aged 18–55 years reported that, on work-nights, the average sleep duration was 6 h and 58 min and that 33% of the respondents slept less than 7 h per night (Fig. 1A left panel8). Among the pediatric population, adolescents carry the strongest sleep debt. While laboratory studies have shown that physiological sleep need is about 9 h across all ages of adolescence,11 sleep duration on school nights is 7 h and 12 min for 9–12th grade American teens7 and 7 h and 45 min for 15–19 years old French adolescents.9 In both countries the amount of sleep that adolescents believe they need to feel their best during the day is higher than the amount of sleep that they actually achieve (9 h and 02 min in France, 8 h and 00 min in the US), with the optimal sleep duration reported by French adolescents matching findings on sleep need obtained in laboratory studies.11 In France, 78% of adolescents get an insufficient (<8 h) or borderline sufficient (8 h to 9 h) amount of sleep on school nights and this proportion reaches a striking 87% for US adolescents (Fig. 1B7, 9). Not surprisingly, in both countries, adults and adolescents who report insufficient sleep are much more likely to also report sleepiness, tiredness, irritability, depressed mood, and higher intake of caffeinated beverages.
To date, an ever-increasing number of cross-sectional as well as prospective epidemiologic studies (reviewed in chapter 5 “Sleep duration and cardiometabolic risk: a review of the epidemiologic evidence”) have provided evidence for an association between short sleep and the prevalence or incidence of obesity or diabetes, after controlling for age, body mass index (BMI) and various other confounders. The present review will summarize the current laboratory evidence indicating that recurrent sleep curtailment is associated with a constellation of metabolic and endocrine alterations, strongly suggesting that short sleep is an important, though still widely underestimated, non-traditional lifestyle factor involved in the current epidemic of diabetes and obesity.
Section snippets
Total sleep deprivation studies
The first studies evaluating the impact of sleep deprivation on human health involved various durations of total sleep deprivation (TSD) (Table 1). In the late 1960s, Kuhn et al. compared glucose tolerance in 28 young healthy volunteers after 4–5 control nights with normal bedtimes and after 72–126 h of TSD: the glucose response to an oral glucose tolerance test (OGTT) was higher in the latter condition, indicating reduced glucose tolerance.12 In another early study,13 the effect of 120-h TSD
Sleep duration and appetite regulation
A large number of epidemiologic studies have demonstrated associations between short sleep and higher BMI. One pathway linking short sleep to obesity is increased caloric intake in short sleepers. The following section will present results from laboratory studies that have used TSD paradigms to delineate the respective role of sleep and circadian rhythmicity in the 24-h pattern of hormones involved in the neuroendocrine regulation of appetite, i.e. leptin and ghrelin. We then summarize the
Sleep duration and energy expenditure
Beside the changes in neurohormones involved in the regulation of food intake, reduced energy expenditure (EE) during sleep loss could represent another mechanism contributing to the link between short sleep and increased weight consistently reported in epidemiologic studies.
Relatively few studies have evaluated the impact of sleep restriction on EE. Bosy-Westphal et al. studied 14 healthy lean and obese women after 4 nights of ∼5.5 h in bed, by indirect calorimetry; compared to the rested
Pathways linking sleep loss and increased risk of diabetes and obesity
Multiple pathways are likely to mediate the adverse effect of sleep loss on the risk of obesity and diabetes. Several of these pathways interact with one another. An up-regulation of the activity of orexin neurons may be a primary mechanism linking sleep deprivation and adverse metabolic effects.*4, 5 Another important mechanism, considering that brain is a major user of glucose, is brain glucose utilization, which appears to be reduced after sleep deprivation, as shown by PET studies.58
Fig. 2
Summary
Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that recurrent sleep restriction is associated with a constellation of metabolic and endocrine consequences that may contribute to the pathophysiology of obesity and diabetes mellitus. Recommending sufficient amounts of habitual sleep in these patients may therefore be of great importance. Intervention studies are warranted to determine if strategies aiming at
Conflict of interest
The authors have no conflict of interest.
Acknowledgments
Some of the research described in this article was supported by US National Institute of Health grants P01 AG-11412, U54 RR023560, P60 DK-20595, R01 DK-0716960, R01 HL-075025 and P50-HD057796, by US Department of Defense award W81XWH-07-2-0071, by Belgian “CARE Foundation” grants, by INSERM U628, and by Claude Bernard University of Lyon, France.
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Both authors contributed equally to this work.