leptin and Sleep-Apnea--Obstructive

This narrative review addressed to both clinicians and researchers aims to assess the role of hypoleptinemia in disordered sleep with a particular focus on patients with anorexia nervosa (AN). After introducing circadian rhythms and the regulation of circulating leptin, we summarize the literature on disordered sleep in patients with AN and in fasting subjects in general. We highlight novel single-case reports of substantially improved sleep within days after initiation of off-label metreleptin treatment. These beneficial effects are set in relationship to current knowledge of disordered sleep in animal models of an impaired leptin signaling. Specifically, both absolute and relative hypoleptinemia play a major role in animal models for insomnia, obstructive sleep apnea and obesity hypoventilation syndrome. We pinpoint future research required to complement our understanding of the role of leptin in sleep in patients with acute AN. Moreover, within the section clinical applications we speculate that human recombinant leptin may be useful for the treatment of treatment-resistant sleep-wake disorders, which are associated with (relative) hypoleptinemia. Overall, we stress the role of the hormone leptin in sleep.

Topics: Animals; Anorexia Nervosa; Humans; Leptin; Rodentia; Sleep; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by partial obstruction of upper respiratory tract and repetitive cessation of breathing during sleep. The etiology behind OSA is associated with the occurrence of intermittent hypoxemia, recurrent arousals and intrathoracic pressure swings. These contributing factors may turn on various signaling mechanisms including elevated sympathetic tone, oxidative stress, inflammation, endothelial dysfunction, cardiovascular variability, abnormal coagulation and metabolic defect (

Topics: Cardiovascular Diseases; Humans; Leptin; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is associated with a rise in serum inflammatory markers, which may be attenuated by sleep surgery.. To evaluate whether sleep surgery was associated with improved levels of proinflammatory markers in adults with OSA.. Two authors independently searched Cochrane, Embase, and PubMed databases from inception through June 14, 2022.. Two authors searched the Cochrane, Embase, and PubMed databases for studies comparing preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery.. Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. To ensure relevance to clinicians and patients, the probability of benefit and number needed to treat were calculated for outcomes that demonstrated a statistically significant effect after sleep surgery.. The primary outcome was the preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery, including C-reactive protein (CRP), glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and interleukin-6 (IL-6). Data analysis was performed from April to May 2022.. Of the 3218 studies screened, 26 studies with 1187 patients (mean [SD] age, 42.8 [11.1] years; 932 [78.5%] men and 255 [21.5%] women) were included. Soft-tissue sleep surgery was associated with a large decrease in CRP (SMD, -0.377; 95% CI, -0.617 to -0.137), total cholesterol (SMD, -0.267; 95% CI, -0.417 to -0.116), LDL (SMD, -0.201; 95% CI, -0.344 to -0.058), IL-6 (SMD, -1.086; 95% CI, -1.952 to -0.221), tumor necrosis factor-α (SMD, -0.822; 95% CI, -1.617 to -0.027), triglyceride (SMD, -0.186; 95% CI, -0.301 to -0.071), and leptin (SMD, -0.519; 95% CI, -0.954 to -0.083) in patients with OSA. Meta-regression highlighted that increased age, higher preoperative score for cumulative sleep time percentage with oxyhemoglobin saturation less than 90% (CT90), and greater change in CT90 postoperatively were associated with a greater decrease in serum CRP levels after soft-tissue sleep surgery. A greater reduction in apnea hypopnea index (AHI) was strongly associated with a greater reduction in total cholesterol and LDL. A greater reduction in body mass index and AHI were also associated with a greater increase in HDL.. The findings of this systematic review and meta-analysis of 26 studies suggest that sleep surgery is associated with decreased levels of CRP, total cholesterol, LDL, triglyceride, IL-6, leptin, and TNF-α, which may improve the inflammatory and cardiometabolic profile of patients who undergo sleep surgery.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Sleep; Sleep Apnea, Obstructive; Triglycerides

Obstructive sleep apnea (OSA) as an independent cardiovascular risk factor has been proposed, but the mechanisms underlying cardiovascular disease is far from being completely elucidated. Leptin, an inflammatory cytokine produced by adipocytes, contributes to the modulation of metabolism, respiratory control, and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in children with OSA have shown conflicting results in previous studies.. We performed a meta-analysis to clarify the correlation between leptin expression of the OSA patients following the PRISMA. PubMed, Embase, and Web of Science were systematically searched for relevant studies, and then independently screened by two researchers, and analyzed the data through STATA version 12.0.. In a total of 5 articles including 469 participants, the data analysis showed that serum leptin levels were elevated in children with OSA (MD, 6.36; 95% CI, 0.24-12.49, P < .001), compared to the control group. Subgroup analysis were performed based on body mass index. The results of subgroup analysis demonstrated that the serum leptin concentration was correlated with body mass index in children with OSA (MD, 9.70; 95% CI, 0.22-11.18, P < .001).. The serum leptin levels were elevated in children with OSA, compared to the control group. It could add to our developing understanding of the pathogenesis and potential treatments for children with OSA, and help us to recognize the relevance of OSA in determining cardiovascular issues among children.

Topics: Body Mass Index; Cardiovascular Diseases; Child; Cytokines; Humans; Leptin; Sleep Apnea, Obstructive

Obstructive sleep apnea syndrome (OSAS) is associated with various adipokines. Leptin, a common adipokine, has attracted considerable attention of many researchers in recent years. So far, there has been little agreement on whether blood leptin levels differ in patients with OSAS. Thus, this meta-analysis examined the relationship between serum/plasma leptin levels and the occurrence of OSAS.. WanFang, Embase, CNKI, Medline, SinoMed, Web of Science, and PubMed were searched for articles before March 30, 2021, with no language limitations. STATA version 11.0 and R software version 3.6.1 were used to analyze the obtained data. The weighted mean difference and correlation coefficients were used as the main effect sizes with a random-effects model and a fixed-effects model, respectively. Trial sequential analysis was conducted using dedicated software.. Screening of 34 publications identified 45 studies that met the inclusion criteria of this meta-analysis and meta-regression. Our results suggested that plasma/serum leptin levels were remarkably higher in individuals with OSAS than in healthy individuals. Subgroup analyses were performed based on OSAS severity, ethnicity, age, body mass index, assay type, and sample source. The serum and plasma leptin levels were increased in nearly all OSAS subgroups compared to those in the corresponding control groups. Meta-regression analysis indicated that age, BMI, severity, assay approaches, study design, PSG type and ethnicity did not have independent effect on leptin levels. Furthermore, a positive relationship between the serum/plasma leptin level and apnea-hypopnea index (AHI) was found in the meta-analysis. The results of the trial sequential analysis suggested that the enrolled studies surpassed the required information size, confirming that our study findings were reliable.. Our study results demonstrate that OSAS patients have higher leptin levels in serum/plasma compared to controls, and the serum/plasma leptin level is positively correlated with AHI, especially in adults.

Topics: Adult; Body Mass Index; Case-Control Studies; Humans; Leptin; Obesity; Regression Analysis; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA), obesity, and disturbed glucose homeostasis are usually considered distinct clinical condition, although they are tightly related to each other. The aim of our manuscript is to provide an overview of the current evidence on OSA, obesity, and disturbed glucose homeostasis providing epidemiologic evidence, biological insights, and therapeutic strategies.. The mechanisms hypothesized to be involved in this complex interplay are the following: (1) "direct weight-dependent" mechanisms, according to which fat excess compromises respiratory mechanics, and (2) "indirect weight-dependent" mechanisms such as hyperglycemia, insulin resistance and secondary hyperinsulinemia, leptin resistance and other hormonal dysregulations frequently found in subjects with obesity, type 2 diabetes, and/or sleep disorders. Moreover, the treatment of each of these clinical conditions, through weight loss induced by diet or bariatric surgery, the use of anti-obesity or antidiabetic drugs, and continuous positive airway pressure (CPAP), seems to positively influence the others. These recent data suggest not only that there are multiple connections among these diseases but also that treating one of them may result in an improvement of the others.

Topics: Bariatric Surgery; Body Weight; Continuous Positive Airway Pressure; Diabetes Mellitus, Type 2; Diet; Glucose; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Obesity; Risk Factors; Sleep Apnea, Obstructive; Weight Loss

Obstructive sleep apnea (OSA), characterized by recurrent episodes of apnea during sleep and daytime sleepiness, seriously affects human health and may lead to systemic organ dysfunction. The pathogenesis of OSA is complex and still uncertain, but multiple surveys have shown that obesity is an important factor, and the incidence of OSA in people with obesity is as high as 30%. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and may contribute to OSA. Here, we review the most important and representative research results regarding the correlation between obesity-related adipokines including leptin, adiponectin, omentin-1, chemerin, and resistin and OSA in the past 5 years, provide an overview of these key adipokines, and analyze possible intrinsic mechanisms and influencing factors. The existing research shows that OSA is associated with an increase in the serum levels of leptin, chemerin, and resistin and a decrease in the levels of adiponectin and omentin-1; the findings presented here can be used to monitor the development of OSA and obesity, prevent future comorbidities, and identify risk factors for cardiovascular and other diseases, while different adipokines can be linked to OSA through different pathways such as insulin resistance, intermittent hypoxia, and inflammation, among others. We hope our review leads to a deeper and more comprehensive understanding of OSA based on the relevant literature, which will also provide directions for future clinical research.

Topics: Adipokines; Adiponectin; Chemokines; Cytokines; GPI-Linked Proteins; Humans; Lectins; Leptin; Obesity; Resistin; Risk Factors; Sleep Apnea, Obstructive

Obesity is a global epidemic in developed countries accounting for many of the metabolic and cardiorespiratory morbidities that occur in adults. These morbidities include type 2 diabetes, sleep-disordered breathing (SDB), obstructive sleep apnea, chronic intermittent hypoxia, and hypertension. Leptin, produced by adipocytes, is a master regulator of metabolism and of many other biological functions including central and peripheral circuits that control breathing. By binding to receptors on cells and neurons in the brainstem, hypothalamus, and carotid body, leptin links energy and metabolism to breathing. In this comprehensive article, we review the central and peripheral locations of leptin's actions that affect cardiorespiratory responses during health and disease, with a particular focus on obesity, SDB, and its effects during early development. Obesity-induced hyperleptinemia is associated with centrally mediated hypoventilation with decrease CO

Topics: Adiponectin; Animals; Humans; Leptin; Metabolism, Inborn Errors; Obesity; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Epidemiological studies suggested an association between obesity and sleep disturbances. Obstructive sleep apnea is the most prevalent type of obesity-related sleep disorder that lead to an increased risk for numerous chronic health conditions. In addition the increased visceral adipose tissue might be responsible for the secretion of inflammatory cytokines that could contribute to alter the sleep-wake rhythm. Unhealthy food characterized by high consumption of fat and carbohydrate seems to negatively influence the quality of sleep while diet rich of fiber is associated to more restorative and deeper sleep. Although obesity could cause through several pathogenetic mechanisms an alteration of sleep, it has been reported that subjects suffering from sleep disorders are more prone to develop obesity. Experimental laboratory studies have demonstrated that decreasing either the amount or quality of sleep increase the risk of developing obesity. Experimental sleep restriction also causes physiological, hormonal and food behavioral changes that promote a positive energy balance and a compensatory disproportionate increase in food intake, decrease in physical activity, and weight gain. Thus, the aim of this review is to provide observational evidence on the association of obesity with sleep disturbances and

Topics: Diet; Endocannabinoids; Energy Metabolism; Exercise; Ghrelin; Humans; Hydrocortisone; Leptin; Melatonin; Obesity; Sleep Apnea, Obstructive; Sleep Wake Disorders; Weight Gain

Obesity-related sleep breathing disorders such as obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) cause intermittent hypoxia (IH) during sleep, a powerful trigger of oxidative stress. Obesity also leads to dramatic increases in circulating levels of leptin, a hormone produced in adipose tissue. Leptin acts in the hypothalamus to suppress food intake and increase metabolic rate. However, obese individuals are resistant to metabolic effects of leptin. Leptin also activates the sympathetic nervous system without any evidence of resistance, possibly because these effects occur peripherally without a need to penetrate the blood-brain barrier. IH is a potent stimulator of leptin expression and release from adipose tissue. Hyperleptinemia and leptin resistance may upregulate generation of reactive oxygen species, increasing oxidative stress and promoting inflammation. The current review summarizes recent data on a possible link between leptin and oxidative stress in the pathogenesis of sleep breathing disorders.

Topics: Humans; Hypoxia; Leptin; Obesity; Oxidative Stress; Sleep Apnea, Obstructive

Leptin is a peptide hormone produced mainly in white adipose tissue. It is known to regulate energy homeostasis, inflammation, metabolism, and sympathetic nerve activity. Increasing evidence suggests it has a role in ventilatory function and upper airway obstruction. Leptin levels correlate positively with measurements of adiposity and can potentially provide important insights into the pathophysiology of diseases associated with obesity. Obesity is a strong risk factor for obstructive sleep apnea, a disease characterized by periodic upper airway occlusion during sleep. The neuromuscular activity that maintains upper airway patency during sleep and the anatomy of upper airway are key factors involved in its pathogenesis. Experimental studies using animal models of a low leptin state such as leptin deficiency have shown that leptin regulates sleep architecture, upper airway patency, ventilatory function, and hypercapnic ventilatory response. However, findings from human studies do not consistently support the data from the animal models. The effect of leptin on the pathophysiology of obstructive sleep apnea is being investigated, but the results of studies have been confounded by leptin's diurnal variation and the short-term effects of feeding, adiposity, age, and sex. Improved study design and methods of assessing functional leptin levels, specifically their central versus peripheral effects, will improve understanding of the role of leptin in sleep apnea.

Topics: Animals; Biomarkers; Disease Models, Animal; Humans; Leptin; Mice; Obesity; Rats; Sleep; Sleep Apnea, Obstructive

Obesity and obstructive sleep apnea (OSA) have a reciprocal relationship. Sleep disruptions characteristic of OSA may promote behavioral, metabolic, and/or hormonal changes favoring weight gain and/or difficulty losing weight. The regulation of energy balance (EB), i.e., the relationship between energy intake (EI) and energy expenditure (EE), is complex and multi-factorial, involving food intake, hormonal regulation of hunger/satiety/appetite, and EE via metabolism and physical activity (PA). The current systematic review describes the literature on how OSA affects EB-related parameters. OSA is associated with a hormonal profile characterized by abnormally high leptin and ghrelin levels, which may encourage excess EI. Data on actual measures of food intake are lacking, and not sufficient to make conclusions. Resting metabolic rate appears elevated in OSA vs.. Findings on PA are inconsistent, but may indicate a negative relationship with OSA severity that is modulated by daytime sleepiness and body weight. A speculative explanation for the positive EB in OSA is that the increased EE via metabolism induces an overcompensation in the drive for hunger/food intake, which is larger in magnitude than the rise in EI required to re-establish EB. Understanding how OSA affects EB-related parameters can help improve weight loss efforts in these patients.

Topics: Eating; Energy Metabolism; Exercise; Humans; Leptin; Obesity; Polysomnography; Sleep Apnea, Obstructive

Children with Down syndrome (DS) are more likely to be overweight or obese than the general population of youth without DS.. To review the prevalence of overweight and obesity and their determinants in youth with DS. The health consequences and the effectiveness of interventions were also examined.. A search using MEDLINE, Embase, Web of Science, Scopus, CINAHL, PsycINFO, SPORTDiscus, LILACS, and COCHRANE was conducted. From a total of 4280 studies, we included 45 original research articles published between 1988 and 2015.. The combined prevalence of overweight and obesity varied between studies from 23% to 70%. Youth with DS had higher rates of overweight and obesity than youths without DS. Likely determinants of obesity included increased leptin, decreased resting energy expenditure, comorbidities, unfavorable diet, and low physical activity levels. Obesity was positively associated with obstructive sleep apnea, dyslipidemia, hyperinsulinemia, and gait disorder. Interventions for obesity prevention and control were primarily based on exercise-based programs, and were insufficient to achieve weight or fat loss.. Population-based research is needed to identify risk factors and support multi-factorial strategies for reducing overweight and obesity in children and adolescents with DS.

Topics: Adolescent; Child; Diet; Down Syndrome; Dyslipidemias; Energy Metabolism; Exercise; Exercise Therapy; Humans; Hyperinsulinism; Leptin; Obesity; Overweight; Prevalence; Risk Factors; Sleep Apnea, Obstructive

Obesity is both a cause and a possible consequence of obstructive sleep apnoea (OSA), as OSA seems to affect parameters involved in energy balance regulation, including food intake, hormonal regulation of hunger/satiety, energy metabolism and physical activity. It is known that weight loss improves OSA, yet it remains unclear why continuous positive airway pressure (CPAP) often results in weight gain.The goal of this systematic review is to explore if and how CPAP affects the behaviour and/or metabolism involved in regulating energy balance.CPAP appears to correct for a hormonal profile characterised by abnormally high leptin and ghrelin levels in OSA, by reducing the circulating levels of each. This is expected to reduce excess food intake. However, reliable measures of food intake are lacking, and not yet sufficient to make conclusions. Although studies are limited and inconsistent, CPAP may alter energy metabolism, with reports of reductions in resting metabolic rate or sleeping metabolic rate. CPAP appears to not have an appreciable effect on altering physical activity levels. More work is needed to characterise how CPAP affects energy balance regulation.It is clear that promoting CPAP in conjunction with other weight loss approaches should be used to encourage optimal outcomes in OSA patients.

Topics: Continuous Positive Airway Pressure; Eating; Energy Metabolism; Ghrelin; Humans; Leptin; Obesity; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea hypopnea syndrome (OSAHS), but previous studies assessing the effect of CPAP on leptin in patients with OSAHS yielded conflicting results. In this study, we conducted a meta-analysis to determine whether CPAP therapy could reduce serum leptin levels.. Databases of PubMed, Elsevier, and SCI were thoroughly searched by 2 independent reviewers.. RevMan (version 5.2) was used for data synthesis. Weighted mean difference (WMD) before and after CPAP therapy was calculated to estimate the effects of CPAP therapy.. A total of 11 studies involving 413 participants were included. Meta-analysis showed that the total WMD for leptin levels was 1.44 units (95% confidence interval: 1.11-1.77, P < .01) before and after CPAP therapy. Subgroup analysis exhibited that leptin was decreased within 3 days after the therapy, and it was further reduced within 1 to 3 months and beyond.. The results of our meta-analysis showed that CPAP could significantly reduce leptin levels in OSAHS patients without concomitant weight loss.

Topics: Continuous Positive Airway Pressure; DNA-Binding Proteins; Humans; Leptin; Sleep Apnea, Obstructive; Transcription Factors; Weight Loss

Several epidemiological studies have been conducted to examine the association between leptin and leptin receptor (LEPR) gene polymorphisms and risk of obstructive sleep apnea (OSA). However, the results remain conflicting rather than conclusive.. The aim of this study was to investigate associations of leptin and LEPR polymorphisms and risk of OSA.. We carried out a search in MEDLINE, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.. Overall, no statistically significant association of OSA risk and polymorphisms of Gln233Arg, Lys109Arg, Lys656Asn, 19A/G, Pro1019Arg, and 2548G/A was found. However, in the stratified analysis by ethnicity, Gln233Arg polymorphism was associated with a significantly decreased risk of OSA in European (homozygote comparison: OR = 0.35, 95% CI = 0.14-0.85, P = 0.02), but not for Asian population.. Our study suggested that leptin and LEPR polymorphisms had no association with OSA risk in all examined patients, whereas there was an association between Gln233Arg polymorphism and OSA risk in Europeans.

Topics: Alleles; Asia; Cross-Cultural Comparison; Cross-Sectional Studies; Europe; Humans; Leptin; Polymorphism, Genetic; Receptors, Leptin; Risk; Sleep Apnea, Obstructive; Statistics as Topic

To summarize recent primary publications and discuss the impact these finding have on current understanding on the development of hypoventilation in obesity hypoventilation syndrome (OHS), also known as Pickwickian syndrome.. As a result of the significant morbidity and mortality associated with OHS, evidence is building for pre-OHS intermediate states that can be identified earlier and treated sooner, with the goal of modifying disease course. Findings of alterations in respiratory mechanics with obesity remain unchanged; however, elevated metabolism and CO2 production may be instrumental in OHS-related hypercapnia. Ongoing positive airway pressure trials continue to demonstrate that correction of nocturnal obstructive sleep apnea and hypoventilation improves diurnal respiratory physiology, metabolic profiles, quality of life, and morbidity/mortality. Finally, CNS effects of leptin on respiratory mechanics and chemoreceptor sensitivity are becoming better understood; however, characterization remains incomplete.. OHS is a complex multiorgan system disease process that appears to be driven by adaptive changes in respiratory physiology and compensatory changes in metabolic processes, both of which are ultimately counter-productive. The diurnal hypercapnia and hypoxia induce pathologic effects that further worsen sleep-related breathing, resulting in a slowly progressive worsening of disease. In addition, leptin resistance in obesity and OHS likely contributes to blunting of ventilatory drive and inadequate chemoreceptor response to hypercarbia and hypoxemia.

