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.

http://www.beauty-review.nl/wp-content/uploads/2014/10/Sleep-apnea-and-daytime-sleepiness-and-fatigue-relation-to-visceral-obesity-insulin-resistance-and-hypercytokinemia.pdf

Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia

Rationale: Cross-sectional association has been reported between sleep-disordered breathing (SDB) and insulin resistance, but no prospective studies have been performed to determine whether SDB is causal in the development of diabetes.Objectives: The purpose of our study was to investigate the prevalence and incidence of type II diabetes in subjects with SDB and whether an independent relationship exists between them.Methods: A cross-sectional and longitudinal analysis was performed in 1,387 participants of the Wisconsin Sleep Cohort. Full polysomnography was used to characterize SDB. Diabetes was defined in two ways: (1) physician-diagnosis alone or (2) for those with glucose measurements, either fasting glucose ⩾ 126 mg/dl or physician diagnosis.Measurements and Main Results: There was a greater prevalence of diabetes in subjects with increasing levels of SDB. A total of 14.7% of subjects with an apnea–hypopnea index (AHI) of 15 or more had a diagnosis of diabetes compared with 2.8% of subjects with an ...

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Association of sleep apnea and type II diabetes: a population-based study.

ContextIn young adults, sleep affects the regulation of growth hormone (GH)
and cortisol The relationship between decreased sleep quality in older adults
and age-related changes in the regulation of GH and cortisol is unknownObjectiveTo determine the chronology of age-related changes in sleep duration
and quality (sleep stages) in healthy men and whether concomitant alterations
occur in GH and cortisol levelsDesign and SettingData combined from a series of studies conducted between 1985 and 1999
at 4 laboratoriesSubjectsA total of 149 healthy men, aged 16 to 83 years, with a mean (SD) body
mass index of 241 (23) kg/m2, without sleep complaints or histories
of endocrine, psychiatric, or sleep disordersMain Outcome MeasuresTwenty-four–hour profiles of plasma GH and cortisol levels and
polygraphic sleep recordingsResultsThe mean (SEM) percentage of deep slow wave sleep decreased from 189%
(13%) during early adulthood (age 16-25 years) to 34% (10%) during midlife
(age 36-50 years) and was replaced by lighter sleep (stages 1 and 2) without
significant increases in sleep fragmentation or decreases in rapid eye movement
(REM) sleep The transition from midlife to late life (age 71-83 years) involved
no further significant decrease in slow wave sleep but an increase in time
awake of 28 minutes per decade at the expense of decreases in both light non-REM
sleep (−24 minutes per decade; P<001) and
REM sleep (−10 minutes per decade; P<001)
The decline in slow wave sleep from early adulthood to midlife was paralleled
by a major decline in GH secretion (−372 µg per decade; P<001) From midlife to late life, GH secretion further
declined at a slower rate (−43 µg per decade; P<02) Independently of age, the amount of GH secretion was significantly
associated with slow wave sleep (P<001) Increasing
age was associated with an elevation of evening cortisol levels (+193 nmol/L
per decade; P<001) that became significant only
after age 50 years, when sleep became more fragmented and REM sleep declined
A trend for an association between lower amounts of REM sleep and higher evening
cortisol concentrations independent of age was detected (P<10)ConclusionsIn men, age-related changes in slow wave sleep and REM sleep occur with
markedly different chronologies and are each associated with specific hormonal
alterations Future studies should evaluate whether strategies to enhance
sleep quality may have beneficial hormonal effects

https://jamanetwork.com/journals/jama/articlepdf/192981/JCI00039.pdf

Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men.

Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization. 8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia.

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Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders.

Positive airway pressure (PAP) is used to treat obstructive sleep apnea (OSA), central sleep apnea (CSA), and chronic hypoven- tilation. This document provides a systematic analysis and grading of peer-reviewed, published clinical studies pertaining to application of PAP treatment in adults. The paper is divided into 5 sections, each addressing a series of questions. The first section deals with whether efficacy and/or effectiveness have been demonstrated for continuous PAP (CPAP) treat- ment based on a variety of parameters and the level of OSA severity. Next, CPAP titration conducted with full, attended polysomnography in a sleep laboratory is compared with titration done under various other conditions. The third section investigates what can be expected regarding adherence and compliance with CPAP treatment as measured by subjective and ob- jective methods and what factors may influence these parameters. Side effects and the influence of other specific factors on efficacy, effectiveness and safety of CPAP therapy are evaluated in the fourth section. Finally, the use of bilevel PAP therapy is reviewed for both patients with OSA and those with other selected nocturnal breathing disorders. Each section also contains a brief summary and suggestions for future research.

/pdf/evaluation-of-positive-airway-pressure-treatment-for-sleep-4b0sal1wh9.pdf

Evaluation of positive airway pressure treatment for sleep related breathing disorders in adults.

Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.

Hormonal and Metabolic Profiles in Subjects with Obstructive Sleep Apnea Syndrome and the Acute Effects of Nasal Continuous Positive Airway Pressure (CPAP) Treatment

L. A. Ashworth

Papers

Hormonal and Metabolic Profiles in Subjects with Obstructive Sleep Apnea Syndrome and the Acute Effects of Nasal Continuous Positive Airway Pressure (CPAP) Treatment