The relationship between the Triglyceride-Glucose (TyG) index and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) remains unclear. This study aimed to investigate the association between TyG index-related parameters (TyG, TyG-Body Mass Index (BMI), TyG-Waist Circumference (WC)) and OSAHS. Consecutive subjects referred to our sleep center were enrolled in this study and categorized into four groups based on the severity of OSAHS, as determined by the apnea-hypopnea index (AHI). Multivariate regression analysis was performed to identify independent risk factors associated with TyG index-related parameters in OSAHS. The study included 1250 participants, categorized into 114 without OSAHS, 212 with mild OSAHS, 257 with moderate OSAHS, and 667 with severe OSAHS. Significant differences were observed in fasting glucose levels, TyG, TyG-BMI, and TyG-WC across increasing severity of OSAHS. Multivariate regression showed that TyG-BMI and TyG-WC were independently associated with oxygen desaturation index (ODI), mean oxygen saturation (MSO2), and age (all p < 0.05). TyG was significantly associated with BMI, ODI, and sex (all p < 0.05). FPG was linked to BMI, age and MSO2, while insulin was associated with lowest oxygen saturation (LaSO2) and AHI (all p < 0.05). OSAHS-induced intermittent hypoxia is independently associated with increased TyG index-related parameters. These findings suggest that intermittent hypoxia may contribute to metabolic disturbances and insulin resistance, highlighting the need for further investigation into its clinical implications.

A dysregulated circadian system is independently associated with both Obstructive Sleep Apnea (OSA) and cardiovascular disease (CVD). OSA and CVD coexistence is often seen in patients with prolonged untreated OSA. However, the role of circadian dysregulation in their relationship is unclear. Half of the human genes, associated biological pathways, and physiological functions exhibit circadian rhythms, including blood pressure and heart rate regulation. Mechanisms related to circadian dysregulation and heart function are potentially involved in the coexistence of OSA and CVD. In this article, we provide a comprehensive overview of circadian dysregulation in OSA and associated CVD. We also discuss feasible animal models and new avenues for future research to understand their relationship. Oxygen-sensing pathways, inflammation, dysregulation of cardiovascular processes, oxidative stress, metabolic regulation, hormone signaling, and epigenetics are potential clock-regulated mechanisms connecting OSA and CVD.

Evaluate the performance of the SANSA device to simultaneously assess obstructive sleep apnea and cardiac arrhythmias.

Participants suspected or known to have obstructive sleep apnea underwent polysomnography while wearing SANSA. SANSA's algorithm was trained using 86 records and tested on 67 to evaluate training bias. SANSA performance was evaluated against ground truth polysomnography scored by the consensus of 3 technologists. Polysomnography scoring from individual testing sites was also evaluated against consensus. Diagnostic performance was evaluated using standard apnea-hypopnea index cutoffs. Apnea-hypopnea index and total sleep time agreement was analyzed using correlation and Bland-Altman plots. Electrocardiogram was reviewed for presence of significant arrhythmias (frequent premature atrial/ventricular complexes and atrial fibrillation).

SANSA's sensitivity and specificity to detect obstructive sleep apnea ranged from 91-97% and 78-97%, respectively, across all severity levels. SANSA total sleep time correlation with consensus polysomnography total sleep time was 0.83 with a mean difference of 3.8 minutes (limits of agreement: -91.1 to 98.7). Significant arrhythmias were detected in 32% of participants. These participants had a greater apnea-hypopnea index (27.5 vs 15.8 events/h, P = .003) and spent nearly twice as long at reduced oxygenation levels (47.5 vs 20.5 minutes under 88% oxygen saturation, P = .009).

SANSA is a promising tool for comprehensive obstructive sleep apnea evaluation, offering the unique advantage of concurrent arrhythmia detection. This dual functionality may improve patient outcomes through early diagnosis and management of both conditions.

Goldstein C, Ghanbari H, Sharma S, et al. Multidiagnostic chest-worn patch to detect obstructive sleep apnea and cardiac arrhythmias. J Clin Sleep Med. 2025;21(5):855-866.

To find out the prevalence of asymptomatic pulmonary hypertension (PHT) in metabolic syndrome patients who have obstructive sleep apnea (OSA).

To find out the presence of asymptomatic PHT by two-dimensional echocardiography (2D ECHO) who have metabolic syndrome by WHO diagnostic criteria and OSA done by polysomnography. In this study, we also assessed the glycemic status in patients with metabolic syndrome with OSA and asymptomatic PHT.

Study population: All patients attending tertiary care outpatient department for type 2 diabetes/prediabetes/dyslipidemia/hypertension/obesity were screened for metabolic syndrome features.

In a pilot study, 34 consecutive patients were found to have metabolic syndrome by the WHO diagnostic criteria. 28 (82%) of metabolic syndrome patients had OSA. 14 out of 28 patients (50%) had PHT by 2D ECHO. Prediabetes was more prevalent, 22 (65%) among patients with metabolic syndrome than diabetes (32%). All but one patient who had no OSA was found to have moderate PHT. Asymptomatic PHT was found in 6/12 (50%) of diabetics and in 8/22 (36%) in prediabetes. Except for one, diabetes duration of all was <10 years and all prediabetes were recently detected within 1 year.

Our findings suggest that PHT is associated with a 4-fold higher occurrence of metabolic syndrome than patients with OSA. It is more prevalent in prediabetes and diabetes. The detection of the association of diabetes mellitus, OSA, and asymptomatic PHT in the pathophysiology of heart failure with preserved ejection fraction requires further longitudinal studies. The prevalence of PHT increases with increasing severity of OSA; therefore, early detection is beneficial.

