Effects on walking performance and lower body strength by short message service guided training after stroke or transient ischemic attack (The STROKEWALK Study): a randomized controlled trial.

OBJECTIVE: To evaluate whetherdaily mobile-phone delivered messages with training instructions during three months increase physical activity and overall mobility in patients soon after stroke or transient ischemic attack. DESIGN: Randomised controlled trial with intention-to-treat analyses. SETTING: University hospital. Data collection from November 2016 until December2018. SUBJECTS: Seventy-nine patients (mean (SD) age 63.9 (10.4) years, 29 were women) were allocated to either intervention (n = 40) or control group (n = 39). Participants had to be independent (modified Ranking Scale ⩽2) and able to perform the six-minute walking test at discharge from the hospital. INTERVENTIONS: The intervention group received standard care and daily mobile phone instructional text messages to perform regular outdoor walking and functional leg exercises. The control group received standard care; that is, primary care follow-up. MAIN MEASURES: Walking performance by six-minute walking test (m), lower body strength by five times chair-stand test (s), the short physical performance battery (0-12 points) and 10-metres walk test (m/s) were assessed at baseline and after three months. RESULTS: The estimated median difference in the six-minute walking test was in favour of the intervention group by 30 metres (95% CI, 55 to 1; effect size 0.64; P = 0.037) and in the chair-stand test by 0.88 seconds (95% CI, 0.02 to 1.72; effect size 0.64; P = 0.034). There were no differences between groups on the short physical performance battery or in 10-metres walking time. CONCLUSIONS: Three months of daily mobile phone text messages with guided training instructions improved composite mobility measures; that is, walking performanceand lower body strength. CLINICAL TRIAL REGISTRY: The study is registered with ClinicalTrials.gov, number NCT02902367.

Factors associated with changes in walking performance in individuals 3 months after stroke or TIA: secondary analyses from a randomised controlled trial of SMS-delivered training instructions in Sweden.

OBJECTIVES: This study aimed to identify factors related to changes in walking performance in individuals 3 months after a stroke or TIA. DESIGN: Cross-sectional study with post hoc analysis of a randomised controlled study. SETTING: University Hospital, Sweden. PARTICIPANTS: 79 individuals, 64 (10) years, 37% women, who were acutely hospitalised because of stroke or TIA between November 2016 and December 2018. Inclusion criteria were patients aged 18 or above and the major eligibility criterion was the ability to perform the 6 min walking test. INTERVENTION: The intervention group received standard care plus daily mobile phone text messages (short message service) with instructions to perform regular outdoor walking and functional leg exercises in combination with step counting and training diaries. The control group received standard care. OUTCOME MEASURES: Multivariate analysis was performed and age, sex, group allocation, comorbidity, baseline 6 min walk test, body mass index (BMI), cognition and chair-stand tests were entered as possible determinants for changes in the 6 min walk test. RESULTS: Multiple regression analyses showed that age (standardised beta -0.33, 95% CI -3.8 to -1.05, p<0.001), sex (-0.24, 95% CI -66.9 to -8.0, p=0.014), no comorbidity (-0.16, 95% CI -55.5 to 5.4, p=0.11), baseline BMI (-0.29, 95% CI -8.1 to -1.6, p=0.004), baseline 6 min walk test (-0.55, 95% CI -0.5 to -0.3, p<0.001) were associated with changes in 6 min walk test 3 months after the stroke event. The regression model described 36% of the variance in changes in the 6 min walk test. CONCLUSIONS: Post hoc regression analyses indicated that younger age, male sex, lower BMI and shorter 6 min walk test at baseline and possible no comorbidity contributed to improvement in walking performance at 3 months in patients with a recent stroke or TIA. These factors may be important when planning secondary prevention actions. TRIAL REGISTRATION NUMBER: NCT02902367.

Ghrelin and obestatin in human neuroendocrine tumors: expression and effect on obestatin levels after food intake.

BACKGROUND: Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs. MATERIALS AND METHODS: The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs. RESULTS: Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals. CONCLUSION: Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.