Topics: Animals; Humans; Hypoxia; Leptin; Metabolic Syndrome; Obesity Hypoventilation Syndrome; Quality of Life; Sleep Apnea, Obstructive

The role of leptin in the development of obstructive sleep apnoea (OSA) has been identified. However, the effects of OSA treatment using continuous positive airway pressure (CPAP) on serum leptin levels remain controversial. To address this issue, a meta-analysis was conducted to evaluate the effects of CPAP therapy on serum leptin levels in OSA.. A comprehensive literature search was performed to identify studies that focused on the effects of CPAP therapy (treatment duration, ≥4 weeks) on the serum leptin levels of OSA patients. Standardised mean difference (SMD) was used to analyse the summary estimates for CPAP therapy.. Fifteen studies involving 427 patients were included in the meta-analysis. Results indicate that the overall SMD of the leptin levels before and after CPAP therapy was 0.137 (95% confidence interval (CI) 0.002 to 0.272); test for overall effect z=1.99 (P=0.046). Sources of heterogeneity were not found by subgroup and meta-regression analyses. Subgroup analyses showed that differences in OSA severity, baseline body mass index, compliance, CPAP duration and leptin assay did not affect the effectiveness of CPAP therapy.. The evidence for the use of CPAP therapy on decrease of leptin levels in OSA patients is low, and stronger evidence is needed.

Topics: Adult; Aged; Continuous Positive Airway Pressure; Female; Humans; Leptin; Male; Middle Aged; Sleep Apnea, Obstructive; Treatment Outcome

The overlap syndrome of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD), in addition to obesity hypoventilation syndrome, represents growing health concerns, owing to the worldwide COPD and obesity epidemics and related co-morbidities. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to a considerable health burden. The coexistence OSA and COPD seems to occur by chance, but the combination can contribute to worsened symptoms and oxygen desaturation at night, leading to disrupted sleep architecture and decreased sleep quality. Alveolar hypoventilation, ventilation-perfusion mismatch and intermittent hypercapnic events resulting from apneas and hypopneas contribute to the final clinical picture, which is quite different from the "usual" COPD. Obesity hypoventilation has emerged as a relatively common cause of chronic hypercapnic respiratory failure. Its pathophysiology results from complex interactions, among which are respiratory mechanics, ventilatory control, sleep-disordered breathing and neurohormonal disturbances, such as leptin resistance, each of which contributes to varying degrees in individual patients to the development of obesity hypoventilation. This respiratory embarrassment takes place when compensatory mechanisms like increased drive cannot be maintained or become overwhelmed. Although a unifying concept for the pathogenesis of both disorders is lacking, it seems that these patients are in a vicious cycle. This review outlines the major pathophysiological mechanisms believed to contribute to the development of these specific clinical entities. Knowledge of shared mechanisms in the overlap syndrome and obesity hypoventilation may help to identify these patients and guide therapy.

Topics: Body Mass Index; Cardiovascular System; Comorbidity; Humans; Leptin; Obesity Hypoventilation Syndrome; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Mechanics; Sleep; Sleep Apnea, Obstructive; Smoking

Recent studies have demonstrated the role of insulin resistance in renal injury related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern similar to that found in diabetic nephropathy. Similarities in the histologic patterns of damage from obesity and diabetes point to overlapping mechanisms of injury. In this review, we will examine the hormonal mechanisms, signaling pathways and injury patterns in renal injury resulting from obesity and attempt to draw conclusions on the reasons for these similarities.

Topics: Adiponectin; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Insulin Resistance; Insulin-Secreting Cells; Kidney; Leptin; Male; Membrane Proteins; Obesity; Podocytes; Resistin; Signal Transduction; Sleep Apnea, Obstructive

This review summarizes the most recent evidence linking decreased sleep duration and poor sleep quality to obesity, focusing upon studies in adults.. Published and unpublished health examination surveys and epidemiological studies suggest that the worldwide prevalence of obesity has doubled since 1980. In 2008, 1 in 10 adults was obese, with women more likely to be obese than men. This obesity epidemic has been paralleled by a trend of reduced sleep duration. Poor sleep quality, which leads to overall sleep loss has also become a frequent complaint. Growing evidence from both laboratory and epidemiological studies points to short sleep duration and poor sleep quality as new risk factors for the development of obesity.. Sleep is an important modulator of neuroendocrine function and glucose metabolism and sleep loss has been shown to result in metabolic and endocrine alterations, including decreased glucose tolerance, decreased insulin sensitivity, increased evening concentrations of cortisol, increased levels of ghrelin, decreased levels of leptin, and increased hunger and appetite. Recent epidemiological and laboratory evidence confirm previous findings of an association between sleep loss and increased risk of obesity.

Topics: Adult; Appetite; Blood Glucose; Female; Ghrelin; Glucose Intolerance; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Neurosecretory Systems; Obesity; Prevalence; Risk Factors; Sleep; Sleep Apnea, Obstructive

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.

Topics: Aging; Animals; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Luteinizing Hormone; Male; Metabolic Syndrome; Obesity; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Spermatogenesis; Testis; Testosterone; Weight Loss

Obstructive sleep apnea syndrome (OSAS) is an often underestimated sleep disorder that has been associated with cardiovascular disease. OSAS is characterized by cycles of apnea and/or hypopnea during sleep caused by the collapse of the upper airways. Intermittent hypoxia deriving from the cycles of apnea/arousals (to retrieve the ventilation) plays a pivotal role in the pathogenesis of the disease. Obesity is the most frequent predisposing condition of OSAS. Recent evidence suggests that OSAS could be considered as a pro-atherosclerotic disease, independently of visceral fat amount. Oxidative stress, cardiovascular inflammation, endothelial dysfunction, and metabolic abnormalities in OSAS could accelerate atherogenesis. The present review is focused on the possible pathophysiological mediators which could favor atherosclerosis in OSAS.

Topics: Atherosclerosis; Cytokines; Disease Progression; Humans; Hypoxia; Inflammation; Leptin; Oxidative Stress; Platelet Aggregation; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is a chronic disease characterized by repetitive partial or complete closure of the upper airway during sleep. OSA tends to be associated with components of metabolic syndrome sharing a common ground of metabolic changes with metabolic syndrome itself. Recent studies showed that subjects with OSA were 6-9 times more likely to have metabolic syndrome than subjects without OSA. Intermittent hypoxia and sleep fragmentation in OSA can initiate intermediary mechanisms (oxidative stress, neurohumoral changes, inflammation) leading to the components of metabolic syndrome. OSA has been suggested to be a novel risk factor, inside the metabolic syndrome, contributing to increased cardiovascular risk. Several studies report that continuous positive airway pressure (CPAP) treatment can reverse pathophysiological changes in OSA, increasing insulin sensitivity and reducing blood pressure. Recent evidences show that CPAP treatment reduces the risk of cardiovascular events and mortality in subjects with OSA. Some subjects with metabolic syndrome can be affected by undiagnosed OSA: CPAP treatment could significantly reduce cardiovascular risk in this subgroup of patients.

Topics: Age Factors; Aged; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Continuous Positive Airway Pressure; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; MEDLINE; Metabolic Syndrome; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Sleep Apnea, Obstructive; Stroke

Collapsible pharyngeal airway size is determined by interaction between structural properties of the pharyngeal airway and neural regulation of the pharyngeal dilating muscles. Obesity seems to have two distinct mechanical influences on the pharyngeal airway collapsibility. First, obesity increases soft tissue surrounding the pharyngeal airway within limited maxillomandible enclosure occupying and narrowing its space (pharyngeal anatomical imbalance). Second, obesity, particularly central obesity, increases visceral fat volume decreasing lung volume. Pharyngeal wall collapsibility is increased by the lung volume reduction, possibly through decreased longitudinal tracheal traction (lung volume hypothesis). Neural compensation for functioning structural abnormalities operating during wakefulness is lost during sleep, leading to pharyngeal obstruction. Instability of the negative feedback of the respiratory system may accelerate cycling of pharyngeal closure and opening. Improvement of the pharyngeal anatomical imbalance and maintenance of lung volume are the keys for safe perioperative airway managements of obese patients with obstructive sleep apnea.

Topics: Airway Resistance; Anesthesia; Functional Residual Capacity; Humans; Hypercapnia; Leptin; Obesity; Perioperative Care; Pharyngeal Muscles; Pharynx; Sleep Apnea, Obstructive; Tongue

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain

The obesity-hypoventilation syndrome (OHS), or alveolar hypoventilation in the obese, has been described initially as the "Pickwickian syndrome". It is defined as chronic alveolar hypoventilation (PaO2<70 mmHg, PaCO2 > or =45 mmHg) in obese patients (body mass index>30 kg/m2) who have no other respiratory disease explaining the hypoxemia-hypercapnia.. The large majority of obese subjects are not hypercapnic, even in case of severe obesity (>40 kg/m2). There are three principal causes, which can be associated, explaining alveolar hypoventilation in obese subjects: high cost of respiration and weakness of the respiratory muscles (probably the major cause), dysfunction of the respiratory centers with diminished chemosensitivity, long-term effects of the repeated episodes of obstructive sleep apneas observed in some patients. The role of leptin (hormone produced by adipocytes) in the pathogenesis of this syndrome, has been recently advocated. OHS is generally observed in subjects over 50 years. Its prevalence has markedly increased in recent years, probably due to the present "epidemic" of obesity. The diagnosis is often made after an episode of severe respiratory failure. Comorbidities, favored by obesity, are very frequent: systemic hypertension, left heart diseases, diabetes.. OHS must be distinguished from obstructive sleep apnea syndrome (OSAS) even if the two conditions are often associated. OSAS may be absent in certain patients with OHS (20% of the patients in our experience). On the other hand obesity may be absent in certain patients with OSAS.. Losing weight is the "ideal" treatment of OHS but in fact it cannot be obtained in most patients. Nocturnal ventilation (continuous positive airway pressure and mainly bilevel non invasive ventilation) is presently the best treatment of OHS and excellent short and long-term results on symptoms and arterial blood gases have been recently reported.

Topics: Age Factors; Chemoreceptor Cells; Diagnosis, Differential; Humans; Leptin; Obesity Hypoventilation Syndrome; Respiratory Muscles; Respiratory Therapy; Sleep Apnea, Obstructive; Work of Breathing

Hypertension and obesity are major components of the cardiometabolic syndrome and are both on the rise worldwide, with enormous consequences on global health and the economy. The relationship between hypertension and obesity is multifaceted; the etiology is complex and it is not well elucidated. This article, reviews the current knowledge on obesity-related hypertension. Further understanding of the underlying mechanisms of this epidemic will be important in devising future treatment avenues.

Topics: Adipocytes; Adiponectin; Animals; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Obesity; Renin-Angiotensin System; Sleep Apnea, Obstructive; Sympathetic Nervous System

To review the concept of a possible link between asthma and obstructive sleep apnea syndrome (OSAS) and the impact on asthma symptoms of treatment of OSAS with continuous positive airway pressure (CPAP) in patients with both conditions.. The Ovid, MEDLINE, and PubMed databases from 1950 to the present were searched for relevant articles regarding a possible relationship between asthma and OSAS and the effectiveness of CPAP in treating OSAS.. Articles describing pathophysiologic conditions occurring in OSAS that may be linked to asthma pathogenesis were used for this review.. The data suggest that OSAS is an independent risk factor for asthma exacerbations. CPAP has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Ameliorative mechanisms of treatment with CPAP include mechanical and neuromechanical effects, gastroesophageal acid reflux suppression, local and systemic anti-inflammatory effects (including suppression of increased serum levels of inflammatory cytokines, chemokines, and vascular endothelial growth factor), cardiac function improvements, leptin level suppression, weight reduction, and sleep restoration.. Asthma and OSAS are increasingly troublesome public health issues. Mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics. We describe potential mechanisms whereby CPAP, the first line of therapy for OSAS, might modify airway smooth muscle function and asthma control in patients with both disorders. Despite the ever-increasing population of patients with both disorders, large, prospective, randomized controlled studies are necessary to more fully evaluate CPAP and asthma outcomes.

Topics: Asthma; Continuous Positive Airway Pressure; Gastroesophageal Reflux; Heart; Humans; Inflammation; Leptin; Obesity; Respiratory Mechanics; Risk Factors; Sleep; Sleep Apnea, Obstructive

The sympathetic nervous system is activated in human obesity and in the analogous experimental obesity produced by overfeeding. The causes remain uncertain and may be multiple. The consequences include hypertension, probably attributable to activation of the sympathetic outflow to the kidneys, and, more disputed, insulin resistance. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of the firing characteristics of individual sympathetic fibers (increased rate of nerve firing in normal-weight hypertensives, increased number of active fibers firing at a normal rate in obesity-hypertension) and the sympathetic outflows involved. The underlying mechanisms and the adverse consequences of the two modes of sympathetic activation may differ. Should antihypertensive drug therapy in obesity-hypertension specifically target the existing neural pathophysiology? Such an approach can be advocated on theoretical grounds. Perhaps more important is the requirement that chosen antihypertensives do not cause weight gain or insulin resistance.

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Hyperinsulinism; Hypertension; Leptin; Obesity; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System; Weight Loss

The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. beta-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympathoinhibition remains an important goal in the therapeutic management of the metabolic syndrome.

Topics: Adipokines; Cytokines; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Risk Assessment; Sensitivity and Specificity; Sleep Apnea, Obstructive; Sympathetic Nervous System

The prevalence of obesity has considerably increased during the past thirty years. Possible consequences of obesity on respiratory physiology include a restrictive disorder, changes in ventilatory mechanics and an alteration of respiratory drive. Apart from the well established relation between obesity and obstructive sleep apnea-hypopnea syndrome, obesity is associated with two other respiratory disorders. On one hand, epidemiological and animal data suggest a causal relationship between obesity and asthma. On the other hand, morbid obesity is associated, through an alteration of the respiratory drive involving leptin, with a diurnal and nocturnal alveolar hypoventilation defining the obesity-hypoventilation syndrome. These data emphasize the necessity for the medical practitioner to investigate any respiratory symptomatology in obese patients.

Topics: Animals; Asthma; Body Mass Index; Humans; Leptin; Obesity; Obesity Hypoventilation Syndrome; Prevalence; Respiratory Tract Diseases; Sleep Apnea, Obstructive; Switzerland

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

The metabolic syndrome, an emerging public health problem, represents a constellation of cardiovascular risk factors. It has been suggested that the presence of obstructive sleep apnea (OSA) may increase the risk of developing some of the features of the metabolic syndrome, including hypertension, insulin resistance, and type 2 diabetes. In this article, we discuss the parallels between the metabolic syndrome and obstructive sleep apnea and describe possible OSA-related factors that may contribute to the metabolic syndrome, specifically the roles of obesity, hypertension, dyslipidemia, sex hormones, inflammation, vascular dysfunction, leptin, insulin resistance, and sleep deprivation.

Topics: Female; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea syndrome (OSAS) is usually associated with conditions known to increase insulin resistance and cardiovascular risk, such as hypertension, obesity, and diabetes. Thus, investigating whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure treatment (CPAP) might improve insulin sensitivity brings up considerable methodological problems. Even if insulin sensitivity improves, it is hard to distinguish between an effect of CPAP treatment, e.g. in the reduction of nocturnal sympathetic activity caused by the sleep disturbance, and concomitant factors, such as weight loss. Two recent investigations were able to prove that OSAS is an independent risk factor for insulin resistance: one study in a statistical approach, the other by demonstrating a significant improvement of insulin sensitivity already two days after onset of CPAP therapy, thus clearly ruling out such confounding factors as changes in lifestyle or weight loss. However, it is still not clear if this improvement in insulin sensitivity is accompanied by an improvement in the usually elevated cardiovascular risk of patients with OSAS. Since a decrease in elevated markers of subclinical inflammation--nowadays regarded as the main culprit of cardiovascular complications and atherosclerosis--such as Interleukin-6 and C-reactive protein has been reported during CPAP therapy, and since an improvement in left ventricular function and a decrease in blood pressure were also reported under CPAP treatment, there are several good reasons to assume an improvement in metabolical function in OSAS patients due to CPAP treatment.

Topics: Continuous Positive Airway Pressure; Humans; Insulin Resistance; Leptin; Models, Biological; Obesity; Sleep Apnea, Obstructive

The obesity hypoventilation syndrome, which is defined as a combination of obesity and chronic hypoventilation, utimately results in pulmonary hypertension, cor pulmonale, and probable early mortality. Since the classical description of this syndrome nearly fifty years ago, research has led to a better understanding of the pathophysiologic mechanisms involved in this disease process, and to the development of effective treatment options. However, recent data indicate the obesity hypoventilation syndrome is under-recognized, and under-treated. Because obesity has become a national epidemic, it is critical that physicians are able to recognize and treat obesity-associated diseases. This article reviews current definitions of the obesity hypoventilation syndrome, clinical presentation and diagnosis, present understanding of the pathophysiology, and treatment options.

Topics: Humans; Hypoventilation; Leptin; Obesity; Respiration, Artificial; Respiratory System; Sleep Apnea, Obstructive; Syndrome; Weight Loss

Obstructive sleep apnea is a common disorder that is often unrecognized and underappreciated. Emerging evidence suggests that there is a causal link between obstructive sleep apnea and hypertension. This relationship appears to be independent of other comorbidities that have been previously linked to hypertension, such as obesity. The majority of studies support the contention that alleviation of sleep disordered breathing has a clinically significant beneficial impact on decreasing both nighttime and daytime blood pressure. A pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension is not fully elucidated. However, there is consistent evidence that autonomic mechanisms are implicated. Sympathetic activation along with humoral responses to repetitive episodes of hypoxemia and apnea over the longer term may cause vasoconstriction, endothelial dysfunction, and possibly hypertension. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to hypertension in this patient population.

Topics: Blood Pressure; Endothelin-1; Female; Humans; Hypertension; Leptin; Male; Obesity; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System

Obstructive sleep apnoea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension. Although the association between OSA and the metabolic syndrome tends to confound studies of the independent effects of OSA on vascular disease, recent evidences from basic science to epidemiological and clinical studies suggest that OSA may add worsening pathophysiological conditions to obesity. OSA contributes to the imbalance between vasodilators and vasoconstrictors, in particular through oxidative stress-dependent catabolism of nitric oxide, increased sympathetic nerve activity, enhanced renin-angiotensin system activity and endothelin synthesis. Additionally, several recent studies suggest that OSA may be a circumstance favouring central and vascular resistance to leptin. The beneficial effects of this hormone in normal subjects, are lost during endothelial dysfunction and OSA. Moreover, high leptin concentrations, within a range observed during OSA, display adverse effects on endothelial function and vascular physiology. Through of a yet unknown mechanism, OSA per se accounts for part of the elevated serum leptin concentration reported in patients. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnoea and the ensuing acute hemodynamic changes during sleep. Accordingly, vasopressor mediators and leptin concentration are shifted toward normal values by CPAP. Thus, in addition to this effective therapy, evaluation of specific strategies targeting leptin sensitivity and vasopressor mediators may open novel perspectives for treatment of OSA and its associated end-organ damages.

Topics: Adolescent; Adult; Animals; Cardiovascular Diseases; Comorbidity; Endothelium, Vascular; Humans; Leptin; Oxidative Stress; Rats; Sleep Apnea, Obstructive; Sympathetic Nervous System

There is a very high prevalence of OSA in obese individuals and a high prevalence of obesity in patients with OSA. The pathophysiology of OSA is intimately linked to obesity. Anatomic and functional considerations of the pharyngeal airway, the CNS, central obesity, and leptin likely interact in the development of OSA in obese individuals. OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. The diagnosis of OSA requires the clinician's awareness of its potential to cause a spectrum of acute and chronic neurocognitive, psychiatric, and nonspecific symptoms in patients who may be unaware that their sleep is disturbed. Symptoms and examination findings help predict which obese individuals have OSA, and polysomnography is the gold standard by which to make the diagnosis and assess the effects of treatment. Numerous disease states are associated with both OSA and obesity, and it is becoming clear that the relationships are mediated by complex interrelated mechanisms. Common diseases and disease mechanisms in OSA and obesity suggest that conditions related to obesity may be better managed if patients, particularly those who are morbidly obese, are evaluated and treated for previously undiagnosed OSA. OSA is cured in only specific cases with craniofacial or upper airway surgery, and the general application of UVP is not efficacious. OSA also can be cured with sufficient lifestyle-mediated or surgical weight loss; however, in the absence of long-term weight maintenance, OSA returns with weight gain. Although not curative, nasal CPAP is the initial treatment of choice for most patients because of its noninvasive approach and technical efficacy. It is limited, however, by patient acceptance and long-term compliance. Advances in mask comfort and use of humidified air should increase its acceptance. Future management strategies include newer generations of positive airway devices that automatically titrate pressures (which are not yet recommended by expert organizations) and multidisciplinary approaches to managing the care of patients with OSA.