Conventional metrics such as the apnea-hypopnea index (AHI) may not fully capture the diverse clinical manifestations of obstructive sleep apnea (OSA). This study aims to establish a novel OSA subtype classification based on the patterns of apneic and hypopneic hypoxic burden (HB), a potential biomarker that more accurately reflects the severity and duration of respiratory events. We further examined the associations of these HB-based subtypes with cardiometabolic risk and brain health outcomes.

We retrospectively analyzed polysomnography data from 1000 participants including normal, mild, moderate, and severe OSA patients. We performed hierarchical clustering based on apneic and hypopneic HB to identify OSA subtypes. We then compared the prevalence of cardiometabolic syndrome (CMS) and brain health outcomes using the brain age index (BAI) among these subtypes.

Five distinct subtypes were identified: 'good sleepers' (subtype 1), 'light hypopneic HB' (subtype 2), 'mild HB' (subtype 3), 'moderate HB' (subtype 4), and 'severe HB with marked apneic HB' (subtype 5). The prevalence of CMS (particularly hypertension) was significantly higher in subtypes 2-5 (p < 0.001) compared to subtype 1. BAI was higher in subtypes 4 (3.2 years, p < 0.0001) and 5 (11.1 years, p < 0001) compared to subtype 1. Greater daytime sleepiness was observed in HB-based subtypes 2 and 5 compared to subtype 1 (p < 0.001), whereas no significant differences were found among groups classified by OSA severity using AHI.

Our study demonstrates that the HB-based subtypes of OSA are significantly associated with various clinical features and outcomes. These insights could be utilized to improve risk stratification and guide the design of future OSA studies.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.

The identification of Obstructive Sleep Apnea (OSA) is done by a Polysomnography test which is often done in later ages. Being able to notify potential insured members at earlier ages is desirable. For that, we develop predictive models that rely on Electronic Health Records (EHR) and predict whether a person will go through a sleep apnea test after the age of 50. A major challenge is the variability in EHR records in various insured members over the years, which this study investigates as well in the context of controls matching, and prediction. Since there are many temporal variables, the RankLi method was introduced for temporal variable selection. This approach employs the t-test to calculate a divergence score for each temporal variable between the target classes. We also investigate here the need to consider the number of EHR records, as part of control matching, and whether modeling separately for subgroups according to the number of EHR records is more effective. For each prediction task, we trained 4 different classifiers including 1-CNN, LSTM, Random Forest, and Logistic Regression, on data until the age of 40 or 50, and on several numbers of temporal variables. Using the number of EHR records for control matching was found crucial, and using learning models for subsets of the population according to the number of EHR records they have was found more effective. The deep learning models, particularly the 1-CNN, achieved the highest balanced accuracy and AUC scores in both male and female groups. In the male group, the highest results were also observed at age 50 with 100 temporal variables, resulting in a balanced accuracy of 90% and an AUC of 93%.

The basic definitions of obstructive sleep apnea (OSA), its epidemiology, its clinical features and complications, and the morbidity and mortality of OSA are discussed. Included in this treatise is a discussion of the various symptomatic and polysomnographic phenotypes of COPD that may enable better treatment and impact mortality in persons with OSA. The goal of this article is to serve as a reference for life and disability insurance company medical directors and underwriters when underwriting an applicant with probable or diagnosed sleep apnea. It is well-referenced (133 ref.) allowing for more in-depth investigation of any aspect of sleep apnea being queried.

The association between TyG-BMI index and the risk of obstructive sleep apnea (OSA), a recently identified biomarker indicating insulin resistance, has yet to be elucidated. Therefore, this study aimed to investigate the association between TyG-BMI index and the risk of OSA using the NHANES database.

Analyses were performed on NHANES data conducted between 2015 and 2018. Logistic regression, stratified analyses, curve-fitting analyses, and threshold effects analyses were utilized to assess the association between TyG-BMI index and the risk of OSA.

The study included 4,588 participants. Multifactorial logistic regression analyses found a significant association between TyG-BMI and increased risk of OSA [OR: 1.54 (CI:1.39-1.70)]. In stratified analyses, age interacted with the association, with TyG-BMI being associated with increased risk of OSA only in a subgroup of subjects younger than 60 years [1.31 (1.14-1.50)], but gender, smoking status, and alcohol use, did not influence the association. The presence of diabetes, hypertension, and cardiovascular diseases also modified the association, but the number of the included subjects with such conditions was significantly lower, therefore the significance of associations was not observed in those subgroups. Additionally, the risk was non-linearly associated, with the inflection point of TyG-BMI at 12.09, after which the lower slope in the risk was observed.

This study demonstrates that elevated levels of the TyG-BMI index are correlated with risk for OSA, underscoring the significance of these findings in facilitating early prevention or timely intervention for OSA.

