UMLS:C0037315 - FACTA Search

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Query: UMLS:C0037315 (sleep apnea)
8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During sleep, maintenance of rhythmic breathing is critically dependent on the level of PCO(2), such that if the prevailing spontaneous PCO(2) decreases below the apneic threshold, central sleep apnea (CSA) occurs. Several studies have shown that in patients with systolic heart failure (SHF), presence of a low, awake arterial PCO(2) (Pa(CO(2))) increases the likelihood of developing CSA during sleep. We therefore sought to determine if a low Pa(CO(2)) is a predictor of CSA in patients with cirrhosis of the liver and with normal left ventricular systolic function. In 13 hypocapnic (Pa(CO(2)) < 36 mm Hg, mean = 33 mm Hg) patients with SHF and a mean left ventricular ejection fraction of 23%, the mean apnea-hypopnea index, was 28/hour. CSA accounted for most of the breathing disorders. In 10 hypocapnic (Pa(CO(2)) < 36 mm Hg, mean = 32 mm Hg) patients with cirrhosis and a normal left ventricular ejection fraction (60%), the mean apnea-hypopnea index was 2/hour. The maximum central apnea index was 0.2/hour. There were no significant differences in age, demographics, pulmonary function tests, Pa(O(2)), Pa(CO(2)), minute and alveolar ventilation, and ventilatory responses to CO(2) between the two groups. We conclude that, in contrast to SHF, presence of hypocapnia does not predict CSA in cirrhosis.
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PMID:Hypocapnia is not a predictor of central sleep apnea in patients with cirrhosis. 1565 65

Obstructive sleep apnea (OSA) is a prevalent disorder particularly among middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness.' In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNFalpha plasma levels and the body-mass-index (BMI). In subsequent studies, we showed that IL-6, TNFalpha, and insulin levels were elevated in sleep apnea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnea. Furthermore, our findings that women with the polycystic ovary syndrome (PCOS) (a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness, suggests a pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnea and sleepiness in obese patients may be manifestations of the Metabolic Syndrome, include: obesity without sleep apnea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity, and age; increased prevalence of sleep apnea in post-menopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA; lack of effect of continuous positive airway pressure (CPAP) in obese patients with apnea on hypercytokinemia and insulin resistance indices; and that the prevalence of the metabolic syndrome in the US population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnea in general random samples. Finally, the beneficial effect of a cytokine antagonist on EDS in obese, male apneics and that of exercise on SDB in a general random sample, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnea in humans. In conclusion, accumulating evidence provides support to our model of the bi-directional, feed forward, pernicious association between sleep apnea, sleepiness, inflammation, and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
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PMID:Sleep apnea is a manifestation of the metabolic syndrome. 1589 51

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin-resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically manifest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.
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PMID:Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. 1644 67