Topics: Blood Coagulation Disorders; Cardiovascular Diseases; Drug Therapy; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Life Style; Obesity; Sleep Apnea, Obstructive; Surgical Procedures, Operative

Topics: Animals; Body Composition; Disease Models, Animal; Humans; Hypoventilation; Leptin; Mice; Mice, Obese; Obesity; Respiratory Physiological Phenomena; Sleep Apnea, Obstructive

Epidemiologic studies have reported that obstructive sleep apnea syndrome (OSAS) is a common disorder affecting about four percent of adult males and two percent of adult females. This difference in OSAS prevalence suggests that the female gender may reduce the risk of sleep breathing disorders in adults. We review several interrelated factors that may explain the differences in risk related to gender. These include differences in obesity and the distribution of adipose tissue, upper-airway anatomy, upper-airway muscle function, control of ventilation, the effect of sex hormones and leptin. The gender related protective effect decreases in females who are postmenopausal and not on hormone replacement therapy.

Topics: Adipose Tissue; Biomechanical Phenomena; Female; Humans; Leptin; Male; Middle Aged; Obesity; Pharyngeal Muscles; Postmenopause; Progesterone; Sex Distribution; Sleep Apnea, Obstructive; Testosterone

Leptin is a circulating hormone that is expressed abundantly and specifically in adipose tissue. Leptin induces a complex response involving control of body weight, energy expenditure and fat distribution. It is difficult for patients with obstructive sleep apnea-hypopnea syndrome to reduce and maintain their weights. Therefore, it is important to understand the circadian rhythms and regulation of serum leptin levels in order to control the body weight of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. Heat shock protein(HSP) 72 is generally known to be a stress-inducible isoform that is barely detectable under unstressed conditions but which is rapidly synthesized during or after stress. Recent data suggest that OSAHS may have significant effects on the serum leptin levels and HSP72 levels in peripheral blood mononuclear cells(PBMC) of patients with OSAHS.

Topics: Adipose Tissue; Body Weight; Circadian Rhythm; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Humans; Leptin; Sleep Apnea, Obstructive; Stress, Physiological

Topics: Animals; Biomarkers; Body Mass Index; Humans; Leptin; Obesity; Respiratory Function Tests; Risk Factors; Sleep Apnea, Obstructive

OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS.. Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters?. The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function.. Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS.. ClinicalTrials.gov; No.: NCT02295202; URL: www.. gov.

Topics: Adiponectin; Adult; Continuous Positive Airway Pressure; Female; Humans; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Sleep Apnea, Obstructive

Obesity increases susceptibility to chronic pain, increases metabolism, and is associated with obstructive sleep apnea syndrome (OSAS), all which can complicate perioperative pain management of patients. In addition, obesity and OSAS can cause elevation of the adipose-derived hormone leptin, which increases metabolism. We hypothesized that obesity along with sleep apnea and leptin independently enhance morphine pharmacokinetics.. Children 5-12 years of age who were presenting for surgery were administered a morphine dose of 0.05 mg/kg. Blood was collected at baseline and at subsequent preset times for pharmacokinetic analysis of morphine and its metabolites. Three groups were studied: a nonobese group with severe OSAS, an obese group with severe OSAS, and a control group.. Thirty-four patients consisting of controls (n = 16), nonobese/OSAS (n = 8), and obese/OSAS (n = 10) underwent analysis. The obese/OSAS group had a higher dose-adjusted mean maximum morphine concentration (CMAX) over 540 minutes compared to the controls (P < .001) and those with only OSAS (P = .014). The obese/OSAS group also had lower volume of distribution (Vd) when compared to OSAS-only patients (P = .007). In addition, those in the obese/OSAS group had a higher morphine 3-glucuronide (M3G) maximum concentration (P = .012) and a higher ratio of M3G to morphine than did the control group (P = .011). Time to maximum morphine 6-glucuronide (M6G) concentration was significantly lower in both nonobese/OSAS and obese/OSAS groups than in the control group (P < .005). C-reactive protein (CRP), interleukin (IL)-10, and leptin were all higher in the obese/OSAS group than in controls (P = .004, 0.026, and <0.001, respectively), and compared to OSAS-only patients, CRP (P = .013) and leptin (P = .002) levels were higher in the obese/OSAS group.. The combination of obesity and OSAS was associated with an increase in morphine metabolism compared with that in normal-weight controls. Our previous study in mice demonstrated that obesity from leptin deficiency decreased morphine metabolism, but that metabolism normalized after leptin replacement. Leptin may be a cause of the increased morphine metabolism observed in obese patients.

Topics: Age Factors; Analgesics, Opioid; Biomarkers; Biotransformation; Child; Child, Preschool; Drug Dosage Calculations; Female; Humans; Leptin; Male; Models, Biological; Morphine; Pediatric Obesity; Sleep Apnea, Obstructive; Surgical Procedures, Operative

Increased leptin and decreased adiponectin levels are reported in coronary artery disease (CAD) as well as in obstructive sleep apnoea (OSA). Less is known regarding the impact of continuous positive airway pressure (CPAP) on these biomarkers. We aimed to determine variables associated with leptin and adiponectin in adults with CAD and nonsleepy OSA, and evaluate the effect of CPAP adjusted for confounding factors.. This was one of the secondary outcomes of the RICCADSA trial, conducted in Sweden between 2005 and 2013. From 244 revascularized CAD and OSA patients (apnoea-hypopnoea index >15/h) without excessive daytime sleepiness (Epworth Sleepiness Scale score <10), 196 with blood samples at baseline, after 3, and 12 months were included in the randomized controlled trial arm; of those, 98 were allocated to auto-titrating CPAP, and 98 to no-CPAP.. No significant changes in leptin and adiponectin levels were observed during follow-up, whereas Body-Mass-Index and waist circumference increased in both CPAP and no-CPAP groups with no significant between-group differences. Alterations in plasma leptin were determined by changes in waist circumference (beta coefficient 2.47; 95% confidence interval 0.77-4.40), whereas none of the analyzed parameters was predictive for changes in adiponectin levels. No association was found with CPAP adherence.. CPAP had no significant effect on leptin and adiponectin in this cohort of nonsleepy OSA patients. An increase in waist circumference predicted an increase in plasma levels of leptin after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA regardless of CPAP treatment.

Topics: Adiponectin; Aged; Biomarkers; Cohort Studies; Continuous Positive Airway Pressure; Coronary Artery Disease; Female; Humans; Leptin; Male; Sleep Apnea, Obstructive; Sweden

To explore the effect and mechanism of electroacupuncture (EA) for Z syndrome without organic lesion (metabolic syndrome combined with obstructive sleep apnea hypopnea syndrome).. Fifty-eight patients with Z syndrome were divided into three groups according to mild,moderate and severe degree. Acupuncture and EA were used at Daimai (GB 26), Zhongwan (CV 12), Xiawan (CV 10), Zusanli ST 36), Qihai (CV 6) and Huaroumen (ST 24), etc., once a day and five times a week. The treatment of ten times was a course, and two courses were acquired continuously. Sleep respiration monitoring (PSG) was done before EA and in one week after treatment respectively. Triacylglycerol (TG) fasting blood glucose (FBG) fasting insulin (INS) and serum leptin (Lep) were tested before and after treatment in the three groups.. After treatment apnea hypopnea index (AHI) and the percentage of the time of arterial oxygen saturation (SaO₂) less than 90% taken in the total sleep time (SLT 90%) were improved apparently than those before treatment in the three groups (all P < 0.05). The levels of TG, FPG, INS and Lep were decreased after treatment in all groups (all P < 0.05).. EA can improve AHI and nocturnal hypoxia of Z syndrome, and the mechanism may be related to decreasing the indices of metabolism syndrome and leptin.

Topics: Acupuncture Therapy; Adult; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Sleep; Sleep Apnea, Obstructive; Treatment Outcome; Triglycerides; Young Adult

Strategies designed to reduce adiposity and cardiovascular-accompanying manifestations have been based on nutritional interventions conjointly with physical activity programs. The aim of this 13-week study was to investigate the putative benefits associated to hypoxia plus exercise on weight loss and relevant metabolic and cardiorespiratory variables, when prescribed to obese subjects with sleep apnea syndrome following dietary advice. The participants were randomly distributed in the following three groups: control, normoxia, and hypoxia. All the subjects received dietary advice while, additionally, normoxia group was trained under normal oxygen concentration and Hypoxia group under hypoxic conditions. There was a statistically significant decrease in fat-free mass (Kg) and water (%) on the control compared to normoxia group (p < 0.05 and p < 0.01, respectively). Body weight, body mass index, and waist circumference decreased in all the groups after the study. Moreover, leukocyte count was increased after the intervention in hypoxia compared to control group (p < 0.05). There were no statistically significant variations within groups in other variables, although changes in appetite were found after the 13-week period. In addition, associations between the variations in the leukocyte count and fat mass have been found. The hypoxia group showed some specific benefits concerning appetite and cardiometabolic-related measurements as exertion time and diastolic blood pressure, with a therapeutical potential.

Topics: Adiponectin; Adult; Biomarkers; Blood Pressure; C-Reactive Protein; Exercise Therapy; Humans; Hypoxia; Leptin; Lipids; Male; Middle Aged; Sleep Apnea, Obstructive; Treatment Outcome

In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA.

Topics: Adiponectin; Blood Glucose; Body Mass Index; C-Reactive Protein; Case-Control Studies; Continuous Positive Airway Pressure; Cross-Over Studies; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type I; Sex Factors; Sleep Apnea, Obstructive; Treatment Outcome

Hypertension, coronary heart diseases, obesity, diabetes mellitus are often present in patients with obstructive sleep apnea (OSA). The aim of the study was to estimate the serum leptin concentration and sympathetic activity in patients with obstructive sleep apnea and in control group.. 51 persons (F6, M45) were included into the study. The control group (GK) consisted of 15 snoring person (15 M) in the age x = 44.19 +/- 14.60, study group (GB) consisted of 36 patients with OSA (6F, 30M) in the age 5 1.47 +/- 8.95 years.. Leptin was measured by RIA methods using the HUMAN LEPTIN RIA KIT (LINCO Research, Inc).: adrenaline and noradrenaline were measured in the serum by HPLC methods (BIO-RAD).. The serum concentrations of leptin (ng/mL), adrenaline and noradrenaline (pg/mL) in patients with OSA compared with control group were respectively 15.55 +/- 11.26 : 61.2 +/- 27.4: 523.2 +/- 165.1 vs 10.34+/- 6.86 : 47.7 +/- 27.3: 447.9 +/- 102.6. There was positive significant correlation between leptin concentration and BMI (r = 0,34) and serum leptin and adrenalin concentration (r = 0,34). The serum leptin concentration was significantly higher in the female group. In the male group there was tendency to increase leptin concentration together with degree of OSA grade estimated by AHI and AHI <50 leptin concentration 12.23+/- 6.96 ng/mL vs AHI>50 and leptin concentration 13.35 +/- 3.54ng/ml.. 1. In the group of patients with OSA the serum concentrations of leptin, adrenaline and noradrenaline were higher then in control group. 2. There are positive statistical significant correlation between serum leptin levels and BMI and serum adrenaline concentration in the study group. 3. The serum leptin concentration was higher in the female group. 4. There was tendency to increased leptin concentration in the study group together with degree of OSA grade estimated by AHI. 5. Our results confirm correlation between leptin and sympathetic activity and their influences on obesity and degree of OSA grade in studied group.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Epinephrine; Female; Hemodynamics; Humans; Leptin; Male; Middle Aged; Norepinephrine; Obesity; Severity of Illness Index; Sleep Apnea, Obstructive; Snoring; Sympathetic Nervous System

Obstructive sleep apnea (OSA) has a close relation with obesity and perturbation in adipokines and hepatokines, which are linked to OSA consequences such as insulin resistance, dyslipidemia, and endothelial dysfunction. This study aimed to assess the relation of C1q/TNF-related protein 9 (CTRP9) and angiopoietin-like protein 3 (ANGPTL3) with OSA and biochemical measurements.. Serum levels of ANGPTL3, CTRP9, adiponectin, leptin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion protein 1 (VCAM-1) were determined in 74 OSA patients and 27 controls using enzyme-linked immunosorbent assay kits.. Levels of ANGPTL3, CTRP9, leptin, ICAM-1, and VCAM-1 were increased in the patients compared to the controls, whereas adiponectin levels decreased. ANGPTL3 had a positive correlation with total cholesterol, triglyceride, low-density lipoprotein cholesterol, ICAM-1, and VCAM-1 and was inversely correlated with leptin. CTRP9 showed a positive correlation with body mass index, insulin resistance, ICAM-1, and VCAM-1.. The results indicated the relation of ANGLTP3 and CTRP9 with OSA and its complications, which suggested a possible role for these factors in the consequences of OSA.

Topics: Adiponectin; Angiopoietin-Like Protein 3; Cholesterol; Humans; Insulin Resistance; Intercellular Adhesion Molecule-1; Leptin; Lipid Metabolism; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

Obesity is a dramatically increasing disease, accompanied with comorbidities such as cardiovascular disease and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS per se are associated with systemic inflammation. However, the multifactorial impact of obesity, OSAS, and its concomitant diseases on the immunological characteristics of circulating monocytes has not yet been fully resolved. Monocyte subsets of 82 patients with obesity were analyzed in whole blood measurements in terms of the CD14/CD16 cell surface expression patterns and different monocytic adhesion molecules using flow cytometry. Plasma levels of adipokines adiponectin and leptin of all patients were evaluated and correlated with accompanying cellular and clinical values. Whole blood measurements revealed a significant overall redistribution of CD14/CD16 monocyte subsets in patients with obesity. Monocytic adhesion molecules CD11a, CD11b, and CX3CR1 were significantly elevated. The observed alterations significantly correlated with plasma leptin levels and diabetes status as crucial amplifying factors. The additive impact of obesity, diabetes, and OSAS on the immunological balance of peripheral blood monocytes requires a coordinated regimen in terms of therapeutic treatment, respiratory support, and weight loss to improve the systemic immunity in these patients.

Topics: Diabetes Mellitus; Humans; Leptin; Monocytes; Obesity; Sleep Apnea, Obstructive

Leptin hormone plays an important role in metabolic control and is elevated in obstructive sleep apnea (OSA). The aim of this study was to assess the hypothesis that surgical treatment will reduce leptin levels in OSA patients.. Prospective study.. Twenty-three patients with multilevel OSA underwent modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty between April 2018 and September 2019. Serum leptin level was measured preoperatively and 3 months postoperatively for all patients and 18 control subjects. All patients were evaluated before and 3 months after surgery by history taking, clinical examination, polysomnography, cephalometry, and Epworth Sleepiness Scale.. Preoperatively, patients with OSA had a higher Leptin level (18.46 ± 4.73 ng/mL) than did control subjects (7.07 ± 1.26 ng/mL) (P < .001). Surgery resulted in a significant reduction in the level of leptin from 18.46 ± 4.73 ng/mL to 8.03 ± 2.22 ng/mL (P < .001). Reductions in leptin level was correlated with changes in apnea hypopnea index (AHI) (r = 0.61, P = .002) and minimum oxygen saturation (SaO2) (r = -0.54, P = .008).. Effective multilevel surgery in the form of modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty could significantly reduce leptin level in OSA patients and this reduction is correlated with the degree of OSA improvement in term of AHI and SaO2.. 4 Laryngoscope, 131:E665-E670, 2021.

Topics: Adult; Humans; Leptin; Male; Middle Aged; Pharynx; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Tongue

To investigate the different pathophysiologies of obstructive sleep apnea (OSA) phenotypes using cluster analysis. Differences between leptin/adiponectin levels in the resulting OSA phenotypes were also examined.. In total, 1057 OSA patients were selected, and a retrospective survey of clinical records, polysomnography results, and blood gas data was conducted. Patients were grouped into four clusters by their OSA severity, PaCO2, body mass index (BMI), and sleepiness. A k-means cluster analysis was performed, resulting in a division into four subpopulations. The Tukey or Games-Howell tests were used for intergroup comparisons.. Among the 20 clinical OSA items, four common factors (Epworth Sleepiness Scale [ESS], BMI, Apnea-Hypopnea Index [AHI], and PaCO2) were extracted by principal component analysis, and a cluster analysis was performed using the k-means method, resulting in four distinct phenotypes. The Clusters 1 (middle age, symptomatic severe OSA) and 4 (young, obese, symptomatic very severe OSA) exhibited high leptin levels. C-reactive protein levels were also elevated in Cluster 4, indicating a different pathophysiological background. No apparent differences between clusters were observed regarding adiponectin/leptin ratios and adiponectin levels. Classification into groups based on phenotype showed that Epworth Sleepiness Scale [ESS] score and disease severity were not correlated, suggesting that sleepiness is affected by multiple elements.. The existence of multiple clinical phenotypes suggests that different pathophysiological backgrounds exist such as systemic inflammation and metabolic disorder. This classification may be used to determine the efficacy of continuous positive airway pressure treatment that cannot be determined by the AHI.

Topics: Cluster Analysis; Female; Humans; Leptin; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive

Topics: Atherosclerosis; Biomarkers; Humans; Leptin; Sleep Apnea, Obstructive; Ultrasonography

Systemic inflammation has been documented in obstructive sleep apnea (OSA). However studies on childhood OSA and systemic inflammation are limited. This study aimed to determine the relation between OSA in overweight/obese children and various inflammatory markers.. In this cross sectional study, we enrolled 247 overweight/ obese children from pediatric outpatient services. We evaluated demographic and clinical details, anthropometric parameters, body composition and estimation of inflammatory cytokines such as interleukin (IL) 6, IL-8, IL-10, IL-17, IL-18, IL-23, macrophage migration inhibitory factor (MIF), high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1) and leptin levels. Overnight polysomnography was performed.. A total of 247 children (190 with OSA and 57 without OSA) were enrolled. OSA was documented on polysomnography in 40% of patients. We observed significantly high values body mass index, waist circumference (WC), % body fat, fasting blood glucose (FBG), alanine transaminase (ALT), alkaline phosphate, fasting insulin and HOMA-IR in children with OSA. Inflammatory markers IL-6, IL-8, IL-17, IL-18, MIF, Hs CRP, TNF- α, PAI-1, and leptin levels were significantly higher in OSA patients (p<0.05). There was strong positive correlation of IL-6, IL-8, IL-17, IL-23, MIF, Hs CRP, TNF-A, PAI-1 and leptin with BMI, % body fat, AHI, fasting Insulin, triglyceride, FBG, WC, HOMA-IR, AST and ALT.. Children with OSA have increased obesity, insulin resistance and systemic inflammation. Further studies are require to confirm our findings and evaluate their utility in diagnosis of OSAs, assessing severity and possible interventions.

Topics: Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Overweight; Pediatric Obesity; Sleep Apnea, Obstructive

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.

Topics: Adult; Aged; Cell Line, Tumor; Female; Humans; Leptin; Male; Melanoma; Melanoma, Cutaneous Malignant; Middle Aged; Obesity; Skin Neoplasms; Sleep Apnea, Obstructive; Transforming Growth Factor beta1

Nasal continuous positive airway pressure (CPAP) alleviates sleepiness in patients with obstructive sleep apnoea syndrome (OSAS), but part of OSAS patients keep gaining weight. Leptin and insulin-like growth factor-1 (IGF-1) interact with energy balance, and CPAP therapy has been suggested to influence these endocrine factors. We hypothesised that leptin would decrease during long-term CPAP therapy, and weight gain would associate with OSAS severity, lower CPAP adherence, lower IGF-1, and leptin concentrations.. Consecutive patients (n = 223) referred to sleep study with suspected OSAS were enrolled. Patients underwent cardiorespiratory polygraphy at baseline. Questionnaires were completed, and blood samples were drawn both at baseline and after 3 years. A total of 149 (67%; M 65, F 84) patients completed the follow-up. Plasma samples were available from 114 patients, 109 of which with CPAP adherence data (49 CPAP users, 60 non-users).. At baseline, the CPAP users were more obese and had more severe OSAS than the non-users. Leptin concentrations did not differ. After follow-up, leptin concentrations were higher in CPAP users (30.2 ng/ml vs. 16.8 ng/ml; p = 0.001). In regression analysis, increase in leptin concentrations was independent of age, baseline body mass index (BMI), or the change in BMI. Leptin concentrations increased among females (- 8.9 vs. 12.7 ng/ml; p < 0.001); whereas in men, CPAP did not have an effect, if not opposed the natural decrease in leptin observed in men not using CPAP. Change in IGF-1 levels did not differ.. Our results suggest increase in leptin concentrations during long-term CPAP therapy among females.