This study investigated the relationship between obstructive sleep apnea and haemoglobin A1c (HbA1c) among Hispanics/Latinos in the United States and assessed whether this relationship was moderated by glycaemic status. This was a cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos cohort. The sample consisted of 13,394 participants with valid measures of obstructive sleep apnea, HbA1c, and study covariates. Obstructive sleep apnea was assessed with the apnea-hypopnea index and categorised as obstructive sleep apnea if the apnea-hypopnea index was ≥5 events/h. HbA1c measures were obtained through fasting blood samples. Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG) and use of antihyperglycaemic medications were used to define glycaemic status (i.e., normoglycaemia [FPG < 5.6 mmol/L (< 100 mg/dL) and 2h-PG < 7.8 mmol/L (140 mg/dL)], prediabetes [FPG 5.6-6.9 mmol/L (100-125 mg/dL), and/or 2h-PG 7.8-11.0 mmol/L (140-199 mg/dL)], diabetes without treatment [FPG > 7.0 mmol/L (≥ 126 mg/dL) and/or 2h-PG ≥ 11.1 mmol/L (≥ 200 mg/dL)], and diabetes with treatment. Multivariable linear regression was used to calculate adjusted least square means. Overall, 25.9% of the sample had obstructive sleep apnea and 49.2% had normal glycaemic levels, 36.1% had prediabetes, 6.5% diabetes without receiving treatment, and 8.3% diabetes and undergoing treatment for it. Participants with obstructive sleep apnea had significantly higher adjusted mean HbA1c (adjusted mean [standard error] 5.85 [0.03)]) than those without (5.70 [0.02)]; p < 0.001). Models stratified by diabetes status showed that the association between obstructive sleep apnea (versus not) and higher HbA1c was only for participants with normal glycaemic status (adjusted mean [standard error] 5.27 [0.01] versus 5.30 [0.01]; p = 0.013) and prediabetes (5.59 [0.01] versus 5.66 [0.01]; p < 0.001). In conclusion, obstructive sleep apnea was associated with higher HbA1c in a diverse sample of Hispanic/Latino adults in the United States. This association was present only for participants with normal glycaemic status or with prediabetes. Studies are needed to further understand the clinical implications of the association between obstructive sleep apnea and HbA1c according to glycaemic status.

Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined.

This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored.

A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients.

Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

Numerous evidence reports direct correlation between cognitive impairment, Alzheimer's disease and sleep disorders, in particular obstructive sleep apnea. Both obstructive sleep apnea and Alzheimer's disease are highly prevalent conditions whose incidence increases with age. Several studies demonstrate how sleep-disordered breathing may lead to poor cognition, even though the underlying mechanisms of this association remain partially unclear. According to the most recent studies, obstructive sleep apnea may be considered a modifiable risk factor for cognitive dysfunction. In the present review, the authors aim to integrate recent research examining obstructive sleep apnea and Alzheimer's disease biomarkers, also focusing on the mechanisms that support this correlation, including but not limited to the role of hypoxia and cardiovascular risk. Moreover, the potential favourable effect of obstructive sleep apnea therapy on cognitive function is discussed, to evaluate the benefits deriving from appropriate treatment of sleep-disordered breathing on cognition.

Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short- versus long-term exposure to intermittent hypoxia (IH) on pro-inflammatory mediators within vulnerable organs impacted by OSA.

Experimental animal study.

A total of 8-10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short-term) or 6 weeks (long-term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro-inflammatory mediators from peripheral tissues.

We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short-term exposure to IH. Although there were tissue-specific alterations in the gene expression of pro-inflammatory mediators, with down-regulation in the lung and up-regulation in the heart, we also observed reduced protein levels of pro-inflammatory mediators in the serum, lung, and heart following short-term exposure to IH. Long-term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart.

We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs.

NA Laryngoscope, 134:S1-S11, 2024.

Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the "common soil" of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings.

We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models.

The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc.

The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Rationale: Recent studies have shown that sleep apnea-specific intermittent hypoxemia quantified by the hypoxic burden (HB) predicted cardiovascular disease (CVD)-related mortality in community-based and clinical cohorts. Calculation of HB is based on manual scoring of hypopneas and apneas, which is time-consuming and prone to interscorer variability. Objective: To validate a novel method to quantify the HB that is based on automatically scored desaturations. Methods: The sample included 5,655 middle-aged or older adults from the Sleep Heart Health Study (52.8% women; age, 63.2 ± 11.3 yr). The original HB method was based on a subject-specific search window obtained from an ensemble average of oxygen saturation signals (as measured by pulse oximetry) and synchronized with respect to the termination of scored respiratory events. In this study, however, the search window was obtained from ensemble average of oxygen saturation signals that synchronized with respect to the minimum of all automatically identified desaturations (⩾2% and other thresholds, including 3% and 4%, in sensitivity analyses). The time interval between the two maxima around the minimum saturation was defined as the search window. The oximetry-derived HB (HBOxi) was defined as the total area under all desaturation curves (restricted by the search window) divided by the total sleep time. Logistic and Cox regression models assessed the adjusted odds ratio (aOR)/hazard ratio of excessive daytime sleepiness (EDS), hypertension (HTN), and CVD mortality per 1-standard deviation increase in HBOxi after adjusting for several covariates and confounders. Results: The Spearman's rank correlation between HB (median [interquartile range], 34.4 [18.4-59.8] % min/h) and HBOxi (median [interquartile range], 34.5 [21.6-53.8] % min/h) was 0.81 (P < 0.001). Similar to HB, HBOxi was significantly associated with EDS (aOR [95% confidence interval (CI)], 1.17 [1.09-1.26] per standard deviation), HTN (aOR [95% CI], 1.13 [1.05-1.21]), and CVD mortality (adjusted hazard ratio [95% CI], 1.15 [1.01-1.30]) in fully adjusted models. Conclusions: The HBOxi was highly correlated with the HB based on manually scored apneas and hypopneas and was associated with EDS, HTN, and CVD mortality with similar effect sizes as previously reported. This method could be incorporated into wearable technology that accurately records oxygen saturation signals.

