Insufficient sleep undermines dietary efforts to reduce adiposity.

BACKGROUND: Sleep loss can modify energy intake and expenditure. OBJECTIVE: To determine whether sleep restriction attenuates the effect of a reduced-calorie diet on excess adiposity. DESIGN: Randomized, 2-period, 2-condition crossover study. SETTING: University clinical research center and sleep laboratory. PATIENTS: 10 overweight nonsmoking adults (3 women and 7 men) with a mean age of 41 years (SD, 5) and a mean body mass index of 27.4 kg/m² (SD, 2.0). INTERVENTION: 14 days of moderate caloric restriction with 8.5 or 5.5 hours of nighttime sleep opportunity. MEASUREMENTS: The primary measure was loss of fat and fat-free body mass. Secondary measures were changes in substrate utilization, energy expenditure, hunger, and 24-hour metabolic hormone concentrations. RESULTS: Sleep curtailment decreased the proportion of weight lost as fat by 55% (1.4 vs. 0.6 kg with 8.5 vs. 5.5 hours of sleep opportunity, respectively; P = 0.043) and increased the loss of fat-free body mass by 60% (1.5 vs. 2.4 kg; P = 0.002). This was accompanied by markers of enhanced neuroendocrine adaptation to caloric restriction, increased hunger, and a shift in relative substrate utilization toward oxidation of less fat. LIMITATION: The nature of the study limited its duration and sample size. CONCLUSION: The amount of human sleep contributes to the maintenance of fat-free body mass at times of decreased energy intake. Lack of sufficient sleep may compromise the efficacy of typical dietary interventions for weight loss and related metabolic risk reduction. PRIMARY FUNDING SOURCE: National Institutes of Health.

Changes in serum TSH and free T4 during human sleep restriction.

STUDY OBJECTIVES: To examine whether recurrent sleep restriction is accompanied by changes in measures of thyroid function. DESIGN: Two-period crossover intervention study. SETTING: University clinical research center and sleep laboratory. PARTICIPANTS: 11 healthy volunteers (5F/6M) with a mean (+/- SD) age of 39 +/- 5 y and BMI 26.5 +/- 1.5 kg/m2. INTERVENTION: Randomized exposure to 14 days of sedentary living with ad libitum food intake and 5.5- vs. 8.5-h overnight sleep opportunity. MEASUREMENTS AND RESULTS: Serum thyroid-stimulating hormone (TSH) and free thyroxine (T4) were measured at the end of each intervention. Partial sleep restriction was accompanied by a modest but statistically significant reduction in TSH and free T4, seen mainly in the female participants of the study. CONCLUSIONS: Compared to the well-known rise in TSH and thyroid hormone concentrations during acute sleep loss, tests obtained after 14 days of partial sleep restriction did not show a similar activation of the human thyroid axis.

Association between sleep and morning testosterone levels in older men.

STUDY OBJECTIVES: The circulating testosterone levels of healthy men decline with advancing age. This process is characterized by considerable inter-individual variability, the causes of which are of significant biological and clinical interest but remain poorly understood. Since sleep quantity and quality decrease with age, and experimentally-induced sleep loss in young adults results in hormonal changes similar to those that occur spontaneously in the course of aging, this study examined whether some of the variability in circulating testosterone levels of older men can be related to objective differences in their sleep. DESIGN: Observational study. SETTING: General community and university clinical research center. PARTICIPANTS: Twelve healthy men ages 64 to 74 years. INTERVENTIONS: Three morning blood samples were pooled for the measurement of total and free testosterone. In addition to overnight laboratory polysomnography, wrist activity monitoring for 6-9 days was used to determine the amount of nighttime sleep of the participants in everyday life settings. MEASUREMENTS AND RESULTS: The main outcome measures were total sleep time and morning testosterone levels. Sleep time in the laboratory was correlated with the usual amount of nighttime sleep at home (Pearson's r = 0.842; P = 0.001). Bivariate correlation and multiple linear regression analyses revealed that the amount of nighttime sleep measured by polysomnography was an independent predictor of the morning total (Beta 0.792, P = 0.017) and free (Beta 0.741, P = 0.029) testosterone levels of the subjects. CONCLUSIONS: Objectively measured differences in the amount of nighttime sleep are associated with a significant part of the variability in the morning testosterone levels of healthy older men.