Topics: Adult; Aged; Continuous Positive Airway Pressure; Female; Humans; Insulin-Like Growth Factor I; Leptin; Long-Term Care; Male; Middle Aged; Patient Compliance; Polysomnography; Sex Factors; Sleep Apnea, Obstructive

Topics: Adiponectin; Case-Control Studies; Glutathione; Humans; Leptin; Malondialdehyde; Metabolic Syndrome; Oxidative Stress; Sleep Apnea, Obstructive; Superoxide Dismutase

This study is designed to investigate the effects of obstructive sleep apnea/hypopnea syndrome (OSA) surgery on serum leptin levels and metabolic disturbances, both of which contribute to the risk of cardiovascular diseases.. Case series with planned data collection.. Tertiary referral medical center.. A retrospective chart review of 101 consecutive patients with OSA who refused or failed conservative therapy and who then underwent upper airway surgery for OSA treatment was conducted. The personal medical history, anthropometric measurements, subjective symptoms, and objective polysomnographic parameters and fasting morning blood samples for leptin and metabolic biomarkers measurements were collected preoperatively and at a minimum of 3 months postoperatively.. Eighty patients with OSA (69 men and 11 women; mean [SD] age of 42.2 [10.2] years) with complete data were included in the final analysis. At least 3 months after surgery, serum leptin, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels and the mean systolic blood pressure (SBP) (night and morning) significantly decreased. According to the classical definition of surgical success, 40 subjects had successful surgery and were categorized as surgical responders, and the other 40 patients who failed surgery were categorized as surgical nonresponders. Significant reductions in serum leptin, total cholesterol, LDL-C, and triglyceride levels and improvement of mean SBP (morning) occurred in surgical responders but not in nonresponders.. Effective OSA surgery improves serum leptin, lipid profiles, and SBP. Further studies are needed to investigate the role of serial measurements of these biomarkers in monitoring surgical outcome of OSA treatment.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Female; Humans; Leptin; Male; Middle Aged; Polysomnography; Retrospective Studies; Risk Factors; Sleep Apnea, Obstructive

Topics: Adolescent; Adult; Blood Pressure; Body Mass Index; Diabetes Mellitus; Dyslipidemias; Female; Follow-Up Studies; Gastrectomy; Ghrelin; Humans; Hypertension; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Preoperative Period; Prospective Studies; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Growing evidence suggests an independent relationship between obstructive sleep apnea syndrome (OSAS) and metabolic syndrome (MS). Patients with OSAS always show clustering of metabolic components. However, the understanding of interplay between OSAS and metabolic components is still lacking.. Participants were consecutively enrolled from our sleep center during the period 2009-2013. Anthropometric variables, metabolic indicators, and sleep parameters were collected from all participants. The factor structure for MS in OSAS and non-OSAS was examined by confirmatory factor analysis.. The OSAS and non-OSAS demonstrated clustering of metabolic components. MS in patients with OSAS was strongly associated with insulin resistance (standardized factor loading = 0.93, p < 0.001), obesity (loading = 0.92, p < 0.001), and the lipid profile (loading = 0.72, p < 0.001). Furthermore, insulin resistance was correlated with obesity and lipid profile (r = 0.86, p < 0.001; r = 0.68, p < 0.001, respectively). Obesity and lipid profile were also highly correlated in OSAS (r = 0.66, p < 0.001). In non-OSAS, MS was strongly associated with insulin resistance, obesity, and lipid profile (loading = 0.95, p < 0.001; loading = 0.74, p < 0.001; loading = 0.68, p < 0.001, respectively). Insulin resistance was most strongly associated with fasting insulin (loading = 0.65, p < 0.001). Lipid profile was most strongly associated with TG (loading = 0.88, p < 0.001). Obesity was most strongly associated with BMI (loading = 0.80, p < 0.001).. OSAS is more prone to show clustering of metabolic components compared with non-OSAS. In particular, insulin resistance, obesity, and the lipid profile were independently and strongly correlated with MS in OSAS.

Topics: Adult; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) during pregnancy has been associated with adverse maternal outcomes. However, the effect of maternal OSA on fetal growth is less clear. The placenta is a critical organ for fetal growth and development and the principal determinant of birthweight. We aimed to investigate the effect of maternal OSA on placental growth and function.. Placentas of women recruited to a prospective longitudinal study were consecutively obtained immediately after delivery. Each placenta was measured for length, width, and thickness. Total RNA was isolated for gene expression analysis of VEGF, VEGF receptor, PIGF, and leptin. Histological and morphometric evaluations of the placenta were performed.. A total of 53 placentas were investigated. Ten women (19%) had OSA, and the weight of their placentas was significantly higher compared with the placentas of the controls (526.1 ± 83.9 vs. 425.7 ± 95.5 g, p = 0.004). There was a significant positive correlation between placental weight and the log apnea-hypopnea index even after controlling for maternal body mass index (BMI; r = 0.31, p = 0.04). The birthweight/placental weight ratio was significantly lower in women with OSA compared with controls (p = 0.03). Placental weight and newborn triceps adiposity thickness correlated positively after controlling for maternal BMI (r = 0.29, p = 0.04). Leptin expression was 1.8-fold higher in placentas of women with OSA compared with controls (p = 0.02). No histological differences were found between the groups.. Maternal OSA is associated with increased placental weight that correlated with OSA severity and neonatal adiposity independently of maternal BMI. Placental leptin overexpression may mediate/underlie the above findings.Trial Registration: Clinical Trials NCT00931099.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; Female; Humans; Infant, Newborn; Leptin; Longitudinal Studies; Obesity; Placenta; Placentation; Pregnancy; Prospective Studies; Sleep Apnea, Obstructive

Central and peripheral chemosensitivity i.e. ventilatory response to CO. Ventilatory response to hypercapnic-hyperoxic and hypercapnic-hypoxic gas mixtures in patients with OSA (n = 46) and healthy individuals (n = 45) was measured. C-reactive protein (CRP), leptin, adiponectin, and endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) were measured in blood samples.. Mediation analysis revealed that association of chemoresponse to CO. Inflammatory and anti-inflammatory factors could explain differential alterations in peripheral and central ventilatory chemoresponse in patients with OSA.

Topics: Adiponectin; Adult; C-Reactive Protein; Cannabinoid Receptor Agonists; Endocannabinoids; Humans; Inflammation; Leptin; Middle Aged; Obesity; Oxygen; Pulmonary Ventilation; Sleep Apnea, Obstructive

To investigate prenatal, perinatal, and early childhood factors, including cord and early childhood plasma leptin, on a clinical diagnosis of obstructive sleep apnea (OSA) among children in the Boston Birth Cohort.. We conducted a secondary analysis of 2867 mother-child pairs from the Boston Birth Cohort who were enrolled between 1998 and 2014 at Boston Medical Center and followed from birth to age 16 years. Child's OSA was defined based on clinical diagnoses documented in the medical record. Plasma leptin was measured in cord and early childhood blood samples. Logistic regression was used to examine individual and combined effects of early life factors on the risk of OSA, adjusting for potential confounders.. The mean age of the study children was 6.39 years (SD = 3.77); 49.3% were girls, and 209 (7.3%) had ever been diagnosed with OSA. Four significant risk factors for OSA were identified: maternal obesity/diabetes during pregnancy (OR, 1.63; 95% CI, 1.21-2.21; P = .001), preterm/low birth weight (OR, 1.74; 95% CI, 1.30-2.32; P < .001), early childhood obesity (OR, 1.89; 95% CI, 1.37-2.62; P < .001), and high leptin levels in early childhood (OR, 1.94; 95% CI, 1.22-3.09; P = .005). The presence of all these 4 risk factors significantly amplified the odds of OSA by about 10 times (OR, 9.95; 95% CI, 3.42-28.93; P < .001) compared with those lacking these factors.. Our findings, if further confirmed, provide new insight into the early life risk factors of pediatric OSA and underscore the need for early screening and prevention of OSA among children with those risk factors.

Topics: Body Mass Index; Case-Control Studies; Child, Preschool; Diabetes Complications; Female; Humans; Leptin; Male; Maternal Age; Obesity; Pregnancy; Pregnancy Complications; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is a common sleep disorder that is influenced by various environmental and genetic factors. The potential associations of leptin and leptin receptor (LEPR) polymorphisms with OSA have been studied in different populations; however, the results remain inconclusive. The aim of this study was to examine the association between LEPR gene polymorphisms and OSA risk.. A total of 322 samples were used, including 226 OSA subjects and 96 controls. Targeted sequencing of the entire LEPR gene was performed in all subjects. Polysomnography was used to diagnose obstructive sleep apnea. The associations between variants and OSA were determined by multivariate regression analyses.. Four single-nucleotide polymorphisms of LEPR were identified in all subjects. The genotype frequency of locus rs3790435 was significantly different between the OSA and control groups. Specifically, the variant genotype rs3790435 CC in LEPR was associated with a lower risk of OSA (OR 0.462, 95% CI 0.250-0.854, p = 0.014) in a recessive model after controlling for potential confounders. After BMI stratification, obese patients with this variant genotype were found to have a lower risk of developing OSA. Moreover, subjects with the rs3790435 CC genotype were found to have a statistically lower apnea-hypopnea index (AHI) and higher nadir oxygen saturation than the TT/CC genotypes without differences in plasma leptin levels.. Our study identified a novel variant of LEPR in patients with OSA, and specifically found an association between rs3790435 polymorphisms and OSA risk in Chinese Han subjects.

Topics: Adult; Aged; Asian People; Case-Control Studies; China; Cross-Sectional Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Leptin; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Protective Factors; Receptors, Leptin; Risk Assessment; Risk Factors; Sequence Analysis, DNA; Sleep Apnea, Obstructive

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Topics: Adipocytes; Adipokines; Adiponectin; Animals; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Rats; RNA, Small Interfering; Sleep Apnea, Obstructive; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h

Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Catecholamines; Circadian Clocks; Continuous Positive Airway Pressure; Humans; Hypertension; Hypotension; Leptin; Linear Models; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) associated with obesity is known to improve after bariatric surgery, but little is known about early changes in this condition after surgery.. To study the clinical course of OSA after bariatric surgery SETTING: Children's hospital in the United States METHODS: Adolescents and young adults with obstructive sleep apnea undergoing vertical sleeve gastrectomy (n = 6) or gastric bypass (n = 1) were enrolled in this prospective study. Participants underwent formal polysomnography before and at 3 and 5 weeks after bariatric surgery. Anthropometric measurements and assay for orexin and leptin were also performed at study visits. Thirty-one adolescents who underwent 2 polysomnography studies that were 4 weeks apart served as control patients.. These observations suggest that OSA responds early and out of proportion to weight loss after metabolic and or bariatric surgery, thus weight independent factors may at least in part be responsible for early improvement in OSA postoperatively.

Topics: Adolescent; Case-Control Studies; Child; Female; Gastrectomy; Gastric Bypass; Humans; Leptin; Male; Obesity, Morbid; Orexins; Pediatric Obesity; Polysomnography; Postoperative Care; Prospective Studies; Sleep Apnea, Obstructive; Treatment Outcome; Young Adult

The aim of this study was to compare serum leptin, apolipoprotein A1 (ApoA1), apolipoprotein J (ApoJ) and apolipoprotein H (ApoH) levels in males with obstructive sleep apnea and hypopnea syndrome (OSAHS) to those in healthy control subjects and to examine the possible relation between neurocognitive performance and these factors/serum markers in the subjects.. In this observational, cross-sectional study, a full-night polysomnography and sensitive neuropsychological assessment were performed on 50 newly diagnosed Chinese male patients and 30 healthy subjects. Fasting blood samples were used to measure leptin and ApoA1, ApoH and ApoJ levels using ELISA.. Compared with normal control subjects, OSAHS patients have significantly lower levels of ApoA1 and higher levels of leptin, ApoH and ApoJ. After adjustment for age, years of education, body mass index (BMI) and apnea-hypopnea index, leptin and ApoA1 were associated with global cognitive function, and leptin level was positively correlated with inhibition reaction time. ApoJ was negatively correlated with visual reproduction and logical memory performance. Multiple regression analysis shows that from age, BMI, education year, biomarker levels and the parameters of PSG, only the variables of leptin and education year added to the prediction of the Montreal cognitive assessment score in a statistically significant way.. Abnormal expression of leptin and apolipoproteins and poor performance on neuropsychological tests were observed in patients with OSAHS. There is also an association between serum leptin, ApoA1, and ApoJ levels and cognitive performance in the patients.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins; China; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Leptin; Male; Middle Aged; Neuropsychological Tests; Polysomnography; Sleep Apnea, Obstructive

The aim of this study is to assess the effect of obstructive sleep apnea syndrome (OSAS) severity on leptin levels in children.. Children with habitual snoring underwent overnight polysomnography. Fasting venous blood samples were obtained between 8 AM and 9 AM, following the night of the sleep study. Children with an apnea-hypopnea index of ≥ 5/h were included in the moderate-to-severe OSAS group while those with an apnea-hypopnea index of < 5/h formed the mild OSAS/primary snoring group.. 47 children (51% male and 49% female; mean age 7.8 ± 2.6 years) were recruited. Twenty seven participants were diagnosed with moderate-to-severe OSAS, and twenty children who had AHI < 5 were included in the mild OSAS/primary snoring. The two groups did not differ regarding age, gender and body mass index z score (p> 0.05). Furthermore there were no differences in log serum leptin levels (p= 0.749). Log serum leptin levels correlated with the BMI z score in the whole study group (p= 0.001; r= 0.499) but they were not associated with apnea-hypopnea index, mean and lowest oxygen saturation during sleep.. Serum leptin levels are affected by adiposity but not by OSAS severity among children with habitual snoring.

Topics: Adolescent; Biomarkers; Body Mass Index; Child; Female; Humans; Infant; Leptin; Male; Pediatric Obesity; Polysomnography; Severity of Illness Index; Sleep Apnea, Obstructive; Snoring

Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear.. To explore the underlying mechanism by which patients with OSA gain weight after CPAP.. A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity.. BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain.. Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).

Topics: Basal Metabolism; Continuous Positive Airway Pressure; Energy Intake; Energy Metabolism; Exercise; Female; Ghrelin; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Norepinephrine; Polysomnography; Sleep Apnea, Obstructive

Obesity hypoventilation and obstructive sleep apnea are common complications of obesity linked to defects in respiratory pump and upper airway neural control. Leptin-deficient ob/ob mice have impaired ventilatory control and inspiratory flow limitation during sleep, which are both reversed with leptin. We aimed to localize central nervous system (CNS) site(s) of leptin action on respiratory and upper airway neuroventilatory control.. We localized the effect of leptin to medulla versus hypothalamus by administering intracerbroventricular leptin (10 μg/2 μL) versus vehicle to the lateral (n = 14) versus fourth ventricle (n = 11) of ob/ob mice followed by polysomnographic recording. Analyses were stratified for effects on respiratory (nonflow-limited breaths) and upper airway (inspiratory flow limitation) functions. CNS loci were identified by (1) leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and (2) projections of respiratory and upper airway motoneurons with a retrograde transsynaptic tracer (pseudorabies virus).. Both routes of leptin administration increased minute ventilation during nonflow-limited breathing in sleep. Phrenic motoneurons were synaptically coupled to the nucleus of the solitary tract, which also showed STAT3 phosphorylation, but not to the hypothalamus. Inspiratory flow limitation and obstructive hypopneas were attenuated by leptin administration to the lateral but not to the fourth cerebral ventricle. Upper airway motoneurons were synaptically coupled with the dorsomedial hypothalamus, which exhibited STAT3 phosphorylation.. Leptin relieves upper airway obstruction in sleep apnea by activating the forebrain, possibly in the dorsomedial hypothalamus. In contrast, leptin upregulates ventilatory control through hindbrain sites of action, possibly in the nucleus of the solitary tract.

Topics: Animals; Hypothalamus; Hypoventilation; Leptin; Male; Mice; Motor Neurons; Obesity; Phosphorylation; Polysomnography; Respiration; Respiratory System; Sleep; Sleep Apnea, Obstructive; Solitary Nucleus; STAT3 Transcription Factor

Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea.

Topics: Absorptiometry, Photon; Adipokines; Adiponectin; Adolescent; Body Fat Distribution; C-Reactive Protein; Comorbidity; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Obesity, Abdominal; Polysomnography; Receptors, Cytokine; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor, Type I; Sex Factors; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Young Adult

Topics: Alleles; Humans; Leptin; Polymorphism, Genetic; Receptors, Leptin; Sleep Apnea, Obstructive

Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions.. To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community.. Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin.. Out of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST).. A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.

Topics: Adenoidectomy; Adiponectin; Adolescent; Biomarkers; Chemokine CCL2; Child; Child, Preschool; Female; Humans; Inflammation; Interleukin-18; Interleukin-6; Leptin; Male; Matrix Metalloproteinase 9; Muscle Proteins; Pediatric Obesity; Plasminogen Activator Inhibitor 1; Polysomnography; Sleep Apnea, Obstructive; Tonsillectomy; Transcription Factors

There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment.. Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment.. Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA.. Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of CPAP treatment. Methods to prevent OSA as well as treatment in its early stage may be recommended.

Topics: Appetite; Continuous Positive Airway Pressure; Cross-Sectional Studies; Fasting; Female; Follow-Up Studies; Ghrelin; Glucose; Humans; Insulin; Leptin; Male; Middle Aged; Polysomnography; Postprandial Period; Prospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive

There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). Several potential mechanisms have been purported to explain how sleep apnea may alter leptin levels. We investigated whether repeated apneas, hypoxia, or excessive daytime sleepiness influenced the levels of leptin in OSAS patients. We also evaluated whether a 3-month continuous positive airway pressure (CPAP) treatment affected leptin levels in patients.. Randomly selected 31 untreated, otherwise healthy male, overweight [body mass index (BMI) >25 kg/m(2)] obstructive sleep apnea syndrome (OSAS) patients [apnea-hypopnea index (AHI) ≥15] and 25 control (AHI <5) were included in this study. To confirm the diagnosis, all subjects underwent standard polysomnography. Serum samples were taken at 07:00-08:00 a.m. after overnight fasting. The OSAS patients that had regular CPAP treatment (n=26) were re-evaulated 3 months later.. Leptin levels (50.5±17.5 grams/L in OSAS and 56.3±25.5 grams/L in controls) and lipid profiles (TC, TGs, HDL-C, and LDL-C) between patient and control groups did not differ (P>0.05). Leptin levels were not correlated with the AHI, oxygen saturation, or excessive daytime sleepiness. CPAP treatment did not significantly change the (BMI), waist and neck circumference, or leptin levels in OSAS patients. Furthermore, we found no correlation between the decrease in serum leptin levels and parameters that were improved by CPAP treatment.. Leptin levels and lipid profile of overweight subjects with and without OSAS were not different, and our results suggest that OSAS-related parameters and CPAP treatment do not play a significant role in the serum leptin levels.

Topics: Adult; Biomarkers; Continuous Positive Airway Pressure; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Polysomnography; Risk Factors; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome

Experimental models of intermittent hypoxia (IH) have been developed during the last decade to investigate the consequences of obstructive sleep apnea. IH is usually associated with detrimental metabolic and vascular outcomes. However, paradoxical protective effects have also been described depending of IH patterns and durations applied in studies. We evaluated the impact of short-term IH on vascular and metabolic function in a diet-induced model of metabolic syndrome (MS).. Mice were fed either a standard diet or a high fat diet (HFD) for 8 weeks. During the final 14 days of each diet, animals were exposed to either IH (1 min cycle, FiO2 5% for 30s, FiO2 21% for 30s; 8 h/day) or intermittent air (FiO2 21%). Ex-vivo vascular reactivity in response to acetylcholine was assessed in aorta rings by myography. Glucose, insulin and leptin levels were assessed, as well as serum lipid profile, hepatic mitochondrial activity and tissue nitric oxide (NO) release.. Mice fed with HFD developed moderate markers of dysmetabolism mimicking MS, including increased epididymal fat, dyslipidemia, hepatic steatosis and endothelial dysfunction. HFD decreased mitochondrial complex I, II and IV activities and increased lactate dehydrogenase (LDH) activity in liver. IH applied to HFD mice induced a major increase in insulin and leptin levels and prevented endothelial dysfunction by restoring NO production. IH also restored mitochondrial complex I and IV activities, moderated the increase in LDH activity and liver triglyceride accumulation in HFD mice.. In a mouse model of MS, short-term IH increases insulin and leptin levels, restores endothelial function and mitochondrial activity and limits liver lipid accumulation.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Glycolysis; Hypoxia; Insulin; Leptin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Nitric Oxide; Sleep Apnea, Obstructive

Leptin takes part in regulation of energy balance, neuronal functions, pain and mood. It may act as intermediary marker for various components of HRQOL in patients of obstructive sleep apnea syndrome.. To document the correlation among leptin levels, obesity and HRQoL in OSAS patients.. A tertiary care hospital based cross-sectional study was done in 224 subjects aged 18-65 years, after taking informed consent. Subjects with previous history of smoking, Liver disease, COPD, CHD, T2 DM, asthma, cancer, end stage renal disease, heart failure, any endocrine disorder including Cushing syndrome, thyroid, on systemic steroid or any continuous medication for last 6 months, on dieting or suffering from any disability condition (other than obesity and OSAS) affecting their HRQoL were excluded from the study. All subjects underwent Polysomnography. Leptin assay was done by ELISA method. Hindi version of HRQoL tool SF-36 was used to evaluate HRQoL.. SPSS 20 was used to analyse data. Three groups (AHI <5, 5 to 15 and >15) were compared. Significant differences were observed in BMI, NC, WC, WHR and ESS. Differences were not significant in sleep architecture and Leptin level. SF-36 HRQoL, scores were observed decreased with increase in severity of disease. Leptin level was found significantly correlated with "Role limitations due to physical health problems", "Social functioning", Hypopnea and obesity indices.. In these subjects Obesity indices are the most important correlates of Leptin level. Oxygen desaturation indices with exception of Hypopnea and HRQoL may not be exclusively correlated to leptin levels.

