Hanne Kj Gonnissen

Effects of sleep fragmentation on appetite and related hormone concentrations over 24 h in healthy men.

In addition to short sleep duration, reduced sleep quality is also associated with appetite control. The present study examined the effect of sleep fragmentation, independent of sleep duration, on appetite profiles and 24 h profiles of hormones involved in energy balance regulation. A total of twelve healthy male subjects (age 23 (sd 4) years, BMI 24·4 (sd 1·9) kg/m²) completed a 24 h randomised crossover study in which sleep (23.30-07.30 hours) was either fragmented or non-fragmented. Polysomnography was used to determine rapid-eye movement (REM) sleep, slow-wave sleep (SWS) and total sleep time (TST). Blood samples were taken at baseline and continued hourly for the 24 h period to measure glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1) and melatonin concentrations. In addition, salivary cortisol levels were measured. Visual analogue scales were used to score appetite-related feelings. Sleep fragmentation resulted in reduced REM sleep (69·4 min compared with 83·5 min; P< 0·05) and preservation of SWS without changes in TST. In fragmented v. non-fragmented sleep, glucose concentrations did not change, while insulin secretion was decreased in the morning, and increased in the afternoon (P< 0·05), and GLP-1 concentrations and fullness scores were lower (P< 0·05). After dinner, desire-to-eat ratings were higher after fragmented sleep (P< 0·05). A single night of fragmented sleep, resulting in reduced REM sleep, induced a shift in insulin concentrations, from being lower in the morning and higher in the afternoon, while GLP-1 concentrations and fullness scores were decreased. These results may lead to increased food intake and snacking, thus contributing to a positive energy balance.

Effects of sleep fragmentation in healthy men on energy expenditure, substrate oxidation, physical activity, and exhaustion measured over 48 h in a respiratory chamber

BACKGROUND Epidemiologic studies show an inverse or U-shaped relation between sleep duration and BMI. Decreases in total energy expenditure (TEE) and physical activity have been suggested to be contributing factors. OBJECTIVE The objective was to assess the effect of sleep fragmentation on energy metabolism and energy balance in healthy men. DESIGN Fifteen healthy male subjects [mean ± SD BMI (in kg/m(2)): 24.1 ± 1.9; age: 23.7 ± 3.5 y] were included in a randomized crossover study in which energy expenditure, substrate oxidation, and physical activity (by radar) were measured twice for 48 h in a respiration chamber while subjects were monitored by electroencephalography to determine slow-wave sleep (SWS), rapid eye movement (REM) sleep, and total sleeping time (TST). During 2 nights, sleep (2330-0730 h) was either fragmented or nonfragmented. RESULTS Fragmented sleep led to reductions in TST, SWS, and REM sleep (P < 0.001). TEE did not differ (9.96 ± 0.17 compared with 9.83 ± 0.13 MJ/d, NS) between the sleep groups, nor did the components of energy expenditure, with the exception of activity-induced energy expenditure (AEE; 1.63 ± 0.15 compared with 1.42 ± 0.13 MJ/d for fragmented and nonfragmented sleep, respectively; P < 0.05). Physical activity, exhaustion, sleepiness, respiratory quotient (RQ), and carbohydrate oxidation were elevated in comparison with nonfragmented sleep [physical activity counts: 2371 ± 118 compared with 2204 ± 124 counts/d, P < 0.02; exhaustion: 40.1 ± 3.8 compared with 21.8 ± 2.4 mm (by using a visual analog scale; VAS), P < 0.001; sleepiness: 47.4 ± 4.2 compared with 33.9 ± 4.6 mm (VAS), P < 0.001; RQ: 0.94 ± 0.04 compared with 0.91 ± 0.03, P < 0.05; and carbohydrate oxidation: 346.3 ± 23.8 compared with 323.7 ± 22.5 g/d, P < 0.05], whereas fat oxidation was reduced (29.1 ± 9.1 compared with 61.0 ± 6.6 g/d, P < 0.01). CONCLUSIONS Fragmented compared with nonfragmented sleep induced reductions in the most important sleep phases, which coincided with elevated AEE, physical activity, exhaustion, and sleepiness. RQ and carbohydrate oxidation increased and fat oxidation decreased, which may predispose to overweight. This trial is registered at www.who.int/ictrp and www.trialregister.nl as NTR1919.

Chronobiology, endocrinology, and energy- and food-reward homeostasis

Energy‐ and food‐reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy‐ and food‐reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid‐eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic‐pituitary‐adrenal (HPA)‐axis activity, and gut‐peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose‐insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA‐IR) index, leptin concentrations and HPA‐axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward.