Insulin-mediated glucose disposal varies widely in apparently healthy human beings, and the more insulin resistant an individual, the more insulin they must secrete in order to prevent the development of type 2 diabetes. However, the combination of insulin resistance and compensatory hyperinsulinemia increases the likelihood that an individual will be hypertensive, and have a dyslipidemia characterized by a high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentration. These changes increase risk of cardiovascular disease (CVD), and in 1988, this cluster of related abnormalities was designated as comprising a syndrome (X). Several other clinical syndromes are now known to be associated with insulin resistance and compensatory hyperinsulinemia. For example, polycystic ovary syndrome appears to be secondary to insulin resistance and compensatory hyperinsulinemia. More recently, studies have shown that the prevalence of insulin resistance/hyperinsulinemia is increased in patients with nonalcoholic fatty liver disease, and there are reports that certain forms of cancer are more likely to occur in insulin resistant/hyperinsulinemic persons. Finally, there is substantial evidence of an association between insulin resistance/hyperinsulinemia, and sleep disordered breathing. Given the rapid increase in the number of clinical syndromes and abnormalities associated with insulin resistance/hyperinsulinemia, it seems reasonable to suggest that the cluster of these changes related to the defect in insulin action be subsumed under the term of the insulin resistance syndrome. In addition to the identification of additional clinical syndromes related to insulin resistance/hyperinsulinemia, a number of new risk factors have been recognized that would increase CVD risk in these individuals. Thus, in addition to a high TG and a low HDL-C, the atherogenic lipoprotein profile in insulin resistant/hyperinsulinemic individuals also includes the appearance of smaller and denser low density lipoprotein particles, and the enhanced postprandial accumulation of remnant lipoproteins; changes identified as increasing risk of CVD. Elevated plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be associated with increased CVD, and there is evidence of a significant relationship between PAI-1 and fibrinogen levels and both insulin resistance and hyperinsulinemia. Evidence is also accumulating that sympathetic nervous system (SNS) activity is increased in insulin resistant, hyperinsulinemic individuals, and, along with the salt sensitivity associated with insulin resistance/hyperinsulinemia, increases the likelihood that these individuals will develop essential hypertension. The first step in the process of atherogenesis is the binding of mononuclear cells to the endothelium, and mononuclear cells isolated from insulin resistant/hyperinsulinemic individuals adhere with greater avidity. This process is modulated by adhesion molecules produced by endothelial cells, and there is a significant relationship between degree of insulin resistance and the plasma concentration of the several of these adhesion molecules. Further evidence of the relationship between insulin resistance and endothelial dysfunction is the finding that asymmetric dimethylarginine, an endogenous inhibitor of the enzyme nitric oxide synthase, is increased in insulin resistant/hyperinsulinemic individuals. Finally, plasma concentrations of several inflammatory markers are elevated in insulin resistant subjects. It is obvious that the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia contains many well-recognized CVD risk factors, choosing which one, or ones, that are primarily responsible for the accelerated atherogenesis that characterizes this syndrome is not a simple task. Indeed, efforts to try to do so by the use of multiple regression analysis of epidemiological data may be more misleading than helpful.
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PMID:Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. 1648 19

Polycystic ovary syndrome (PCOS) is a syndrome, which can be defined as a group of recognisable patterns of symptoms or abnormalities that indicate a particular medical situation. The current definition of PCOS requires the presence of two of the following three conditions: (i) oligo- and/or anovulation; (ii) clinical and/or biochemical signs of hyperandrogenism; and (iii) polycystic ovaries--and the exclusion of other aetiologies. It is generally accepted that the prevalence of PCOS is approximately 5-10%, and that of polycystic ovaries alone is 21-23%. Other features of PCOS are obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, obstructive sleep apnoea and infertility. An approach to a patient with possible PCOS should be directed towards making a diagnosis and screening for associated endocrine abnormalities. Therapeutic interventions are directed towards addressing the needs of the patient at present and towards preventing long-term complications of the syndrome. Body mass index, which is a primary mediator in the relationship between PCOS and health-related quality of life in obese PCOS adolescents, may play a similar role in other PCOS patients. Any intervention directed at reducing central obesity will not only improve quality of life but also correct hyperinsulinism and improve fertility and lipid and androgen profiles. It is also the only currently available intervention that can have a lifelong impact on reducing possible long-term complications of the syndrome. Lifestyle modification is the cardinal intervention. Pharmacological treatments are available for specific indications. Infertility can be treated with clomifene (clomiphene citrate), metformin, gonadotropins or surgery to the ovaries. Cyproterone (alone or in combination with ethinylestradiol) and spironolactone are the main drugs used in the treatment of hirsutism. Other drugs that can be considered include flutamide, ketoconazole and finasteride. Women with PCOS require ongoing surveillance to detect impaired glucose tolerance, hyperlipidaemia, endometrial hyperplasia and consequent complications. Obese women, in particular, require regular glucose tolerance testing because of the potential for rapid progression from normal to impaired glucose tolerance and diabetes. The focus of this article is the epidemiology, diagnosis and management of this common endocrine disorder. Diagnostic and co-morbid features are discussed separately to facilitate understanding of PCOS. Symptom-directed strategies, as well as short- and long-term goals of treatment, are outlined.
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PMID:Diagnosis and management of polycystic ovary syndrome: a practical guide. 1674 5