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.

Estimating cardiac autonomic activity during sleep: impedance cardiography, spectral analysis, and Poincaré plots.

OBJECTIVE: To compare noninvasive measures of cardiac autonomic activity during sleep. METHODS: The absolute and normalized (n.u.) high and low frequency peaks from the spectral analysis of R-R intervals (HF, LF, HFn.u., LFn.u.), LF/HF ratio, pre-ejection period (PEP) from impedance cardiography, and the autocorrelation coefficient (rRR) as illustrated in Poincaré plots were measured during night-time sleep in 9 young healthy subjects. Heart rate and blood pressure were also recorded. RESULTS: Heart rate was significantly associated with cardiac sympathetic activity (PEP, average r=-0.46), but not with cardiac parasympathetic activity (HF, average r=-0.17). rRR was significantly associated with heart rate (average r=0.41), and LF/HF (average r=0.69), but not with PEP or HF. From NREM to REM sleep, heart rate, LFn.u., LF and rRR significantly increased, HFn.u. significantly decreased, LF/HF showed an increasing trend (P=0.07) and PEP showed a decreasing trend (P=0.06). Blood pressure and HF were highly variable without significant changes from NREM to REM sleep. CONCLUSIONS: Cardiac parasympathetic activity (HF) does not vary greatly between sleep stages. Cardiac sympathetic activity (PEP) decreases linearly during sleep. rRR and LF/HF can track sympathovagal changes during sleep, but cannot differentiate between changes in cardiac parasympathetic and sympathetic activity. The relative advantages and disadvantages of the different measures are discussed.

Differences in insulin secretion and sensitivity in short-sleep insomnia.

OBJECTIVE: Short-sleep insomnia is associated with increased risk of diabetes. The role of altered insulin secretion and action in this association is poorly understood. DESIGN: Observational study. SETTING: Academic clinical research center. PARTICIPANTS: Nondiabetic individuals with insomnia (mean [standard deviation] age 48 [9] y, body mass index 25.6 [3.9] kg/m(2)) with ≤ 6 h (short sleep, n = 14) and > 6 h of sleep (n = 14) during overnight laboratory polysomnography. MEASUREMENTS AND RESULTS: Standard oral glucose testing was used to assess glucose tolerance, beta-cell function (homeostasis model assessment [HOMA-B]; second-phase insulin secretion) and insulin resistance (HOMA-IR; insulin sensitivity index). There was no significant difference in hemoglobin A1C and fasting or 2-h blood glucose concentrations between sleep groups. Short-sleep insomnia sufferers had lower fasting and postchallenge serum insulin concentrations associated with lower estimates of fasting and glucose-stimulated insulin secretion, and increased insulin sensitivity. CONCLUSIONS: Individuals with short-sleep insomnia appear to have higher indices of systemic insulin sensitivity and secrete less insulin without changes in overall glucose tolerance.

Effects of sleep restriction on the human plasma metabolome.

This study examined the effects of recurrent sleep restriction on the plasma metabolome of adults with familial risk of type 2 diabetes. Eleven healthy adults (6M/5F; mean [SD] age: 26 [3]years; BMI 23.5 [2.3]kg/m(2)) with parental history of type 2 diabetes participated in a two-condition, two-period randomized crossover study at the Clinical Resource Center at an academic hospital. Each participant completed two 8-night inpatient sessions with restricted (5.5-h time-in-bed) vs. adequate (8.5-h time-in-bed) sleep opportunity while daily food intake and physical activity were carefully controlled. A combination of two UHPLC/MS/MS platforms and one GC/MS platform was used to measure 362 biochemicals in fasting plasma samples collected from study participants the morning after each 8-night sleep treatment. Relative concentrations of 12 amino acids and related metabolites were increased when sleep was curtailed. Sleep restriction also induced elevations in several fatty acid, bile acid, steroid hormone, and tricarboxylic acid cycle intermediates. In contrast, circulating levels of glucose, some monosaccharides, gluconate, and five-carbon sugar alcohols tended to decline when sleep was reduced. Recurrent sleep curtailment affected multiple pathways of intermediary metabolism in adults at risk for type 2 diabetes. An elevation in plasma amino acids and related biochemicals was the most pronounced metabolic signature seen in response to 8 nights of sleep restriction.

