Sebastian M. Schmid

Short-term sleep loss decreases physical activity under free-living conditions but does not increase food intake under time-deprived laboratory conditions in healthy men

BACKGROUND Short sleep duration is correlated with an increased risk of developing obesity and cardiovascular disease, but the mechanisms behind this relation are largely unknown. OBJECTIVE We aimed to test the hypothesis that acute sleep loss decreases physical activity while increasing food intake, thereby shifting 2 crucial behavioral components of energy homeostasis toward weight gain. DESIGN In 15 healthy, normal-weight men, spontaneous physical activity was registered by accelerometry during the entire experiment, and food intake as well as relevant hormones were assessed during a 15-h daytime period after 2 nights of regular sleep (bed time: 2245-0700) and after 2 nights of restricted sleep (bed time: 0245-0700). Experiments were performed in a crossover design. RESULTS Sleep restriction significantly decreased physical activity during the daytime spent under free-living conditions after the first night of sleep manipulation (P = 0.008). Also, intensities of physical activity were shifted toward lower levels, with less time spent with intense activities (P = 0.046). Total energy intake, feelings of hunger, and appetite as well as ghrelin and leptin concentrations during day 2 remained unaffected by acute sleep restriction. CONCLUSIONS In contrast to our expectation, short-term sleep loss neither increased food intake nor affected concentrations of the hunger-regulating hormones leptin and ghrelin. However, the observed decrease in daytime physical activity may point to another potentially important behavioral mechanism for the health-impairing influence of sleep loss.

A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normal‐weight healthy men

Sleep loss is currently proposed to disturb endocrine regulation of energy homeostasis leading to weight gain and obesity. Supporting this view, a reduction of sleep duration to 4 h for two consecutive nights has recently been shown to decrease circulating leptin levels and to increase ghrelin levels, as well as self‐reported hunger. We hypothesized that similar endocrine alterations occur even after a single night of sleep restriction. In a balanced order, nine healthy normal‐weight men spent three nights in our sleep laboratory separated by at least 2 weeks: one night with a total sleep time of 7 h, one night with a total sleep time of 4.5 h and one night with total sleep deprivation (SD). On a standard symptom‐rating scale, subjects rated markedly stronger feelings of hunger after total SD than after 7 h sleep (3.9 ± 0.7 versus 1.7 ± 0.3; P = 0.020) or 4.5 h sleep (2.2 ± 0.5; P = 0.041). Plasma ghrelin levels were 22 ± 10% higher after total SD than after 7 h sleep (0.85 ± 0.06 versus 0.72 ± 0.04 ng mL−1; P = 0.048) with intermediate levels of the hormone after 4.5 h sleep (0.77 ± 0.04 ng mL−1). Serum leptin levels did not differ between conditions. Feelings of hunger as well as plasma ghrelin levels are already elevated after one night of SD, whereas morning serum leptin concentrations remain unaffected. Thus, our results provide further evidence for a disturbing influence of sleep loss on endocrine regulation of energy homeostasis, which on the long run may result in weight gain and obesity.

Hypoglycemia Unawareness in Older Compared With Middle-Aged Patients With Type 2 Diabetes

OBJECTIVE Older patients with type 2 diabetes are at a particularly high risk for severe hypoglycemic episodes, and experimental studies in healthy subjects hint at a reduced awareness of hypoglycemia in aged humans. However, subjective responses to hypoglycemia have rarely been assessed in older type 2 diabetic patients. RESEARCH DESIGN AND METHODS We tested hormonal, subjective, and cognitive responses (reaction time) to 30-min steady-state hypoglycemia at a level of 2.8 mmol/l in 13 older (≥65 years) and 13 middle-aged (39–64 years) type 2 diabetic patients. RESULTS Hormonal counterregulatory responses to hypoglycemia did not differ between older and middle-aged patients. In contrast, middle-aged patients showed a pronounced increase in autonomic and neuroglycopenic symptom scores at the end of the hypoglycemic plateau that was not observed in older patients (both P < 0.01). Also, seven middle-aged patients, but only one older participant, correctly estimated their blood glucose concentration to be <3.3 mmol/l during hypoglycemia (P = 0.011). A profound prolongation of reaction times induced by hypoglycemia in both groups persisted even after 30 min of subsequent euglycemia. CONCLUSIONS Our data indicate marked subjective unawareness of hypoglycemia in older type 2 diabetic patients that does not depend on altered neuroendocrine counterregulation and may contribute to the increased probability of severe hypoglycemia frequently reported in these patients. The joint occurrence of hypoglycemia unawareness and deteriorated cognitive function is a critical factor to be carefully considered in the treatment of older patients.

