Slobodanka Pejovic

Insomnia with Objective Short Sleep Duration is Associated with Type 2 Diabetes: A Population-based Study

OBJECTIVE We examined the joint effects of insomnia and objective short sleep duration, the combination of which is associated with higher morbidity, on diabetes risk. RESEARCH DESIGN AND METHODS A total of 1,741 men and women randomly selected from Central Pennsylvania were studied in the sleep laboratory. Insomnia was defined by a complaint of insomnia with duration of ≥1 year, whereas poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, or early final awakening. Polysomnographic sleep duration was classified into three categories: ≥6 h of sleep (top 50% of the sample); 5–6 h (approximately third quartile of the sample); and ≤5 h (approximately the bottom quartile of the sample). Diabetes was defined either based on a fasting blood glucose >126 mg/dl or use of medication. In the logistic regression model, we simultaneously adjusted for age, race, sex, BMI, smoking, alcohol use, depression, sleep-disordered breathing, and periodic limb movement. RESULTS Chronic insomnia but not poor sleep was associated with a higher risk for diabetes. Compared with the normal sleeping and ≥6 h sleep duration group, the highest risk of diabetes was in individuals with insomnia and ≤5 h sleep duration group (odds ratio [95% CI] 2.95 [1.2–7.0]) and in insomniacs who slept 5–6 h (2.07 [0.68–6.4]). CONCLUSIONS Insomnia with short sleep duration is associated with increased odds of diabetes. Objective sleep duration may predict cardiometabolic morbidity of chronic insomnia, the medical impact of which has been underestimated.

Selective effects of CPAP on sleep apnoea-associated manifestations

Background  Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.

Leptin and Hunger Levels in Young Healthy Adults After One Night of Sleep Loss

Short‐term sleep curtailment associated with activation of the stress system in healthy, young adults has been shown to be associated with decreased leptin levels, impaired insulin sensitivity, and increased hunger and appetite. To assess the effects of one night of sleep loss in a less stressful environment on hunger, leptin, adiponectin, cortisol and blood pressure/heart rate, and whether a 2‐h mid‐afternoon nap reverses the changes associated with sleep loss, 21 young healthy individuals (10 men, 11 women) participated in a 7‐day sleep deprivation experiment (four consecutive nights followed by one night of sleep loss and two recovery nights). Half of the subjects were randomly assigned to take a mid‐afternoon nap (14:00–16:00 hours) the day following the night of total sleep loss. Serial 24‐h blood sampling and hunger scales were completed on the fourth (predeprivation) and sixth day (postdeprivation). Leptin levels were significantly increased after one night of total sleep loss, whereas adiponectin, cortisol levels, blood pressure/heart rate, and hunger were not affected. Daytime napping did not influence the effects of sleep loss on leptin, adiponectin, or hunger. Acute sleep loss, in a less stressful environment, influences leptin levels in an opposite manner from that of short‐term sleep curtailment associated with activation of the stress system. It appears that sleep loss associated with activation of the stress system but not sleep loss per se may lead to increased hunger and appetite and hormonal changes, which ultimately may lead to increased consumption of ‘comfort’ food and obesity.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

Women sleep objectively better than men and the sleep of young women is more resilient to external stressors: effects of age and menopause

The aims of this study were to: (i) assess gender differences of objective sleep patterns in a general population sample; (ii) evaluate the effects of menopause and hormone treatment (HT) on the sleep of the same cohort; and (iii) examine gender differences in sleep resilience towards external stressors. The participants were (i) 1324 subjects without sleep complaints, recruited from the general population of Central Pennsylvania that spent one night in the sleep laboratory and (ii) 66 young, healthy volunteers whose sleep was disturbed during night four by an external stressor, i.e. 24‐h blood drawing (average of nights 2 and 3 versus night 4). Women compared with men in the general population sample had significantly higher percentage of sleep time, lower percentage of stage 1, and higher percentage of slow wave sleep. Also, menopause, in the absence of HT, was associated with prolonged sleep latency and decreased deep sleep. Finally, young, healthy women compared with men experienced less sleep disturbance because of blood draws as indicated by a significantly smaller change in per cent sleep time, and percentage of stage 1 sleep. These findings suggest that women without sleep complaints sleep objectively better across age than men and the sleep of young women is more resistant to external stressors. Also, gonadal hormones exert a beneficial effect on women’s sleep. This gender dimorphism in sleep regulation may have been to protect women from the demands of infant and child care, and in part, might contribute to women’s lower cardiovascular risks and greater longevity.

Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females

In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA. OSA is associated with sleepiness and inflammation/insulin resistance in nonobese males and females http://ow.ly/qesMA

Obesity and sleep disturbances: meaningful sub-typing of obesity.

Abstract Obesity, excessive daytime sleepiness (EDS), and self-reported short sleep duration appear to be on the rise, while there is evidence that obesity and these sleep disorders are strongly connected. In this paper, we review data that challenge the common belief that the sleep apnoea and sleep loss, frequently associated with obesity, are the primary determinants of obesity-related objective daytime sleepiness and subjective fatigue (tiredness without increased sleep propensity). Specifically, obesity is associated with objective and subjective EDS regardless of the presence of sleep apnoea. The association between obesity and EDS was confirmed in recent studies of large random samples of the general population or clinical samples, which showed that the primary determinants of subjective EDS were depression, metabolic disturbances, i.e. obesity/diabetes and insulin resistance, and lack of physical activity, and, secondarily, sleep apnoea or sleep loss. Paradoxically, within the obese, with or without sleep apnoea, those who slept objectively better at night are sleepier (objectively) during the day than those who slept worse. The distinguishing factor between those that slept better vs. those that slept worse appears to be level of emotional stress. Furthermore, many studies reported that obesity is associated with self-reported short sleep duration; however, it appears that short sleep duration is a marker of emotional stress rather than a reflection of true sleep loss. Based on these data, we propose that obesity-related deeper sleep and objective EDS are primarily related to metabolic disturbances, whereas obesity-related poorer sleep and subjective fatigue appear to be the result of psychological distress. Furthermore, based on data from studies in normal controls and patients with sleep disorders, it appears that the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines determines the level of sleep/arousal within the 24-hour cycle, i.e. “eucortisolemia” or “hypocortisolemia” plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness, whereas “hypercortisolemia” plus hypercytokinemia is associated with low sleep efficiency and fatigue. In conclusion, we propose that the above-reviewed data provide the basis for a meaningful phenotypic and pathophysiologic sub-typing of obesity. One subtype is associated with emotional distress, poor sleep, fatigue, HPA axis “hyperactivity,” and hypercytokinemia while the other is associated with non-distress, better sleep but more sleepiness, HPA axis “normo or hypoactivity,” and hypercytokinemia. This proposed sub-typing may lead to novel, preventive and therapeutic strategies for obesity and its associated sleep disturbances.

Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure.

Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic–pituitary–adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use. 72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment. In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls. These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension. OSA in nonobese men/slightly obese women is associated with HPA axis activation and CPAP lowers HPA axis activity http://ow.ly/Stn94

Objective, but Not Subjective, Sleepiness is Associated With Inflammation in Sleep Apnea

Study objectives: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro‐inflammatory cytokines, that is, interleukin‐6 (IL‐6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL‐6 and decreased levels of cortisol. Methods: We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8‐hour in‐lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty‐four‐hour profiles of IL‐6 and cortisol levels were assessed on the fourth day. Results: The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24‐hour (&bgr; = −0.34, p = .01), daytime (&bgr; = −0.30, p = .02) and nighttime (&bgr; = −0.38, p < .01) IL‐6 levels, and significantly decreased daytime (&bgr; = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL‐6 levels or decreased cortisol levels. Conclusions: Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low‐grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.

Sleep, Sleep Disorders, and Stress

Sleep appears to be an important element in maintaining equilibrium or homeostasis, which is vital for the survival of living organisms. In this article, we review the association between sleep, sleep disorders, and stress, which has been defined as a state of disharmony, or threatened homeostasis.