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Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.
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PMID:Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. 1072 86

BACKGROUND: Prader-Willi Syndrome (PRWS) is an uncommon neuroendocrine disorder of genetic origin, described in 1956 by Prader, Labhart and Willi. The main clinical manifestations in the adult are mental retardation, hyperphagia with gross obesity, hypogonadismcriptorhismus and short stature. The life expectancy of the affected individual ranges between 20 and 30 years rarely beyond - due to complications related to excessive obesity. Sustained dieting combined with behavior modification programs, as well as gastric restrictive surgery for obesity, proved to have a high failure rate in PRWS, due to the patients' inability to cooperate in changing their eating habits. METHODS: Biliopancreatic Diversion (BPD), which does not require the patient's cooperation in changing eating habits after surgery, was performed in two PRWS patients (13- and 22-years-old), both with excessive obesity, severe respiratory distress, day sleepiness and limited mobility. RESULTS: Two years after surgery, the 13-year-old had lost 80% of her overweight, while the 22-year-old, after 1 year, had lost 34%. Recent laboratory tests showed normal data in both patients. Their respiratory distress had subsided completely, their mobility improved dramatically, and their self-image and alertness enhanced. CONCLUSION: BPD resulted in an improved quality of life in these patients.
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PMID:Biliopancreatic Diversion in Prader-Willi Syndrome Associated with Obesity. 1073 Dec 52

Sleep problems (i.e., insomnia) affect midlife women as they approach and pass through menopause at rates higher than at most other stages of life. The purpose of this article is to critically review what is known about insomnia (perceived poor sleep) and physiologically assessed sleep, as well as sleep-related disordered breathing (SDB), in women according to menopausal status and the role of hypothalamic-pituitary-ovarian (HPO) hormones. Self-report evidence that sleep difficulties are related to the hormonal changes of menopause is mixed. Data from studies in which sleep was physiologically measured reveal that sleep problems appear corequisite with hot flashes and sweats. Results are difficult to compare across studies because of varying methodologies in how sleep quality and patterns were assessed and how age cohorts and menopausal status were defined. The risk of SDB increases with age, although women are less susceptible at any age than men. As with men, snoring, obesity, and high blood pressure are clear risk factors. Some women may be underdiagnosed for SDB, as they have somewhat different symptom manifestations than men. Usually, frank apnea is not as evident. Primary care clinicians should be mindful of the potential for SDB in women who are obese, have high blood pressure, are cognizant of snoring, and report morning headaches and excessive daytime sleepiness. Improved care will result from consistently incorporating sleep insomnia assessments into practice as a basis for referring to sleep centers as necessary or prescribing sleep-enhancing behavioral and pharmacological treatments.
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PMID:Sleep disturbance in menopause. 1074 14

Sleep-related breathing disorders, ranging from habitual snoring to the increased upper airway resistance syndrome to sleep apnea, are now recognized as major health problems. The majority of patients have excessive daytime sleepiness and tiredness. Neuropsychological dysfunction results in poor work performance, memory impairment, and even depression. Until recently, the coexistence of cardiovascular and cerebrovascular diseases with sleep-related breathing disorders was thought to be the result of shared risk factors, such as age, sex, and obesity. However, in the past 5 years several epidemiologic studies have demonstrated that sleep-related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic tone, and altered baroreflex control during sleep. Sleep apnea may lead to the development of cardiomyopathy and pulmonary hypertension. Early recognition and treatment of sleep-related breathing disorders may improve cardiovascular function.
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PMID:Sleep-related breathing disorders and cardiovascular disease. 1075 96

Obesity is a well-known cause of upper airway narrowing, respiratory failure and resulting hypoxemia and hypercapnia, and cardiac arrhythmias during sleep. Obese patients are prone to snore loudly and to develop obstructive sleep apnea syndrome and also obesity-hypoventilation syndrome. Repeated nocturnal upper airway obstruction may cause respiratory failure and cor pulmonale and frequent awakenings, and result in nocturnal choking, with daytime drowsiness, somnolence and irritability. The purpose of this article is to review the evidence for these accepted facts and to consider a variety of new information that relates to the pathogenesis, symptomatology and treatment of sleep disorders caused by obesity.
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PMID:Sleep-related Disorders in the Obese. 1076 3