The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established; however, the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both the CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. The HF diet reduced mitochondrial density and hepatic antioxidant capacity. The CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.

Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD. The central nervous system (CNS) evolved to respond to and anticipate changes in the external (and internal) environment to adapt survival mechanisms to perceived stresses (challenges to normal biological function), including the aforementioned Western lifestyle cofactors. Within the CNS of vertebrates in the wild, the biological clock circuitry surveils the environment and has evolved mechanisms for the induction of the obese, insulin-resistant state as a survival mechanism against an anticipated ensuing season of low/no food availability. The peripheral tissues utilize fat as an energy source under muscle insulin resistance, while increased hepatic insulin resistance more readily supplies glucose to the brain. This neural clock function also orchestrates the reversal of the obese, insulin-resistant condition when the low food availability season ends. The circadian neural network that produces these seasonal shifts in metabolism is also responsive to Western lifestyle stressors that drive the CNS clock into survival mode. A major component of this natural or Western lifestyle stressor-induced CNS clock neurophysiological shift potentiating the obese, insulin-resistant state is a diminution of the circadian peak of dopaminergic input activity to the pacemaker clock center, suprachiasmatic nucleus. Pharmacologically preventing this loss of circadian peak dopaminergic activity both prevents and reverses existing metabolic syndrome in a wide variety of animal models of the disorder, including high fat-fed animals. Clinically, across a variety of different study designs, circadian-timed bromocriptine-QR (quick release) (a unique formulation of micronized bromocriptine-a dopamine D2 receptor agonist) therapy of type 2 diabetes subjects improved hyperglycemia, hyperlipidemia, hypertension, immune sterile inflammation, and/or adverse cardiovascular event rate. The present review details the seminal circadian science investigations delineating important roles for CNS circadian peak dopaminergic activity in the regulation of peripheral fuel metabolism and cardiovascular biology and also summarizes the clinical study findings of bromocriptine-QR therapy on cardiometabolic outcomes in type 2 diabetes subjects.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.

The objective was to analyze the clinical implications of manual scoring of sleep studies using peripheral arterial tonometry (PAT) and to compare the manual and automated scoring algorithms.

Patients with suspected sleep-disordered breathing underwent sleep studies using PAT. The recordings were analyzed using a validated automated computer-based scoring and a novel manual scoring algorithm. The two methods were compared regarding sleep stages and respiratory events.

Recordings of 130 patients were compared. The sleep stages and time were not significantly different between the scoring methods. PAT-derived apnea-hypopnea index (pAHI) was on average 8.4 events/h lower in the manually scored data (27.5±17.4/h vs.19.1±15.2/h, p<0.001). The OSA severity classification decreased in 66 (51%) of 130 recordings. A similar effect was found for the PAT-derived respiratory disturbance index with a reduction from 31.2±16.5/h to 21.7±14.4/h (p<0.001), for automated and manual scoring, respectively. A lower pAHI for manual scoring was found in all body positions and sleep stages and was independent of gender and body mass index. The absolute difference of pAHI increased with sleep apnea severity, while the relative difference decreased. Pearson's correlation coefficient between pAHI and oxygen desaturation index (ODI) significantly improved from 0.89 to 0.94 with manual scoring (p<0.001).

Manual scoring results in a lower pAHI while improving the correlation to ODI. With manual scoring, the OSA category decreases in a clinically relevant proportion of patients. Sleep stages and time do not change significantly with manual scoring. In the authors' opinion, manual oversight is recommended if clinical decisions are likely to change.

Obstructive sleep apnea (OSA) is the most common sleep-realted respiratory disorder. It is frequently comorbid with cardiovascular, cerebrovascular, and metabolic diseases and is commonly observed in populations with these comorbidities. Investigators aimed to assess the effect of OSA on glycemic control in patients with diabetes.

In this cross-sectional study, 266 adult patients with diabetes mellitus (DM) attending the outpatient endocrinology clinic at the Guilan University of Medical Sciences were enrolled. Patients completed a checklist that included demographic characteristics, factors, and laboratory results in addition to Berlin and STOP-BANG questionnaires to evaluate the risk of OSA. Data were analyzed by independent t-test, Mann-Whitney U test, and Chi-squared or Fisher's exact tests using the Statistical Package for the Social Sciences (SPSS) version 17.

A total of 266 patients with DM were enrolled in this study (34.6% males, mean age 47.00 ± 19.04 years). Based on the Berlin Questionnaire, 38.6% of all participants were at high risk of developing OSA. Based on the STOP-BANG Questionnaire (SBQ), 45.1% were at moderate and high risks. Additionally, this questionnaire showed a significant difference between low and moderate-to-severe groups regarding sex, age, body mass index (BMI), neck size, other chronic diseases, types of DM, use of insulin, Berlin Questionnaire, fasting blood sugar (FBS), and mean HbA1c.

Based on the SBQ, our results indicated a significant relationship between OSA and glycemic control according to mean HbA1c and FBS. Therefore, by controlling the OSA, we may find a way to acheieve better glycemic control in diabetic patients.

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.

To examine the association between maternal sleep disordered breathing (SDB) and glucose metabolism in early gestation.

Women with body mass index (BMI) ≥27 kg/m2 and singleton pregnancies underwent in-home sleep study (HSAT) and homeostatic model assessment (HOMA) in early pregnancy. Insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were derived. Exclusion criteria included pregestational diabetes, use of continuous positive airway pressure and chronic steroid therapy. We performed linear regression analyses to evaluate the association between continuous measures of SDB (respiratory event index (REI), and oxygen desaturation index (ODI)) and glucose metabolism parameters (HOMA-IR and HOMA %B). Analyses were adjusted for a set of a priori selected variables which included gestational age, maternal age, BMI, ethnicity, race, and parity.

