Amy C. Reynolds

Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men

Background Sleep restriction is associated with development of metabolic ill-health, and hormonal mechanisms may underlie these effects. The aim of this study was to determine the impact of short term sleep restriction on male health, particularly glucose metabolism, by examining adrenocorticotropic hormone (ACTH), cortisol, glucose, insulin, triglycerides, leptin, testosterone, and sex hormone binding globulin (SHBG). Methodology/Principal Findings N = 14 healthy men (aged 27.4±3.8, BMI 23.5±2.9) underwent a laboratory-based sleep restriction protocol consisting of 2 baseline nights of 10 h time in bed (TIB) (B1, B2; 22:00–08:00), followed by 5 nights of 4 h TIB (SR1–SR5; 04:00–08:00) and a recovery night of 10 h TIB (R1; 22:00–08:00). Subjects were allowed to move freely inside the laboratory; no strenuous activity was permitted during the study. Food intake was controlled, with subjects consuming an average 2000 kcal/day. Blood was sampled through an indwelling catheter on B1 and SR5, at 09:00 (fasting) and then every 2 hours from 10:00–20:00. On SR5 relative to B1, glucose (F 1,168 = 25.3, p<0.001) and insulin (F 1,168 = 12.2, p<0.001) were increased, triglycerides (F 1,168 = 7.5, p = 0.007) fell and there was no significant change in fasting homeostatic model assessment (HOMA) determined insulin resistance (F 1,168 = 1.3, p = 0.18). Also, cortisol (F 1,168 = 10.2, p = 0.002) and leptin (F 1,168 = 10.7, p = 0.001) increased, sex hormone binding globulin (F 1,167 = 12.1, p<0.001) fell and there were no significant changes in ACTH (F 1,168 = 0.3, p = 0.59) or total testosterone (F 1,168 = 2.8, p = 0.089). Conclusions/Significance Sleep restriction impaired glucose, but improved lipid metabolism. This was associated with an increase in afternoon cortisol, without significant changes in ACTH, suggesting enhanced adrenal reactivity. Increased cortisol and reduced sex hormone binding globulin (SHBG) are both consistent with development of insulin resistance, although hepatic insulin resistance calculated from fasting HOMA did not change significantly. Short term sleep curtailment leads to changes in glucose metabolism and adrenal reactivity, which when experienced repeatedly may increase the risk for type 2 diabetes.

Total sleep deprivation, chronic sleep restriction and sleep disruption

Sleep loss may result from total sleep deprivation (such as a shift worker might experience), chronic sleep restriction (due to work, medical conditions or lifestyle) or sleep disruption (which is common in sleep disorders such as sleep apnea or restless legs syndrome). Total sleep deprivation has been widely researched, and its effects have been well described. Chronic sleep restriction and sleep disruption (also known as sleep fragmentation) have received less experimental attention. Recently, there has been increasing interest in sleep restriction and disruption as it has been recognized that they have a similar impact on cognitive functioning as a period of total sleep deprivation. Sleep loss causes impairments in cognitive performance and simulated driving and induces sleepiness, fatigue and mood changes. This review examines recent research on the effects of sleep deprivation, restriction and disruption on cognition and neurophysiologic functioning in healthy adults, and contrasts the similarities and differences between these three modalities of sleep loss.

Sleep and obsessive-compulsive disorder (OCD)

Obsessive-compulsive disorder (OCD) is a chronic mental illness that can have a debilitating effect on daily functioning. A body of research reveals altered sleep behaviour in OCD sufferers; however, findings are inconsistent and there is no consensus on the nature of this relationship. Understanding sleep disturbance in OCD is of critical importance given the known negative consequences of disturbed sleep for mood and emotional wellbeing. A systematic literature search was conducted of five databases for studies assessing sleep in adults diagnosed with OCD. Fourteen studies met inclusion criteria and qualitative data analysis methods were used to identify common themes. There was some evidence of reduced total sleep time and sleep efficiency in OCD patients. Many of the sleep disturbances noted were characteristic of depression. However, some OCD sufferers displayed delayed sleep onset and offset and an increased prevalence of delayed sleep phase disorder (DSPD). Severe OCD symptoms were consistently associated with greater sleep disturbance. While the sleep of OCD patients has not been a major focus to date, the existing literature suggests that addressing sleep disturbance in OCD patients may ensure a holistic approach to treatment, enhance treatment efficacy, mitigate relapse and protect against the onset of co-morbid psychiatric illnesses.