Effects of a novel weight-loss combination product containing orlistat and acarbose on obesity: A randomized, placebo-controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. METHODS: The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI ≥30 kg/m2 or ≥28 kg/m2 with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. RESULTS: Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. CONCLUSIONS: This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.

Potential effects on cardiometabolic risk factors and body composition by short message service (SMS)-guided training after recent minor stroke or transient ischaemic attack: post hoc analyses of the STROKEWALK randomised controlled trial.

OBJECTIVES: To evaluate effects of mobile phone text-messaging exercise instructions on body composition, cardiometabolic risk markers and self-reported health at 3 months after stroke. DESIGN: Randomised controlled intervention study with per-protocol analyses. SETTING: University Hospital in Sweden. PARTICIPANTS: Seventy-nine patients (mean (SD) age 64 (10) years, 37% female) ≥18 years with good motor function (modified Rankin Scale ≤2) and capable to perform 6 min walking test at hospital discharge were randomised to either intervention (n=40) or control group (n=39). Key exclusion criteria: subarachnoid bleeding, uncontrolled hypertension, severe psychiatric problems or cognitive limitations. INTERVENTIONS: The intervention group received beyond standard care, daily mobile phone instructional text messages to perform regular outdoor walking and functional leg exercises. The control group received standard care. MAIN OUTCOME MEASURES: Fat mass and fat-free mass were estimated by bioelectric impedance analysis. Cardiometabolic risk factors like blood lipids, glycated haemoglobin and blood glucose were analysed at baseline and after 3 months. RESULTS: Both groups changed favourably in fat-free mass (1.83 kg, 95% CI 0.77 to 2.89; p=0.01, effect size (ES)=0.63 vs 1.22 kg, 95% CI 0.39 to 2.0; p=0.05, ES=0.54) and fat mass (-1.30 kg, 95% CI -2.45 to -0.14; p=0.029, ES=0.41 vs -0.76 kg, 95% CI -1.74 to 0.22; p=0.123, ES=0.28). Also, many cholesterol related biomarkers improved; for example, total cholesterol -0.65 mmol/L, 95% CI -1.10 to -0.2; p=0.06, ES: 0.5 vs -1.1 mmol/L, 95% CI -1.47 to -0.56; p>0.001, ES=0.8. However, there were no between-group differences. At 3 months, 94% and 86%, respectively, reported very good/fairly good health in the text messaging and control groups. CONCLUSIONS: No clear effect of 3 months daily mobile phone delivered training instructions was detected on body composition, cardiovascular biochemical risk factors or self-perceived health. Further research is needed to evaluate secondary prevention efforts in larger populations after recent stroke. TRIAL REGISTRATION NUMBER: NCT02902367.

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose.

The safety of a novel modified-release oral capsule with orlistat and acarbose (MR-OA) was investigated in 67 obese middle-aged White men with a body mass index of 32 to 40 kg/m2 or 30 to 32 kg/m2 plus waist circumference >102 cm. The purpose of this investigation was to compare MR-OA with the existing conventional orlistat regarding systemic safety defined as plasma orlistat concentration at the end of the treatment period of 14 days. Participants took the MR-OA fixed-dose combination formulation 3 times a day together with a major meal. Three different doses of MR-OA were evaluated-60/20, 90/30, and 120/40 (mg orlistat/mg acarbose)-as well as 1 reference group who received the conventional orlistat, Xenical, with 120 mg of orlistat. Blood plasma was sampled on days 1 and 14. The orlistat plasma concentrations of the MR-OA dose showed a delayed absorption and were lower compared with conventional orlistat at the end of the study. All doses were safe and well tolerated without any unexpected adverse events and no serious adverse events. The delay in the rise of orlistat plasma concentration indicates that the modified-release properties of the MR-OA formulation are effective. The systemic exposure of orlistat resulting from MR-OA was similar, albeit a bit lower than the conventional orlistat with 120 mg of orlistat. We can therefore assume that the safety profile regarding the orlistat moiety of MR-OA is comparable to the conventional orlistat and a promising approach for weight control in obese patients. Further clinical evaluation is underway.

