Impact of obstructive sleep apnea on the 24-h metabolic hormone profile.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Day-night variations in endothelial dysfunction markers and haemostatic factors in sleep apnoea.

Patients with sleep apnoea have a significant alteration in the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population. The aim of this study was to investigate the influence of sleep apnoea on the diurnal variations in various haemostatic parameters (factor VII, von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40 ligand (sCD40L)). We studied 26 male patients with obstructive sleep apnoea syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30 events · h(-1)) and 13 patients with mild-to-moderate OSAS (AHI <30 events · h(-1))) and 12 controls of similar body mass index (BMI) and waist circumference. In each subject, six different samples were obtained over 24 h. Although all the markers values tended to be higher in patients with severe OSAS, differences did not reach statistical significance at any time. PAI-1 levels were significantly related to BMI (p<0.001), mean (p<0.001) and minimal (p = 0.047) nocturnal oxygenation saturation. ADMA levels were significantly related to arousal index (p = 0.046). The results of this study suggest that day-night variations in factor VII:antigen (Ag), von Willebrand factor:Ag, PAI-1, sCD40L and ADMA levels may be dependent on either the obesity index or metabolic dysfunction rather than on sleep apnoea alone.

Plasma levels of neuropeptides and metabolic hormones, and sleepiness in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients. METHODS: We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score ≥ 13 (mean ± SD, 15.7 ± 2.3) and 132 patients without EDS as defined by an ESS score ≤ 9 (6.5 ± 1.9). All patients had an apnea-hypopnea index (AHI) ≥ 20 h(-1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 ± 11.2 yrs vs. 50.7 ± 9.9 yrs), body mass index (BMI) (31.8 ± 5.6 kg m(-2) vs. 32.1 ± 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 ± 19.1 h(-1) vs. 43 ± 19.2 h(-1)). RESULTS: OSA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than OSA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time. CONCLUSION: Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep-wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA).

Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea.

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 lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, C-reactive protein and 8-isoprostanes were determined. Prevalence of MS was higher in OSAS than in the control group (38 versus 21%; p=0.006). OSAS patients had higher FFAs levels than controls (mean±sd 12.2±4.9 versus 10.5±5.0 mg·dL(-1); p=0.015). 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); p=0.04). In a multiple regression model, after adjustment for age, sex, BMI and the presence of MS, FFAs were significantly associated with apnoea/hypopnoea index (p=0.04). This study shows that FFAs are elevated in OSAS and could be one of the mechanisms involved in the metabolic complications of OSAS.

Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial.

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) micromol/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) micromol/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.

Insulin resistance and daytime sleepiness in patients with sleep apnoea.

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.

beta3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea.

Obesity is an important risk factor for obstructive sleep apnoea syndrome (OSAS), insulin resistance and cardiovascular disease. The substitution of tryptophan 64 with arginine (Trp64Arg) polymorphism (Arg variant) of the beta(3)-adrenergic receptor (ADRB3) has been associated with obesity. In this study, the prevalence of the Trp64Arg ADRB3 polymorphism in a large group of patients with OSAS and its association with body mass index (BMI), insulin resistance and hypertension were evaluated. ADRB3 genotype was determined in 387 patients with OSAS and 137 healthy subjects recruited from three Spanish tertiary hospitals. The distributions of the ADRB3 genotypes were similar in OSAS and controls, and, in a multivariate model, the risk of OSAS was not associated with the presence of the Arg variant of the ADRB3 gene. However, BMI was higher in those patients with OSAS who carried this genetic variant than in those with the Trp variant. Furthermore, a linear trend for higher BMI was found in those with the Arg variant (56, 75 and 100% for Trp/Trp, Trp/Arg and Arg/Arg, respectively). Insulin resistance, blood pressures and serum levels of lipids and glucose were not associated with the presence of the Arg variant of the ADRB3 gene. The presence of the arginine 64 allele of the beta(3)-adrenergic receptor gene does not increase the risk of obstructive sleep apnoea syndrome, but is associated with the development of obesity in those patients who suffer obstructive sleep apnoea syndrome.

Prostaglandin D synthase (beta trace) levels in sleep apnea patients with and without sleepiness.

BACKGROUND: Excessive daytime sleepiness (EDS) occurs often in patients with obstructive sleep apnea syndrome (OSAS). However, not all patients present EDS. We hypothesized that the prostaglandin D2 system (PGD2) may be involved in the pathogenesis of EDS associated with OSAS. METHODS: We measured the levels of lipocalin-type PGD synthase (L-PGDS), the enzyme that produces PGD2, in the serum of 47 patients with OSAS (26 with and 21 without EDS) and 18 healthy controls. RESULTS: Patients with EDS had higher levels of L-PGDS (0.73+/-0.06 mg/L) than patients without EDS (0.58+/-0.03 mg/L, p<0.05) and controls (0.62+/-0.02 mg/L, p<0.05). L-PGDS levels in patients without EDS and controls were similar. CONCLUSION: The increased levels of circulating L-PGDS detected in OSAS patients with EDS suggest a possible role of the prostaglandin D system in the pathophysiology of daytime sleepiness in these patients.

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment.

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), gamma-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h.night-1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4+/-0.16 versus 1.50+/-0.10 mmol.L-1), vitamin A (64+/-19 versus 74+/-17 microg.dL-1) and vitamin E levels (1,525+/-499 versus 1,774+/-503 microg.dL-1), and increased values of GGT (42+/-22 versus 32+/-16 U.L-1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50+/-0.13 mmol.L-1) and the activity of GGT (30+/-14 U.L-1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

[Metanephric stromal tumor: report of two cases and bibliographic review]. / Tumor del estroma metanéfrico: presentación de dos casos en adultos y revisión de la literatura.

OBJECTIVE: Metanephric Stromal Tumors (MST) are pediatric renal neoplasms not very common in adults. This study revises its classification, incidence and evolution and also some specific characteristics of the cases diagnosed in adults. METHODS: We present two cases of MST diagnosed in adults of 72 and 77 years old respectively. Abdominal pain due to a more than 4 Kg. mass was the initial presentation in both cases. The tumors were completely resected. Four and ten years after excision patients are alive without disease. RESULTS: Characteristic histologic features include a proliferation of fusocellular cells with alternating cellularity that imparts a nodular appearance and onion-skin cuffing around entrapped renal tubules or vascular structures. No mitoses or atypia was found but extensive necrosis and fibrosis were present. A majority of stromal cells were vimentine and CD-34 positive. Stains for CK and EMA highlighted entrapped native tubules. Both cases were previously classified as mesoblastic nephromas. According to the 2002 ONS classification of tumours of the urinary system, they have been revised and re-classified as MST CONCLUSION: MST are pediatric benign tumors exceptionally diagnosed in adults. Metanephric stromal tumors are divided into 3 categories based on the presence of epithelial cells, stroma and epithelial cells plus stromal. Complete excision is the treatment of choice and the prognosis is excellent.

Harlequin foetus in four siblings.

Four siblings (three males, one female), affected by harlequin foetus, are presented. Genetic aspects and classification of this variety of ichthyosis are discussed.