The metabolic burden of sleep loss

In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep loss has become common in modern societies. An increasing number of epidemiological studies show an association between short sleep duration, sleep disturbances, and circadian desynchronisation of sleep with adverse metabolic traits, in particular obesity and type 2 diabetes. Furthermore, experimental studies point to distinct mechanisms by which insufficient sleep adversely affects metabolic health. Changes in the activity of neuroendocrine systems seem to be major mediators of the detrimental metabolic effects of insufficient sleep, through favouring neurobehavioural outcomes such as increased appetite, enhanced sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The effect of curtailed sleep on physical activity and energy expenditure is less clear, but changes are unlikely to outweigh increases in food intake. Although long-term interventional studies proving a cause and effect association are still scarce, sleep loss seems to be an appealing target for the prevention, and probably treatment, of metabolic disease.

Mild Sleep Restriction Acutely Reduces Plasma Glucagon Levels in Healthy Men

BACKGROUND Sleep loss has repeatedly been suggested to affect glucose metabolism adversely, raising the question as to the impact of subtle forms of sleep loss. OBJECTIVE The aim of the study was to assess the effects of a single night of sleep restriction to 4.5 h on endocrine parameters of glucose metabolism. DESIGN We conducted crossover, balanced experiments including two conditions, i.e. one night of 4.5 h and one night of 7 h of sleep. SUBJECTS AND MEASUREMENTS In 10 healthy men, circulating concentrations of insulin, C-peptide, epinephrine, norepinephrine, GH, ACTH, cortisol, and glucagon were measured after sleep and sleep restriction, respectively, during basal rest and a subsequent stepwise hypoglycemic clamp. RESULTS Mild sleep restriction induced a robust reduction in basal plasma glucagon levels that persisted throughout the hypoglycemic clamp (P < 0.03). Basal glucose, insulin, and C-peptide levels were unaffected by sleep restriction. Also, basal and hypoglycemia-stimulated concentrations of epinephrine, norepinephrine, and GH were unchanged after sleep restriction. Concentrations of ACTH (P < 0.05) and cortisol (P < 0.001) were reduced after sleep loss during baseline and at the start of hypoglycemia, but reached roughly comparable levels in both conditions at the end of the clamp (ACTH, P > 0.06; cortisol, P > 0.93). CONCLUSION Our data show that mild restriction of nocturnal sleep to 4.5 h has a reducing effect on circulating glucagon levels. This finding provides further evidence for the notion that glucose homeostasis is sensitive to subtle changes in sleep duration.

Sleep timing may modulate the effect of sleep loss on testosterone

Sleep loss has been shown to reduce secretory activity of the pituitary–gonadal axis in men, but the determinants of this effect are unknown.

Poor prediction of resting energy expenditure in obese women by established equations.

The objective of the study was to evaluate the accuracy of established prediction equations that calculate resting energy expenditure (REE) in obese women. This was a cross-sectional study. In 273 mildly to severely obese women (age, 41.7 +/- 13.2 years; body mass index, 42.8 +/- 7.0 kg/m(2)), REE was measured by indirect calorimetry (mREE), along with fat mass (FM) and fat-free mass (FFM) by bioelectrical impedance analysis. Eleven established equations were used to predict REE (pREE), with 9 equations basing on the anthropometric parameters body weight and height and 2 equations including body composition parameters (FM, FFM). All equations provided pREE values that significantly correlated with mREE (r > 0.66, P < .001), although 8 equations systematically underestimated mREE (P < .05). Of note, even the best equation was not able to accurately predict mREE with a deviation of less than +/-10% in more than 70% of the tested women. Furthermore, equations using body composition data were not superior in predicting REE as compared with equations exclusively including anthropometric variables. Multiple linear regression analyses revealed 2 new equations--one including body weight and age and another including FM, FFM, and age--that explained 56.9% and 57.2%, respectively, of variance in mREE. However, when these 2 new equations were applied to an independent sample of 33 obese women, they also provided an accurate prediction (+/-10%) of mREE in only 56.7% and 60.6%, respectively, of the women. Data show that an accurate prediction of REE is not feasible using established equations in obese women. Equations that include body composition parameters as assessed by bioelectrical impedance analysis do not increase the accuracy of prediction. Based on our results, we conclude that calculating REE by standard prediction equations does not represent a reliable alternative to indirect calorimetry for the assessment of REE in obese women.