The Children’s Report of Sleep Patterns – Sleepiness Scale: A Self-Report Measure for School-Aged Children

OBJECTIVE To establish the psychometric properties of a self-report measure of daytime sleepiness for school-aged children. METHODS Three hundred eighty-eight children aged 8-12years (inclusive) from paediatricians offices, sleep clinic/labs, childrens hospitals, schools, and the general population were recruited. A multi-method approach was used to validate the Childrens Report of Sleep Patterns--Sleepiness Scale (CRSP-S), including self-report measures (questions about typical sleep), parent-report measures (Childrens Sleep Habits Questionnaire [CSHQ], proxy version of CRSP-S, Childrens Sleep Hygiene Scale [CSHS], morningness-eveningness) and objective measures (actigraphy and polysomnography [PSG]). RESULTS The CRSP-S was shown to be internally consistent (Cronbachs alpha = 0.77) and the scales unidimensionality was supported by a one-factor confirmatory factor analysis. A Rasch-Masters Partial Credit model demonstrated that items cover a broad range of sleepiness experiences with minimal redundancy, gaps in coverage, or bias against age, gender, or clinical groups. Test-retest reliability was 0.82. Construct and convergent validity were demonstrated with actigraphy, parental reports of childrens sleepiness, sleep disturbances, sleep hygiene, circadian preference, and comparison of groups of children (e.g., sleep clinic/lab vs. school children). CONCLUSIONS The CRSP-S is a reliable and valid self-report measure of sleepiness for school-aged children. As an adjunct to parental report measures and objective measures of sleep, the CRSP-S provides a brief and psychometrically robust measure of childrens sleepiness. Children who endorse sleepiness should have a more detailed screening for underlying sleep disruptors or causes of insufficient sleep.

The shift work and health research agenda: Considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease

Prevalence and impact of metabolic disease is rising. In particular, overweight and obesity are at epidemic levels and are a leading health concern in the Western world. Shift work increases the risk of overweight and obesity, along with a number of additional metabolic diseases, including metabolic syndrome and type 2 diabetes (T2D). How shift work contributes to metabolic disease has not been fully elucidated. Short sleep duration is associated with metabolic disease and shift workers typically have shorter sleep durations. Short sleep durations have been shown to elicit a physiological stress response, and both physiological and psychological stress disrupt the healthy functioning of the intestinal gut microbiota. Recent findings have shown altered intestinal microbial communities and dysbiosis of the gut microbiota in circadian disrupted mice and jet lagged humans. We hypothesize that sleep and circadian disruption in humans alters the gut microbiota, contributing to an inflammatory state and metabolic disease associated with shift work. A research agenda for exploring the relationship between insufficient sleep, circadian misalignment and the gut microbiota is provided.

Sickness absenteeism is associated with sleep problems independent of sleep disorders: results of the 2016 Sleep Health Foundation national survey

Introduction: Sleep disorders are associated with sickness absenteeism (SA), at significant economic cost. Correlates of absenteeism are less well described in nonclinical samples. Participants and methods: We determined the relationship between markers of inadequate sleep and SA in a sample of 551 working adults aged ≥18 years across Australia. We considered diagnosed obstructive sleep apnea (OSA) and insomnia symptoms, daytime symptoms, and sleepiness with respect to sickness absenteeism (missing ≥1 day of work in the past 28 days because of problems with physical or mental health). Results: Sickness absenteeism was reported by 27.0% of participants and was more frequent in younger participants, university graduates, and those experiencing financial stress. Sickness absenteeism was independently associated with insomnia (odds ratio [OR] = 2.5, confidence interval [CI] = 1.5‐4.0], OSA (OR = 9.8, CI = 4.7‐20.7), sleep aid use (OR = 3.0, CI = 1.9‐4.7), and daytime symptoms (OR = 3.0, CI = 2.0‐4.6) and inversely associated with perception of getting adequate sleep (OR = 0.6, CI = 0.4‐0.9). Associations persisted in the population free of insomnia and/or OSA. Conclusions: In adults without clinical sleep disorders, sleep behaviors are contributing to sickness absenteeism. An increased focus at an organizational level on improvement of sleep hygiene is important to reduce lost work performance.

