Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function

OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF-I axis, adrenal and thyroid activity. It is still unclear whether these alterations simply reflect overweight or include peculiar hypoxia-induced hormonal alterations. Hormonal evaluations have been generally performed in basal conditions but we have recently reported that OSAS is characterized by a more severe reduction of the GH releasable pool in comparison to simple obesity. We aimed to extend our evaluation of anterior pituitary function to corticotroph, thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison with simply obese and normal subjects. SUBJECTS AND METHODS: In 15 male patients with OSAS [age, mean +/- SEM 43.5 +/- 1.6 years; body mass index (BMI) 39.2 +/- 3.1 kg/m2; apnoea/hypopnoea index, (AHI) 53.4 +/- 8.7], 15 male patients with simple obesity (OB, age 39.7 +/- 1.2 years; BMI 41.2 +/- 2.0 kg/m2; AHI 3.1 +/- 1.2 events/h of sleep) and in 15 normal lean male subjects (NS, age 38.2 +/- 1.4 years; BMI 21.2 +/- 0.8 kg/m2; AHI 1.9 +/- 0.8 events/h of sleep) we evaluated: (a) the ACTH and cortisol responses to CRH [2 microg/kg intravenously (i.v.)] and basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 microg/kg iv) as well as FT3 and FT4 levels. RESULTS: Twenty-four-hour UFC levels in OSAS and OB were similar and within the normal range. Basal ACTH and cortisol levels were similar in all groups. However, the ACTH response to CRH in OSAS (Deltapeak: 30.3 +/- 3.8 pmol/l; DeltaAUC: 682.8 +/- 128.4 pmol*h/l) was markedly higher (P < 0.001) than in OB (Deltapeak: 9.3 +/- 1.4 pmol/l; DeltaAUC 471.5 +/- 97.3 pmol*h/l), which, in turn, was higher (P < 0.05) than in NS (Deltapeak: 3.3 +/- 0.9 pmol/l; DeltaAUC 94.7 +/- 76.7 pmol*h/l). On the other hand, the cortisol response to CRH was not significantly different in the three groups. Basal FT3 and FT4 levels as well as the TSH response to TRH were similar in all groups. Similarly, both basal PRL levels and the PRL response to TRH were similar in the three groups. CONCLUSIONS: With respect to patients with simple abdominal obesity, obese patients with OSAS show a more remarkable enhancement of the ACTH response to CRH but a preserved TSH and PRL responsiveness to TRH. These findings indicate the existence of a peculiarly exaggerated ACTH hyper-responsiveness to CRH that would reflect hypoxia- and/or sleep-induced alterations of the neural control of corticotroph function; this further alteration is coupled to the previously described, peculiar reduction of somatotroph function.     

Obstructive sleep apnoea syndrome, plasma adiponectin levels, and insulin resistance