Enhanced Thermic Effect of Food After Roux-en-Y Gastric Bypass Surgery

CONTEXT The mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) surgery are incompletely understood. OBJECTIVE Our objective was to investigate changes in metabolic processing of ingested food that may contribute to the weight-reducing effect of RYGB surgery. DESIGN AND SETTING This was a cross-sectional case-control study at the Interdisciplinary Obesity Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland. PATIENTS Ten formerly obese women (mean ± SEM body mass index [BMI] = 26.6 ± 0.9 kg/m(2)) who had undergone RYGB surgery 41.9 ± 9.7 months before, 8 severely obese women (BMI = 40.8 ± 2.0 kg/m(2)), and 10 lean women (BMI = 20.9 ± 0.6 kg/m(2)). INTERVENTION Intervention was a standardized liquid meal test. MAIN OUTCOME The thermic effect of food (TEF), respiratory quotient, and circulating levels of glucose, insulin, and C-peptide were assessed before and repeatedly during the first 90 minutes after the ingestion of a standardized liquid mixed meal containing 39.2 g carbohydrates, 15.4 g protein, and 2.8 g fat. RESULTS TEF area under curve (0-90 minutes) was significantly greater in RYGB patients than in severely obese and lean women (both P < .01). After ingestion of the mixed meal, the respiratory quotient increased to significantly greater values in the RYGB patients than in the severely obese and lean group (P < .001 for ANOVA time × group interaction). Also, the postprandial rise in circulating glucose, insulin, and C-peptide levels was remarkably higher in the RYGB patients than in the other 2 groups (all P < .001 for ANOVA time × group interaction). CONCLUSION Data demonstrate an enhanced TEF after RYGB surgery. Although this observation likely contributes to the weight-reducing effects of the surgery, data also point to an altered metabolic processing of food in RYGB patients characterized by an enhanced glucose absorption and postprandial carbohydrate oxidation.

Pituitary-gonadal and pituitary-thyroid axis hormone concentrations before and during a hypoglycemic clamp after sleep deprivation in healthy men.

Total sleep deprivation (TSD) exerts strong modulatory effects on the secretory activity of endocrine systems that might be related to TSD-induced challenges of cerebral glucose metabolism. Here, we investigate whether TSD affects the course of male pituitary-gonadal and pituitary-thyroid axis related hormones during a subsequent 240-min hypoglycemic clamp. Ten healthy men were tested on 2 different conditions, TSD and 7-hour regular sleep. Circulating concentrations of total testosterone, prolactin (PRL), thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxin (fT4) were measured during baseline and a subsequent hypoglycemic clamp taking place in the morning. Basal, i.e. at 07∶00 am measured, concentrations of total testosterone (P = 0.05) and PRL (P<0.01) were lower while the values of TSH (P = 0.02), fT3 (P = 0.08), and fT4 (P = 0.04) were higher after TSD as compared to regular sleep. During the subsequent hypoglycemic clamp (all measurements from baseline to the end of the clamp analyzed) total testosterone concentrations in the regular sleep (P<0.01) but not in the TSD condition (P = 0.61) decreased, while PRL levels increased (P = 0.05) irrespectively of the experimental condition (P = 0.31). TSH concentrations decreased during hypoglycemia (P<0.01), with this decrease being more pronounced after TSD (P = 0.04). However, at the end of the hypoglycemic clamp concentrations all of the above mentioned hormones did not differ between the two sleep conditions. Our data indicate a profound influence of TSD on male pituitary-gonadal and pituitary-thyroid axis hormones characterized by reduced basal testosterone and PRL levels and increased TSH levels. However, since concentrations of these hormones measured at the end of the 240-min hypoglycemic clamp were not affected by TSD it can be speculated that the influence of TSD on the two endocrine axes is rather short lived or does not interact in an additive manner with their responses to hypoglycemia.

Short-term nocturnal hypoglycaemia increases morning food intake in healthy humans.

Aims  Hypoglycaemia during wakefulness increases hunger and food intake. Patients with Type 1 diabetes mellitus are at high risk of recurrent hypoglycaemia and weight gain. Given the background of frequent hypoglycaemic episodes during night‐time sleep in diabetic patients, we investigated morning food intake after nocturnal hypoglycaemia.