Objective: To determine factors affecting sleep disturbances in children.Background: Factors affecting sleep disturbances have been studied extensively in adults, but relatively few studies have been done in children.Methods: As part of the twelfth survey of the Tucson Epidemiologic Study of Obstructive Airways Disease (TESOAD, 1991-1992), children, ages 3-14, of adult cohort members were administered a health questionnaire which contained items related to sleep problems as well as items related to respiratory diseases and symptoms. Participants were classified as having sleep disturbances if they reported disorders of initiating and maintaining sleep (DIMS), excessive daytime sleepiness (EDS) or snoring. Potential factors affecting sleep included age, gender, obesity, asthma, other bronchial problems, cough and sputum production, wheezing and rhinitis.Results: The overall prevalence rates were 16.8, 4 and 22.9% for DIMS, EDS, and snoring, respectively. We found a significantly higher prevalence of DIMS in 11-14-year-old girls (30.4%) and snoring (32.3%) in 3-6-year-old boys. Certain respiratory factors were more prevalent in children with sleep disturbances. Multivariate analysis revealed that risk factors for DIMS included female gender, age 11-14 and wheezing. The risk for EDS was increased in those children with cough and sputum production. Cough and sputum production also were risk factors for snoring as was rhinitis and age 3-6.Conclusions: We conclude that in children as in adults, respiratory symptoms are associated with sleep disturbances. Further, the increased insomnia seen in adult women may begin in early adolescence.
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PMID:Factors affecting sleep disturbances in children and adolescents. 1076 52

The cross-sectional area of the upper airway is known to be lung volume dependent. If, and to what extent, lung volume variables correlate to nocturnal obstructive apnoeas and oxygen desaturations independently of other factors known to affect lung volumes and sleep disordered breathing is still unclear. A total of 92 subjects were examined by ambulatory recording of nocturnal obstructive apnoeas and desaturations. Sixty-nine of the subjects had a history of snoring and 23 were healthy subjects without complaints of snoring and daytime sleepiness. All subjects performed static and dynamic spirometry for measurements of lung volumes. To evaluate the correlation between lung volume variables and apnoea index (AI) and oxygen desaturation index (ODI), simple and multiple regression analysis was performed. Expiratory reserve volume (ERV) was found to be lower in subjects with snoring and apnoeas (ERV = 1.0 l) than in non-snoring subjects (ERV = 1.7 l), (P<0.001). Forced expiratory volume in 1 sec (FEV1)/vital capacity (VC) was slightly, but significantly (P = 0.031), lower in subjects with snoring and nocturnal apnoeas and desaturations. In the multiple regression analysis ERV was found to be independently correlated to both AI (R2=0.13; P=0.001) and ODI (R2 = 0.11; P = 0.002). Multiple regression analysis also revealed that ERV, body mass index (BMI) and habitual smoking together accounted for 43% of the variation in AI and 48% of the variation in ODI. We find a significant independent association between ERV and nocturnal obstructive apnoea and oxygen desaturation frequency. Our results indicate that ERV is correlated to these events to a similar extent, as is obesity.
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PMID:Lung volume and its correlation to nocturnal apnoea and desaturation. 1078 34