Barriers and Enablers to Modifying Sleep Behavior in Adolescents and Young Adults: A Qualitative Investigation

ABSTRACT Objective: Many young adults obtain less than the recommended sleep duration for healthy and safe functioning. Behavior change interventions have had only moderate success in increasing sleep duration for this cohort. This may be because the way young adults think about sleep, including their willingness and ability to change sleep behavior, is unknown. The purpose of the present study was to determine what changes, if any, young adults are willing to make to their sleep behavior, and to identify factors that may enable or prevent these changes. Participants: Fifty-seven young adults (16–25 years; 57% female) took part in focus groups addressing (a) willingness to change, (b) desired outcomes of change, and (c) barriers to change in regards to sleep behavior. Methods: An inductive approach to data analysis was employed, involving data immersion, coding, categorization, and theme generation. Results: Participants were willing to change sleep behavior, and had previously employed strategies including advancing bedtime and minimizing phone use, with limited success. Desired changes were improved waking function, advanced sleep onset, optimized sleep periods, and improved sleep habits. Barriers to making these changes included time demands, technology use, difficulty switching off, and unpredictable habits. Young adults want to improve sleep behavior and waking function; this is an important first step in modifying behavior. Notably, participants wanted more efficient and better quality sleep, rather than increasing sleep duration. Conclusion: The reported barriers to sleep, particularly using technology for social purposes, will require innovative and specialized strategies if they are to be overcome.

Circadian Rhythms Versus Daily Patterns in Human Physiology and Behavior

The endogenous circadian timekeeping system modulates human physiology and behavior with a near 24 h periodicity conferring adaptation to the ~24 h solar light-dark cycle. Thus, the circadian timekeeping system times physiology and behavior so that it is prepared for environmental changes. The term circadian implies an endogenous “clock-driven” process. However, not all observed daily patterns in physiology and behavior are clock driven and instead may be due to environmental or behavioral factors. For example, the barren rock on the top of a mountain shows a daily temperature oscillation that is not endogenous to the rock but instead is caused by the sun heating the rock during the day and radiative heat loss after sunset. Other factors such as wind, rain, and cloud cover impact the observed daily temperature oscillation of the rock. Similarly, some of the daily patterns observed in physiology and behavior are driven by external factors, while others arise from the interaction between circadian and behavioral processes (e.g., sleep-wake, fasting-feeding). To improve understanding of the mechanisms underlying observed daily patterns in physiology and behavior in humans, a variety of circadian protocols have been implemented (Tables 13.1 and 13.2). These protocols will be reviewed in the following pages, and the strengths and limitations of each will be discussed. First, we review markers of the endogenous clock in humans. Table 13.1 Comparison of common experimental procedures for circadian protocols Constant routine Ultrashort sleep-wake schedule Forced desynchrony Shift of sleep to daytime Ambient light Constant dim light (e.g., 1.5 lx in the angle of gaze) Alternating rapid LD cycle (e.g., 20 min, 60 min, or 90 min day) Alternating dim LD cycle (e.g., 20 h, 28 h, or 42.85 h days) Shift of LD cycle on a 24 h day Ambient temperature Constant thermoneutral Controlled yet alternating due to changes in activity and bed microclimate during sleep opportunity Controlled yet alternating due to changes in activity and bed microclimate during sleep opportunity Controlled yet alternating due to changes in activity and bed microclimate during sleep opportunity Food intake/meals Continuous IV feeding or miniature meals divided into isocaloric hourly snacks Snacks Typical BLDS Typical BLDS Posture Bed rest with head of bed raised to 35–45° Alternating ambulatory during wakefulness and supine during sleep Alternating ambulatory during wakefulness and supine during sleep Alternating ambulatory during wakefulness and supine during sleep Wakefulness-sleep Continuous wakefulness Alternating wakefulness and sleep Alternating wakefulness and sleep Alternating wakefulness and sleep Duration Day to days Days Days to weeks Days LD light-dark, BLDS breakfast, lunch, dinner, snack, IV intravenous Table 13.2 Outcomes derived from circadian protocols Constant routine Ultrashort sleep-wake schedule Forced desynchrony Shift of sleep to the daytime Circadian phase Yes, gold standard No, except for melatonin phase Not ideal, except for melatonin phase Not ideal, except for melatonin phase Circadian amplitude Yes No Yes No Circadian period No Yes Yes, gold standard No Circadian oscillations in physiology and behavior Yes Yes Yes Yes Circadian versus sleep-wake modulation of physiology and behavior and interactions No No Yes, gold standard Yes

