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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

ABSTRACT: BACKGROUND:Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear. METHODS:Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0?nM and 5?nM insulin-induced pAKT/AKT expression changes by western blotting. RESULTS:When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n?=?24; p?

SUBMITTER: Khalyfa A

PROVIDER: S-EPMC6195831 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

Khalyfa Abdelnaby A Gozal David D Masa Juan F JF Marin José Maria JM Qiao Zhuanghong Z Corral Jaime J González Mónica M Marti Sergi S Kheirandish-Gozal Leila L Egea Carlos C Sánchez-Quiroga M-Ángeles MÁ de Terreros Francisco J Gómez FJG Barca F Javier FJ

International journal of obesity (2005) 20180611 6

<h4>Background</h4>Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, t ...[more]

PMID: 29892042

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Project description:ObjectiveTo examine the association between sleep-disordered breathing and stroke outcomes, and determine the contribution of sleep-disordered breathing to outcome disparities in Mexican Americans.MethodsIschemic stroke patients (n = 995), identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2015), were offered participation in a sleep-disordered breathing study including a home sleep apnea test (ApneaLink Plus). Sleep-disordered breathing (respiratory event index ≥10) was determined soon after stroke. Neurologic, functional, cognitive, and quality of life outcomes were assessed at 90 days poststroke. Regression models were used to assess associations between sleep-disordered breathing and outcomes, adjusted for sociodemographics, prestroke function and cognition, health-risk behaviors, stroke severity, and vascular risk factors.ResultsMedian age was 67 years (interquartile range [IQR] = 59-78); 62.1% were Mexican American. Median respiratory event index was 14 (IQR = 6-25); 62.8% had sleep-disordered breathing. Sleep-disordered breathing was associated with worse functional outcome (mean difference in activities of daily living/instrumental activities of daily living score = 0.15, 95% confidence interval [CI] = 0.01-0.28) and cognitive outcome (mean difference in modified Mini-Mental State Examination = -2.66, 95% CI = -4.85 to -0.47) but not neurologic or quality of life outcomes. Sleep-disordered breathing accounted for 9 to 10% of ethnic differences in functional and cognitive outcome and was associated with cognitive outcome more strongly for Mexican Americans (β = -3.97, 95% CI = -6.63 to -1.31) than non-Hispanic whites (β = -0.40, 95% CI = -4.18 to 3.39, p-interaction = 0.15).InterpretationSleep-disordered breathing is associated with worse functional and cognitive function at 90 days poststroke. These outcomes are reasonable endpoints for future trials of sleep-disordered breathing treatment in stroke. If effective, sleep-disordered breathing treatment may somewhat lessen ethnic stroke outcome disparities. ANN NEUROL 2019;86:241-250.

Project description:BackgroundThis study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB).MethodsA random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (?18?years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations.ResultsThe prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 - 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12?mL and 20?mL in FEV1 and FVC respectively in men, and 4?mL and 7?mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women.ConclusionsIn this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may contribute up to one quarter of this association.

Project description:BACKGROUND:Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES:The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN:Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS:Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION:Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

Dataset Information

Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

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