OBJECTIVE: To investigate whether sleep-disordered breathing and/or plasma adiponectin levels are associated with insulin resistance independent of obesity or fat distribution in obstructive sleep apnoea syndrome (OSAS). DESIGN: Cross-sectional clinical study. PATIENTS: Two-hundred and thirteen Japanese patients with OSAS aged 27-80 years were divided into three groups: 30 with mild OSAS [apnoea-hypopnoea index (AHI) = 10.3 +/- 0.9 episodes/h, minimum oxygen saturation (min SpO2) = 87.3 +/- 0.9%], 98 with moderate OSAS (AHI = 28.9 +/- 0.6 episodes/h, min SpO2 = 82.1 +/- 0.7%), and 85 with severe OSAS (AHI = 68.1 +/- 2.8 episodes/h, min SpO2 = 72.3 +/- 1.6%). Twenty-one patients undergoing diabetic treatments (two mild, nine moderate and 10 severe) were excluded from the assessment of insulin resistance and plasma adiponectin measurements. MEASUREMENTS: Fat distribution [evaluated according to visceral (V) and subcutaneous (S) fat areas using computed tomography scanning at the umbilical level], blood pressure, metabolic parameters and hormones including insulin and adiponectin were measured. After full polysomnography, venous blood was collected between 0600 and 0700 h. RESULTS: Severe OSAS patients were more hypertensive than mild and moderate OSAS. Fasting plasma glucose (FPG) and fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels were all higher in severe OSAS than mild and moderate OSAS patients. HOMA-IR was correlated not only with obesity [body mass index (BMI), V and S areas] but also with apnoea (AHI, min SpO2 and desaturation time). Additionally, HOMA-IR was correlated positively with haemoglobin (Hb)A1c, systolic (SBP) and diastolic blood pressure (DBP), triglycerides and free fatty acids (FFA), and negatively with high density lipoprotein (HDL)-cholesterol, suggesting that insulin resistance is a key component of the metabolic syndrome in OSAS. Plasma adiponectin levels were not different between mild, moderate and severe OSAS groups. Plasma adiponectin levels were correlated with HOMA-IR and V area, but not AHI or min SpO2. Stepwise multiple regression analysis, however, revealed that BMI, AHI and plasma adiponectin were independently associated with HOMA-IR. CONCLUSION: Sleep-disordered breathing was associated with insulin resistance independent of obesity. Although plasma adiponectin was also an independent determinant of HOMA-IR in OSAS patients, plasma adiponectin was more closely related to obesity than to sleep apnoea. Although treatment of sleep-disordered breathing with nasal continuous positive airway pressure reportedly improves insulin sensitivity, our findings suggest that treatment of obesity is also essential in ameliorating insulin resistance at least through increased plasma adiponectin levels in OSAS.     

阻塞性睡眠呼吸暂停低通气综合征与胰岛素抵抗的关系

目的探讨阻塞性睡眠呼吸暂停低通气综合征（OSAHS）与胰岛素抵抗（IR）的关系。方法选男性肥胖OSAHS患者60例（肥胖OSAHS组）、非OSAHS肥胖男性60例（肥胖非OSAHS组）、体重正常非OSAHS男性60例（正常体重非OSAHS组）,计算3组受试者的腰臀比和体重指数（BMI）;观察脉搏血氧饱和度（SpO2）;测空腹血糖,用高度特异的单克隆抗体夹心放大酶联免疫分析法测真胰岛素（TI）,IR的体内稳定状态模式评估方法（HOMA-IR）评估IR;行多导睡眠图（PSG）监测,计算呼吸暂停低通气指数（AHI）。结果同样是肥胖者,肥胖OSAHS组TI、HOMA—IR高于肥胖非OSAHS组,而最低SpO2低于肥胖非OSAHS组;在非OSAHS者中,肥胖非OSAHS组TI、HOMA-IR高于正常体重非OSAHS组,而最低SpO2低于正常体重非OSAHS组。协方差分析校正年龄、BMI、腰臀比的影响后,肥胖OSAHS组的TI、HOMA-IR仍明显高于肥胖非OSAHS组和正常体重非OSAHS组,肥胖非OSAHS组的TI、HOMA—IR明显高于正常体重非OSAHS组。多元线性回归分析显示MTU、HOMA—IR均与年龄和最低SpO2呈负相关,与BMI、腰臀比、AHI呈正相关;当以TU作因变量时,腰臀比是影响肥胖OSAHS组IR的主要因素,AHI与最低SpO2是TI的独立影响因素;当以HOMA—IR作因变量时,腰臀比是其主要影响因素,AHI与最低SpO2是其独立影响因素。结论OSAHS与IR独立相关,OSAHS可能经IR这一中间途径导致心血管疾病。     