One hundred and ninety-two pregnant women with median (interquartile range) BMI of 35.14 (8.30) kg/m2 underwent HSAT and HOMA assessment at 11.14 (3) and 15.35 (4.14) gestational weeks, respectively. REI and ODI, as continuous values, were associated with HOMA-IR after adjusting for covariates. OSA (obstructive sleep apnea) diagnosis (REI > 5 events per hour) was not associated with HOMA-IR after adjusting for BMI (p ≥ 0.05). None of the parameters were associated with HOMA %B (p > 0.07).

SDB and insulin resistance are associated in early pregnancy, with a dose response association between respiratory event index severity and insulin resistance. Further studies are needed to establish if pregnant women with overweight and obesity may benefit from early SDB screening to improve glucose metabolic outcome. Clinical trials: NCT02412696, Positive Airway Pressure, Sleep Apnea, and the Placenta (PAP-SAP) https://clinicaltrials.gov/ct2/show/NCT02412696?term=Bourjeily&draw=2&rank=2 and NCT02917876, Predictors of De-novo Development of Obstructive Sleep Apnea in Pregnancy (Predictors) https://clinicaltrials.gov/ct2/show/NCT02917876?term=Bourjeily&draw=2&rank=1.

Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA), but its outcomes for the pregnant are still undefined. This study aims to review current CPAP intervention during pregnancy, discuss published trials, and propose relevant issues that have yet to be addressed satisfactorily about the cardiovascular, metabolic, fetal, and neonatal effects of CPAP treatment during gestation. Two authors independently conducted a systematic review until March 28th, 2021 on PubMed, BVS, and Cochrane Library, using PRISMA guidelines, and risk of bias. Discrepancies were reconciled by a third reviewer. Of 59 identified citations, eight original trials have submitted a total of 90 pregnant women to polysomnography and CPAP therapy. Four studies performed in samples with hypertension or preeclampsia presented blood pressure decrease or maintained the antihypertensive drug dose in the CPAP group. After CPAP utilization, one trial registered cardiac output and stroke volume increase with heart rate and peripheral vascular resistance decrease, which were correlated with birth weight increment. Others documented a higher Apgar in the CPAP group and more fetal movements during CPAP use. There was a reduction in serum uric acid and tumor necrosis factor-alpha in the CPAP groups whose blood pressure decreased. However, two weeks of CPAP use in women with gestational diabetes and OSA did not improve glucose levels but raised the insulin secretion in those adherents to CPAP. Despite these positive results without adverse effects, randomized controlled trials with standardized follow-up in larger populations are required to determine CPAP therapy recommendations in pregnancy.

This meta-analysis assessed the effect of long-term (>6 weeks) noninvasive positive airway pressure (PAP) on diastolic function in patients with obstructive sleep apnea (OSA).

We searched the databases for randomized clinical trials including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 20, 2019. The search was not restricted to time, publication status, or language. Two independent investigators screened the studies and extracted the data, in duplicate. Risk of bias was assessed using Cochrane collaboration tools.

A total of 2,753 abstracts were resulted from literature search. A total of 9 randomized clinical trials assessing the effect of long-term (>6 weeks) PAP on diastolic function in patients with OSA including 833 participants were included. The following echo parameters were found in treated patients: a decrease in deceleration time (-39.49 ms CI [-57.24, -21.74]; p = 0.000), isovolumic relaxation time (-9.32 ms CI [-17.08, -1.57]; p = 0.02), and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (-1.38 CI [-2.6, -0.16]; p = 0.03). However, changes in left-atrial volume index and the ratio of early to late mitral inflow velocities were not statistically different. The risk of bias was mild to moderate among the studies.

Our results suggest that chronic treatment of moderate to severe OSA with noninvasive PAP is associated with improvement in echocardiographic findings of diastolic dysfunction.

Obstructive sleep apnoea (OSA) is an underdiagnosed condition frequently associated with glycaemic control impairment in patients with type 2 diabetes.

To assess the relationship between glycometabolic parameters and OSA in obese non-diabetic subjects.

Ninety consecutive subjects (mean age 44.9 ± 12 years, mean BMI 42.1 ± 9 kg/m²) underwent polysomnography and a 2-h oral glucose tolerance test (OGTT).

OSA was identified in 75% of subjects, with a higher prevalence of males compared to the group of subjects without OSA (62% vs 32%, p = 0.02). Patients with OSA had comparable BMI (42.8 kg/m² vs 39.4 kg/m²), a higher average HbA1c (5.8% vs 5.4%, p < 0.001), plasma glucose at 120 min during OGTT (2 h-PG; 123 mg/dl vs 97 mg/dl, p = 0.009) and diastolic blood pressure (81.1 mmHg vs 76.2 mmHg, p = 0.046) than obese subjects without OSA. HbA1c and 2 h-PG were found to be correlated with the apnoea-hypopnoea index (AHI; r = 0.35 and r = 0.42, respectively) and with percent of sleep time with oxyhaemoglobin saturation < 90% (ST90; r = 0.44 and r = 0.39, respectively). Further, in a linear regression model, ST90 and AHI were found to be the main determinants of 2 h-PG (β = 0.81, p < 0.01 and β = 0.75, p = 0.02, respectively) after controlling for age, sex, waist circumference, physical activity, and C-reactive protein. Similarly, ST90 and AHI persisted as independent determinants of HbA1c (β = 0.01, p = 0.01 and β = 0.01, p = 0.01, respectively).