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by repeated upper airway narrowing or collapse during sleep. The obstruction is caused by the soft palate and/or base of tongue collapsing against the pharyngeal walls because of decreased muscle tone. These episodes are accompanied by hypoxaemia, surges in blood pressure, brief arousal from sleep and pronounced snoring. Individuals with occult disease are at heightened risk of motorway accidents because of excessive sleepiness, sustained hypertension, myocardial infarction, and stroke. The signs and symptoms of SAHS may be recognisable in the dental practice. Common findings in the medical history include daytime sleepiness, snoring, hypertension, and type 2 diabetes mellitus. Common clinical findings include male gender, obesity, increased neck circumference, excessive fat deposition in the palate, tongue (macroglossia) and pharynx, a long soft palate, a small recessive mandible and maxilla, and calcified carotid artery atheromas on panoramic and lateral cephalometric radiographs. Dentists who recognise these signs and symptoms have an opportunity to diagnose patients with occult SAHS. After confirmation of the diagnosis by a physician, dentists can participate in the management of the disorder by fabricating mandibular advancement appliances that enlarge the retroglossal space by anterior displacement of the tongue and performing corrective upper airway surgery that prevents recurrent airway obstruction.
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PMID:Dentistry's role in the diagnosis and co-management of patients with sleep apnoea/hypopnoea syndrome. 1097 58

Obstructive sleep apnea is a state-dependent syndrome. It is characterized by repeated collapse of the upper airway as the result of the loss of waking neuromuscular drive as the brain changes from wakefulness to sleep. This produces a state-dependent decrease in muscle tone, which, together with other predisposing factors such as obesity and anatomical narrowing of the upper airway, results in the spectrum of sleep disordered breathing. Sleep-disordered breathing describes the continuum from simple snoring (pharyngeal vibration), to flow limitation (hypopnea), to complete cessation of breathing (apnea). Obstructive sleep apnea (OSA) is the common description of what is now appreciated as the sleep apnea/hypopnea syndrome. The cardinal symptoms are snoring, observed apneas, and excessive daytime sleepiness. The immediate physical consequences are hypoxia, repeated sympathetic discharges, increased cardiac load, and repeated brain arousals. The repetitive arousals are required to restore airway patency, resulting in severely fragmented sleep and consequent sleep deprivation. The syndrome, untreated, produces significant cognitive and cardiorespiratory morbidity, and potential mortality. Compared to matched controls, patients with undiagnosed sleep apnea use twice the health resources and spend double the health-care dollars in the 10 years prior to diagnosis. Both trends are reversed by successful treatment. It is by definition a sleep-related illness and can be observed and evaluated only when the patient is asleep. Polysomnography is the laboratory procedure to study sleep and its protean dysfunctions. Multiple physiologic parameters are required to document the various types of sleep disorders as well as to establish the origin of pathologic sleep fragmentation. Complete polysomnography includes (but is not limited to) electroencephalogram (EEG), electrooculogram ((EOG), electromyogram (EMG), electrocardiogram (ECG), respiratory effort, air flow, and oxygen saturation. Treatment options for obstructive sleep apnea include continuous positive airway pressure (CPAP), oral appliances, uvulopalatal and/or maxillomandibular surgery, positional control, and weight loss. The efficacy of each depends on the individual anatomy and the severity of the sleep-disordered breathing. CPAP is accepted as the most reliable treatment regardless of anatomy and severity. It is currently the only treatment modality which can be titrated during sleep and requires simultaneous polysomnography.
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PMID:Obstructive sleep apnea, polysomnography, and split-night studies: consensus statement of the Connecticut Thoracic Society and the Connecticut Neurological Society. 1098 71

An overweight patient (body mass index of 34 kg/m(2)) with narcolepsy associated with cataplexy is described. Polysomnography did not indicate obstructive sleep apnea. Her obesity was treated with sibutramine, a norepinephrine, serotonin and dopamine reuptake inhibiting medication and her severe cataplexy remitted. Clinicians must be aware that sibutramine may suppress cataplexy when evaluating excessive daytime sleepiness in an overweight patient taking this anti-obesity medication. Therefore a negative history of cataplexy in these cases may be misleading and narcolepsy may be overlooked in the differential diagnosis. Sibutramine should be discontinued before polysomnography and multiple sleep latency testing but may be a useful medication in the management of obese narcoleptic patients with cataplexy. With the discovery of decreased hypocretin 1 levels in humans with narcolepsy, a neuropeptide that modulates sleep and feeding, the association between narcolepsy and obesity requires more attention.
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PMID:Narcolepsy and obesity: remission of severe cataplexy with sibutramine. 1115 84


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