Distinct associations between energy balance and the sleep characteristics slow wave sleep and rapid eye movement sleep.

Context:Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB).Objective:To investigate inter-individual relationships between EB (EB=∣energy intake–energy expenditure∣, MJ/24 h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48 h stays in the controlled environment of a respiration chamber.Subjects and methods:A total of 16 men (age 23±3.7 years, BMI 23.9±1.9 kg m−2) stayed in the respiration chamber twice for 48 h to assure EB. Electroencephalography was used to monitor sleep (2330–0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum.Results:The subjects slept on average 441.8±49 min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r=−0.43, P<0.03), and positively related to the amount of REM sleep (r=0.40, P<0.05). Relevant parameters such as hunger, reward, stress and orexigenic hormone concentrations were related to overeating, as well as to the amount of SWS and REM sleep, however, after inclusion of these parameters in a multiple regression, the amount of SWS and REM sleep did not add to the explained variance of EB, which suggests that due to their individual associations, these EB parameters are mediator variables.Conclusion:A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations.

Sleep duration, sleep quality and body weight: parallel developments.

The increase in obesity, including childhood obesity, has developed over the same time period as the progressive decrease in self-reported sleep duration. Since epidemiological studies showed an inverse relationship between short or disturbed sleep and obesity, the question arose, how sleep duration and sleep quality are associated with the development of obesity. In this review, the current literature on these topics has been evaluated. During puberty, changes in body mass index (BMI) are inversely correlated to changes in sleep duration. During adulthood, this relationship remains and at the same time unfavorable metabolic and neuro-endocrinological changes develop, that promote a positive energy balance, coinciding with sleep disturbance. Furthermore, during excessive weight loss BMI and fat mass decrease, in parallel, and related with an increase in sleep duration. In order to shed light on the association between sleep duration, sleep quality and obesity, until now it only has been shown that diet-induced body-weight loss and successive body-weight maintenance contribute to sleep improvement. It remains to be demonstrated whether body-weight management and body composition improve during an intervention concomitantly with spontaneous sleep improvement compared with the same intervention without spontaneous sleep improvement.

Concomitant changes in sleep duration and body weight and body composition during weight loss and 3-mo weight maintenance

BACKGROUND An inverse relation between sleep duration and body mass index (BMI) has been shown. OBJECTIVE We assessed the relation between changes in sleep duration and changes in body weight and body composition during weight loss. DESIGN A total of 98 healthy subjects (25 men), aged 20-50 y and with BMI (in kg/m(2)) from 28 to 35, followed a 2-mo very-low-energy diet that was followed by a 10-mo period of weight maintenance. Body weight, body composition (measured by using deuterium dilution and air-displacement plethysmography), eating behavior (measured by using a 3-factor eating questionnaire), physical activity (measured by using the validated Baeckes questionnaire), and sleep (estimated by using a questionnaire with the Epworth Sleepiness Scale) were assessed before and immediately after weight loss and 3- and 10-mo follow-ups. RESULTS The average weight loss was 10% after 2 mo of dieting and 9% and 6% after 3- and 10-mo follow-ups, respectively. Daytime sleepiness and time to fall asleep decreased during weight loss. Short (≤7 h) and average (>7 to <9 h) sleepers increased their sleep duration, whereas sleep duration in long sleepers (≥9 h) did not change significantly during weight loss. This change in sleep duration was concomitantly negatively correlated with the change in BMI during weight loss and after the 3-mo follow-up and with the change in fat mass after the 3-mo follow-up. CONCLUSIONS Sleep duration benefits from weight loss or vice versa. Successful weight loss, loss of body fat, and 3-mo weight maintenance in short and average sleepers are underscored by an increase in sleep duration or vice versa. This trial was registered at clinicaltrials.gov as NCT01015508.

Sleep Architecture When Sleeping at an Unusual Circadian Time and Associations with Insulin Sensitivity

Circadian misalignment affects total sleep time, but it may also affect sleep architecture. The objectives of this study were to examine intra-individual effects of circadian misalignment on sleep architecture and inter-individual relationships between sleep stages, cortisol levels and insulin sensitivity. Thirteen subjects (7 men, 6 women, age: 24.3±2.5 y; BMI: 23.6±1.7 kg/m2) stayed in a time blinded respiration chamber during three light-entrained circadian cycles (3x21h and 3x27h) resulting in a phase advance and a phase delay. Sleep was polysomnographically recorded. Blood and salivary samples were collected to determine glucose, insulin and cortisol concentrations. Intra-individually, a phase advance decreased rapid eye movement (REM) sleep and slow-wave sleep (SWS), increased time awake, decreased sleep and REM sleep latency compared to the 24h cycle. A phase delay increased REM sleep, decreased stage 2 sleep, increased time awake, decreased sleep and REM sleep latency compared to the 24h cycle. Moreover, circadian misalignment changed REM sleep distribution with a relatively shorter REM sleep during the second part of the night. Inter-individually, REM sleep was inversely associated with cortisol levels and HOMA-IR index. Circadian misalignment, both a phase advance and a phase delay, significantly changed sleep architecture and resulted in a shift in rem sleep. Inter-individually, shorter REM sleep during the second part of the night was associated with dysregulation of the HPA-axis and reduced insulin sensitivity. Trial Registration: International Clinical Trials Registry Platform NTR2926 http://apps.who.int/trialsearch/