Beyond the traditional clinical parameters, the presence of a normal-high value of 2 h-PG and HbA1c should raise suspicion of the presence of OSA in obese subjects.

Sleep apnea syndrome (SAS) is a prevalent disorder characterized by recurrent apnea or hypoxia episodes leading to intermittent hypoxia (IH) and arousals during sleep. Currently, the relationship between SAS and metabolic diseases is being actively analyzed, and SAS is considered to be an independent risk factor for the development and progression of insulin resistance/type 2 diabetes (T2DM). Accumulating evidence suggests that the short cycles of decreased oxygen saturation and rapid reoxygenation, a typical feature of SAS, contribute to the development of glucose intolerance and insulin resistance. In addition to IH, several pathological conditions may also contribute to insulin resistance, including sympathetic nervous system hyperactivity, oxidative stress, vascular endothelial dysfunction, and the activation of inflammatory cytokines. However, the detailed mechanism by which IH induces insulin resistance in SAS patients has not been fully revealed. We have previously reported that IH stress may exacerbate insulin resistance/T2DM, especially in hepatocytes, adipocytes, and skeletal muscle cells, by causing abnormal cytokine expression/secretion from each cell. Adipose tissues, skeletal muscle, and the liver are the main endocrine organs producing hepatokines, adipokines, and myokines, respectively. In this review, we focus on the effect of IH on hepatokine, adipokine, and myokine expression.

Obstructive sleep apnea (OSA) is a common sleep disorder with multiple comorbidities including hypertension, diabetes, and cardiovascular disorders. Detected based on an overnight sleep study is called polysomnography (PSG); OSA still remains undiagnosed in majority of the population mainly attributed to lack of awareness. To overcome the limitations posed by PSG such as patient discomfort and overnight hospitalization, newer technologies are being explored. In addition, challenges associated with current management of OSA using continuous positive airway pressure (CPAP), etc. presents several pitfalls.

Conventional and modern detection/management techniques including PSG, CPAP, smart wearable/pillows, bio-motion sensors, etc., have both pros and cons. To fulfill the limitations in OSA diagnostics, there is an imperative need for new technology for screening of symptomatic and more importantly asymptomatic OSA patients to reduce the risk of several associated life-threatening comorbidities. In this line, molecular marker-based diagnostics have shown great promises.

A detailed overview is presented on the OSA management and diagnostic approaches and recent advances in the molecular screening methods. The potentials of biomarker-based detection and its limitations are also portrayed and a comparison between the standard, current modern approaches, and promising futuristic technologies for OSA diagnostics and management is set forth.ABBREVIATIONS AHI: Apnea hypopnea index; AI: artificial intelligence; CAM: Cell adhesion molecules; CPAP: Continuous Positive Airway Pressure; COVID-19: Coronavirus Disease 2019; CVD: Cardiovascular disease; ELISA: Enzyme linked immunosorbent assay; HSAT: Home sleep apnea testing; IR-UWB: Impulse radio-ultra wideband; MMA: maxillomandibular advancement; PSG: Polysomnography; OSA: Obstructive sleep apnea; SOD: Superoxide dismutase; QD: Quantum dot.

Although the benefits of bariatric surgery have been clearly established, it is not known whether they are as important in patients with obstructive sleep apnoea (OSA). Primary aim: to evaluate whether patients with moderate-to-severe OSA (apnoea-hypopnea index (AHI) ≥ 15 events/h) treated by continuous positive airway pressure/non-invasive ventilation (median [IQR] adherence 6.5 h/night [5; 7.9] at baseline) lose the same amount of body weight 1 year after bariatric surgery as patients with no or mild OSA. Secondary objectives: to compare the evolution of type 2 diabetes and hypertension after bariatric surgery, and surgical complication rates between groups.

Analyses were performed in 371 patients included in a prospective cohort of bariatric surgery, the Severe Obesity Outcome Network cohort. Subjects having moderate-to-severe OSA (n = 210) at baseline were compared with other subjects (n = 161).

Excess weight loss (%EWL) at 1 year was lower in patients with moderate-to-severe OSA than in patients without (64.9%EWL [46.9; 79.5] vs. 73.8%EWL [56.6; 89.3], p < 0.01). Multivariable analysis showed that age, initial body mass index and type of surgery, but not OSA status, were associated with 1-year %EWL. Diabetes remitted in 25 (41%) patients with moderate-to-severe OSA and 16 (48%) patients with no or mild OSA (p = 0.48). Hypertension remitted in 28 (32.9%) patients with moderate-to-severe OSA and 9 (40.9%) with no or mild (p = 0.48). Complication rates were 28 (13.3%) in patients with moderate-to-severe OSA and 12 (7.5%) in patients with no or mild OSA (p = 0.07).

Patients with OSA lose less body weight after bariatric surgery. This was related to older age and a higher baseline body mass index. However, the improvements of diabetes and hypertension were similar to that of patients without OSA, and the risk of surgical complications was not higher.

The aim of this study was to verify the association among obstructive sleep apnea, functional capacity, and metabolic control.

This was a cross-sectional study involving individuals of both sexes with clinical diagnosis of diabetes mellitus type 2 who were above 18 years of age. The assessment consisted of a volunteer identification form, a 2-minute step test, and the Stop-Bang questionnaire. In order to assess metabolic control, HbA1c and fasting glucose data were collected from medical records.

