No abstract

Background: Excessive daytime sleepiness (EDS), obesity and insulin resistance (IR) occur frequently in patients with obstructive sleep apnoea syndrome (OSAS). We hypothesised that in these patients, EDS is a marker of IR, independent of obesity. Methods: We studied 44 patients with OSAS (22 with and 22 without EDS) matched for age (¡5 years), body mass index (BMI ¡3 kg/m 2 ) and severity of OSAS (as determined by the apnoea-hypopnoea index (AHI)), and 23 healthy controls. Patients (n = 35) were re-examined after 3 months of effective therapy with continuous positive airway pressure (CPAP). EDS was assessed by both subjective (Epworth Sleepiness Scale) and objective (Multiple Sleep Latency Test) methods. IR was determined by the HOMA index. Serum levels of glucose, triglycerides, cholesterol, cortisol, insulin, thyrotropin, growth hormone and insulin-like growth factor I (IGF-I) were also determined. Results: Despite the fact that age, BMI and AHI were similar, patients with EDS had higher plasma levels of glucose (p,0.05) and insulin (p,0.01), as well as evidence of IR (p,0.01) compared with patients without EDS or healthy controls. CPAP treatment reduced cholesterol, insulin and the HOMA index and increased IGF-1 levels in patients with EDS, but did not modify any of these variables in patients without EDS. Conclusion: EDS in OSAS is associated with IR, independent of obesity. Hence EDS may be a useful clinical marker to identify patients with OSAS at risk of metabolic syndrome.The obstructive sleep apnoea syndrome (OSAS) is a common disorder defined by the occurrence of repeated episodes of upper airway obstruction and airflow cessation (apnoeas) that normally lead to arterial hypoxaemia and sleep disruption. 1 A number of clinical features, such as obesity, excessive daytime sleepiness (EDS) and insulin resistance (IR), are often but not invariably present in these patients. 2-7The relationship between obesity, IR and EDS in patients with OSAS is complex and poorly understood. [8][9][10] Obesity is generally regarded as a risk factor for both OSAS and IR.11 12 However, factors other than obesity appear to play a significant role in the development of IR and metabolic disturbances in patients with OSAS, 8 13-16 including sleep fragmentation, increased sympathetic activity and intermittent hypoxia. 17-21On the other hand, experimental evidence shows that intermittent hypoxaemia during sleep triggers neural damage to brain regions that promote and control wakefulness through a convergence of oxidative and inflammatory events that ultimately lead to neuronal cell loss and EDS. 22 23 In this study, we hypothesised that EDS in OSAS is associated with IR, independent of obesity, and that the abolishment of nocturnal apnoeas by continuous positive airway pressure (CPAP) therapy improves both EDS and IR. To test this hypothesis, we studied two groups of patients with OSAS (22 each) who were carefully matched for severity of OSAS, obesity and age, but who were clearly different in terms of the presence or ...

Background: Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency. Methods: A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities. Results: Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2-78.2) vs 20.0 (12.5-52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165-650) vs 590 (251-1465) mmol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2-58.7) pg/ml at baseline vs 22.5 (16.2-35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177-707) vs 1373 (981-1517) mmol/l, p = 0.0001) after CPAP. Conclusions: OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

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.

Background: Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS). Objectives: This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population. Methods: A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined. Results: In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, p_trend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, p_trend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, p_trend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, p_trend = 0.049). Conclusions: These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials.

Obesity and metabolic syndrome (MS) occur frequently in patients with obstructive sleep apnoea syndrome (OSAS). We hypothesised that circulating free fatty acids (FFAs) are elevated in OSAS patients independently of obesity. This elevation may contribute to the development of MS in these patients.We studied 119 OSAS patients and 119 controls. Participants were recruited and studied at sleep unit of our institution (Hospital Universitari Son Dureta, Palma de Mallorca, Spain) and were matched for sex, age and body mass index (BMI). The occurrence of MS was analysed by clinical criteria. Serum levels of FFAs, glucose, triglycerides, cholesterol, high-density lipoproteincholesterol, aspartate aminotransferase, alanine aminotransferase, c-glutamyltransferase, C-reactive protein and 8-isoprostanes were determined.Prevalence of MS was higher in OSAS than in the control group (38 versus 21%; p50.006). OSAS patients had higher FFAs levels than controls (mean¡SD 12.2¡4.9 versus 10.5¡5.0 mg?dL -1 ; p50.015). Among subjects without MS, OSAS patients (OSAS+ MS-) showed higher levels of FFAs than controls (OSAS-MS-) (11.6¡4.7 versus 10.0¡4.4 mg?dL -1 ; p50.04). In a multiple regression model, after adjustment for age, sex, BMI and the presence of MS, FFAs were significantly associated with apnoea/hypopnoea index (p50.04).This study shows that FFAs are elevated in OSAS and could be one of the mechanisms involved in the metabolic complications of OSAS.

TL in circulating leukocytes is shorter in patients with OSAS than subjects without OSAS. The mechanism of this observation is unresolved since it appears independent of chronological age, the severity of OSAS and/or the presence of cardiovascular or metabolic alterations but the potential utility of TL as a biomarker of increased cardiovascular risk in these patients justifies further studies.

Background: Endothelial dysfunction and cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSA). Circulating endothelial progenitor cells (EPCs) contribute to repair dysfunctional endothelium and have been related to increased cardiovascular risk. Objectives: We tested the hypothesis that the number of circulating EPCs may be altered in OSA patients. Methods: EPCs (CD34+ VEGF-R2+) were isolated and quantified from peripheral blood samples of OSA patients (n = 13) and healthy controls (n = 13) matched for age and sex. All subjects were free of any other known cardiovascular risk factors. The plasma levels of vascular endothelial growth factor (VEGF) were also determined, and the endothelium-dependent and endothelium-independent vascular function was assessed in all subjects. Results: Patients with OSA had lower levels of EPCs (p < 0.05) and higher plasma levels of VEGF (p < 0.05) than controls. Endothelial function was not different between OSA and controls. Conclusions: Patients with OSA free of any other known cardiovascular risk factor show a reduced number of circulating EPCs and an increase in plasma VEGF levels. These alterations may contribute to future endothelial dysfunction in these patients.