Topics: Activities of Daily Living; Adult; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Health Status; Humans; Leptin; Male; Middle Aged; Obesity; Polysomnography; Quality of Life; Severity of Illness Index; Sleep Apnea, Obstructive; Social Participation; Waist-Hip Ratio

The correlations between the levels of cytokines, apnea, and obesity are not well understood. The aim of this study was to investigate the relationship between sleep apnea, body mass index (BMI) and plasma levels of leptin, ghrelin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).. Levels of leptin, ghrelin, IL-6, and TNF-α were compared in 20 obese (BMI > 30 kg/m²) and 6 non-obese patients (BMI < 27 kg/m²) with Obstructive Sleep Apnea Syndrome (OSAS), and in 13 obese and 11 non-obese control subjects without OSAS. All patients were investigated with Polysomnography (PSG) and ENT examination with flexible endoscopy and Müller's maneuver. Twelve patients were treated with continuous positive airway pressure (CPAP) and 14 with surgery. Fasting leptin, ghrelin and cytokine levels were measured at baseline, 2 days and 6 months after initiation of CPAP treatment, and 6 months after surgery.. Leptin, ghrelin and cytokine levels did not change significantly from baseline after 2 days of CPAP. After 6 months of CPAP or surgery, leptin, IL-6, and TNF-α levels were decreased in all OSAS patients. No difference in ghrelin levels was observed.. Elevated leptin levels are not determined by obesity alone, since they decreased with Apnea Hypopnea Index reduction. Higher pro-inflammatory cytokine basal levels observed in patients with OSAS were not correlated with BMI.

Topics: Adult; Body Mass Index; Continuous Positive Airway Pressure; Cytokines; Female; Ghrelin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive; Time Factors; Tumor Necrosis Factor-alpha

In this study, we aimed to establish a chronic intermittent hypoxia model in rats and explore the possible role of vaspin in insulin sensitivity.. Healthy male Wistar rats were randomly divided into two groups: normal control group (NC) and chronic intermittent hypoxia group (CIH). The NC group was raised under physiological conditions and the CIH group was kept in the plexiglass chamber between 9 am and 5 pm undergoing intermittent hypoxic challenge for 8 hours/day for 8 weeks. Arterial blood pressure of rats (tail cannulation) was measured before and after the study. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS), vaspin, and leptin levels were measured. Vaspin mRNA expression in visceral adipose tissues was measured with Real Time-PCR. The protein levels of vaspin, Akt and phospho-Akt in visceral tissues were determined by Western-blot.. At baseline, all the measurements in the CIH and NC groups were comparable. By the end of the experiment, the blood pressure of the CIH group was significantly higher than the NC group. The levels of FPG, FINS, TG, TC, leptin, and vaspin in the CIH group were significantly higher than in NC group. Plasma vaspin levels were correlated with FINS, HOMA-IR, and TG levels. Vaspin expression in both mRNA and protein levels in visceral adipose tissues of the CIH group were clearly higher than the NC group. Phospho-Akt protein level was decreased in visceral adipose tissues of the CIH group compared to the NC group.. In the chronic intermittent hypoxia rat model, the expression of vaspin in visceral adipose tissues and plasma were increased, which were correlated with insulin resistance.

Topics: Animals; Arterial Pressure; Biomarkers; Blood Glucose; Cholesterol; Disease Models, Animal; Hypoxia; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Wistar; RNA, Messenger; Serpins; Sleep Apnea, Obstructive; Time Factors; Triglycerides; Up-Regulation

Leptin, a pleiotropic protein hormone produced mainly by fat cells, regulates metabolic activity and many other physiological functions. The intrinsic circadian rhythm of blood leptin is modulated by gender, development, feeding, fasting, sleep, obesity, and endocrine disorders. Hyperleptinemia is implicated in leptin resistance. To determine the specificity and sensitivity of leptin concentrations in sleep disorders, we summarize here the alterations of leptin in four conditions in animal and human studies: short duration of sleep, sleep fragmentation, obstructive sleep apnea (OSA), and after use of continuous positive airway pressure (CPAP) to treat OSA. The presence and causes of contradictory findings are discussed. Though sustained insufficient sleep lowers fasting blood leptin and therefore probably contributes to increased appetite, obesity and OSA independently result in hyperleptinemia. Successful treatment of OSA by CPAP is predicted to decrease hyperleptinemia, making leptin an ancillary biomarker for treatment efficacy. Current controversies also call for translational studies to determine how sleep disorders regulate leptin homeostasis and how the information can be used to improve sleep treatment.

Topics: Appetite; Biomarkers; Continuous Positive Airway Pressure; Humans; Leptin; Obesity; Sleep Apnea, Obstructive; Sleep Deprivation; Sleep Wake Disorders; Treatment Outcome

Epicardial fat thickness (EFT), an indicator of visceral obesity, and leptin are 2 novel markers for studying the obstructive sleep apnea (OSA) population. This study aimed to investigate the effects of gender on leptin levels and EFT, and the relation with OSA severity.. A total of 149 patients with OSA (female/male 55/94 and mean age 50.8 ± 9.2 years) and 50 control patients (female/male 24/26 and mean age 48.9 ± 8.8 years) were included in the study. The study population was divided into 4 groups according to apnea/hypopnea index (AHI) as control (AHI <5), the mild OSA (AHI 5-14), the moderate OSA (AHI 15-29), and the severe OSA (AHI ≥30). EFT was obtained from parasternal long-axis and parasternal short-axis echocardiographic images.. Leptin levels among females were significantly higher than among males (10.5 [7.8] vs. 5.4 [4.5] ng/mL, P = 0.001, respectively). Among women, leptin levels were significantly higher in the severe OSA group compared to the control group (9.8 [9.0] vs. 15.5 [10.1] ng/mL, P = 0.05, respectively). Conversely, no relation was observed between OSA severity and the leptin levels among men. EFT was not significantly different between the 2 genders (P > 0.05). EFT was thicker in the severe OSA group than in the control and mild OSA groups among women, whereas EFT was not changed according to OSA severity among males (P > 0.05).. Leptin and EFT may be a valuable parameter in the evaluation of OSA severity in women than in men.

Topics: Adipose Tissue; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Obesity; Pericardium; Polysomnography; Prospective Studies; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Sleep Apnea, Obstructive

Intermittent hypoxia (IH), resulted from recurring episodes of upper airway obstruction, is the hallmark feature and the most important pathophysiologic pathway of obstructive sleep apnea (OSA). IH is believed to be the most important factor causing systemic inflammation. Studies suggest that insulin resistance (IR) is positively associated with OSA. In this study, we hypothesized that the recurrence of IH might result in cellular and systemic inflammation, which was manifested through the levels of proinflammatory cytokines and adipokines after IH exposure, and because IR is linked with inflammation tightly, this inflammatory situation may implicate an IR status.. We developed an IH 3T3-L1 adipocyte and rat model respectively, recapitulating the nocturnal oxygen profile in OSA. In IH cells, nuclear factor kappa B (NF-κB) DNA binding reactions, hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1), necrosis factor alpha (TNF-α), interleukin (IL) -6, leptin, adiponectin mRNA transcriptional activities and protein expressions were measured. In IH rats, blood glucose, insulin, TNF-α, IL-6, leptin and adiponectin levels were analyzed.. The insulin and blood glucose levels in rats and NF-κB DNA binding activities in cells had significantly statistical results described as severe IH>moderate IH>mild IH>sustained hypoxia>control. The mRNA and protein levels of HIF-1α and Glut-1 in severe IH group were the highest. In cellular and animal models, both the mRNA and protein levels of TNF-α, IL-6 and leptin were the highest in severe IH group, when the lowest in severe IH group for adiponectin.. Oxidative stress and the release of pro-inflammatory cytokines/adipokines, which are the systemic inflammatory markers, are associated with IH closely and are proportional to the severity of IH. Because IR and glucose intolerance are linked with inflammation tightly, our results may implicate the clinical relationships between OSA and IR.

Topics: Adipocytes; Adipokines; Adiponectin; Animals; Blood Glucose; Cytokines; Glucose Transporter Type 1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Models, Animal; NF-kappa B; Oxidative Stress; Oxygen; Rats; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep.. An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions.. Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth.. Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Topics: Adult; Female; Humans; Leptin; Obesity, Morbid; Pharynx; Pulmonary Ventilation; Sleep; Sleep Apnea, Obstructive

This study evaluated the effects of uvulopalatopharyngoplasty (UPPP) on serum leptin levels and endothelial function in patients with obstructive sleep apnea syndrome (OSAS).. Fifteen healthy subjects and 35 patients with moderate to severe OSAS who desired UPPP were prospectively enrolled. The serum levels of leptin and nitric oxide derivative (NOx) from their peripheral blood samples were measured by enzyme-linked immunosorbent assay. All subjects participated in sleep studies, which were repeated 3 months after UPPP in the patients with OSAS.. Before UPPP, the patients with OSAS had a higher serum level of leptin and a lower NOx level than did the control subjects. The serum leptin levels in the 17 of the 35 patients with OSAS who were surgical responders decreased from 24.2 ± 6.1 ng/mL before operation to 15.9 ± 6.0 ng/mL after operation. The serum NOx levels in these 17 patients increased from 18.5 ± 7.5 µmol/L before operation to 27.3 ± 8.2 µmol/L after operation. In the 18 patients who were unresponsive to surgery, the serum leptin and NOx levels remained impaired after the UPPP.. Successful treatment of OSAS with UPPP leads to the normalization of serum leptin and NOx levels.

Topics: Adult; Biomarkers; Body Mass Index; Endothelium, Vascular; Female; Free Radical Scavengers; Humans; Leptin; Male; Nitric Oxide; Obesity; Otorhinolaryngologic Surgical Procedures; Palate, Soft; Pharynx; Plastic Surgery Procedures; Polysomnography; Prospective Studies; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Treatment Outcome; Uvula

The aim of this study was to investigate the relations between nitric oxide (NO) and leptin levels in a cohort of untreated adult Obstructive sleep apnea syndrome (OSAS) patients. Between June 1, 2012, and January 1, 2013, we evaluated a total of 58 subjects including 36 OSAS patients and 22 healthy controls, both polysomnographically confirmed. Following the completion of polysomnographic evaluation, serum samples were taken at 08:00. Leptin, leptin receptor, NO2 (-) and NO3 (-) levels were analyzed by commercial ELISA kits. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Inc., Chicago, IL, USA). There was no statistically significant difference between the OSAS patients and control groups with relation to the demographic parameters and body mass index (p > 0.05). Significantly higher serum leptin and plasma NO levels were found in OSAS patients compared to the controls (p < 0.001). In this study, higher leptin levels which were positively correlated with NO levels in OSAS group may indicate a possible link with increased incidence of airway pathologies in these patients.

Topics: Adolescent; Adult; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Obesity; Polysomnography; Prospective Studies; Receptors, Leptin; Sleep Apnea, Obstructive; Young Adult

There is compelling evidence that obstructive sleep apnoea (OSA) can affect metabolic syndrome (MetS) and cardiovascular risk, but the intermediate mechanisms through which it occurs have not been well defined. We explored the impact of OSA in morbidly obese patients with MetS on adipokines, pro-inflammatory markers, endothelial dysfunction, and atherosclerosis markers.. We included 52 morbidly obese patients in an observational study matched for age, gender and central obesity in 3 groups (OSA-MetS, Non-OSA-MetS, and Non OSA-non-MetS). Anthropometrical, blood pressure, and fasting blood measurements were obtained the morning after an overnight polysomnography. VEGF, soluble CD40 ligand (sCD40L), TNF-α, IL-6, leptin, adiponectin, and chemerin were determined in serum by ELISA. OSA was defined as apnea/ hypopnea index ≥ 15 and MetS by NCEP-ATP III.. Cases and control subjects did not differ in age, BMI, waist circumference, and gender (43 ± 10 years, 46 ± 5 kg/m(2), 128 ± 10 cm, 71% females). The cases had severe OSA with 47 (32-66) events/h, time spent < 90% SpO2 7% (5%-31%). All groups presented similar serum cytokines, adipokines, VEGF, and sCD40L levels.. In a morbidly obese population with established MetS, the presence of OSA did not determine any differences in the studied mediators when matched by central obesity. Morbidly obese NonOSA-NonMetS had a similar inflammatory, adipokine VEGF, and sCD40L profile as those with established MetS, with or without OSA. Obesity itself could overwhelm the effect of sleep apnea and MetS in the studied biomarkers.. Salord N; Gasa M; Mayos M; Fortuna-Gutierrez AM; Montserrat JM; Sánchez-de-la-Torre M; Barceló A; Barbé F; Vilarrasa N; Monasterio C. Impact of OSA on biological markers in morbid obesity and metabolic syndrome.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; CD40 Ligand; Chemokines; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Obesity, Morbid; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Obstructive sleep apnea (OSA) is a common disorder resulting in a myriad of adverse vascular risks, including altered inflammatory/anti-inflammatory adipokine balance. Recent studies are yet to agree on how this balance responds to the OSA severity. As it is customary in these studies to obtain a single blood sample in participants after completion of the nocturnal polysomnogram (PSG), we hypothesized that these adipokines' early ultradian pulsatility might contribute to the reported contradictory results.. Fasting serum leptin and adiponectin were measured every 15 minutes for one hour in the morning after the diagnostic PSG for 13 adults recruited consecutively from the Salem VAMC Sleep Clinic between September 2006 and October 2007.. No differences in the timed paired samples of leptin (P = 0.30) and adiponectin (P = 0.28) were found in OSA participants (mean apnea-hypopnea index 21.1).. Customary protocol of obtaining a single blood sample for leptin and adiponectin after nocturnal PSG seems appropriate.

Topics: Adiponectin; Circadian Rhythm; Humans; Leptin; Male; Middle Aged; Prospective Studies; Sleep Apnea, Obstructive; Time Factors

Obstructive sleep apnea (OSA) has been associated with metabolic disorders. Sleep-disordered breathing could generate an altered rhythm in the expression of metabolic hormones, which could predispose to metabolic disorders. The aim of this study was to evaluate the effect of sleep apnea on diurnal variations in metabolic hormones.. Thirty-seven male, newly diagnosed, patients with OSA with an apnea-hypopnea index (AHI) > or = 20/h and 11 male controls (AHI <10/h) matched for body mass index (±3 kg/m2) were included. Six different samples were obtained from each subject during a period of 24h. Levels of the metabolic hormones ghrelin, leptin, resistin, and adiponectin were measured in plasma by immunoassay.. Patients with OSA (AHI (mean±SD) 46±26/h) were older than the controls (42±9 vs. 33±9 years, P=0.01). Differences in metabolic hormones between groups did not reach statistical significance at any point in the evaluation. No significant differences were observed in the area under the curve for any of the hormones analysed. Likewise, we did not detect diurnal variations in metabolic hormones.. The results of this study indicate that the day-night variations in the levels of several metabolic hormones are not influenced by the presence of sleep apnea.

Topics: Adiponectin; Adult; Case-Control Studies; Circadian Rhythm; Enzyme-Linked Immunosorbent Assay; Gastrointestinal Hormones; Ghrelin; Humans; Leptin; Male; Metabolic Diseases; Resistin; Sleep Apnea, Obstructive

Published studies showed conflicting results of the associations between adiponectin and leptin levels and obstructive sleep apnoea (OSA). In obese patients, plasma leptin is elevated and adiponectin is decreased, and we postulate that these adipokines could be potential markers of clinical and metabolic perturbations in patients with OSA.. 147 patients with suspected OSA had polysomnography to determine the Respiratory Disturbance Index (RDI). We measured fasting plasma glucose (FPG), fasting serum insulin, plasma leptin, adiponectin, and full lipid profile. Patients were classified on the basis of the RDI, degree of adiposity, and insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMAIR)).. 28.6% of subjects had normal polysomnography, 34.8% had mild OSA, 19.6% had moderate OSA, and 17% had severe OSA. Obesity was more prevalent in subjects with moderate-severe OSA (47%). Adiponectin decreased significantly (P = 0.041) with increasing severity of OSA. Though BMI was significantly higher in subjects with severe OSA, paradoxically, leptin was lowest in those subjects independent of gender dimorphism.. Adiponectin is an independent marker of disease severity in patients with OSA. The paradoxical decrease in circulating leptin, which suggests impaired secretion, deserves further studies as a potential marker of severe OSA.

Topics: Adiponectin; Adult; Aged; Biomarkers; Female; Humans; Leptin; Male; Middle Aged; Neck; Severity of Illness Index; Sex Characteristics; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, whereas the underlying mechanism is still eluding, the thought participants are chronic intermittent hypoxia with consequent increase in the reactive oxygen species, leading to endothelial cell damage and dysfunction in these patients. As the hydroxyl radical (·OH) mediates the vascular smooth muscle relaxation, identification of its scavengers might reveal sentinel markers of decreased vascular responsiveness and worse long-term comorbid outcome. We therefore assessed leptin's scavenger effect on (∙)OH using the electronic paramagnetic resonance (EPR) method.. The (∙)OH was generated by the Fenton reaction in the presence of spin-trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DMPO) with various concentrations of leptin (0.25, 2.5, and 25 μg/ml) and without leptin. EPR spectrometer settings were: modulation frequency, 100 kHz; X band microwave frequency, 9.5 GHz; microwave power, 20 mW (milliwatts); modulation amplitude, 1.0 G (gauss); time constant, 160 s; scan time, 200 s; and receiver gain, 1 × l0(5). EPR signal intensity between 3,440 and 3,540 G of measurements taken in at least three separate experiments was reported. Mannitol, a known (∙)OH scavenger, at 100 mM significantly decreased the DMPO-OH adduct formation and was used as the active-control agent.. Leptin added to aqueous solutions at all concentrations was associated with a statistically significant decrease in EPR signal compared with controls due to its scavenging activity towards the ·OH.. Leptin could be further investigated as a sentinel biomarker of decreased vascular responsiveness and future risk of atherosclerotic disease in obese OSA patients.

Topics: Electron Spin Resonance Spectroscopy; Endothelium, Vascular; Free Radical Scavengers; Humans; Hydroxyl Radical; Leptin; Mannitol; Oxidative Stress; Sleep Apnea, Obstructive; Vasodilation

To investigate the change of serum leptin levels in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) before and after surgery.. The cases were divided into effective (n=44) and non-effective (n=13) groups according to PSG. The effective cases were divided into decreased (> or = 5%, n=25) and non-decreased(<5%, n=19) BMI. The level of serum leptin was detected by radioimmunoassay.. The level of serum leptin after treatment (9.1 +/- 2.6 microg/L) was as high as before treatment (9.3 +/- 2.3 microg/L) in 13 non-effective cases. The level of serum leptin after treatment (7.15 +/- 1.23 microg/L) was significantly decreased than before treatment (12.79 +/- 2.98 microg/L) in 25 cases of decreased BMI (> or = 5%). The level of serum leptin after treatment (7.15 +/- 1.23 microg/L) was significantly decreased than before treatment (12.79 +/- 2.98 microg/L) in 19 cases of non-decreased BMI (<5%). Leptin level of all cases showed a positive correlation with AHI (P < 0.01).. The level of serum leptin in patients with OSAHS are increased. The serum leptin level of effective patients with OSAHS after treatment was significantly decreased. The level of serum leptin reflects the degree of AHI in patients with OSAHS.