Update on energy homeostasis and insufficient sleep.

Driven by the demands and opportunities of modern life, many people habitually sleep less than 6 h a night. In the sleep clinic, chronic sleep restriction is recognized by the diagnosis of insufficient sleep syndrome (ICSD-9, 307.49-4), which is receiving increased scrutiny as a potential risk to metabolic health. Its relevance for the practicing endocrinologist is highlighted by a stream of epidemiological data that show an association of insufficient sleep with increased incidence of obesity and related morbidities. A central theme of this update is the notion that sleep loss incurs additional metabolic cost, which triggers a set of neuroendocrine, metabolic, and behavioral adaptations aimed at increasing food intake and conserving energy. Although this coordinated response may have evolved to offset the metabolic demands of extended wakefulness in natural habitats with limited food availability, it can be maladaptive in the context of a modern environment that allows many to overeat while maintaining a sedentary lifestyle without sufficient sleep. Importantly, such sleep loss-related metabolic adaptation may undermine the success of behavioral interventions based on reduced caloric intake and increased physical activity to lower metabolic risk in obesity-prone individuals. This emerging perspective is based on data from recently published human interventional studies and requires further experimental support. Nevertheless, it now seems prudent to recommend that overweight and obese individuals attempting to reduce their caloric intake and maintain increased physical activity should obtain adequate sleep and, if needed, seek effective treatment for any coexisting sleep disorders.

Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss.

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-h blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean (s.d.) age 41 (5) years; BMI 27.4 (2.0) kg/m(2)) completed two 14-day treatments with hypocaloric diet and 8.5- or 5.5-h nighttime sleep opportunity in random order 7 (3) months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free fatty acids (FFA), 24-h blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 (0.3) BMI units) during each treatment. Bedtime restriction reduced sleep by 131 (30) min/day. Recurrent sleep curtailment decreased 24-h serum insulin concentrations (i.e., enhanced 24-h insulin economy) without changes in oral glucose tolerance and 24-h glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA, which suppressed normally following glucose ingestion, and lower total and low-density lipoprotein cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-h insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

Sleep and eating behavior in adults at risk for type 2 diabetes.

Insufficient quantity and quality of sleep may modulate eating behavior, everyday physical activity, overall energy balance, and individual risk of obesity and type 2 diabetes. We examined the association of habitual sleep quantity and quality with the self-reported pattern of eating behavior in 53 healthy urban adults with parental history of type 2 diabetes (30 F/23 M; mean (s.d.) age: 27 (4) years; BMI: 23.9 (2.3) kg/m(2)) while taking into consideration the amount of their everyday physical activity. Participants completed 13 (3) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Overnight laboratory polysomnography was used to screen for sleep disorders. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index. Eating behavior was assessed using the original 51-item and the revised 18-item version of the Three-Factor Eating Questionnaire including measures of cognitive restraint, disinhibition, hunger, and uncontrolled and emotional eating. In multivariable regression analyses adjusted for age, BMI, gender, race/ethnicity, level of education, habitual sleep time measured by wrist actigraphy and physical activity measured by waist accelerometry, lower subjective sleep quality was associated with increased hunger, more disinhibited, uncontrolled and emotional eating, and higher cognitive restraint. There was no significant association between the amount of sleep measured by wrist actigraphy and any of these eating behavior factors. Our findings indicate that small decrements in self-reported sleep quality can be a sensitive indicator for the presence of potentially problematic eating patterns in healthy urban adults with familial risk for type 2 diabetes.

Sleep restriction decreases the physical activity of adults at risk for type 2 diabetes.