Effects of a novel combination of orlistat and acarbose on tolerability, appetite, and glucose metabolism in persons with obesity.

OBJECTIVE: There is an unmet medical need for a safe and effective weight loss product with minimal systemic side-effects. In this study, the effect of a novel modified-release fixed-dose combination of orlistat and acarbose (MR-OA) was compared with conventional orlistat (CO) regarding tolerability, appetite and glucose metabolism. METHODS: Sixty-seven men with obesity, aged 24 to 60 years with body mass indexes (BMIs) 33 to 40 kg m-2 or BMIs 30 to 32 kg m-2 and waist circumference above 102 cm were included. They were randomized to either three different doses of the test formulation MR-OA (60 mg orlistat/20 mg acarbose, 90/30 and 120/40) or CO (Xenical, 120 mg orlistat) for a 2-week study of daily treatment. The participants spent days 1 and 14 at the clinical research centre where they received standardized meals, had blood sampling and filled in questionnaires regarding tolerability and appetite after meals. In days 2 to 13, the participants were at home and continued to fill in the questionnaires daily. RESULTS: In the MR-OA groups, reports of liquid and oily stools as well as faecal incontinence were fewer, whereas reports of gastric distension and flatulence were higher, compared with the CO group. More participants reported decreased hunger in the 90/30 and 120/40 MR-OA, and postprandial plasma glucose concentration was reduced in all MR-OA groups compared with CO. CONCLUSIONS: This study shows that by using a modified-release dosage form, orlistat and acarbose can be combined without compromising tolerability. Furthermore, MR-OA shows promising effects regarding reduction of appetite and reduces postprandial glucose. Tolerability is coupled to compliance and thereby efficacy of a treatment; therefore, this novel combination MR-OA could be an effective approach for weight loss treatment. A follow-up study in a more diverse population and for a longer duration with weight loss as primary outcome variable is planned.

Protocol and pilot study of a short message service-guided training after acute stroke/transient ischemic attack to increase walking capacity and physical activity.

Physical activity in community-living individuals after a stroke is usually scarce. This protocol describes a study that will evaluate a method to increase physical activity by performing a 3-month outdoor walking and muscle strengthening program and will examine the 3-month and 1-year effects of this program on individuals with acute stroke (AS) or transient ischemic attack (TIA). In a prospective randomized controlled trial in Uppsala, Sweden, 80 individuals with AS or TIA who maintained cognitive and motor function will be randomized into groups for continuous training for three months or for regular standard care. The training will be supervised by daily cellphone-delivered messages (short message services; SMS), and the intensity, duration and workload will be gradually increased. The primary outcome is a change in walking capacity according to the 6-Minute Walk Test and chair-rising at three months. Secondary outcomes include mobility, gait speed, handgrip strength, body composition (fat mass and muscle mass), biochemical risk-markers, health-related quality of life, and cardiovascular events. Adherence to the training program will be documented with a self-reported diary and step counts over two weeks. The major study started in November 2016, and results are expected in 2019. In a pilot study of 15 subjects post-stroke (mean-age 65 years), we observed improved walking capacity (increasing from 23 to 255 m) and chair-rising (decreasing 2.42 s) from baseline to three months. SMS-guided outdoor training will be tested as a potential therapeutic strategy to increase physical activity and thereby improve walking capacity and physical function following a stroke.

Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle.

Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia. We studied six healthy subjects after an overnight fast and during an induced 5-hour period of hyperglycemia with hyperinsulinemia. Muscle fatty acid oxidation was calculated using stable isotope methodology combined with blood sampling from the femoral artery and vein of one leg. Muscle functional CPT-1 activity was assessed by concurrently infusing an LCFA tracer and a CPT-independent medium-chain fatty acid tracer. Muscle biopsies were obtained from the vastus lateralis after the periods of fasting and hyperglycemia with hyperinsulinemia. Hyperglycemia with hyperinsulinemia decreased LCFA oxidation, but had no effect on LCFA uptake or medium-chain fatty acid oxidation across the leg. Malonyl-CoA concentration significantly increased from 0.13 +/- 0.01 to 0.35 +/- 0.07 nmol/g during hyperglycemia with hyperinsulinemia. We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle.