Topics: Adult; Aged; Humans; Intraoperative Period; Leptin; Middle Aged; Sleep Apnea, Obstructive

As in obstructive sleep apnea (OSA), the chronic cycles of hypoxia and reoxygenation are thought to be conducive of oxidative stress (OS) with generation of reactive oxygen species, identifying effective mechanisms of protection against oxidant-mediated tissue damage becomes of outmost importance. Leptin's role had been recently extended into that of participant to OS; while its exact role in this process is yet to be defined, elevated leptin levels correlate significantly with several indices of OSA disease severity such as nocturnal hypoxemia, possibly acting as a counteractive mechanism against the chronic intermittent hypoxia-related OS and serving as a marker of future risk of atherosclerotic disease. We therefore investigated leptin's antioxidant mechanism on superoxide (O (2) (-•) ) anions using spectrophotometry and electron paramagnetic resonance (EPR).. The O (2) (-•) was generated by oxidation of xanthine (XAN) by xanthine oxidase (XO) in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide with various concentrations of leptin (0.001, 0.01, 0.1, and 1 mg/ml) and without leptin. Signal intensity between 3,440 and 3,540 G was expressed as standard means ± SD. The activity of leptin on XO was determined by monitoring the conversion of XAN to uric acid at 293 nm using a Beckman DU 800 UV-visible spectrophotometer.. Leptin added to aqueous solutions at 0.1 and 1 mg/ml concentrations was associated with a statistically significant decrease in the EPR signal due to leptin's direct scavenging activity towards the O (2) (-•) .. Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA.

Topics: Antioxidants; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Humans; In Vitro Techniques; Leptin; Oxidative Stress; Reactive Oxygen Species; Sleep Apnea, Obstructive; Superoxides

Obstructive sleep apnea (OSA) increases the risk for insulin resistance (IR). The mechanisms that link the two are not clear and are frequently confounded by obesity. OSA is associated with alterations in adipose-derived hormones (adipokines) that increase IR; however, previous studies have focused on middle-aged and older adults. The objective of this study was to determine if IR and alterations in adipokines exist in young men with OSA, independent of obesity.. Subjects were assigned into the following groups based on body mass index and presence of OSA: obese with OSA (OSA, n = 12), obese without OSA (NOSA, n = 18), and normal weight without OSA (CON, n = 15). Fasting blood was obtained for batch analysis of biomarkers of IR. The homeostasis model assessment (HOMA) method was used to assess IR.. HOMA and leptin were higher in the OSA group than the CON group. There were no differences in insulin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) between the OSA and NOSA groups. Adiponectin was lower in the OSA group vs. NOSA and CON; however, when controlled for central abdominal fat (CAF), the difference was nullified. When controlled for total body adiposity, however, CAF was 24 % higher in the subjects with OSA vs. subjects without OSA.. These findings suggest that excess CAF in young men with OSA may contribute to risk for type 2 diabetes indirectly by a degree that would otherwise not be reached through obesity, although further research is needed.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adolescent; Adult; Body Mass Index; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Obesity, Abdominal; Overweight; Polysomnography; Risk Factors; Sleep Apnea, Obstructive; Virginia; Young Adult

The inflammatory state caused by obesity increases the level of adipokines, such as leptin, with a direct impact on the central respiratory regulation. The present study addresses this problem by evaluation of the association of sleep apnea diagnosis in relation to body fat measured by dual-energy X-ray absorptiometry (DXA), anthropometric parameters and biochemical variables. All patients carried out overnight polysomnography, anthropometric evaluations [Body Mass Index (BMI), neck and waist circumference], body composition analyzed by DXA and blood sample collection (lipid profile, fasting glycemia, insulin, glycated hemoglobin, C-reactive protein and serum leptin levels). Obstructive sleep apnea-hypopnea syndrome (OSAHS) was defined by the apnea-hypopnea index (AHI) from the overnight polysomnography. According to the AHI, the women were divided into two groups: with and without apnea. Twenty-seven of them had OSAHS (AHI = 22.04 ± 17.55). The main results are the following: (a) BMI was not capable of predicting OSAHS in this study (p = 0.204); (b) for each 1 % increase in TBF %, the probability of having sleep apnea increased by 12.8 %; (c) comparing all variables (anthropometrics, DXA and blood sample), serum leptin was the only variable with a significant difference between the groups (p = 0.0257). The results reinforce the role of total body fat and leptin in the etiology of OSAHS and the need to include the evaluation of corporal composition measures by DXA in studies of sleep apnea.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Body Composition; Body Mass Index; Brazil; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Obesity; Polysomnography; Predictive Value of Tests; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by excessive daytime sleepiness and repetitive upper airway obstruction episodes during sleep. Clinically, obesity is a major risk factor for developing OSAS. However, OSAS has been associated with hormonal and metabolic alterations that could predispose patients to obesity. The aim of this study was to investigate the independent role of apneas and obesity on plasma levels of metabolic hormones (adiponectin, ghrelin, and leptin) in patients with OSAS.. We have studied patients with OSAS and controls with and without obesity. All patients were male, had an apnea-hypopnea index of 20/h or greater, and were eligible for nasal continuous positive airway pressure (nCPAP) treatment. Patients were considered obese (n = 28) when their BMI was higher than 30 kg/m(2) and non-obese (n = 21) when it was lower than 27 kg/m(2). Non-obese control subjects (n = 20) were non-snorers with a normal cardiorespiratory sleep study, while obese control subjects (n = 10) were recruited from those obese subjects who were visited in our sleep unit and for whom OSAS was excluded by full polysomnography. A single blood sample was obtained from an antecubital vein in all participants after the completion of the nocturnal sleep laboratory recording. Plasma leptin, adiponectin, and ghrelin levels were determined by radioimmunoassay.. The adiponectin, ghrelin, and leptin plasma levels were similar in both patients and controls. There were differences in leptin and adiponectin plasma levels between the obese and non-obese in both patient and control groups. In the case of ghrelin, differences between obese and non-obese subjects were only seen in patients. There were no significant differences in hormone levels between the obese controls and obese patients or between non-obese controls and non-obese patients. After 3 months of nCPAP treatment, adiponectin levels decreased significantly both in obese and non-obese patients, and leptin levels decreased in obese patients. Finally, nCPAP did not reduce ghrelin in either obese or non-obese patients.. The basal levels of leptin, adiponectin, and ghrelin were mostly associated with obesity. We found that sleep apnea was not a determinant factor in leptin, adiponectin, and ghrelin hormonal levels. Interestingly, nCPAP treatment diminishes leptin in obese OSA patients and adiponectin levels in obese and non-obese patients with OSAS.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Continuous Positive Airway Pressure; Ghrelin; Humans; Leptin; Male; Middle Aged; Obesity; Polysomnography; Prospective Studies; Reference Values; Sleep Apnea, Obstructive; Spain; Statistics as Topic; Triglycerides

Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob(-)/ob(-) mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P(N)) to determine the passive expiratory critical pressure (P(CRIT)) and active responses to reductions in P(N), including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the P(N) threshold at which IFL developed, maximum inspiratory airflow (Vi(max)), and genioglossus electromyographic (EMG(GG)) activity. Elevations in body weight were associated with progressive elevations in P(CRIT) (0.1 ± 0.02 cmH(2)O/g), independent of mouse strain. P(CRIT) was also elevated in ob(-)/ob(-) compared with BL6 mice (1.6 ± 0.1 cmH(2)O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P(N) threshold and lower VI(max). Very obese ob(-)/ob(-) mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and P(N) threshold (from -0.8 ± 1.1 to -5.6 ± 0.8 cmH(2)O) and increase in VI(max) (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P(CRIT) in leptin-treated mice did not differ significantly from that seen in nontreated ob(-)/ob(-) mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.

Topics: Animals; Disease Models, Animal; Electromyography; Infusions, Subcutaneous; Leptin; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Pressure; Pulmonary Ventilation; Recombinant Proteins; Respiratory Mechanics; Sleep Apnea, Obstructive; Tidal Volume; Weight Gain

Topics: Animals; Leptin; Lung; Male; Obesity; Sleep Apnea, Obstructive

Topics: Ghrelin; Glucose Intolerance; Humans; Leptin; Sleep Apnea, Obstructive

Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established.. Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified.. Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group.. In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

Topics: Apelin; Case-Control Studies; Female; Ghrelin; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Sleep Apnea, Obstructive

In OSAS patients CPAP therapy decreases cardiovascular morbidity and mortality. Homocysteine and leptin may play a role in development of ischaemic heart disease (IHD) in patients with OSAS. The aim of the study was to assess the influence of 3 month CPAP therapy on cardiovascular risk factors in patients with OSAS without IHD (pure OSAS) and with OSAS and IHD.. Therapy with CPAP was started in 42 OSAS without IHD (pure OSAS) and 23 OSAS and IHD patients. Plasma concentration of homocysteine, serum concentration of leptin, C-reactive protein (CRP), fibrinogen, lipids, and markers of visceral adiposity (MVA) were measured before and after treatment.. There were no significant changes in homocysteine, leptin, fibrinogen and CRP concentrations in neither group. In OSAS and IHD no change in serum lipids and MVA were found. In pure OSAS group total cholesterol and LDL cholesterol concentrations significantly decreased (202.5 ± 38.5 mg/dl v. 186.7 ± 33.5 mg/dl, p = 0.001 and 127.3 ± 32.9 mg/dl v. 116.4 ± 26.9 mg/dl, p = 0.02, respectively). Triglycerides did not significantly change (p = 0.09). There were no significant changes in BMI (30.4 ± 3.8 v. 30.6 ± 3.6, p = 0.5), waist circumference (108.5 ± 8.0 cm v. 107.0 ± 7.5 cm, p = 0.09) and waist to hip ratio (1.03 ± 0.04 v. 1.01 ± 0.03, p = 0.07).. Three month CPAP therapy did not change homocysteine and leptin concentration in neither group. However, it significantly decreased serum lipids concentration in patients with pure OSAS, but not in patients with OSAS and IHD, suggesting beneficial effects of CPAP therapy on cardiovascular risk factors.

Topics: Adult; Aged; Biomarkers; Cholesterol, LDL; Continuous Positive Airway Pressure; Female; Homocysteine; Humans; Leptin; Male; Middle Aged; Risk Factors; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome

Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]).. We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT.. Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was significantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] pmol/L vs 51.1[47.3, 61] pmol/L; p = 0.04). No differences in ghrelin, PYY or NPY were observed between patients with IGT and those without. However OSA patients with IGT had significantly higher value of leptin at both 22:30 (10.9 [7.7, 15.9] ng/mL vs 7.4 [5.6, 12.3] ng/mL, p = 0.02) and 07:00 (11.6 [7.6, 16.2] ng/mL vs 6.9 [5.4, 12.6] ng/mL, p = 0.024) than those without. In multivariate analysis the only major association of leptin was body mass index.. Clinically significant abnormalities of appetite regulating hormones are not present in OSA. Appetite regulating hormones did not differ in OSA patients with and without impaired glucose tolerance.

Topics: Blood Glucose; Dipeptides; Ghrelin; Glucose Intolerance; Glucose Tolerance Test; Humans; Leptin; Middle Aged; Neuropeptide Y; Risk Factors; Sleep Apnea, Obstructive

To explore the roles of hypertension and serum leptin in obstructive sleep apnea hypopnea syndrome (OSAHS).. Totally 60 patients with OSAHS (OSAHS group) and 40 age- and body mass index (BMI)-matched non-OSAHS individuals (non-OSAHS group) were enrolled in this study. The neck circumference (NC), waist/hip rate (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), leptin, fasting blood glucose (FBG), triglyceral (TG), cholesterol (Chol), and true insulin (TI) were measured before and after sleep . The correlations between hypertension/serum leptin level and OSAHS were analyzed.. The blood pressure(in the morning), especially DBP was significantly higher in OSAHS group than in non-OSAHS control group (89.75+/-2.04) mmHg vs. (81.63+/-1.91) mmHg, P<0.01. DBP in OSAHS group was positively correlated with serum leptin and apnea hypopnea index (AHI) (r=0.282, P<0.05; r=0.318, P<0.01). Logistic regression analysis showed that BMI (P=0.029), heart rate in the morning (P =0.030), and leptin (P=0.049) were independently correlated with the development of hypertension.. OSAHS may independently affect blood pressure, especially DBP, after waking up. BMIHR in the morning and serum leptin may be the independent correlates of hypertension.

Topics: Adult; Case-Control Studies; Humans; Hypertension; Leptin; Male; Middle Aged; Sleep Apnea, Obstructive

To evaluate the impact of multilevel obstructive sleep apnea surgical treatment on sleep-disordered breathing severity, health-related measures, and quality of life, and to examine the association between changes in sleep-disordered breathing severity and these other outcomes.. Prospective cohort study.. Subjects with obstructive sleep apnea unable to tolerate positive airway pressure therapy and with evidence of multilevel (palate and hypopharynx) obstruction underwent uvulopalatopharyngoplasty, tonsillectomy, and genioglossus advancement, with or without hyoid suspension. All subjects had preoperative and postoperative study assessments, including blood draw for C-reactive protein, interleukin-6, homocysteine, homeostasis model of insulin resistance, and leptin, and evaluation with the Functional Outcomes of Sleep Questionnaire.. Thirty subjects underwent multilevel surgical treatment. The mean apnea-hypopnea index decreased from 44.9 +/- 28.1 to 27.8 +/- 26.4 events/hour (P = .008). Thirteen (43%) subjects in this heterogeneous sample achieved a response to surgery (defined as an apnea-hypopnea index reduction of >or=50% to an absolute level <15 events/hour), and body mass index 32 kg/m(2). Responders had decreased C-reactive protein levels that were independent of changes in body weight.

Topics: Adult; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cohort Studies; Female; Homeostasis; Homocysteine; Humans; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Prospective Studies; Quality of Life; Sleep; Sleep Apnea, Obstructive; Surveys and Questionnaires

This study shows the possibility that multilevel surgery for obstructive sleep apnea (OSA) is helpful to improve the levels of pro-inflammatory cytokines and adipokines, which are related to complications of OSA.. The effects of multilevel surgery on adipokines and pro-inflammatory cytokines in patients with OSA were assessed.. Fifty-one patients with OSA underwent uvulopalatopharyngoplasty and radiofrequency tongue base reduction. Body mass index (BMI), Epworth sleepiness scale (ESS) and subjective symptoms using visual analog scales were assessed at baseline and 4 weeks after treatment. Adiponectin, leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were measured with a LINCOplex Human Immunoassay at baseline and 4 weeks after surgical treatment.. Significant improvements in subjective symptoms and ESS were found at 4 weeks after multilevel surgery. No significant change in BMI was observed. Adiponectin level was significantly increased after surgical treatment. Postoperative leptin, IL-6, and TNF-α levels were significantly decreased. The percent changes of adiponectin, leptin, IL-6, and TNF-α after multilevel surgery were not significantly different among patients with mild, moderate, and severe OSA.

Topics: Adipokines; Adiponectin; Adult; Aged; Cytokines; Electrosurgery; Female; Humans; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Palate, Soft; Patient Satisfaction; Pharynx; Polysomnography; Reference Values; Sleep Apnea, Obstructive; Tongue; Tumor Necrosis Factor-alpha; Uvula

Topics: Adiponectin; Biomarkers; Cohort Studies; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Sleep Apnea, Obstructive

to investigate the association of sleep apnea severity with insulin resistance, leptin, adipose-fatty acid binding protein (A-FABP) and visfatin levels and to evaluate the confounding role of obesity.. prospective study.. the study included obese patients who were referred to the sleep laboratory. Patients were divided into two main groups according to their Apnea-Hypopnea Index (AHI). Measurements of body weight, height, blood pressure, waist circumference (WC), and neck circumference (NC) were taken on the night of the sleep study. Blood samples were taken after polysomnography. Insulin resistance was estimated with the homeostasis model assessment (HOMA) index.. group A included 34 patients with obstructive sleep apnea syndrome (OSAS) and group B included 19 patients without OSAS. OSAS patients had significant higher visfatin levels; however, other parameters were similar. Leptin and A-FABP were significantly correlated with body mass index (BMI) in both groups. OSAS patients had significant higher NC and WC despite a BMI similar to that of group B, and strong correlations of these two variables were found with HOMA. Group A had higher visfatin levels than did group B.. insulin resistance was not directly associated with BMI and/or AHI, but it was aggravated by nocturnal hypoxemia owing to apnea severity. NC was also a good predictor for insulin resistance and should not be ignored during the treatment selection for the patients with OSAS. Visfatin may have a potential role as a screening marker for OSAS.

Topics: Adult; Fatty Acid-Binding Proteins; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Sleep Apnea, Obstructive

The obesity pandemic is claiming its presence even among youngest of children and is clearly on the rise. Although the extent and implications of this massive increase in the prevalence of overweight and obese children are unclear, they are anticipated to be deleterious to global health outcomes and life expectancy. The potential interrelationships between sleep and obesity have gained recent attention. In this chapter, we initially examine the critical evidence supporting or refuting such proposed associations. In addition, the potential reciprocal roles of obesity and obstructive sleep apnea in the facilitation of their pathophysiology are also reviewed, along with their amplificatory effects on their respective morbidities.

Topics: Adolescent; Airway Resistance; Child; Comorbidity; Humans; Leptin; Obesity; Prevalence; Sleep Apnea, Obstructive; Sleep Wake Disorders

Leptin plays a key role in obstructive sleep apnea syndrome (OSAS). Leptin production in human airways has been previously evaluated by measuring leptin concentration in the exhaled breath condensate and in the induced sputum. The aim was to study leptin expression in the cells of induced sputum and in exhaled breath condensate of subjects with OSAS. Moreover, leptin concentrations in the blood were measured in the same groups of subjects. We enrolled four groups of patients: (1) obese patients with OSAS (OO); (2) non-obese patients with OSAS (NOO); (3) obese patients without OSAS (ONO); and (4) non-obese subjects without OSAS (C). Leptin expression was evaluated by immunocytochemistry in the sputum cells of the enrolled subjects. The concentrations of leptin in the exhaled breath condensate and plasma were measured by using a specific enzyme immunoassay. Leptin protein expression and the percentage of macrophages and neutrophils expressing leptin were higher in the induced sputum of OO, NOO and ONO patients than in C. Leptin concentrations in the exhaled breath condensate were significantly higher in OO patients (5.12 (3.8-6.6) ng ml(-1)) than in NOO (4.1 (3.9-5.2) ng ml(-1)) and ONO (4.2 (3.6-5.0) ng ml(-1)) patients. The concentration of leptin in plasma was significantly more elevated in OO (36 (24-65.9) ng ml(-1)) than in NOO (30.2 (12.4-51.4) ng ml(-1)), whereas it was not significantly different in ONO patients. This study showed that leptin in sputum and in the exhaled breath condensate is higher in obese patients with OSAS than in obese subjects without OSAS. Moreover, different mechanisms for determining leptin concentrations in the exhaled breath condensate and the blood are suggested.

Topics: Adult; Breath Tests; Exhalation; Female; Humans; Immunoenzyme Techniques; Leptin; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive; Sputum

To develop an intermittent hypoxia/reoxygenation (IH/ROX) rabbit carotid artery model and then investigate the inflammation status of rabbit carotid artery endothelium after IH exposure and its relationship with leptin.. After anesthetization, rabbit's right common carotid artery was cleared of surrounding tissue with anatomic microscope, cannulated to its distal part and the proximal part was ligated. Preparations were challenged by changing the PO(2) of the gas mixture equilibrating the perfusate. Alternate perfusing (2 mL/min) of equilibrated perfusate bubbled with normoxia or hypoxia gas mixtures formed IH/ROX cycles in the right carotid common artery, simulating the pattern of hypoxic episodes seen in obstructive sleep apnea (OSA), or continuous perfusing of hypoxia perfusate to form continuous hypoxia (CH) modes. Sixty adult male New Zealand White rabbits (2.5-3.0 kg) were separated into six groups, ten per group. Groups were: A, intermittent normoxia (IN) group, perfused with perfusion equilibrated with 21% O(2) [PO(2) about 141 +/- 2.87 mmHg] for 15 s and 21% O(2) for 1 min 45 s, 60 cycles; B, severe IH group, 5% O(2) [PO(2) about 35.2 +/- 1.27 mmHg] 15 s and 21% O(2) 1 min 45 s, 60 cycles; C, mild IH group, 10% O(2) [PO(2) about 54.3 +/- 3.31 mmHg] 15 s and 21% O(2) 1 min 45 s, 60 cycles; D, severe IH+Lep group, protocol was the same with severe IH group; E, CH group, IN for 1 h 45 min and then 5% O(2) for 15 min; and F, Lep group, the same with IN group. Right common carotid artery parts distal to the cannula were harvested after exposure, and endothelial cell layers were gotten from longitudinal outspread vessels. Nuclear factor kappaB (NFkappaB) DNA binding activities of partial cell layers were measured with electrophoretic mobility shift assay in the IN group, severe IH group, mild IH group, and CH group nuclear extracts. The other part of the cell layers in the IN group, severe IH group, severe IH+Lep group, and Lep group were cultured for 2 h, and during the culture procedure, recombinated human leptin solutions were added to culture dishes of severe IH+Lep group and Lep group (resulted concentration, 10 ng/mL). Enzyme-linked immunosorbent assay was used to analyze medium interleukin-6 (IL-6) concentrations, reverse transcription polymerase chain reaction was used to analyze endothelial cell Ras homology A (RhoA) mRNA expression levels. Statistical analysis was done with SPSS 11.5 software package.. NFkappaB DNA binding activities were significantly different between groups (F = 112.428, P < 0.001). This activity in the severe IH group (4.27 +/- 0.64) was higher than that in the mild IH group (2.33 +/- 0.45, P < 0.001), IN group (1.00 +/- 0.26, P < 0.001), and CH group (1.15 +/- 0.36, P < 0.001). RhoA mRNA expression levels were different in groups (F = 26.634, P < 0.001).This level in the severe IH+Lep group (2.54 +/- 0.53) was higher than that in the severe IH group (1.57 +/- 0.44, P = 0.002), IN group (1.00 +/- 0.31, P < 0.001), and Lep group (1.31 +/- 0.30, P < 0.001). IL-6 concentrations were different in groups (F = 79.922, P < 0.001). IL-6 concentration in the severe IH+Lep group (1591.50 +/- 179.57 pg/mL) was higher than that in the severe IH group (1217.20 +/- 320.62 pg/mL, P = 0.036), IN group (325.40 +/- 85.26 pg/mL, P < 0.001), and Lep group (517.40 +/- 183.09 pg/mL, P < 0.001).. IH/ROX activated the inflammation pathway significantly in the endothelium, which was more intensive than CH and intensity-dependent. When exposed to both IH/ROX and leptin, inflammation occurs more dramatically. It means that synergic activating roles were performed by IH/ROX and leptin. This study may have a clinical implication that IH can cause endothelial damage through activated inflammation in OSA patients, and if the OSA patients have obesity at the same time, the endothelial damage or the inflammation would be more significant because of elevated leptin level as a synergic factor.

