Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome
ABSTRACT 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.
Article: Hypoventilation syndromes.[Show abstract] [Hide abstract]
ABSTRACT: In patients with impaired inspiratory muscle function or altered respiratory system mechanics, an imbalance between load and capacity can arise. The ventilatory control system normally compensates for this by increasing drive to maintain adequate alveolar ventilation levels, thereby keeping arterial CO2 within its normal range. To reduce work of breathing, a pattern of reduced tidal volume and increased respiratory rate occurs. This pattern itself may eventually reduce effective ventilation by increasing dead space ventilation. However, the impact of sleep on breathing and its role in the development of diurnal respiratory failure is often overlooked in this process. Sleep not only reduces respiratory drive, but also diminishes chemoresponsiveness to hypoxia and hypercapnia creating an environment where significant alterations in oxygenation and CO2 can occur. Acute increases in CO2 load especially during rapid eye movement sleep can initiate the process of bicarbonate retention which further depresses ventilatory responsiveness to CO2. Treatment of hypoventilation needs to be directed toward factors underlying its development. Nocturnal noninvasive positive pressure therapy is the most widely used and reliable strategy currently available to manage hypoventilation syndromes. Although this may not consistently alter respiratory muscle strength or the mechanical properties of the respiratory system, it does appear to reset chemosensitivity by reducing bicarbonate, resulting in a more appropriate ventilatory response to CO2 during wakefulness. Not only is diurnal hypoventilation reduced with noninvasive ventilation, but quality of life, functional capacity and survival are also improved. However, close attention to how therapy is set up and used are key factors in achieving clinical benefits. © 2014 American Physiological Society. Compr Physiol 4: 1639-1676, 2014.
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ABSTRACT: To assess the prevalence, clinical characteristics, and predictors of obesity hypoventilation syndrome (OHS) in a large sample of Saudi patients with obstructive sleep apnea (OSA). This prospective observational study consisted of 1693 patients who were diagnosed to have sleep-disordered breathing using type I attended polysomnography (PSG) between January 2002 and December 2012 in the University Sleep Disorders Center (USDC) at King Saud University Hospital, Riyadh, Kingdom of Saudi Arabia. Out of 1693 OSA patients, OHS was identified in 144 (8.5%) (women 66.7%). Compared with the pure OSA patients, the OHS patients were significantly older (57.4±13.4 years versus 46.8±13.7 years), had a higher body mass index (44.6±10.8 versus 35.7±9.2 kg/m2), a higher daytime partial pressure of carbon dioxide (PaCO2) (56.5±12.7 versus 41.6±6.7 mmHg), a longer duration of nocturnal oxygen saturation (nSaO2) <90% (71.0±34.3 versus 10.5±20.5 minutes), and a higher apnea hypopnea index (68.2±47.1 versus 46.5±34.1 events/hour). A multivariate logistic regression analysis showed that serum bicarbonate (odds ratio [OR]=1.17, p=0.0001, confidence interval [CI]=1.10-1.25), and duration of nSaO2 <90% (OR=1.05, p=0.0001, CI=1.04-1.06) were predictors of OHS. Obesity hypoventilation syndrome is common among Saudi OSA patients referred to the Sleep Disorders Center. Serum bicarbonate and duration of nSaO2 <90% are independent predictors of OHS among patients with OSA.Saudi medical journal 02/2015; 36(2):181-9. DOI:10.15537/smj.2015.2.9991 · 0.55 Impact Factor
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