阻塞性睡眠呼吸暂停患者血清瘦素水平的研究

目的　探讨瘦素在阻塞性睡眠呼吸暂停综合征 (OSAS)患者体内的变化。方法　选择年龄及体重指数 (BMI)差异无显著性的OSAS患者 5 8例和单纯肥胖者 2 1例 ,用多导睡眠呼吸监测仪进行监测 ,用放射免疫法测定所有对象的血清瘦素。结果　 (1)无论男性还是女性 ,OSAS患者瘦素水平 [(6 1± 1 7) μg/L ,(19 5± 9 9) μg/L]平均高于单纯肥胖者 [(4 5± 1 7) μg/L ,(10 5± 2 4) μg/L](P <0 0 1,P <0 0 5 )。 (2 )单纯肥胖者及OSAS患者血清瘦素水平分别与BMI呈显著正相关 (r=0 5 9,P <0 0 1;r=0 6 4,P <0 0 1) ,同时OSAS患者血清瘦素水平分别与呼吸暂停及低通气指数 (AHI) (r=0 47,P <0 0 1)和颈围 (r=0 6 4,P <0 0 1)也有明显的正相关。结论　OSAS患者血清瘦素水平比单纯肥胖者更高 ,除了肥胖、颈围宽外 ,OSAS本身也是引起瘦素水平升高的原因。     

Association of Sleep Apnea Severity and Obesity with Insulin Resistance,C-Reactive Protein,and Leptin Levels in Male Patients with Obstructive Sleep Apnea

Obesity is the major confounding factor in the relationship between obstructive sleep apnea and increased risk for cardiovascular disease. The aim of the study was to investigate the association of sleep apnea severity with insulin resistance, leptin, and CRP levels in a cohort of male patients. Sixty-seven men referred to our sleep laboratory for evaluation of suspected obstructive sleep apnea syndrome (OSAS) were divided into three groups according to apnea severity: non-OSAS group (n=15), mild to moderate OSAS group (n=26), and severe OSAS (n=26). Insulin resistance was estimated by the homeostasis model assessment method. HOMA values were similar in the three groups: (3.2+/-2.2 vs. 3.3+/-1.8 vs. 3.6+/-1.5, respectively, p=0.71). Leptin levels were higher in the mild to moderate OSAS group (23.1+/-21.8 ng/ml, p<0.05) and in the severe OSAS group (20.2+/-17.5 ng/ml, p<0.05) than in the non-OSAS group (9.4+/-6.4 ng/ml). CRP levels were significantly higher in severe sleep apnea (0.35+/-0.3 vs. 0.19+/-0.1 mg/dl, p<0.05). In multiple regression analyses, waist-to-hip ratio (WHR) was the most significant determinant of HOMA estimation for insulin resistance. WHR and the percentage of total sleep time spent with hypoxemia (%TST with SaO2 <90%) were significant predictors for leptin levels, while body mass index (BMI) and the %TST with SaO2 <90% were the best predicting parameters for CRP levels. Insulin resistance estimated by the HOMA method in male patients with OSAS was not associated with sleep apnea severity independent of obesity. The severity of nocturnal hypoxemia was associated with leptin and CRP levels independent of obesity.     

Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome.

Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.     

Nasal obstruction as a risk factor for sleep apnoea syndrome.

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.     

Comparison of respiratory polysomnographic parameters in matched cohorts of upper airway resistance and obstructive sleep apnea syndrome patients.

OBJECTIVE: To compare respiratory nocturnal polysomnography (NPSG) characteristics between matched cohorts of upper airway resistance syndrome (UARS) and obstructive sleep apnea syndrome (OSAS) patients. METHODS: All patients received 13-channel NPSG, including esophageal pressure (Pes) manometry. By definition, OSAS patients had an apnea-hypopnea index (AHI, number of apneas/hypopneas per hour total sleep time) > or = 15, and UARS patients had an AHI < 5. Respiratory effort-related arousal (RERA) was defined as the absence of apnea/hypopnea with > or = 10 s duration of progressive negative Pes, culminating in an arousal or microarousal. UARS patients, by definition, had > or = 15 RERAs per hour. Fifteen consecutively diagnosed UARS patients were matched with OSAS patients on the basis of body mass index (BMI) and gender. RESULTS: Respiratory disturbance index (sum of the AHI and RERA per hour) was the same for both cohorts: UARS, 36+/-4; OSAS, 42+/-6 (p = 0.34). There were no differences between cohorts for mean inspiratory Pes nadirs for each 30-s epoch of sleep compared for each sleep stage over an entire night. For randomly selected breaths from supine stage 2 sleep, the mean inspiratory Pes nadir was the same for the cohorts: UARS, -16.6+/-2 cm H2O; OSAS, -16.1+/-3 cm H2O (p = 0.30). Differences between cohorts for each parameter fell within respective 95% confidence intervals. CONCLUSION: With the exception of AHI, respiratory NPSG parameters were the same for UARS and OSAS patients when BMI and gender were controlled for.     

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.     

Impact of obstructive sleep apnoea on left ventricular mass and global function.

Obstructive sleep apnoea syndrome (OSAS) might be a cause of heart failure. The present study aimed to assess left ventricular mass and myocardial performance index (MPI) in OSAS patients. A total of 67 subjects without any cardiac or pulmonary disease, referred for evaluation of OSAS, had overnight polysomnography and echocardiography. According to apnoea-hypopnoea index (AHI), subjects were classified into three groups: mild OSAS (AHI: 5-14; n = 16), moderate OSAS (AHI: 15-29; n = 18), and severe OSAS (AHI: > or = 30; n = 33). Thickness of interventricular septum (IVS) and posterior wall (LVPW) were measured by M-mode, along with left ventricular mass (LVM) and LVM index (LVMI). Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by D?ppler echocardiography. There were no differences in age or body mass index among the groups, but blood pressures were higher in severe OSAS compared with moderate and mild OSAS. In severe OSAS, thickness of IVS (11.2+/-1.1 mm), LVPW (11.4+/-0.9 mm), LVM (298.8+/-83.1 g) and LVMI (144.7+/-39.8 g x m(-2)) were higher than in moderate OSAS (10.9+/-1.3 mm; 10.8+/-0.9 mm; 287.3+/-74.6 g; 126.5+/-41.2 g x m(-2), respectively) and mild OSAS (9.9+/-0.9 mm; 9.8+/-0.8 mm; 225.6+/-84.3 g; 100.5+/-42.3 g x m(-2), respectively). In severe OSAS, MPI (0.64+/-0.14) was significantly higher than in mild OSAS (0.50+/-0.09), but not significantly higher than moderate OSAS (0.60+/-0.10). In conclusion, severe and moderate obstructive sleep apnoea syndrome patients had higher left ventricular mass and left ventricular mass index, and also left ventricular global dysfunction.     

QT interval dispersion in obstructive sleep apnoea syndrome patients without hypertension.

QT interval dispersion (QT(d)) reflects inhomogeneity of repolarisation. Delayed cardiac repolarisation leading to the prolongation of the QT interval is a well-characterised precursor of arrhythmias. Obstructive sleep apnoea syndrome (OSAS) can cause cardiovascular complications, such as arrhythmias, myocardial infarction, and systemic and pulmonary hypertension. The aim of this study was to assess QT(d) in OSAS patients without hypertension. A total of 49 subjects without hypertension, diabetes mellitus, any cardiac or pulmonary diseases, or any hormonal, hepatic, renal or electrolyte disorders were referred for evaluation of OSAS. An overnight polysomnography and a standard 12-lead ECG were performed in each subject. According to the apnoea-hypopnoea index (AHI), subjects were divided into control subjects (AHI <5, n = 20) and moderate-severe OSAS patients (AHI > or =15, n = 29). QT(d) (defined as the difference between the maximum and minimum QT interval) and QT-corrected interval dispersion (QT(cd)) were calculated using Bazzet's formula. In conclusion, the QT(cd) was significantly higher in OSAS patients (56.1+/-9.3 ms) than in controls (36.3+/-4.5 ms). A strong positive correlation was shown between QT(cd) and AHI. In addition, a significantly positive correlation was shown between QT(cd) and the desaturation index (DI). The AHI and DI were significantly related to QT(cd) as an independent variable using stepwise regression analysis. The QT-corrected interval dispersion is increased in obstructive sleep apnoea syndrome patients without hypertension, and it may reflect obstructive sleep apnoea syndrome severity.     

Obstructive sleep apnoea and oral breathing in patients free of nasal obstruction.

Although there is an association between nasal obstruction, oral breathing and obstructive sleep apnoea syndrome (OSAS), it remains unknown whether increased oral breathing occurs in patients with OSAS who are free of nasal obstruction. The present study evaluated the relationship between breathing route and OSAS in patients without nasal obstruction. The breathing route of 41 snorers (25 male; aged 26-77 yrs) with normal nasal resistance was examined during overnight polysomnography using a nasal cannula/pressure transducer and an oral thermistor. In total, 28 patients had OSAS (apnoeics) and 13 patients were simple snorers. Apnoeics had a higher percentage of oral and oro-nasal breathing epochs. Oral and oro-nasal breathing epochs were positively related with apnoea/hypopnoea index (AHI) and duration of apnoeas/hypopnoeas and inversely related to oxygen saturation. Additionally, oro-nasal breathing epochs correlated with body mass index (BMI). In multiple linear regression analysis, oral breathing epochs were independently related only to AHI (r2 = 0.443), and oro-nasal breathing epochs were independently related to AHI (r2 = 0.736) and BMI (r2 = 0.036). In conclusion, apnoeics spent more time breathing orally and oro-nasally than simple snorers, and the apnoea/hypopnoea index is a major determinant of the time spent breathing orally and oro-nasally.     

Platelet function in patients with obstructive sleep apnoea syndrome.

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.     

There is no relationship between chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: a population study

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS) are common diseases. Some recent studies suggest an increased prevalence of COPD among subjects with OSAS. OBJECTIVES: The study objective was to evaluate whether there is an epidemiological relationship between COPD and OSAS in a random population sample. MATERIALS AND METHODS: The study population, 356 males (53%) and 320 females, mean age 56.6+/-8.2 years (range 41-72), was selected from a voting list for parliamentary election in Warsaw. The investigation included lung diseases and smoking history with polysomnography and spirometry. RESULTS: OSAS was diagnosed in 76 subjects (11.3%), 59 males (8.8%) and 17 females (2.5%), mean apnea/hypopnea index (AHI) was 25.3+/-16.1, mean overnight SaO2 92.1+/-3.3%, minimum SaO2 76.9+/-9.4%, and SaO2<90%=18.9+/-23.9% of total sleep time. COPD was diagnosed in 72 subjects (10.7%), 39 males and 33 females. Severity of airflow limitation was assessed according to European Respiratory Society (ERS) guidelines: mild in 70%, moderate in 22%, and severe in 8%. In 7 subjects (9.2% of OSAS population, 1% of total population) OSAS and COPD overlapped. Polysomnographic variables were compared between overlap (overlap syndrome, OS) and OSAS subjects. In the OS mean AHI was 19.0 versus 25.3 in OSAS (nonsignificant), mean SaO2 89.6 versus 92.3% in OSAS (p<0.005), and time spent in SaO2<90% was 25.4 versus 18.2% in OSAS (p=0.04). CONCLUSIONS: COPD in subjects with OSAS was as frequent as in the general population. In the OS group mean arterial blood saturation was lower and time spent in desaturation was longer than in OSAS. The presented data suggest a more severe course of sleep-disordered breathing in subjects with coexisting COPD.     

The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes

BACKGROUND: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. OBJECTIVES: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. METHODS: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 +/- 21.3; body mass index (BMI) 37.3 +/- 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 +/- 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. RESULTS: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 +/- 2.94 vs. 2.74 +/- 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 +/- 0.6%; not significant). Fasting leptin levels showed no significant changes. CONCLUSIONS: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.     

Long-term treatment with continuous positive airway pressure improves quality of life in obstructive sleep apnoea syndrome.

Continuous positive airway pressure (CPAP) is an established treatment of obstructive sleep apnoea syndrome (OSAS). While it is known that CPAP reverses the pathological breathing pattern and improves daytime sleepiness, there are no sufficient data on the long-term influence of CPAP on quality of life in patients with OSAS. Thirty-nine patients with polysomnographically verified OSAS (apnoea/hypopnoea index (AHI): (mean+/-SD) 46.8+/-21.8 events x h(-1)) were prospectively studied. All patients answered three quality of life measures (Complaint List, Nottingham Health Profile Part 1 (NHP), and Verbal Analogue-Scale "quality of life") prior to the initiation of CPAP therapy. After a mean of 9 months they were re-evaluated by polysomnography, and completed the questionnaires once again. As expected, CPAP was effective in treating the sleep-related breathing disorder. AHI decreased significantly from (mean+/-SD) 46.8+/-21.8 events x h(-1) to 3.3+/-6.3 events x h(-1), and minimum oxygen saturation increased from 77.1+/-9.3% to 89.9+/-3.4%, while body mass index did not change significantly (31.3+/-5.4 versus 30.8+/-4.8 kg x m(-2)). During long-term treatment with CPAP the Complaint List revealed a significant improvement of the extent of subjective impairment due to physical and general complaints (26.4+/-9.9 versus 20.4+/-11.1), and NHP a significant improvement of emotional reactions (19.8+/-21.7 versus 11.1+/-14.0) and energy (50.8+/-36.6 versus 32.1+/-36.7), but not of pain, physical mobility, sleep, social isolation, and quality of life as assessed by the It is concluded that long-term continuous positive airway pressure therapy is effective in improving not only pathological breathing patterns but also parameters that estimate quality of life in patients with obstructive sleep apnoea syndrome.     

Influence of treatment on leptin levels in patients with obstructive sleep apnoea.

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.     

Effect of obesity and erect/supine posture on lateral cephalometry: relationship to sleep-disordered breathing.

Craniofacial and upper airway anatomy, obesity and posture may all play a role in compromising upper airway patency in patients with the sleep apnoea/hypopnoea syndrome. The aim of this study was to investigate the relationship between obesity, facial structure and severity of sleep-disordered breathing using lateral cephalometric measurements and to assess the effect of body posture on cephalometric measurements of upper airway calibre variables in obese and non-obese subjects. Lateral cephalometry was carried out in erect and supine postures in 73 awake male subjects randomly selected from patients referred for polysomnography who had a wide range of apnoea/hypopnoea frequencies (1-131 events x h sleep(-1)). Subjects were divided into non-obese (body mass index (BMI) < 30 kg x m(-2); n=42) and obese (BMI > or = 30 kg x m(-2); n=31) groups. Significant but weak correlations were found between apnoea/hypopnoea index (AHI) and measurements reflecting upper airway dimensions: uvular protrusion-posterior pharyngeal wall (r=-0.26, p<0.05) and hyoid-posterior pharyngeal wall (r=0.26, p<0.05). Multiple regression using both upper airway dimensions improved the correlation to AHI (r=0.34, p=0.01). Obese subjects had greater hyoid-posterior pharyngeal wall distances than non-obese subjects, both erect (42+/-5 versus 39+/-4 mm, respectively (mean+/-SD) p<0.01) and supine (43+/-5 versus 40+/-4 mm, p<0.05). Skeletal craniofacial structure was similar in obese and non-obese subjects. In conclusion, measurements reflecting upper airway size were correlated with the severity of sleep-disordered breathing. Differences in upper airway size measurements between obese and non-obese subjects were independent of bony craniofacial structure.     

Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome

To clarify the impairment of the GH/IGF-I axis in obstructive sleep apnea syndrome (OSAS), in 13 adult male patients with OSAS (OSA) as well as 15 weight-matched patients with simple obesity (OB) and 10 normal lean male subjects (NS), we studied: 1) the GH response to GHRH (1 micro g/kg iv) plus arginine (30 g iv); and 2) the IGF-I and IGF binding protein-3 responses to a very low dose recombinant human (rh)GH treatment (5.0 microg/kg sc per day for 4 d). The GH response to arginine plus GHRH in OSA was lower than in OB (P < 0.05), which in turn was lower than in NS (P < 0.001). Basal IGF-I levels in OSA were lower than in OB (P < 0.05), which in turn were lower than in NS (P < 0.03). As opposed to OB and NS, in OSA a very low rhGH dose did not affect IGF-I. Adjusting for age and basal values, rhGH-induced IGF-I rise in OSA was lower than in OB (P < 0.01). IGF binding protein-3, glucose, and insulin levels in the three groups were not modified by rhGH. OSA show a more marked impairment of the maximal secretory capacity of somatotroph cells together with reduced IGF-I sensitivity to rhGH stimulation. These findings suggest that OSAS is connoted by a concomitant impairment of GH secretion and sensitivity.