Topics: Animals; Carotid Artery, Common; DNA Primers; DNA, Complementary; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Hypoxia; Interleukin-6; Leptin; Male; NF-kappaB-Inducing Kinase; Protein Serine-Threonine Kinases; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; rhoA GTP-Binding Protein; RNA, Messenger; Sleep Apnea, Obstructive

Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA).. Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System.. There were 176 patients; 68% were male, mean age = 50 +/- (SD) 11 years, mean apnea/hyponea index (AHI) = 22.9 +/- 22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%) = 5.4% +/- 15, and mean body mass index (BMI) = 32.2 +/- 8 kg/m(2). In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin.. We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.

Topics: Adult; Coronary Artery Disease; Cytokines; Female; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Oxygen; Polysomnography; Reference Values; Risk Factors; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

Biomarkers of adipose tissue may affect glucose and lipid metabolism and present pro-inflammatory properties, thus could be involved in the pathobiochemistry of cardiovascular disease (CVD). The coexistence of sleep apnea syndrome (OSA) and metabolic risk factors of CVD is worth explaining. The aim of the study was to compare the serum adipocytokines in subjects with and without OSA, who had all elevated body mass index (BMI).. Overweight (BMI: 25.0-29.9 kg/m2) and obese (BMI: 30.0-39.9 kg/m2) OSA-suspected Caucasian males, aged 30-63, with no acute disease or chronic disorder underwent polysomnographic evaluation to select OSA-positive (AHI > or = 5) and OSA-negative (AHI <5) subjects. Four subgroups were created of 18 persons each: Over(weight)-OSA-Neg, Over-OSA-Pos, Obese-OSA-Neg, Obese-OSA-Pos. In all subjects, plasma carbohydrate and lipid metabolism parameters, and serum uric acid, resistin and leptin concentrations were determined.. A decreased resistin level was observed in Over-OSA-Pos vs. Over-OSA-Neg subjects (P=0.037) as well as in Obese-OSA-Pos vs. Obese-OSA-Neg (P=0.045). No differences in leptin concentrations were observed. A positive correlation between leptin and BMI was in both overweight subgroups and a negative one between resistin and fasting glucose was in both obese subgroups.. OSA may decrease the serum resistin level in subjects with excess body mass and also may contribute to glucose metabolism, but has no influence on the leptin level.

Topics: Adipokines; Adult; Female; Humans; Leptin; Male; Middle Aged; Resistin; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation.. We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines.. Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy.. Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05).. In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production.

Topics: Adult; Continuous Positive Airway Pressure; Cross-Sectional Studies; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Polysomnography; Resistin; Sleep Apnea, Obstructive

Topics: Abdomen; Adipose Tissue; Adult; Female; Humans; Insulin Resistance; Leptin; Male; Obesity; Sleep Apnea, Obstructive

Local and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements.. About 45 OSA patients (mean AHI 40+/-25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-alpha and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed.. An increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements.. Increased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity.

Topics: Adult; Biomarkers; Breath Tests; C-Reactive Protein; Case-Control Studies; Dinoprost; Female; Forced Expiratory Volume; Humans; Hydrogen-Ion Concentration; Interleukin-6; Leptin; Linear Models; Lung; Male; Middle Aged; Polysomnography; Sleep Apnea, Obstructive; Smoking; Tumor Necrosis Factor-alpha; Vital Capacity

Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development.. Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes.. A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12 months after surgery.. Obese patients showed significantly higher VEGF-A levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty.. Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.

Topics: Adipokines; Adult; Aged; Bariatric Surgery; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Hypertension; Insulin; Leptin; Middle Aged; Obesity, Morbid; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A; Weight Loss; Young Adult

Leptin is an hormone that regulates body weight. Studies have shown increasing leptin concentrations according to body mass index (BMI) and intermittent hypoxia. Our aim is to evaluate the basal leptin levels in OSA patients and its possible relation to OSA severity, independently of confounders and investigate the Autoadjusting-CPAP effect on leptin values.. In ninety eight male patients with moderate to severe OSA leptin serum levels were evaluated before therapy, 9 days and 6 months after therapy.. In this group mean age was 55.3 years, mean BMI was 33.2 Kg/m2 and mean Apnoea- Hypopnea Index (AHI) was 51.7/h. Mean basal serum leptin value was 12.1 ug/L. Univariate analysis showed a significant correlation between serum leptin values and BMI (R = 0.68; p < 0.001), waist-hip ratio (R = 0.283; p = 0.004) and AHI (R = 0.198; p = 0.048); in stepwise multiple regression analysis only BMI (p < 0.001) was a predictor of serum leptin values. One week after therapy, mean leptin serum level decreased to 11.0 ug/L and 6 months after it was 11.4 ug/L. (p = 0.56 and p = 0.387, respectively). Baseline leptin serum levels positively correlate with BMI, fat distributio and OSA severity. BMI is the only predictor of basal leptin levels.Treatment with Autoadjusting-CPAP has a small effect on leptin levels.

Topics: Aged; Body Mass Index; Body Weight; Continuous Positive Airway Pressure; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Regression Analysis; Severity of Illness Index; Sleep Apnea, Obstructive

Obstructive sleep apnea syndrome (OSAS) is frequently complicated by metabolic syndrome, including diabetes and hypertension. Both OSAS and metabolic syndrome are strongly associated with obesity. Recently, adiponectin and leptin, which are secreted by adipose tissue, have been considered to play important roles in the progression of these diseases. Thus, to examine the association between leptin, adiponectin and OSAS, we measured the serum level of these adipocytokines in the same OSAS patients.. Sixty-eight consecutive Japanese men, who recorded all-night polysomnography, were enrolled in this study, and were divided into three groups, control (n=15), moderate OSAS (n=21) and severe OSAS (n=32). We measured serum levels of adiponectin and leptin by ELISA.. Serum leptin levels were positively correlated with apnea hypopnea index (AHI) (r=0.552, p<0.001), the percentage of time with less than 90% hemoglobin saturation level in total sleep time (%T<90) (r=0.399, p<0.001) and body mass index (BMI) (r=0.807, p<0.0001). These parameters were suggested as the determinant factor for the serum leptin level by stepwise multiple regression analysis. On the other hand, serum adiponectin levels showed a positive correlation with age (r=0.361, p=0.005) and HDL-cholesterol level (r=0.274, p=0.039). Although there was no significant correlation between serum adiponectin levels and AHI or %T<90, serum adiponectin levels were chosen at a determinant factor of %T<90.. These results suggested that the increasing severity of OSAS induces an increase in setum leptin concentration, but the serum adiponectin levels may be regulated independently of the degree of OSAS, obesity and serum leptin levels in patients with OSAS.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; Cholesterol, HDL; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysomnography; Sleep Apnea, Obstructive

Topics: Acclimatization; Altitude; Animals; Feedback, Physiological; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Leptin; Sleep Apnea, Obstructive

Obstructive sleep apnea is common in obese people. Leptin is an adipocyte-derived signaling factor that has an important role in metabolic control. There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the relation between polymorphisms of the leptin and leptin receptor (LEPR) genes and OSAS.. The study population consisted of 130 patients with OSAS and 50 healthy control subjects. All the subjects were Japanese. Diagnostic polysomnography was performed in all patients and control subjects. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and three single nucleotide polymorphisms (SNPs) [Lys109Arg (A/G) in exon 4, Gln223Arg (A/G) in exon 6, and Lys656Asn (G/C) in exon 14] in the LEPR gene were examined.. There were no significant differences in allelic frequencies and genotype distributions of the examined polymorphisms of the leptin and LEPR genes between OSAS patients and control subjects. For the LEPR gene, the wild-type alleles of the Gln223Arg and Lys656Asn SNPs had a marginally significant effect on mild OSAS, which was defined as an apnea-hypopnea index from 10 and 20 events/h in the dominant model.. The tetranucleotide repeat polymorphism of the leptin gene and the Lys109Arg, Gln223Arg, and Lys656Asn SNPs in the LEPR gene were not associated with OSAS in the Japanese population. Further studies are required to confirm the association of the wild types of Gln223Arg and Lys656Asn SNPs with the severity of OSAS.

Topics: Humans; Leptin; Male; Middle Aged; Polymorphism, Genetic; Receptors, Leptin; Sleep Apnea, Obstructive

Leptin levels have been reported to be higher in patients with obstructive sleep apnea (OSA) than in control subjects with matching age and body mass index (BMI). Although animal studies have shown that leptin augments hypercapnic ventilatory response (HCVR), the effect of leptin on HCVR has not been clarified in OSA.. To investigate whether leptin could augment HCVR during wakefulness in patients with OSA.. Of 134 consecutive patients with OSA, 13 eucapnic and 16 hypercapnic patients with OSA, and 12 control subjects matched for sex, age, and BMI were selected. Fasting serum leptin levels were collected, and HCVR during wakefulness assessed by the slope between minute ventilation and end-tidal PCO(2).. There was a significant positive relationship between serum leptin levels and HCVR in the group including control subjects and eucapnic patients with OSA (r = 0.42, p < 0.05). Subgroup analyses suggest that serum leptin levels and HCVR were significantly higher in eucapnic patients with OSA than in control subjects. On the other hand, hypercapnic patients had lower HCVR than eucapnic patients (p < 0.05), whereas serum leptin levels were similar between the two OSA subgroups.. Leptin levels and HCVR are correlated as long as the eucapnic condition is maintained. We speculate that a stimulating effect of leptin on HCVR may be masked by the hypoventilation state.

Topics: Body Mass Index; Carbon Dioxide; Comorbidity; Humans; Hypercapnia; Hypoventilation; Leptin; Polysomnography; Respiratory Muscles; Sleep Apnea, Obstructive; Wakefulness

Topics: Adult; Carbon Dioxide; Comorbidity; Humans; Hypercapnia; Hypoventilation; Leptin; Male; Middle Aged; Obesity; Respiration; Sleep Apnea, Obstructive; Work of Breathing

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Humans; Hypoventilation; Leptin; Obesity; Respiration, Artificial; Respiratory System; Sleep Apnea, Obstructive; Syndrome; Weight Loss

The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons.

Topics: Adiponectin; Atherosclerosis; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Lipomatosis, Multiple Symmetrical; Male; Middle Aged; Obesity; P-Selectin; Resistin; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

Associations between SDB, the metabolic syndrome, and circulating levels of adipokines have emerged in adults but have not been examined in snoring children, who, in contradistinction to adults, display insulin resistance and lipid abnormalities as a function of adiposity rather than SDB. Therefore, we aimed to examine associations between circulating adipokines levels, insulin resistance, and measures of SDB in children.. Prospective study.. Polysomnographic evaluation and assessment of plasma levels of leptin, adiponectin, resistin, glucose, insulin, and CRP.. 130 children (mean age 8.2 +/- 2.8 years; 39% obese) were studied.. Log adiponectin levels were lower in obese than nonobese children (3.8 +/- 0.31 vs 4.0 +/- 0.30 corresponding to 8,381.4 +/- 5,841.0 vs 12,853.2 +/- 7,780.2 ng/ml, P < 0.0001) and were inversely correlated with BMI Z scores (r = -0.47, P < 0.0001) but not with log AHI. Log leptin concentrations were higher in the obese group than the nonobese group (4.2 +/- 0.32 vs 3.4 +/- 0.57 corresponding to 19,542.6 +/- 13,643.6 vs 5,875.5 +/- 8,425.7 pg/ml, P < 0.0001), correlated with BMI Z scores (r = 0.64, P < 0.0001), and were significantly lower in children with AHI < or = 1/hr than children with AHI > 1/hr (P = 0.006) and in children with SpO2 nadir > or = 90% than children with SpO2 nadir < 90%, even after controlling for BMI Z score (P < 0.03). No significant differences were found in log resistin levels as a function of obesity or AHI. Significant correlations between log adiponectin levels and log Insulin/Glucose (I/G) ratios (-0.28, P = 0.006) and between log leptin levels and log I/G ratios (r = 0.66, P < 0.0001) emerged.. In close agreement with the absence of a measurable effect of SDB on insulin resistance in children, circulating adipokines levels are primarily attributable to the ponderal index. However, SDB and associated hypoxemia may contribute to the elevation of leptin levels.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Female; Humans; Infant; Insect Hormones; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Oligopeptides; Polysomnography; Pyrrolidonecarboxylic Acid; Resistin; Risk Factors; Sleep Apnea, Obstructive; Statistics as Topic

Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.

Topics: Adolescent; Arousal; Blood Glucose; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Models, Statistical; Obesity; Oxygen; Polysomnography; Signal Processing, Computer-Assisted; Sleep Apnea, Obstructive; Software

Leptin is believed to play a significant role in the pathogenesis of obstructive sleep apnea syndrome (OSAS) as well as progression of OSAS-related obesity. It is also known that other factors such as gender and diurnal variations in serum strongly affect the measurement results making repeated blood sampling necessary for leptin precise monitoring. Since renal metabolism and urine secretion are the main elimination mechanism for leptin, in this study we evaluated urine relevance for leptin secretion monitoring. Serum and urine (collected during the day and overnight) sampled from 169 OSAS patients and 41 controls were assayed by immunoenzymatic method specific for human leptin. Only 5 (17%) controls and 10 (5.8%) OSAS patients had undetectable urine leptin. We observed significant relationships between serum and urinary leptin in both day-time (r=0.656, P<0.001) and night-time (r=0.518, P<0.001) samples and between day and night-time urine leptin (r=0.811, P<0.001). Significance values did not alter when urinary leptin levels were expressed as the ratio to urinary creatinine. Gender-related differences in leptin concentrations were present both in serum (P<0.001) and overnight urine (P<0.01) in the OSAS group. However, mean night-time urine leptin was lower in the OSAS patients (P<0.05) and their subgroups stratified according to disease severity (P<0.01), while serum leptin levels were comparable in both groups. We conclude that assaying leptin in urine by immunoenzymatic method is a reliable and useful non-invasive alternative for its serum measurement. However, night-time urine leptin levels better reflect differences in its turnover due to gender and OSAS severity.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Circadian Rhythm; Female; Humans; Immunoenzyme Techniques; Leptin; Male; Middle Aged; Reproducibility of Results; Severity of Illness Index; Sex Factors; Sleep Apnea, Obstructive

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels.. The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations.. We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study.. The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred.. Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Topics: Body Mass Index; Carbon Dioxide; Continuous Positive Airway Pressure; Female; Humans; Hypercapnia; Hypoventilation; Hypoxia; Leptin; Male; Middle Aged; Obesity; Oxygen; Polysomnography; Positive-Pressure Respiration; Prospective Studies; Sleep Apnea, Obstructive; Syndrome

To explore the level of serum leptin in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and obesity and patients with normal body mass.. Polysomnography (PSG) was performed in 53 patients with OSAHS and in 41 simple obesity and in 62 patients with normal body mass. The level of serum leptin was detected by radioimmunoassay. The stature, weight, neck collar, hip circumference, waistline were measured.. (1) Serum leptin level in patients with OSAHS and obesity was higher than patients with normal body mass. At the same time, serum leptin level in patients with OSAHS was higher than obesity ( P < 0.05). (2) Serum leptin levels were positive significantly correlated with BMI in both OSAHS patients and simple obesity, but only the leptin level in patients with OSAHS was significantly correlated with apnea and hypopnea index (AHI) and proportion of neck circumference and waist-hip ratio (WHR).. The rise of the serum leptin level in obesity was resisted of leptin. The serum leptin level of patients with OSAHS correlated with AHI shows that OSAHS maybe one reason of arising serum leptin's rising. Leptin could stimulate aspirator centrum.

Topics: Adult; Aged; Body Weight; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is one of the most often sleep disturbance. Not treated patients have 2-3 times more risk for death because of the cardiovascular diseases. Leptin and homocysteine are the risk factors for cardiovascular diseases. Treatment by nCPAP has positive influence for health care and reduction of hypertension in this group. The aim of this study was to evaluate an effect of 3 weeks nCPAP therapy on a serum leptin and homocysteine concentrations in patients with OSA.. The study group consisted of 48 male patients in the age x=51,2?7,5 years old, OSA was diagnosed by polisomnographic study The leptin concentration was evaluated by RIA methods (HUMAN LEPTIN RIA KIT), the homocysteine concentration was evaluated byAxis Homocysteine EIA test. Patients were treated by nCPAP during 3 weeks. Only 29 patients were effectively treated for this time. The compliance was: 5.07 +/-1.81 h. In the group of 29 patients the serum leptin and homocysteine concentration before and after treatment were 11,05+/-5,59 ng/mL vs 11,07+/-7,16 ng/mL i 10,98+/-2,79 micromol/L vs 10,34+/-2,99 micromol/L. In the all study group the statistical important correlation between leptin and AHI, mean and minimal saturation overnight, fibrinogene concentration, BMI, WHR, waist circumference, heart rate and between homocysteine and heart rate were observed.. 3 weeks therapy does not have any effect on leptin and homocysteine concentrations in the studied group of patients with OSA. Serum leptin concentration correlates with AHI, TMB90, as well as with mean and minimal saturation during a sleep. This indicates a potentially higher risk of cardiovascular diseases in the studied group.

Topics: Biomarkers; Cardiovascular Diseases; Continuous Positive Airway Pressure; Homocysteine; Humans; Leptin; Male; Middle Aged; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of body weight, energy balance, and sympathetic tone. This study investigates the independent role of apneas and obesity on NPY and leptin plasma levels in patients with obstructive sleep apnea syndrome (OSAS). To this end we compared their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control subjects without OSAS. Patients who used continuous positive airway pressure for more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY levels were increased (p < 0.01) in patients with OSAS independently of obesity. Leptin levels were also increased in OSAS but this was mostly associated to obesity. Continuous positive airway pressure treatment reduced NPY levels in all patients and leptin levels only in nonobese patients (p < 0.01). We concluded that NPY and leptin plasma levels are increased in patients with OSAS. Yet, whereas the former appear independent of obesity, the latter are mostly associated with obesity.

Topics: Analysis of Variance; Biomarkers; Case-Control Studies; Continuous Positive Airway Pressure; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Obesity; Prospective Studies; Sleep Apnea, Obstructive; Statistics, Nonparametric

Obesity and visceral fat accumulation (VFA) are risk factors for the development of obstructive sleep apnea-hypopnea syndrome (OSAHS), and a subgroup of OSAHS patients acquire hypoventilation. Circulating leptin, an adipocyte-derived signaling factor, increases in accordance with body mass index (BMI); under experimental conditions, leptin selectively decreases visceral adiposity and it is also a respiratory stimulant.. To investigate whether the location of body fat deposits, ie, the distribution of VFA and subcutaneous fat accumulation (SFA), contributes to hypoventilation and whether circulating levels of leptin are involved in the pathogenesis of hypoventilation, which is often observed in OSAHS.. We assessed VFA and SFA by abdominal CT scan, and measured lung function and circulating levels of leptin in 106 eucapnic and 79 hypercapnic male patients with OSAHS.. In the whole study group, circulating leptin levels correlated with BMI (r = 0.56), VFA (r = 0.24), and SFA (r = 0.47), but not with Po(2) or sleep mean arterial oxygen saturation (Sao(2)). BMI, percentage of predicted vital capacity, FEV(1)/FVC ratio, apnea-hypopnea index, sleep mean Sao(2), VFA, and SFA were not significantly different between two groups. Circulating leptin levels were higher in the hypercapnic group than in the eucapnic group. Logistic regression analysis indicated that serum leptin was the only predictor for the presence of hypercapnia (beta = 0.21, p < 0.01).. These results suggest that the location of body fat deposits may not contribute to the pathogenesis of hypoventilation, and circulating leptin may fail to maintain alveolar ventilation in hypercapnic patients with OSAHS.