STUDY OBJECTIVE: To test the hypothesis that recurrent sleep curtailment will result in decreased physical activity in adults at risk for type 2 diabetes. DESIGN: Two-condition 2-period randomized crossover study. SETTING: University General Clinical Research Center. PARTICIPANTS: Eighteen healthy patients with parental history of type 2 diabetes (9 females and 9 males, age 27 yr [standard deviation 3], body mass index 23.7 [2.3] kg/m²). INTERVENTIONS: Two week-long inpatient sessions with 8.5 or 5.5-hr nighttime sleep opportunity. Participants who exercised regularly (39%) could follow their usual exercise routines during both sessions. MEASUREMENTS AND RESULTS: Sleep and total body movement were measured by wrist actigraphy and waist accelerometry. Subjective mood and vigor was assessed using visual analog scales. The main outcome was the comparison of total activity counts between sleep conditions. Ancillary endpoints included changes in sedentary, light, and moderate plus vigorous activity, and their association with changes in mood and vigor. Daily sleep was reduced by 2.3 hr (P < 0.001) and total activity counts were 31% lower (P = 0.020) during the 5.5-hr time-in-bed condition. This was accompanied by a 24% reduction in moderate-plus-vigorous activity time (P = 0.005) and more sedentary behavior (+21 min/day; P = 0.020). The decrease in daily activity during the 5.5-hr time-in-bed condition was seen mostly in participants who exercised regularly (-39 versus -4% in exercisers versus nonexercisers; P = 0.027). Sleep loss-related declines in physical activity correlated strongly with declines in subjective vigor (R = 0.90; P < 0.001). CONCLUSIONS: Experimental sleep restriction results in decreased amount and intensity of physical activity in adults at risk for type 2 diabetes.

Changes in insulin secretion and action in adults with familial risk for type 2 diabetes who curtail their sleep.

OBJECTIVE: Experimental sleep deprivation is accompanied by changes in glucose regulation. However, the effects of chronic sleep insufficiency on insulin secretion and action in populations at high risk for type 2 diabetes are not known. This study examined the relationship between objectively documented habitual sleep curtailment and measures of insulin sensitivity, insulin secretion, and oral glucose tolerance in free-living adults with parental history of type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 47 healthy participants with parental history of type 2 diabetes (26 female/21 male, mean [SD] age 26 [4] years and BMI 23.8 [2.5] kg/m(2)) completed 13 (SD = 2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. Indices of diabetes risk based on oral glucose tolerance tests were compared between participants with habitual short sleep and those with usual sleep duration >6 h/day. RESULTS: Consistent with a behavioral pattern of habitual sleep curtailment, short sleepers obtained an average of 1.5 h less sleep per night and showed signs of increased sleep pressure. Participants who habitually curtailed their sleep had considerably higher indices of insulin resistance and increased insulin secretion but maintained normal glucose tolerance similar to that of subjects who slept more. CONCLUSIONS: Young lean adults with parental history of type 2 diabetes who habitually curtail their sleep have increased insulin resistance and compensatory hyperinsulinemia--a pattern that has been associated with higher risk of developing diabetes in such susceptible individuals.

Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance.