Subjective and objective assessment of physical activity - Influence of newly diagnosed exercise induced bronchoconstriction and gender.

AIM: To investigate if occurrence of newly diagnosed exercise induced bronchoconstriction (EIB) would affect adolescents' ability to assess their physical activity. METHODS: 99 selected adolescents with and 47 adolescents without self-reported exercise induced dyspnea were included. All of the 146 adolescents then performed a standardized exercise challenge test on a treadmill with dry-air inhalation to detect EIB. Free living physical activity was assessed during seven days with both accelerometer (objective assessment) and a validated activity diary (subjective assessment). Height, weight and subjective sleep were recorded. RESULTS: Out of the 146 adolescents 49 were diagnosed with EIB. Forty-six of the adolescents with EIB (35 girls and 11 boys) and 84 of the control adolescents (45 girls and 39 boys) had complete 7 day activity diary and accelerometer data. There were no differences in age, BMI and sleep between EIB and control adolescents. Boys with EIB overestimated subjective assessment compared to objective assessment more than girls with EIB. No difference was seen between control boys and girls. Furthermore, boys with EIB reported a much higher frequency of high intensity exercise than girls with EIB, but no difference was observed between control boys and girls. CONCLUSION: Adolescent boys with newly diagnosed EIB overestimated their physical activity compared to EIB girls. Caution may thus be used when choosing methods measuring level of physical activity in this group and especially when investigating gender differences.

Preserved Fat-Free Mass after Gastric Bypass and Duodenal Switch.

BACKGROUND: Concerns for the possibility of an excessive loss of fat-free mass (FFM) and resting metabolic rate (RMR) after bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and duodenal switch (BPD/DS), have been raised. OBJECTIVES: This study aims to examine body composition and RMR in patients after RYGB and BPD/DS and in non-operated controls. METHODS: Body composition and RMR were studied with Bod Pod and indirect calorimetry in weight-stable RYGB (n = 15) and BPD/DS patients (n = 12) and compared with non-operated controls (n = 17). All patients were 30-55 years old and weight stable with BMI 28-35 kg/m2. RESULTS: FFM% was 58% (RYGB), 61% (BPD/DS), and 58% (controls). Body composition did not differ after RYGB and BPD/DS compared to controls, despite 27 and 40% total body weight loss, respectively. No difference in RMR or RMR/FFM was observed (1539, 1617, and 1490 kcal/24 h; and 28.9, 28.4, and 28.8 kcal/24 h/kg). CONCLUSION: Weight-stable patients with BMI 28-35 kg/m2 after RYGB and BPD/DS have a body composition and RMR similar to that of non-operated individuals within the same BMI interval.

Effects of acutely displaced sleep on testosterone.

CONTEXT: It is not yet clear whether the diurnal variation in testosterone is regulated by circadian or homeostatic (sleep) influences. OBJECTIVE: The present study tested whether testosterone is driven by a circadian-independent sleep effect by shifting sleep acutely to daytime in a 24-h sampling regiment. DESIGN, SETTING, AND PARTICIPANTS: In the sleep laboratory, seven healthy young men (age, 22-32 yr) participated in three conditions: habituation (sleep between 2300-0700 h), night sleep (2300-0700 h), and day sleep (0700-1500 h), the latter two in a balanced order. INTERVENTION AND MAIN OUTCOME MEASURE: Serum testosterone was, in all conditions, sampled by hourly blood drawing for 24 h during constant bed rest. RESULTS: Mean testosterone levels increased as a log-linear function of time (hours) across both sleep periods (b = 4.88; P < 0.001), from 15.3 +/- 2.1 to 25.3 +/- 2.2 nmol/liter during night sleep and from 17.3 +/- 2.1 to 26.4 +/- 2.9 nmol/liter during day sleep. Similarly, mean testosterone levels decreased with time (log-linear) awake (b = -1.80; P < 0.001). There was also evidence of a weak circadian component (acrophase ranging between 0651-0924 h) and an increase with time in the laboratory. Moreover, all these effects, except for the increase during sleep, differed significantly between individuals. CONCLUSION: In conclusion, testosterone increased during sleep and fell during waking, whereas circadian effects seemed marginal. Individual differences were pronounced.

Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. OBJECTIVE: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. DESIGN: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. RESULTS: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. CONCLUSIONS: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.

Increased VLDL-TAG turnover during and after acute moderate-intensity exercise.

PURPOSE AND METHODS: Breakdown rates of very low density lipoprotein triacylglycerols (VLDL-TAG) were quantified before (3 h), during (45 min), and after (3 h) moderate physical exercise at 40% VO2 max in young sedentary subjects (four male and four female, age 29.8 +/-1.6 yr, BMI 24.1 +/- 0.9 kg x m, VO2max 37.0 +/- 1.7 mL x kg x min), using boluses of H5-glycerol (100 mu mol x kg) and H2-palmitate (6.6 mu mol x kg). The catabolic rates of VLDL-TAG were calculated from the decay in the isotopic enrichment using a single-pool model. The results were compared with those obtained during 6 h of rest in five of the same volunteers. RESULTS: VLDL-TAG concentration remained constant throughout the study with exercise (P = NS). The fractional catabolic rate was nearly doubled from rest to exercise (P < 0.05 vs rest) and increased to an even greater extent during the early phase of recovery (P < 0.001 vs rest). During the late recovery phase, the value returned to the preexercise value (P = NS vs rest). The values for the absolute catabolic rate (kabs) followed the same trend. CONCLUSION: VLDL-TAG turnover was increased during exercise and during the early phase of recovery.

Performance and sleepiness during a 24 h wake in constant conditions are affected by diet.

This study investigated the effects of high-carbohydrate (HC) and high-fat (HF) diet on cognitive performance, and subjective and objective sleepiness. Seven male participants were kept awake for 24 h in a metabolic ward. Meals were given every 4h and cognitive performance and sleepiness ratings were assessed hourly. The Karolinska Drowsiness Test (KDT, EEG derived) was performed twice after meal. Performance in simple reaction time showed a significant interaction of diet and the post-prandial period, a slower reaction time was observed for the HC-diet 3.5 h after meal intake. Diet did not affect EEG measures but a general post-prandial increase of objective sleepiness was observed 3.5h after meal servings. The HC-diet was significantly associated with an increase of subjective sleepiness. The study demonstrated that the HC-diet caused larger oscillation in performance and increased sleepiness as compared to HF-diet throughout day and night.

Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss.

Shift workers, who are exposed to irregular sleep schedules resulting in sleep deprivation and misalignment of circadian rhythms, have an increased risk of diabetes relative to day workers. In healthy adults, sleep restriction without circadian misalignment promotes insulin resistance. To determine whether the misalignment of circadian rhythms that typically occurs in shift work involves intrinsic adverse metabolic effects independently of sleep loss, a parallel group design was used to study 26 healthy adults. Both interventions involved 3 inpatient days with 10-h bedtimes, followed by 8 inpatient days of sleep restriction to 5 h with fixed nocturnal bedtimes (circadian alignment) or with bedtimes delayed by 8.5 h on 4 of the 8 days (circadian misalignment). Daily total sleep time (SD) during the intervention was nearly identical in the aligned and misaligned conditions (4 h 48 min [5 min] vs. 4 h 45 min [6 min]). In both groups, insulin sensitivity (SI) significantly decreased after sleep restriction, without a compensatory increase in insulin secretion, and inflammation increased. In male participants exposed to circadian misalignment, the reduction in SI and the increase in inflammation both doubled compared with those who maintained regular nocturnal bedtimes. Circadian misalignment that occurs in shift work may increase diabetes risk and inflammation, independently of sleep loss.