Topics: Adipose Tissue; Adult; Aged; Body Composition; Body Mass Index; Humans; Hypercapnia; Hypoventilation; Leptin; Logistic Models; Male; Middle Aged; Oxygen; Polysomnography; Risk Factors; Skinfold Thickness; Sleep Apnea, Obstructive; Statistics as Topic

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated oxygen desaturation. Obesity and visceral fat accumulation (VFA) are risk factors for the development of OSAHS. Circulating leptin increases in accordance with body mass index (BMI), and under experimental conditions intermittent hypoxia stimulates leptin production.. The primary objective of this study was to investigate whether hypoxemia during sleep influences the levels of circulating leptin and whether the location of body fat deposits, ie, the distribution of VFA and subcutaneous fat accumulation (SFA), affects circulating leptin levels in patients with OSAHA who are not obese. We assessed VFA and SFA by abdominal CT scan and measured circulating levels of leptin in 96 male patients with OSAHS and 52 male patients without OSAHS matched for BMI. To be matched for BMI in the two groups, patients whose BMIs were < 27 were selected for the OSAHS group.. In the whole study group, circulating leptin levels correlated with BMI (r = 0.30), VFA (r = 0.44), SFA (r = 0.28), apnea-hypopnea index (AHI) [r = 0.48], sleep mean arterial oxygen saturation (Sao(2)) [r = 0.59], and sleep lowest Sao(2) (r = 0.37). Multiple regression analysis showed that average Sao(2) (p < 0.01) and lowest Sao(2) (p = 0.03) were explanatory variables for serum leptin values, but AHI (p = 0.054), BMI (p = 0.33), VFA (p = 0.11), and SFA (p = 0.36) were not.. These results suggest that sleep hypoxemia may be the main determinant of circulating leptin levels, although the location of body fat deposits could contribute to the elevated circulating leptin levels in patients with OSAHS who are not obese.

Topics: Abdomen; Adipose Tissue; Body Mass Index; Forced Expiratory Volume; Humans; Leptin; Male; Middle Aged; Oxygen; Sleep Apnea, Obstructive; Subcutaneous Tissue; Vital Capacity

To investigate the effect of uvulopalatopharyngoplasty on changes of serum leptin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).. Sixty-one patients with OSAHS diagnosed by polysomnography were treated with uvulopalatopharyngoplasty. Pretreatment and post-uppp serum leptin concentrations in patients with OSAHS and in BMI-matched controls were measured by radioimmunoassay. Correlations between leptin concentrations and AHI, BMI were analyzed.. The concentrations of leptin in patients with OSAHS were higher than that in controls (P < 0.05). Mean levels (x+/-s) of leptin were (9.8+/-2.1) microg/L, (14.2+/-6.7) microg/L, and (19.3+/-7.9) microg/L in patients with severe, mediate and mild obstructive sleep apnea, respectively. Serum leptin levels correlated positively with the degree of OSAHS as reflected by AHI (r = 0. 68, P < 0.01). The leptin concentration of 51 responders after 6 months were significantly decreased (P < 0.01) than that of pre-operation. However, the difference of leptin concentration between pre-operation and post operation was not significant in 9 nonresponders (P > 0.05).. There are higher leptin concentrations in patients with OSAHS, which are significantly correlated to the severity of disease. Serum leptin levels in responders decreased significantly after uvulopalatopharyngoplasty. OSAHS may influence the leptin system, resulting in increased serum leptin level.

Topics: Adult; Case-Control Studies; Humans; Leptin; Male; Middle Aged; Otorhinolaryngologic Surgical Procedures; Sleep Apnea, Obstructive

It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.

Topics: Adipose Tissue; Adult; Aged; Angiogenic Proteins; Animals; Case-Control Studies; Cells, Cultured; Female; Humans; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neovascularization, Physiologic; Severity of Illness Index; Skin; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.

Topics: Body Mass Index; Continuous Positive Airway Pressure; Female; Glucose Clamp Technique; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnoea syndrome (OSAS) is a common disorder in obesity. Leptin, an adipocyte-derived signalling factor, plays an important role in metabolic control. There is growing evidence that leptin regulation is altered in OSAS. Therefore, the aim of this study was to test the hypothesis that effective treatment will influence leptin levels in OSAS patients. Serum leptin levels were determined in 86 consecutive patients (aged 57.5 +/- 11.0 yrs) with polysomnographically verified OSAS. In addition, leptin levels were reassessed and treatment efficacy was evaluated by polysomnography after 6 months of therapy. Patients were treated with continuous or bilevel positive airway pressure, a mandibular advancement device or conservatively, depending on the clinical symptoms. Mean serum leptin levels did not change with treatment in the whole study group (7.3 +/- 5.0 versus 7.5 +/- 4.8 ng.mL-1), however, leptin levels decreased in effectively treated patients (8.5 +/- 5.0 versus 7.4 +/- 5.1 ng.mL-1) while they increased in ineffectively treated patients (5.0 +/- 4.0 versus 7.7 +/- 4.1 ng.mL-1). Furthermore, not only was there a significant and independent correlation between the change in leptin levels with treatment and the change in body mass index, but also with the change in apnoea/hypopnoea index. Effective treatment of sleep-disordered breathing may have significant effects on leptin levels in obstructive sleep apnoea syndrome patients. Changes in leptin levels are related to changes in apnoea/hypopnoea index in obstructive sleep apnoea syndrome patients.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Continuous Positive Airway Pressure; Female; Follow-Up Studies; Humans; Leptin; Logistic Models; Male; Mandibular Advancement; Middle Aged; Oxygen; Patient Compliance; Polysomnography; Sleep Apnea, Obstructive; Treatment Outcome

Several studies have reported an association between obstructive sleep apnea and leptin, a hormone that influences satiety and body weight. We evaluated the relationship of leptin levels and the overnight change in levels with sleep apnea.. Cross-sectional analysis of data from a prospective cohort study.. Case Western Reserve University General Clinical Research Center.. A total of 138 individuals participating in the Cleveland Family Study--59% women, 45% African-American, with mean apnea-hypopnea index (AHI) of 6.9 (range 0-106)--were studied.. None.. Serum leptin was measured at 10:00 pm to 11:00 pm and at 7:00 am to 8:00 am. Leptin levels in both the morning and evening were positively correlated with apnea-hypopnea index (AHI) in age-, sex-, and race-adjusted analyses (P < .0001) but not after additional adjustment for body mass index. The evening/morning leptin ratio, however, was associated with AHI independent of age, sex, race, body mass index, and waist-hip ratio (P = .03). Conversely, AHI was an independent predictor of the leptin ratio (P = .001) and more predictive than arousal index, oxygenation indices, time asleep, or sleep-stage distribution. An AHI > 15 was associated with a 23% increase in leptin ratio.. These findings suggest that sleep apnea may suppress secretion of leptin in the morning. Alternatively, the relative elevation in evening leptin may influence apnea pathogenesis.

Topics: Adolescent; Adult; Arousal; Body Mass Index; Circadian Rhythm; Cohort Studies; Cross-Sectional Studies; Female; Humans; Leptin; Male; Obesity; Prospective Studies; Sleep Apnea, Obstructive

To evaluate the effects of nasal continuous positive airway pressure (nCPAP) on serum leptin concentration and the metabolic parameters in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).. Serum leptin levels and true insulin (TI) levels were measured before and after one night nCPAP therapy in 18 patients. Eight patients received regular nCPAP treatment and had no change of body weight (BMI change < or = 1.5 kg/m2 from baseline) were recruited to the reassessment study 7.5 months after therapy.. After one night use of nCPAP, there was a significant decrease in serum leptin [(8.47 +/- 0.62) microg/L vs (7.32 +/- 0.64) microg/L, P = 0.022] without change in other parameters. After 7.5 months of nCPAP treatment, serum leptin levels continued to decrease significantly without changes in BMI [(8.35 +/- 0.83) microg/L vs (6.05 +/- 0.78) microg/L; P = 0.036), and fast blood glucose (FBG) and true insulin (TI) also decreased significantly (P = 0.036) in OSAHS patients. However, triglyceral (TG) and cholesterol (Chol) maintained the pretreatment level (P > 0.05).. OSAHS may have significant effects on the serum leptin levels and the correction of sleep disordered breathing by nCPAP can reduce the serum leptin levels. Decrease of leptin was independent of BMI change. The glucose metabolic disturbance and insulin resistance in OSAHS were improved after 7.5 months of nCPAP treatment.

Topics: Adult; Continuous Positive Airway Pressure; Female; Humans; Leptin; Male; Sleep Apnea, Obstructive

The role of resistin, a "new" white adipose tissue hormone, still needs to be established. Its linkage to insulin sensitivity and body mass was controversial in previous studies.. Twenty obese patients (BMI: 32.1+/-6.9 kg/m2 ) with obstructive sleep apnoea syndrome (OSAS) (Apnoea-Hypopnoea Index: 48.6+/-19.1, underwent measurements of resistin, interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), CRP and the insulin sensitivity index (ISI) by hyperinsulinaemic euglycaemic clamp before, 2 days and 2 months after onset of CPAP treatment.. Resistin remained unchanged during CPAP-therapy and was negatively correlated to ISI (r=-0.359; p=0.006), the latter was significantly improved by CPAP (p<0.001). In a correlation matrix, IL-6 and ICAM-1 were significantly (p=0.001) correlated to resistin (p=0.614 and 0.427). Changes of inflammatory markers under CPAP treatment were related to AHI, as well as resistin changes.. In agreement with previous investigations, we could only demonstrate a weak linkage between ISI and resistin. However, at least in obese patients with OSAS, there is a close relation to subclinical inflammation (IL-6) and endothelial activation (ICAM-1).

Topics: Body Mass Index; C-Reactive Protein; Continuous Positive Airway Pressure; Hormones, Ectopic; Humans; Inflammation; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Middle Aged; Obesity; Patient Compliance; Polysomnography; Resistin; Sleep Apnea, Obstructive; Statistics as Topic

Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients.. We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment.. Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment.. Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Female; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive; Time Factors; Triglycerides

To examine whether circulating leptin levels correlate with the severity of disease in patients with obstructive sleep apnea.. Prospective nonrandomized study.. Referral sleep laboratory for patients with sleep-disordered breathing and biochemistry laboratory. Patients Thirty-two subjects (mean +/- SD age, 47 +/- 12 years) who were referred for suspected sleep apnea underwent an overnight sleep study and fasting morning venous blood sampling. Patients were divided into 3 groups with respect to apnea-hypopnea index: (1) severe sleep apnea (n = 8), apnea-hypopnea index greater than 20; (2) mild sleep apnea (n = 12), apnea-hypopnea index between 5 and 20; and (3) nonapneic control (n = 12), apnea-hypopnea index less than 5.. Leptin levels (mean +/- SD) were 21.2 +/- 8.6, 16.2 +/- 5.2, and 10.6 +/- 7.5 ng/mL (P =.005) in patients with severe and mild obstructive sleep apnea and nonapneic controls, respectively. Plasma leptin levels correlated positively with the degree of sleep-disordered breathing as recorded by the apnea-hypopnea index (r = 0.54, P =.001) and percentage of sleep time spent with oxygen saturation below 90% (r = 0.39, P =.02).. Circulating leptin concentrations in patients with obstructive sleep apnea, independent of body mass index and age, are significantly higher than levels in nonapneic controls and there is a positive relationship between leptin concentrations and the severity of sleep apnea. Hyperleptinemia may be a prognostic marker of obstructive sleep apnea syndrome.

Topics: Adult; Female; Humans; Leptin; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA. Male patients (n=30) with OSA (apnoea/hypopnoea index=58+/-16, BMI=32.6+/-5.3 kg x m(-2)) underwent CPAP treatment. Fasting leptin and ghrelin were measured at baseline and 2 days, and in the case of leptin 2 months after initiation of treatment. Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI <30 kg x m(-2). These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy.

Topics: Adult; Blood Gas Analysis; Body Mass Index; Case-Control Studies; Continuous Positive Airway Pressure; Ghrelin; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Obesity; Peptide Hormones; Polysomnography; Sleep Apnea, Obstructive

To explore the change of serum leptin in patients with obstructive sleep apnea syndrome (OSAS).. Polysomnography was performed in 58 patients with OSAS and in 21 simple obese controls without differences in age and body mass index (BMI). Serum leptin level was measured by radioimmunoassay.. (1) The serum leptin level in patients with OSAS was higher, in both males (6.1 +/- 1.7) microg/L and females (19.5 +/- 9.9) microgram/L, than that in the simple obese controls [male (4.5 +/- 1.7) microgram/L, female (10.5 +/- 2.4) microgram/L] (P < 0.01, P < 0.05). (2) Serum leptin levels were significantly correlated with BMI in both OSAS patients (r = 0.64, P < 0.01) and simple obese controls (r = 0.59, P < 0.01), but only in OSAS patients was the leptin level significantly correlated with apnea and hypopnea index (AHI) (r = 0.47, P < 0.01) and with neck circumference (r = 0.64, P < 0.01).. Serum leptin levels were higher in OSAS patients than in simple obese controls. Besides obesity and neck circumference, OSAS may also influence the leptin system, resulting in increased serum leptin level.

Topics: Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Neck; Obesity; Sleep Apnea, Obstructive

Topics: Body Constitution; Humans; Leptin; Metabolic Syndrome; Obesity; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

s: To determine whether traditional risk factors for cardiovascular disease (CVD) and regional fat distribution, especially the central obesity type and increased parapharyngeal fat pads, are associated with the degree of obstructive sleep apnea (OSA). To determine whether there are interrelationships between body fat, serum leptin levels, and the degree of OSA.. Prospective mono-center cross-sectional study in a university hospital in Germany.. Eighty-five consecutive male patients who were referred for evaluation of suspected OSA.. The major dependent outcome variable was the apnea-hypopnea index (AHI), the average number of apneas and hypopneas per hour of sleep, determined by overnight polysomnography. Independent measures were anthropometric data, body composition analysis (bioelectrical impedance analysis [BIA]), cardiovascular risk factor evaluation (smoking, hypertension, serum lipoproteins, diabetes or impaired glucose tolerance, uric acid, fibrinogen), and leptin. Adipose tissue quantification of the abdominal and neck regions was performed by nuclear MRI (NMR). Significant linear relationships of AHI with fasting blood glucose, uric acid, fibrinogen, body weight, body mass index (BMI), sum of fat skin folds, and percentage of body fat could be established, whereas there was no correlation with age. The presence of OSA was independent of smoking, hypertension, and lipoproteins. NMR scans showed that AHI was significantly correlated with intra-abdominal fat and subcutaneous abdominal fat, whereas subcutaneous fat in the neck region and parapharyngeal fat in the airway vicinity were not correlated. Leptin concentrations correlated with AHI and with biochemical markers of the metabolic syndrome (lipoproteins, glucose) but were not dependent on AHI. Logistic regression analysis found percentage of body fat (BIA) and BMI as good predictors of AHI > 10 with a sensitivity of 95.5% but a low specificity (46.2%). Multiple regression analysis identified the sum of fat skin folds, body weight, and BMI as good predictors for the degree of OSA.. We conclude that OSA is independent from most traditional risk factors for CVD. Regional body fat distribution predicts the presence and degree of OSA, but fat accumulation in the neck and parapharyngeal region are of minor importance. Leptin concentrations when controlled for body fat are not related to the degree of OSA.

Topics: Adult; Aged; Body Composition; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polysomnography; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive

Launois-Bensaude Syndrome (LBS) is a very rare cause of obesity, characterized by a symmetrical accumulation of a very large number of lipomata in different regions of the body, excluding the face, the forearms, and the shanks. Obesity is known to be closely associated with insulin resistance, hyperleptinemia, and obstructive sleep apnea (OSA). We were interested in studying whether these conditions are also present in patients with obesity due to LBS with a similar frequency as in patients with "simple" truncal obesity.. We performed polysomnography and hyperinsulinemic euglycemic clamp studies and measured serum leptin in three patients with LBS and in six patients with "simple" truncal obesity, matched for sex and body mass index (LBS group, 36.39 kg/m(2); controls, 35.82 kg/m(2)).. Polysomnography revealed severe OSA in one LBS patient with marked "horsecollar lipomata." In the other LBS patients, no OSA could be demonstrated. The leptin levels of the two groups were comparable (LBS group, 36.39 microg/liter; controls, 37.18 microg/liter) and the insulin responsiveness index was also comparable in the two groups (LBS group, 3.47 micromol/kg. minute; controls, 3.79 micromol/kg. minute).. Patients with LBS demonstrated similar metabolic features in terms of insulin sensitivity and hyperleptinemia as patients with "simple" truncal obesity. LBS is not strictly associated with OSA.

Topics: Adult; Aged; Body Mass Index; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Lipomatosis, Multiple Symmetrical; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive; Syndrome; Tomography, X-Ray Computed; Uric Acid

Patients with obstructive sleep apnea (OSA) are frequently obese and are predisposed to weight gain. They also have heightened sympathetic drive. We reasoned that noradrenergic activation of beta(3)-receptors on adipocytes would inhibit leptin production, predisposing to obesity in sleep apnea. We therefore tested the hypothesis that obesity and predisposition to weight gain in OSA are associated with low levels of plasma leptin. We prospectively studied 32 male patients (43 +/- 2 yr) with OSA who were newly diagnosed and never treated and who were free of any other diseases. Control measurements were obtained from 32 similarly obese closely matched male subjects (38 +/- 2 yr). Leptin levels were 13.7 +/- 1.3 and 9.2 +/- 1.2 ng/ml in patients with OSA and controls, respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 +/- 1.7 and 0.5 +/- 0.9 kg in sleep apnea patients and similarly obese control subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 +/- 4 and 30 +/- 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18), respectively (P = 0.01). Plasma leptin levels are elevated in newly diagnosed otherwise healthy patients with untreated sleep apnea beyond the levels seen in similarly obese control subjects without sleep apnea. Higher leptin levels in OSA, independent of body fat content, suggest that OSA is associated with resistance to the weight-reducing effects of leptin.

Topics: Adult; Blood Pressure; Body Constitution; Body Mass Index; Heart Rate; Hemodynamics; Humans; Leptin; Male; Muscle, Skeletal; Obesity; Sleep Apnea, Obstructive; Sympathetic Nervous System; Weight Gain

To define the metabolic profile relevant to vascular risks in obstructive sleep apnea (OSA) and the role of leptin resistance in this risk profile.. Case control study.. Sleep Laboratory, Queen Mary Hospital, University of Hong Kong, China.. Thirty OSA subjects were matched with 30 non-OSA subjects for body mass index (BMI), age, sex, and menopausal status. Neck, waist, and hip girth, skinfold thickness, and fasting serum levels of lipids, glucose, insulin, and leptin were compared between these two groups.. Compared with control subjects with a similar BMI but without OSA, the OSA group had a significantly more adverse vascular risk factor profile, including dyslipidemia, higher diastolic BP, insulin resistance, and greater adiposity reflected by skinfold thickness. OSA subjects also had higher circulating leptin levels (9.18+/-4.24 ng/mL vs 6.54+/-3.81 ng/mL, mean +/- SD, p = 0.001). Serum leptin levels correlated positively with BMI, skinfold thickness, serum cholesterol, low-density lipoprotein cholesterol, insulin, insulin/glucose ratio, apnea-hypopnea index, and oxygen desaturation time; multiple stepwise regression analysis identified skinfold thickness, waist/hip ratio, serum low-density lipoprotein cholesterol, and diastolic BP as independent correlates, while only serum insulin and diastolic BP were independent correlates in OSA subjects. After treatment with nasal continuous positive airway pressure for 6 months, there was a significant decrease in circulating leptin (p = 0.01) and triglyceride levels (p = 0.02) without change in other parameters.. Despite controlling for BMI, OSA subjects showed distinct profiles with clustering of vascular risk factors. Hyperleptinemia was present in the OSA subjects, but it can be normalized by treatment with nasal continuous positive airway pressure, suggesting that increased leptin resistance was not the cause of OSA or its associated vascular risks.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Male; Positive-Pressure Respiration; Radioimmunoassay; Risk Factors; Sleep Apnea, Obstructive; Vascular Diseases