CONTEXT: Epidemiological data indicate that reduced sleep duration is associated with increased incidence of type-2 diabetes. OBJECTIVE: The aim of the study was to test the hypothesis that, when part of a Western-like lifestyle, recurrent bedtime restriction may result in decreased glucose tolerance and reduced insulin secretion and action. DESIGN AND SETTING: We conducted a randomized crossover study at a university clinical research center and sleep research laboratory. PARTICIPANTS: Eleven healthy volunteers (five females and six males) with a mean (+/-sd) age of 39 +/- 5 yr and body mass index of 26.5 +/- 1.5 kg/m(2) participated in the study. INTERVENTION: The study included two 14-d periods of controlled exposure to sedentary living with ad libitum food intake and 5.5- or 8.5-h bedtimes. MAIN OUTCOME MEASURES: Oral and iv glucose challenges were used to obtain measures of glucose tolerance, glucose effectiveness, insulin secretion, and insulin sensitivity at the end of each intervention. Secondary measures included circulating concentrations of the glucose counter-regulatory hormones, cortisol, GH, epinephrine, and norepinephrine. RESULTS: Bedtime restriction reduced daily sleep by 122 +/- 25 min. Both study periods were associated with comparable weight gain; however, recurrent sleep restriction resulted in reduced oral glucose tolerance (2-h glucose value, 144 +/- 25 vs. 132 +/- 36 mg/dl; P < 0.01) and insulin sensitivity [3.3 +/- 1.1 vs. 4.0 +/- 1.6 (mU/liter)(-1) x min(-1); P < 0.03], and increased glucose effectiveness (0.023 +/- 0.005 vs. 0.020 +/- 0.005 min(-1); P < 0.04). Although 24-h cortisol and GH concentrations did not change, there was a modest increase in 24-h epinephrine and nighttime norepinephrine levels during the 5.5-h bedtime condition. CONCLUSIONS: Experimental bedtime restriction, designed to approximate the short sleep times experienced by many individuals in Westernized societies, may facilitate the development of insulin resistance and reduced glucose tolerance.

Sleep curtailment is accompanied by increased intake of calories from snacks.

BACKGROUND: Short sleep is associated with obesity and may alter the endocrine regulation of hunger and appetite. OBJECTIVE: We tested the hypothesis that the curtailment of human sleep could promote excessive energy intake. DESIGN: Eleven healthy volunteers [5 women, 6 men; mean +/- SD age: 39 +/- 5 y; mean +/- SD body mass index (in kg/m(2)): 26.5 +/- 1.5] completed in random order two 14-d stays in a sleep laboratory with ad libitum access to palatable food and 5.5-h or 8.5-h bedtimes. The primary endpoints were calories from meals and snacks consumed during each bedtime condition. Additional measures included total energy expenditure and 24-h profiles of serum leptin and ghrelin. RESULTS: Sleep was reduced by 122 +/- 25 min per night during the 5.5-h bedtime condition. Although meal intake remained similar (P = 0.51), sleep restriction was accompanied by increased consumption of calories from snacks (1087 +/- 541 compared with 866 +/- 365 kcal/d; P = 0.026), with higher carbohydrate content (65% compared with 61%; P = 0.04), particularly during the period from 1900 to 0700. These changes were not associated with a significant increase in energy expenditure (2526 +/- 537 and 2390 +/- 369 kcal/d during the 5.5-h and 8.5-h bedtime periods, respectively; P = 0.58), and we found no significant differences in serum leptin and ghrelin between the 2 sleep conditions. CONCLUSIONS: Recurrent bedtime restriction can modify the amount, composition, and distribution of human food intake, and sleeping short hours in an obesity-promoting environment may facilitate the excessive consumption of energy from snacks but not meals.

Sleep deprivation and energy metabolism: to sleep, perchance to eat?

PURPOSE OF REVIEW: Many people currently sleep only 5-6 h per night. Epidemiological studies have demonstrated that self-reported short sleep is associated with an increased incidence of obesity and diabetes, highlighting the importance of this trend for public health. This finding has triggered renewed research into the mechanisms that link the regulation of mammalian sleep and metabolism. RECENT FINDINGS: In rodents, periods of starvation are accompanied by increased vigilance and sleep loss, presumably to help maximize food finding and energetic survival, whereas sleep deprivation results in increased energy expenditure and weight loss, consistent with a role of sleep in energy conservation and tissue maintenance. Information about the corresponding processes in humans is limited. Available data indicate that despite the presence of qualitative and quantitative differences, human sleep and metabolism also share reciprocal connections. SUMMARY: Evolution in an environment with limited resources has established bidirectional links between sleep and energy homeostasis, the molecular mechanisms of which are emerging rapidly. Epidemiological data suggest that the unique ability of humans to restrict their sleep voluntarily in an environment that promotes physical inactivity and overeating may have a negative impact on metabolic health. Randomized intervention trials are needed to confirm the validity of this hypothesis.