Maintenance of energy expenditure on high-protein vs. high-carbohydrate diets at a constant body weight may prevent a positive energy balance.

BACKGROUND & AIMS Relatively high-protein diets are effective for body weight loss, and subsequent weight maintenance, yet it remains to be shown whether these diets would prevent a positive energy balance. Therefore, high-protein diet studies at a constant body weight are necessary. The objective was to determine fullness, energy expenditure, and macronutrient balances on a high-protein low-carbohydrate (HPLC) diet compared with a high-carbohydrate low-protein (HCLP) diet at a constant body weight, and to assess whether effects are transient or sustained after 12 weeks. METHODS A randomized parallel study was performed in 14 men and 18 women [mean ± SD age: 24 ± 5 y; BMI (in kg/m(2)): 22.8 ± 2.0] on diets containing 30/35/35 (HPLC) or 5/60/35 (HCLP) % of energy from protein/carbohydrate/fat. RESULTS Significant interactions between dietary intervention and time on total energy expenditure (TEE) (P = 0.013), sleeping metabolic rate (SMR) (P = 0.040), and diet-induced thermogenesis (DIT) (P = 0.027) appeared from baseline to wk 12. TEE was maintained in the HPLC diet group, while it significantly decreased throughout the intervention period in the HCLP diet group (wk 1: P = 0.002; wk 12: P = 0.001). Energy balance was maintained in the HPLC diet group, and became positive in the HCLP diet group at wk 12 (P = 0.008). Protein balance varied directly according to the amount of protein in the diet, and diverged significantly between the diets (P = 0.001). Fullness ratings were significantly higher in the HPLC vs. the HCLP diet group at wk 1 (P = 0.034), but not at wk 12. CONCLUSIONS Maintenance of energy expenditure on HPLC vs. HCLP diets at a constant body weight may prevent development of a positive energy balance, despite transiently higher fullness. The study was registered on clinicaltrials.gov with Identifier: NCT01551238.

Disadvantageous shift in energy balance is primarily expressed in high-quality sleepers after a decline in quality sleep because of disturbance

BACKGROUND Epidemiologic studies have shown an inverse or U-shaped relation between sleep duration and body mass index (BMI; in kg/m(2)). Moreover, associations between energy balance (EB) and characteristics of quality sleep (QS) have recently been reported. OBJECTIVE We assessed the relation between total energy expenditure (TEE) as well as substrate oxidation and QS after disturbed compared with nondisturbed sleep in EB. DESIGN Fifteen healthy men (mean ± SD BMI: 24.1 ± 1.9; age: 23.7 ± 3.5 y) were included in a randomized crossover study. TEE and substrate oxidation were measured twice for 48 h in a respiration chamber, whereas slow-wave sleep (SWS), rapid eye movement (REM)-sleep, total sleeping time (TST), sleep stage 2 (S2), and QS [(SWS + REM) ÷ TST × 100%] were determined by using electroencephalography. During 2 nights, sleep (2330-0730) was either disturbed or nondisturbed (control). RESULTS Positive correlations were shown for TEE, activity-induced energy expenditure corrected for body mass (AEE/BM), respiratory quotient (RQ), and carbohydrate oxidation with QS and SWS during nondisturbed sleep. Fat oxidation was inversely correlated with QS and SWS. RQ and carbohydrate oxidation were inversely related to REM sleep. During the disturbed condition SWS, REM, TST, and S2 were reduced, and positive correlations were shown between TEE and AEE/BM with QS. The reduction in QS was stronger in high-quality sleepers; QS reduction was positively associated with increases in energy intake, TEE, and EB. CONCLUSION A disadvantageous shift in energy balance is primarily expressed in high-quality sleepers after a decline in QS because of disturbance, implying that good sleepers are most liable to a positive energy balance because of sleep disturbance. This trial was registered at ISRCTN as NTR1919.

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy

Background Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. Objective To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. Methods A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. Results After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). Conclusions In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake. Trial Registration Clinicaltrials.gov NCT01551238.