A total of 100 individuals with diabetes mellitus type 2, of whom 61% were women, were included in this study. According to the Stop-Bang instrument, 26, 57, and 17% of patients had low, intermediate, and high risk of developing OSA, respectively. There was no association between the 2-minute step test and metabolic variables and diabetes mellitus type 2 chronicity with Stop-Bang.

We concluded that there is no association among obstructive sleep apnea measured by means of Stop-Bang instrument, functional capacity measured by means of 2-minute step test, and metabolic variables in individuals with diabetes mellitus type 2.

Obstructive sleep apnea is a risk factor for respiratory depression following opioid administration as well as opioid-induced hyperalgesia. Little is known on how obstructive sleep apnea status is associated with central ventilatory depression in pediatric surgical patients given a single dose of fentanyl.

This was a single-center, prospective trial in children undergoing surgery requiring intubation and opioid administration. Sixty patients between the ages of 2-8 years presenting for surgery at Texas Children's Hospital were recruited. Twenty non-obstructive sleep apnea controls and 30 patients with moderate to severe obstructive sleep apnea met inclusion criteria. Following induction of general anesthesia and establishment of steady-state ventilation, participants received 1 mcg/kg intravenous fentanyl. Ventilatory variables (tidal volume, respiratory rate, end-tidal CO₂ , and minute ventilation) were assessed each minute for 10 min. The primary outcome was the extent of opioid-induced central ventilatory depression over time by obstructive sleep apnea status when compared with baseline values. Secondary aims assessed the impact of demographics and SpO₂ nadir on ventilatory depression.

We found no significant difference in percent decrease in respiratory rate (38.1% and 37.1%; p = .950), tidal volume (6.4% and 5.4%; p = .992), and minute ventilation (35.0 L/min and 35.0 L/min; p = .890) in control and obstructive sleep apnea patients, respectively. Both groups experienced similar percent increases in end-tidal CO₂ (4.0% vs. 2.2%; p = .512) in control and obstructive sleep apnea patients, respectively.

In pediatric surgical patients, obstructive sleep apnea status was not associated with significant differences in central respiratory depression following a single dose of fentanyl (1 mcg/kg). These findings can help determine safe opioid doses in future pediatric obstructive sleep apneapatients.

Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypothesize that deleterious cardiovascular outcomes are concentrated in a subgroup of patients with a heightened pulse-rate response to apneas and hypopneas (ΔHR). Methods: We measured the ΔHR in the MESA (Multi-Ethnic Study of Atherosclerosis) (N = 1,395) and the SHHS (Sleep Heart Health Study) (N = 4,575). MESA data were used to determine the functional form of the association between the ΔHR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the ΔHR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS. Measurements and Main Results: In the MESA, U-shaped relationships were observed between subclinical CVD biomarkers (coronary artery calcium, NT-proBNP [N-terminal prohormone BNP], and Framingham risk score) and the ΔHR; notably, a high ΔHR (upper quartile) was associated with elevated biomarker scores compared with a midrange ΔHR (25th-75th centiles). In the SHHS, individuals with a high ΔHR compared with a midrange ΔHR were at increased risk of nonfatal or fatal CVD and all-cause mortality (nonfatal adjusted hazard ratio [95% confidence interval (CI)], 1.60 [1.28-2.00]; fatal adjusted hazard ratio [95% CI], 1.68 [1.22-2.30]; all-cause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high ΔHR was particularly high in those with a substantial hypoxic burden (nonfatal, 1.93 [1.36-2.73]; fatal, 3.50 [2.15-5.71]; all-cause, 1.84 [1.40-2.40]) and was exclusively observed in nonsleepy individuals. Conclusions: Individuals with OSA who demonstrate an elevated ΔHR are at increased risk of cardiovascular morbidity and mortality. This study identifies a prognostic biomarker for OSA that appears useful for risk stratification and patient selection for future clinical trials.

Obstructive sleep apnea (OSA) is thought to affect almost 1 billion people worldwide. OSA has well established cardiovascular and neurocognitive sequelae, although the optimal metric to assess its severity and/or potential response to therapy remains unclear. The apnea-hypopnea index (AHI) is well established; thus, we review its history and predictive value in various different clinical contexts. Although the AHI is often criticized for its limitations, it remains the best studied metric of OSA severity, albeit imperfect. We further review the potential value of alternative metrics including hypoxic burden, arousal intensity, odds ratio product, and cardiopulmonary coupling. We conclude with possible future directions to capture clinically meaningful OSA endophenotypes including the use of genetics, blood biomarkers, machine/deep learning and wearable technologies. Further research in OSA should be directed towards providing diagnostic and prognostic information to make the OSA diagnosis more accessible and to improving prognostic information regarding OSA consequences, in order to guide patient care and to help in the design of future clinical trials.

The recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high altitude but benefits at sea level are less well understood.

All controlled studies of acetazolamide in obstructive sleep apnea and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index.

Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] -15.82, 95% CI: -21.91 to -9.74, P < .00001) in central sleep apnea (MD -22.60, 95% CI: -29.11 to -16.09, P < .00001), but not in obstructive sleep apnea (MD -10.29, 95% CI: -33.34 to 12.77, P = .38). Acetazolamide reduced the respiratory related arousal index (MD -0.82, 95% CI: -1.56 to -0.08, P = .03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13-14.11, P < .00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53-3.04, P = .005), total sleep time (MD 25.74, 95% CI: 4.10-47.38, P = .02), N2 sleep (MD 3.34, 95% CI: 0.12-6.56, P = .04) and sleep efficiency (MD 4.83, 95% CI: 0.53-9.13, P = .03).