Acute Sleep Restriction Reduces Insulin Sensitivity in Adolescent Boys.

BACKGROUND: Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction. OBJECTIVE: We aimed to investigate the effects of partial sleep deprivation on markers of glucose metabolism. Additionally, we aimed to investigate if short sleep duration induces a state of endocrine stress. DESIGN: A randomized crossover design, with 2 experimental conditions: 3 consecutive nights of short sleep (SS, 4 h/night) and long sleep (LS, 9 h/night) duration. SUBJECTS AND MEASUREMENTS: In 21 healthy, normal-weight male adolescents (mean ± SD age: 16.8 ± 1.3 y) we measured pre- and post-prandial glucose, insulin, C-peptide, and glucagon concentrations. Furthermore, we measured fasting cortisol, 24-h catecholamines, and sympathovagal balance. RESULTS: Fasting insulin was 59% higher (P = 0.001) in the SS than the LS condition as was both fasting (24%, P < 0.001) and post-prandial (11%, P = 0.018) C-peptide. Pre- and post-prandial glucose and glucagon were unchanged between conditions. The homeostasis model assessment of insulin resistance (HOMA-IR) index was 65% higher (P = 0.002) and the Matsuda index was 28% lower (P = 0.007) in the SS condition compared to the LS condition. The awakening cortisol response and 24-h norepinephrine were not affected by sleep duration, whereas 24-h epinephrine was 24% lower (P = 0.013) in the SS condition. Neither daytime nor 24-h sympathovagal balance differed between sleep conditions. Short wave sleep was preserved in the SS condition. CONCLUSION: Short-term sleep restriction is associated with decreased insulin sensitivity in healthy normal-weight adolescent boys. There were no indications of endocrine stress beyond this. CITATION: Klingenberg L; Chaput JP; Holmbäck U; Visby T; Jennum P; Nikolic M; Astrup A; Sjödin A. Acute Sleep Restriction Reduces Insulin Sensitivity in Adolescent Boys. SLEEP 2013;36(7):1085-1090.

Sleep restriction is not associated with a positive energy balance in adolescent boys.

BACKGROUND: A short sleep (SS) duration has been linked to obesity in observational studies. However, experimental evidence of the potential mechanisms of sleep restriction on energy balance is conflicting and, to our knowledge, nonexistent in adolescents. OBJECTIVE: We investigated the effects of 3 consecutive nights of partial sleep deprivation on components of energy balance. DESIGN: In a randomized, crossover design, 21 healthy, normal-weight male adolescents (mean ± SD age: 16.8 ± 1.3 y) completed the following 2 experimental conditions, each for 3 consecutive nights: an SS (4 h/night) and a long sleep (LS; 9 h/night) duration. Endpoints were 24-h energy expenditure (EE), spontaneous physical activity (SPA), postintervention diet-induced thermogenesis (DIT), appetite sensations, ad libitum energy intake (EI), and profiles of plasma ghrelin and leptin. RESULTS: The 24-h EE on day 3 was 370 ± 496 kJ higher in the SS condition than in the LS condition (P = 0.003). This difference in EE was explained by prolonged wakefulness in the SS condition and a 19% higher SPA (P = 0.003). In a postintervention breakfast-meal challenge, there was a 0.19-kJ/min smaller incremental AUC in DIT over 4 h in the SS condition than in the LS condition (P = 0.012) with no time × condition effect (P = 0.29). Subjects consumed 13% less energy in the ad libitum meal in the SS condition (P = 0.031), with a concomitant decreased motivation to eat. Concentrations of ghrelin and leptin remained unchanged with sleep restriction. CONCLUSION: Short-term sleep restriction in male adolescents is associated with a small negative energy balance driven by increased EE from prolonged wakefulness and a concomitant decreased EI and motivation to eat. This trial was registered at clinicaltrials.gov as NCT01198431.

Sleeping during the day: effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone.

BACKGROUND: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. METHODS: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. RESULT: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)+22%, P<0.05), and reduced glucose levels (AUC-7%, P<0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's<0.05). CONCLUSION: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples.