Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationship

Obstructive sleep apnoea (OSA) is a common disorder characterized by recurrent episodes of apnoea or hypopnea due to total or partial pharyngeal collapse and temporary upper airway obstruction during sleep. The prevalence of OSA is increasing and currently affects about 30% of men and 13% of women in Europe. Intermittent hypoxia, oxidative stress, systemic inflammation, and sleep fragmentation resulting from OSA can provoke subsequent cardiometabolic disorders. The relationships between endocrine disorders and OSA are complex and bidirectional. Indeed, several endocrine disorders are risk factors for OSA. Compared with the general population, the prevalence of OSA is increased in patients with obesity, hypothyroidism, acromegaly, Cushing syndrome, and type 1 and 2 diabetes. In some cases, treatment of the underlying endocrine disorder can improve, and occasionally cure, OSA. On the other hand, OSA can also induce endocrine disorders, particularly glucose metabolism abnormalities. Whether continuous positive airway pressure (CPAP) treatment for OSA can improve these endocrine disturbances remains unclear due to the presence of several confounding factors. In this review, we discuss the current state-of-the-art based on the review of the current medical literature for key articles focusing on the bidirectional relationship between endocrine disorders and OSA and the effects of treatment. Screening of OSA in endocrine patients is also discussed, as it remains a subject of debate.     

Changes in cognitive function associated with sleep disordered breathing in older people

OBJECTIVES: Sleep disordered breathing (SDB) is very common in older people and is known to be associated with complaints of impaired daily functioning, including excessive daytime sleepiness and cognitive impairments. As part of a larger study on SDB and aging, it became possible to examine the relationship between SDB and cognition in older men and women. DESIGN: A population-based longitudinal study. SETTING: In-home interviews and home sleep recordings in the greater San Diego area. PARTICIPANTS: Community-dwelling people age 65 and older with high risk for SDB were originally studied from 1981 through 1985 and then followed every 2 years. Data from the 46 subjects who completed Visit 3 and Visit 4 are presented. MEASUREMENTS: Subjects were interviewed in the home about their sleep and medical condition before each visit. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Daytime sleepiness was based on self-report. Objective sleep was recorded in the home and scored for sleep, apneas and hypopneas, and oximetry variables. RESULTS: Increases in respiratory disturbance index (RDI) (P= .036) and increases in daytime sleepiness (P= .002) were associated with decreases in cognitive performance (i.e., increases in cognitive impairment). Increases in RDI were also associated with increases in daytime sleepiness (P= .012). Change in MMSE scores was therefore regressed onto changes in RDI, daytime sleepiness, age, and education, resulting in decreases in MMSE scores being associated with increases in daytime sleepiness (P= .019) but not with changes in RDI (P= .515). There was no significant relationship between changes in oxygen saturation levels and changes in MMSE. CONCLUSIONS: The results of this study suggest that declining cognitive function is associated primarily with increases in daytime sleepiness. Although cognitive decline was also associated with increases in RDI, this association did not hold in the more inclusive model which also included variable of SDB, oximetry, sleep and subjective report. One theoretical model could suggest that any relationship between SDB and cognitive function may be mediated by the effect of SDB on daytime sleepiness. These results suggest that older patients suffering from mild to moderate SDB may benefit from the treatment of SDB, even if they are not markedly hypoxemic.     

High prevalence of previously unknown subclinical hypothyroidism in obese patients referred to a sleep clinic for sleep disordered breathing

BACKGROUND AND AIM: To evaluate the prevalence of previously unknown hypothyroidism in adult male and female patients with a wide range of body mass index (BMI) values, referred to a Sleep Clinic because of sleep disordered breathing (SDB). METHODS AND RESULTS: Serum concentrations of thyroid stimulating hormone (TSH) and free thyroxin (fT4), as well as forced vital capacity (FVC), PaO2, PaCO2, the Epworth sleepiness scale (ESS), respiratory disturbance index (RDI), loud snoring, and the percentage of total sleep time (TST) with <90% oxyhemoglobin saturation (TST(saO2<90%)) were measured in 78 overweight and obese adult subjects with no previous diagnosis of hypothyroidism (age: 18-72 years). The prevalence of previously undiagnosed subclinical hypothyroidism in the population as a whole was 11.5%. BMI, TSH and ESS were significantly higher in the hypothyroid than the euthyroid subjects, but there was no significant between-group difference in RDI, TST(saO2<90%) or the other investigated variables, including the prevalence of obstructive sleep apnea (OSA). Among the hypothyroid individuals, BMI, neck circumference, ESS, RDI and TST(Sao2<90%) were significantly higher in those with than in those without OSA. Furthermore, there was a clear trend towards a lower FVC% and higher snoring score in the OSA patients. CONCLUSIONS: Our results demonstrate a higher prevalence of hypothyroidism than that commonly reported in overweight and obese individuals referred to a Sleep Clinic for polysomnography because of SDB, thus suggesting that thyroid function should be evaluated in all obese patients suffering from SDB despite economic concerns.     

An overnight increase in CO2 predicts mortality in sleep disordered breathing

Background and objective: Sleep disordered breathing (SDB) is highly prevalent but under‐recognized. Evidence is accumulating for its role as a predictor of mortality independent of cardiovascular risk factors. The role of hypercapnia in SDB is not known systematically, and between 11 and 43% of patients with SDB develop chronic hypercapnia. Hypercapnia predicts mortality in other respiratory conditions. The role of hypercapnia in independently predicting mortality in patients with SDB after assessing for the presence of airways disease and obesity was investigated. Methods: The records of 396 consecutive patients were examined retrospectively. Univariate and multivariate analyses were performed using Cox proportional hazards regression to determine the association between gas exchange and polysomnography (PSG) variables and all‐cause mortality, adjusted for potential confounders, including age, gender and presence of co‐morbidity and airways disease. Results: The mean age of our patient population was 55 ± 15 years, and the mean body mass index (BMI) was 30.6 ± 6.2 kg/m². Out of the 322 patient population, 258 were men. After 10 years, 25% had died, following a maximum follow‐up of 16.7 years. Mortality among patients with SDB was predicted by a difference between evening and morning PaCO₂ (ΔPaCO₂) of ≥7 mm Hg and evening hypoxaemia (PaO₂ < 65 mm Hg), independent of age and the presence of co‐morbidity and airways disease. There was a significant correlation between minimum oxygen saturation (SpO₂) and ΔPaCO₂ ≥ 7 mm Hg (P = 0.002) and evening PaO₂ < 65 mm Hg (P < 0.001). Conclusions: An overnight increase in CO₂ and evening hypoxaemia are independent mortality predictors in SDB. A low minimum SpO₂ identifies patients in whom morning and evening arterial blood gases are beneficial.     

Prevalence of sleep disturbances: Sleep disordered breathing,short sleep duration,and non-restorative sleep

Recently, interest in sleep disturbances, such as sleep disordered breathing (SDB), short sleep duration, and non-restorative sleep (NRS), has been increasing. The potentially large public health implications of sleep disturbances indicate a need to determine their prevalence in a general population. This review describes the characteristics of population-based sleep cohorts from past to present. Unavoidable methodological and baseline characteristic heterogeneity was found between studies. The prevalence of SDB (apnea hypopnea index (AHI), respiratory disturbance index (RDI), or oxygen desaturation index (ODI) ≥5/h) was 24.0–83.8% in men and 9.0–76.6% in women, and that of moderate-to-severe SDB (AHI, RDI, or ODI ≥15/h) was 7.2–67.2% in men and 4.0–50.9% in women. Additionally, the prevalence of SDB in post-menopausal women was 3–6 times higher than in pre-menopausal women. The prevalence of subjective short sleep duration (<6 h) was 7.5–9.6%, while that of objective short sleep duration (<6 h) was 22.1–53.3%. The prevalence of NRS was 19.2–31.0% in men and 26.3–42.1% in women, as determined from studies using a yes-no questionnaire, while a multi-national survey using a telephone-based expert system showed a wide range of prevalence between countries, from 2.4% to 16.1%. An association between SDB, short sleep duration, and NRS has recently been suggested. To gain a better understanding of the burden of sleep disturbances, a consensus on the definition of several sleep disturbances is needed, as methodological heterogeneity exists, including SDB scoring rules, subjective versus objective data collection for short sleep duration, and the definition of NRS itself.     

Insomnia complaints in patients evaluated for obstructive sleep apnea

Obstructive sleep apnea (OSA) and insomnia are among the most common sleep diagnoses encountered in the sleep clinic population, however little is known about potential interactions or associations between the two disorders. This retrospective, cross-sectional study was designed to determine the prevalence of insomnia complaints in patients undergoing evaluation for OSA and to ascertain which clinical and polysomnographic features are associated with insomnia. Of 255 consecutive patients who underwent polysomnography for clinically suspected OSA, 54.9% reported a complaint of insomnia: 33.4% reported difficulty initiating sleep, 38.8% difficulty maintaining sleep, and 31.4% early morning awakenings. Insomnia complaints were noted more commonly in patients without significant sleep-disordered breathing [apnea hypopnea index (AHI)<10; 81.5%] vs those with sleep-disordered breathing (AHI≥10; 51.8%); p=0.01. Clinical factors associated with insomnia included female gender, psychiatric diagnoses, chronic pain, the absence of regular alcohol use, restless leg symptoms, and reports of nocturnal kicking. Polysomnographic factors associated with insomnia included lower AHI and lower desaturation index (DI). In the subgroup of patients with significant sleep-disordered breathing (AHI≥10, n=228), there was no association between insomnia complaints and AHI or DI. These results suggest that insomnia is a common complaint in patients being evaluated for OSA, but it is not strongly associated with sleep-disordered breathing and may instead reflect other coexisting factors.     

Acoustic arousal responses in children with obstructive sleep apnea

Our objectives were to study the arousal responses to nonrespiratory (acoustic) stimuli in children with obstructive sleep apnea syndrome (OSAS). The acoustic arousal response was studied in children with OSAS due to adenotonsillar hypertrophy compared to normal, age-matched children. Acoustic stimuli were delivered incrementally from 30-100 dB during stage 2, slow wave sleep, and rapid eye movement (REM) sleep. The percentage of children who aroused in response to acoustic stimuli, and the arousal threshold (i.e., sound level at which arousal occurred), were compared between groups and sleep stages. The percentage of children who aroused was similar between children with OSAS and controls. The percentage of children who aroused was lower during slow wave sleep than REM sleep and stage 2 in both OSAS and controls. There were no statistically significant differences in acoustic arousal threshold between OSAS and control children. There was no difference in arousal response to moderate acoustic stimulation between children with OSAS and controls. These results contrast with previous data showing blunted arousal responses to hypercapnia and upper airway loading during sleep in children with OSAS, suggesting that children with OSAS have an arousal deficit specific to respiratory stimuli. However, further studies evaluating arousal to both respiratory and nonrespiratory stimuli in the same subjects are needed.     

Nocturnal body position in sleeping children with and without obstructive sleep apnea

OBJECTIVES: To assess whether body position during sleep differs among children with obstructive sleep apnea (OSAS) and controls, and to assess the effects of body position, obesity, and tonsillar size on respiratory disturbance. Four hundred and thirty consecutive children with polysomnographically demonstrated OSAS. And 185 age-, gender-, and ethnically matched children (Controls) were compared. The effect of sleep body position on respiratory disturbance was examined in OSAS, and also in relation to obesity and tonsillar size. Children with OSAS spent more time in the supine position than Controls (P<0.01), with less time spent in the side position (P<0.005). Obstructive apnea and hypopnea index (AHI) was similar in the three sleep-related positions, but apnea index (AI) was significantly greater (4.6 +/- 0.7/hr TST) in the supine position than in the side position (2.7 +/- 0.3/hr TST; P<0.001) or prone position (3.3 +/- 0.5/hr TST; P<0.01). Tonsillar size was not a contributing factor to positional differences in AI or AHI. Obese OSAS children had increased prone position (20.4 +/- 2.0%TST vs. non-obese: 10.9 +/- 2.5%TST; P<0.05), and displayed increased AHI and AI while supine. Non-obese OSAS increased AHI in prone or side positions compared to supine (P<0.01), with no significant differences in position-dependent AI. Children with OSAS spend more time sleeping supine and less time on the side. Obese children with OSAS are more likely to sleep prone, suggesting that this position may promote upper airway patency in the presence of obesity. Although tonsillar size is not associated with positional differences in breathing, the presence or absence of obesity markedly modifies the effect of body position on respiratory disturbance.     

Comparison of clinical features and polysomnographic findings between men and women with sleep apnea

Background

There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan.

Methods

We conducted a case-matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age ±4 years, (II) AHI ± 4 h of sleep, and (III) BMI ±2 kg/m². This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA.

Results

Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI [men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001], lower supine AHI [men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004], longer total sleep time (TST), and non-rapid eye movement (NREM) sleep stage 3 (N3), %TST [TST in men: 356.3 (IQR, 319.5-392.3); women: 372.0 (IQR, 327.8-404.5); P=0.007; N3, %TST in men: 8.8 (IQR, 3.0-14.6); women: 14.4 (IQR, 8.3-20.4); P<0.001], and better sleep efficiency [men: 80.9 (IQR, 71.0-88.0); women: 83.2 (IQR, 74.5-90.0); P=0.011].

Conclusions

This study revealed that women with SA had a significantly longer TST and N3, %TST, which represents deep sleep. Future prospective studies must be conducted together with polysomnography tests including electromyography of pharyngeal muscle expansion and electroencephalography.     

阻塞性睡眠呼吸暂停低通气综合征与2型糖尿病的相关性研究

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与2型糖尿病并存率较高的可能原因及机制.方法 2008年5月至2009年12月在南京医科大学第一附属医院睡眠中心就诊,经多导睡眠监测104例患者被诊断患有鼾症,分为单纯性鼾症组(即对照组,n=19)及OSAHS组(n=85),根据呼吸暂停低通气指数和最低脉搏氧饱和度将OSAHS患者进一步分为轻度(n=50)及中-重度OSAHS亚组(n=35).比较各组2型糖尿病的发生率.分析多导睡眠监测参数呼吸暂停低通气指数、最低脉搏氧饱和度、平均脉搏氧饱和度,外周循环中代谢参数空腹血糖、真胰岛素与胰岛素原和稳态模型胰岛素抵抗指数(HOMA-IR),以及体重指数、腰围及颈围等的相关性.采用卡方检验、方差分析、Spearman相关分析和Logistic回归分析进行数据统计.结果 所有OSAHS患者中15.3%(13/85)并存有2型糖尿病.中-重度OSAHS组2型糖尿病发病率[25.7%(9/35)]明显高于对照组[5.3%(1/19),X2=4.942,P=0.026)]和轻度OSAHS组[8.0%(4/50),X2=4.011,P=0.045)].Spearman相关分析显示HOMA-IR、胰岛素原水平与最低脉搏氧饱和度、平均脉搏氧饱和度呈显著负相关,与呼吸暂停低通气指数的相关性未达统计学意义.单因素Logistic回归分析提示HOMA-IR和胰岛素原是中-重度OSAHS的危险因素.多因素逐步Logistic回归分析提示HOMA-IR与中一重度OSAHS的发生独立相关.结论 OSAHS与2型糖尿病密切相关,夜间脉搏氧饱和度较低的OSAHS患者易于产生胰岛素抵抗,而胰岛素抵抗在OSAHS与2型糖尿病并存机制中发挥重要作用.