Influence of Gender on Associations of Obstructive Sleep Apnea Symptoms with Chronic Conditions and Quality of Life

Women are less likely than men to be diagnosed with obstructive sleep apnea (OSA). We examined contemporary gender differences in symptoms, health status, and quality of life associated with diagnosed OSA and OSA symptoms in a population-based sample. A 2015 postal/on-line questionnaire of 2889 active participants of The North West Adelaide Health Study (response rate = 54%, male n = 704; female n = 856; age 30–100 years) assessed previously diagnosed OSA, OSA symptoms, insomnia, doctor-diagnosed medical conditions, and the SF-36. In weighted analyses, self-reported diagnosed OSA (men: 12.6%, n = 95; women: 3.3%, n = 27) and OSA symptoms (men: 17.1%; women: 9.7%) were more common in men. Diagnosed OSA showed stronger adjusted associations with typical OSA features in women, including obesity (women-odds ratio (OR), 95% CI: 5.7, 1.9–17.1, men: 2.2, 1.2–4.0), daytime sleepiness (women: 6.4, 2.7–15.6, men: 3.3, 2.1–5.4), and loud snoring (women: 25.4, 9.4–69.1, men: 8.7, 5.2–14.4). Diagnosed OSA was independently associated with cardiovascular disease (CVD) in men, and in women with high cholesterol, respiratory disease, insomnia, and reduced SF-36 Physical Component Summary score. In both sexes, OSA symptoms were significantly associated with depression, insomnia, and moderate to severe impairments in SF-36 physical and mental component summary scores. Diagnosed women showed clinical characteristics overtly related to OSA. A higher index of clinical suspicion of OSA may be required in women for a condition regarded as male-predominant to increase equity in health outcomes.

Sleep Schedule Regularity is Associated with Sleep Duration in Older Australian Adults: Implications for Improving the Sleep Health and Wellbeing of our Ageing Population

ABSTRACT Objectives: The National Sleep Foundation (NSF) recommends 7 to 9 hours of sleep per night for adults ≥ 65 years of age. Sleep duration below 7h per night has been associated with negative health consequences, so enabling older adults to obtain at least 7 hours per night is important for health and wellbeing. However, little is known about behavioral factors that support sleep duration (≥ 7h/24h) in this group. Our aim was to determine factors associated with sleep duration in older adults, and evaluate the utility of sleep schedule regularity in particular, given the relationship between lifestyle regularity (of which sleep is an important component) and health in this population. Methods: A sample of 311 Australian adults (≥ 65 years old; 156 male, 155 female) completed a telephone survey assessing sleep history over the prior 24 hours, sleep schedule regularity, demographic and health factors as part of a larger study of the Australian population. Results: Sleep schedules with variability in bed and rise times of > 60 minutes were associated with increased odds of reporting sleep duration below 7 hours per night (< 7h/24h; OR = 2.38, CI = 1.26–4.48, p = .007). No other behaviors were associated with meeting sleep duration recommendations. Conclusions: Sleep schedule regularity may be associated with sleep duration (≥ 7h/24h) in older adults. Clinical implications: Empowering older adults to maintain sleep schedule regularity may be a practical and efficacious strategy to support sleep durations that are in line with recommendations (≥ 7h/24h).