Acetazolamide improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis.

Registry: PROSPERO; Name: The effect of acetazolamide in patients with sleep apnea at sea level: a systematic review and meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316.

The growing number of patients with obstructive sleep apnea is challenging healthcare systems worldwide. Obstructive sleep apnea is characterized by chronic intermittent hypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascular and metabolic diseases are common in obstructive sleep apnea, also in lean patients. Further, comorbidity burden is not unambiguously linked to the severity of obstructive sleep apnea. There is a growing body of evidence revealing diverse functions beyond the conventional tasks of different organs such as carotid body and gut microbiota. Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associated with insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoring only hypoxia and hypercapnia but also acting as a metabolic sensor. The emerging evidence shows that obstructive sleep apnea and particularly chronic intermittent hypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to be an important factor in the pathophysiology of obstructive sleep apnea and its consequences. The impact of sleep fragmentation and intermittent hypoxia on the development of metabolic syndrome may be mediated via altered gut microbiota. Circadian misalignment seems to have an impact on the cardiometabolic risk in obstructive sleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleep fragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism and predispose to neurocognitive impairment. Moreover, recent data show that obstructive sleep apnea independently predicts impaired lipid levels. This mini-review will provide novel insights into the mechanisms of metabolic dysfunction in obstructive sleep apnea combining recent evidence from basic, translational and clinical research, and discuss the impact of positive airway pressure treatment on metabolic disorders.

To evaluate the relationship between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM).

Retrospective clinical cohort study.

A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code 3620 for diabetic retinopathy (DR). Patients with a secondary cause of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography (OCT) and PSG. The prevalence of severe (apnea-hypopnea index [AHI] ≥30) and nonsevere (AHI <30) OSA was compared between patients with and without DME and refractory DME.

In total, 102 eyes (54 patients) were divided into groups of 40 eyes with DME or 62 eyes without DME. Severe OSA (odds ratio, 7.36; 95% confidence interval [CI]: 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (hazard ratio, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia.

Severe OSA is a risk factor for DME and is associated with having refractory DME.

Obstructive sleep apnea (OSA) is associated with insulin resistance and has been described as a risk factor for type 2 diabetes. Whether OSA adversely impacts pancreatic islet β-cell function remains unclear. We aimed to investigate the association of OSA and short sleep duration with β-cell function in overweight/obese adults with prediabetes or recently diagnosed, treatment-naive type 2 diabetes.

Two hundred twenty-one adults (57.5% men, age 54.5 ± 8.7 years, BMI 35.1 ± 5.5 kg/m²) completed 1 week of wrist actigraphy and 1 night of polysomnography before undergoing a 3-h oral glucose tolerance test (OGTT) and a two-step hyperglycemic clamp. Associations of measures of OSA and actigraphy-derived sleep duration with HbA_1c, OGTT-derived outcomes, and clamp-derived outcomes were evaluated with adjusted regression models.

Mean ± SD objective sleep duration by actigraphy was 6.6 ± 1.0 h/night. OSA, defined as an apnea-hypopnea index (AHI) of five or more events per hour, was present in 89% of the participants (20% mild, 28% moderate, 41% severe). Higher AHI was associated with higher HbA_1c (P = 0.007). However, OSA severity, measured either by AHI as a continuous variable or by categories of OSA severity, and sleep duration (continuous or <6 vs. ≥6 h) were not associated with fasting glucose, 2-h glucose, insulin sensitivity, or β-cell responses.

In this baseline cross-sectional analysis of the RISE clinical trial of adults with prediabetes or recently diagnosed, untreated type 2 diabetes, the prevalence of OSA was high. Although some measures of OSA severity were associated with HbA_1c, OSA severity and sleep duration were not associated with measures of insulin sensitivity or β-cell responses.

Sleep-disordered breathing (SDB) is associated with hypertension, poor glycemic control and dyslipidemia. Usually, apnoea events tend to be more prominent during rapid eye movement (REM) sleep than non-REM (NREM) sleep. We examined which SDB parameters are associated with blood pressure (BP), HbA1c and lipid profile in patients with type 2 diabetes (T2D).

A total of 185 patients with T2D who underwent polysomnography were analysed. Exclusion criteria were: the presence of pulmonary diseases, central sleep apnoea, treated SDB, or REM sleep < 30 min. To predict BP, HbA1c, and lipid profiles, we performed multiple linear regression analyses adjusted for known risk factors. Subsequently, we performed multivariable logistic regression analyses.

Patient characteristics (mean ± standard deviation/median) were as follows: age 58.0 ± 11.8 years, body mass index 26.0 kg/m2 (24.1-28.9 kg/m2 ), systolic BP 134 ± 19 mmHg, mean BP 98 ± 14 mmHg, HbA1c 7.4% (6.8-8.4%), triglyceride 143 mg/dL (97-195 mg/dL), non-high density lipoprotein (non-HDL) cholesterol 143 mg/dL (120-163 mg/dL), REM-apnoea-hypopnea index (AHI) 35.1/h (21.1-53.1/h). The analyses revealed that REM-AHI was independently associated with systolic and mean BP, whereas NREM-AHI was not. A statistically significant association was not observed between REM-AHI and HbA1c or lipid profile.

In patients with T2D, REM-AHI was associated with systolic and mean BP. The alteration of BP, associated with SDB during REM sleep, may be an important pathophysiological link between SDB and cardiovascular diseases.