Premenopausal women with polycystic ovary syndrome (PCOS) are at a much higher risk for excessive daytime sleepiness, fatigue, and insulin resistance than control women. Elevated levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) are presumably part of the pathogenesis of these clinical manifestations. Forty-two obese women with PCOS, 17 body mass index-comparable obese controls, and 15 normal-weight controls free from apnea participated in the study that included one 8-hour nighttime polysomnography, single morning cytokine plasma concentrations, and insulin resistance indices. Women with PCOS exhibited higher plasma concentrations of IL-6 than obese controls, who had intermediate values, or normal-weight controls, who had the lowest values (4.75 +/- 0.5 vs 3.65 +/- 0.4 vs 1.84 +/- 0.3 pg/mL, P < .01). Tumor necrosis factor alpha values were higher in PCOS and obese controls compared with normal-weight controls, but the difference was not statistically significant (4.05 +/- 0.3 vs 3.79 +/- 0.2 vs 3.14 +/- 0.2 pg/mL, P = .103). Based on backward regression analysis, IL-6 levels had a stronger association with the PCOS group than with the obese group, and the sleep or hypoxia variables did not make a significant contribution to either IL-6 or TNF-alpha. Both IL-6 and TNF-alpha correlated positively with body mass index (P < .01) in obese controls but not in women with PCOS. Furthermore, within the PCOS group, IL-6 and TNF-alpha correlated more strongly with indices of insulin resistance than obesity. We conclude that IL-6 levels are elevated in obese women with PCOS independently of obesity or sleep apnea and may represent a pathophysiologic link to insulin resistance.
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PMID:Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea. 1683 44

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.
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PMID:Night-to-night alterations in sleep apnea type in patients with heart failure. 1691 Oct 35

Obesity has epidemic proportions in Western societies and, because of its significant association with morbidity and mortality, is a major public health issue. Excessive daytime sleepiness (EDS) and fatigue (tiredness without increased sleep propensity)--which have been associated with obesity--have a significant impact on individual well-being and public safety. In this article, we review data that challenge the belief that sleep apnea and sleep disruption per se are the primary determinants of obesity-related daytime sleepiness and fatigue. Specifically, it appears that obesity per se is associated with objective and subjective daytime sleepiness compared to normal-weight controls regardless of sleep apnea and sleep loss. Indeed, obese patients without sleep apnea are sleepier compared to nonobese controls whereas within the morbidly obese, those who have high sleep efficiency at night are sleepier than those who have low sleep efficiency. In addition, in recent studies based on large random samples of the general population, the primary determinants of subjective EDS were depression and metabolic disturbances, that is, obesity/diabetes, and not sleep apnea or objective sleep disruption. Furthermore, sleepiness and fatigue are very prevalent in conditions associated with insulin resistance, for instance, the polycystic ovary syndrome (PCOS), independently of sleep apnea or obesity, or in conditions of insufficient physical activity. On the basis of these data, we propose that obesity-related objective daytime sleepiness and fatigue are associated primarily with metabolic and psychological factors and less with sleep apnea and sleep disruption per se. Furthermore, we suggest that objective sleepiness is primarily related to metabolic factors, whereas fatigue appears to be related to psychological distress. Finally, based on data from studies in normal controls and patients with sleep disorders, we propose that the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and proinflammatory cytokines determines the level of sleep/arousal within the 24-h cycle, that is, "hypercortisolemia" plus hypercytokinemia is associated with low sleep efficiency and fatigue, whereas "eucortisolemia" or "hypocortisolemia" plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness.
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PMID:Obesity-related sleepiness and fatigue: the role of the stress system and cytokines. 1714 48

Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the most common endocrine disorder in this population. It is characterized by chronic anovulation and hyperandrogenism. Affected women may present with reproductive manifestations such as irregular menses or infertility, or cutaneous manifestations, including hirsutism, acne, or male-pattern hair loss. Over the past decade, several serious metabolic complications also have been associated with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty liver disease. In addition to treating symptoms by regulating menstrual cycles and improving hyperandrogenism, it is imperative that clinicians recognize and treat metabolic complications. Lifestyle therapies are first-line treatment in women with polycystic ovary syndrome, particularly if they are overweight. Pharmacological therapies are also available and should be tailored on an individual basis. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. A table summarizing treatment recommendations is provided.
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PMID:Polycystic ovary syndrome: diagnosis and treatment. 1727 49

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