Edward O. Bixler

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.

SLEEP APNOEA IN A HYPERTENSIVE POPULATION

50 hypertensive patients and 50 normal controls were evaluated in the sleep laboratory for the presence of sleep apnoea or sleep apnoeic activity. Hypertensive patients were at high risk of sleep apnoea; 15 hypertensive patients (30%) had sleep apnoea and another 17 (34%) had sleep apnoeic activity. In contrast, none of the age-matched and sex-matched control subjects had sleep apnoea, and 24% had sleep apnoeic activity. The degree of oxygen desaturation was correlated with the duration as well as the number of apnoeic events. Presence of sleep apnoea in the patients was significantly correlated with higher blood pressure levels when they were initially seen in the clinic. Patients with the most severe sleep apnoea had the highest initial blood-pressure levels and were more refractory to treatment.

Chronic insomnia and activity of the stress system ☆: A preliminary study

The aim of this study was to assess whether there is an association between chronic insomnia and the activity of the stress system. Fifteen young adult insomniacs (<40 years) were studied. After an adaptation night, each subject was recorded in the sleep laboratory for three consecutive nights. During this period, 24-hour urine specimens were collected for measurements of urinary free cortisol (UFC), catecholamines, and growth hormone (GH). The 24-hour UFC levels were positively correlated with total wake time (p=0.05). In addition, 24-hour urinary levels of catecholamine metabolites, DHPG, and DOPAC were positively correlated with percent stage 1 sleep (p<0.05) and wake time after sleep onset (WTASO) (p<0.05). Norepinephrine tended to correlate positively with percent stage 1 sleep (p=0.063) and WTASO (p=0.074), and negatively with percent slow-wave sleep (p=0.059). Twenty-four-hour urinary GH excretion was detectable in only three insomniacs, two of whom had low indices of sleep disturbance. We conclude that, in chronic insomnia, the activity of both limbs of the stress system (i.e., the HPA axis and the sympathetic system) relates positively to the degree of objective sleep disturbance.

Onset of insomnia: role of life-stress events.

&NA; During the year their insomnia began, chronic insomniacs experienced a greater number of stressful life events compared with previous or subsequent years and compared with good sleepers. In addition, among the life event categories assessed, insomniacs reported a greater number of undesirable events, particularly events related to losses and to ill health. They also had lifelong histories of more illnesses and somatic complaints, beginning with more childhood illnesses and more childhood problems related to eating and sleeping. During childhood, insomniacs reported more frequent discontent with their families, and prior to the onset of insomnia, they had less satisfying relationships with their parents as well as problems in other interpersonal relations and in their self‐concepts. Currently, insomniacs felt considerably less satisfied with their lives, had lower self‐concepts, and had greater difficulty with interpersonal relationships. Thus, stressful life events, mediated by certain predisposing factors of personal vulnerability, were found to be closely related to the onset of chronic insomnia.

Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance

Abstract.  Vgontzas AN, Bixler EO, Chrousos GP (Penn State College of Medicine, Hershey, PA; National Institutes of Health, Bethesda, MD, USA). Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance (Minisymposium). J Intern Med 2003; 254:–.

IL-6 and Its Circadian Secretion in Humans

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.

Sleep deprivation effects on the activity of the hypothalamic–pituitary–adrenal and growth axes: potential clinical implications

Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis.

Insomnia in central Pennsylvania.

OBJECTIVE Establish the association between insomnia and various physical and mental health symptoms as well as objective measures of sleep disturbance while controlling for age, gender and BMI in a large random sample of the general public. METHODS A subsample (N=1741) was selected for a single-night sleep laboratory evaluation from a larger random sample (N=16,583) of the general public (20-100 years old). RESULTS The prevalence of insomnia was 7.5% and difficulty sleeping an additional 22.4%. The complaints were more frequent in women and in non-Caucasian minorities. A multivariate logistic regression analysis indicated that depression was the single strongest factor followed by female gender associated with either insomnia or difficulty sleeping. Minority status and a history of colitis, hypertension and anemia were also associated, but to a lesser degree. The final model did not include age, BMI as well as any of the sleep laboratory findings. CONCLUSION These findings support the conclusion that mental health variables have the primary independent association with a complaint of insomnia. Other factors including minorities and hypertension are also independently associated, though to a lesser degree. Other primary sleep disorders, e.g., sleep apnea, do not seem to play a major role in insomnia. These findings underscore the fact that insomnia is a symptom associated with a wide variety of mental and physical health problems requiring a proper psychiatric and medical management.

Rebound Insomnia and Rebound Anxiety: A Review

Rebound insomnia and rebound anxiety are clinical conditions related to withdrawal of certain benzodiazepine drugs. Numerous studies of benzodiazepine and nonbenzodiazepine hypnotics conducted in our sleep laboratory demonstrated that rebound insomnia developed following withdrawal from benzodiazepines with a rapid or intermediate elimination rate. Several studies conducted by other investigators also indicated the development of rebound insomnia under similar conditions. Rebound insomnia and rebound anxiety are discussed in terms of their interrelationship, clinical implications, and receptor mechanisms. Evidence suggests that drugs producing rebound insomnia and rebound anxiety also show a more rapid development of tolerance and greater potential for drug dependence than benzodiazepines where the parent compound or its metabolites have a long elimination half-life.

Sleep and society: an epidemiological perspective.

The relationship between good health and sleep duration has been clearly established in epidemiological studies, although exactly which factors are involved in altering sleep patterns remains to be fully determined. This, at least in part, reflects the complex and multifactorial mechanisms involved in sleep. Subjective sleep duration has slowly declined over the last 50 years, and suboptimal sleep duration and poor sleep quality are becoming widespread in modern society. Suboptimal sleep duration has a strong association with mortality and morbidity; hence there is a need to more clearly understand the mechanisms involved in regulating sleep duration and patterns and to identify high-risk individuals who are in greatest need of preventive strategies. This review focuses on epidemiological evidence of the relationship between sleep duration and various risk factors, including socioeconomic, behavioural and metabolic aspects.