Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS), and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine, and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine, and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach, and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.

Obstructive sleep apnea (OSA) is highly prevalent yet underdiagnosed. This study aimed to develop a predictive signature, as well as investigate competing endogenous RNAs (ceRNAs) and their potential functions in OSA.

Obstructive sleep apnea (OSA) has been suggested to be associated with a high risk of metabolic syndrome (MS). However, results on whether the association between OSA and risk of MS is independent of obesity, and the effect of nocturnal intermittent hypoxia (IH) on MS, are conflicting. Our purpose was to estimate the magnitude of the independent association between OSA and risk of MS and further explore whether nocturnal IH in OSA plays a role in MS risk.

Obstructive sleep apnea (OSA) is associated with dyslipidemia. However, no study has focused on dyslipidemia in women with OSA. The aim of this study was to determine the prevalence and risk factors for dyslipidemia in women with OSA. Between 2007 and 2013, 570 eligible female patients with suspected OSA were consecutively recruited. The analyzed data consisted of polysomnography parameters, biochemical indicators, and anthropometric measurements. Serum lipid levels and dyslipidemia were compared. Binary logistic regression and multivariate linear regression models were used to determine the independent risk factors influencing serum lipids. After multivariate adjustment, there were essentially no major differences in serum lipid levels among patients with no to mild, moderate, and severe OSA nor did serum lipid levels change with OSA severity. Dyslipidemia in total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoproteins(apo) B and apoE increased with OSA severity, but only in non-obese subjects and those <55 years of age. Age, body mass index, waist to hip ratio, glucose and insulin were major risk factors for most serum lipids after multivariate adjustments. Our results indicate that, in women with OSA, age, obesity/central obesity, and insulin resistance are major determinants of dyslipidemia.

BACKGROUND Endothelial dysfunction, which can be measured by flow-mediated dilatation (FMD), is an early clinical marker of atherosclerosis, which is considered to be the main cause of the observed cardiovascular complications in obstructive sleep apnea (OSA) patients. The association between OSA and endothelial dysfunction has been reported in a number of studies; however, the findings are not entirely consistent. Our aim was to meta-analytically synthesize the existing evidence to explore the association between OSA and endothelial dysfunction. MATERIAL AND METHODS Data from PubMed, EMBASE, the Cochrane library, and Google Scholar for all trials that investigated the relationship between endothelial dysfunction and OSA were systematically reviewed. The minimum inclusion criteria for the studies were reporting of the Apnea-Hypopnea Index (AHI) and FMD measurements (as an indicator of endothelial dysfunction) for both OSA and control groups. Data from case-control studies that met the inclusion criteria were extracted. RESULTS Twenty-eight studies comprising a total of 1496 OSA patients and 1135 controls were included in the meta-analysis. A random-effects model was used. The weighted mean difference in the FMD measurements was -3.07 and the 95% confidence interval was -3.71 to -2.43 (P<0.01). Meta-regression analysis showed that age, sex, body mass index (BMI), blood pressure, glucose, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol did not explain the heterogeneity. CONCLUSIONS This meta-analysis showed that patients with OSA have decreased FMD, which may contribute to the development of atherosclerosis.

The high cost and low availability of polysomnography (PSG) limits the timely diagnosis of OSA. Herein, we developed and validated a simple-to-use nomogram for predicting OSA.

Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system.

Both obstructive sleep apnea (OSA) and decreased serum lipoprotein(a) (Lp(a)) concentrations are associated with insulin resistance. However, their interaction effect on insulin resistance has never been investigated. Therefore, we performed a cross-sectional study on OSA-suspected Chinese Han participants. Laboratory-based polysomnographic variables, biochemical indicators, anthropometric measurements, and medical history were collected. Linear regression and binary logistic regression analyses with interaction terms were used to investigate the potential effects of the interaction between the severity of OSA (assessed by the apnea-hypopnea index (AHI)) and Lp(a) concentrations on insulin resistance (assessed by the homeostasis model assessment of insulin resistance (HOMA-IR)), after adjusting for potential confounders including age, gender, body mass index, waist-to-hip circumference ratio, mean arterial pressure, smoking status, drinking status, and lipid profiles. A total of 4,152 participants were enrolled. In the OSA-suspected population, AHI positively correlated with insulin resistance and serum Lp(a) concentrations independently and inversely correlated with insulin resistance. In addition, the interaction analysis showed that the linear association between lgAHI and lgHOMA-IR was much steeper and more significant in subjects with relatively low Lp(a) concentrations, suggesting a significant positive interaction between lgLp(a) and lgAHI on lgHOMA-IR (P = 0.013). Furthermore, the interaction on a multiplicative scale also demonstrated a significant positive interaction (P = 0.044). A stronger association between AHI quartiles and the presence of insulin resistance (defined as HOMA-IR > 3) could be observed for participants within lower Lp(a) quartiles. In conclusion, a significant positive interaction was observed between OSA and decreased Lp(a) with respect to insulin resistance. This association might be relevant to the assessment of metabolic or cardiovascular disease risk in OSA patients.

Objective: Obstructive sleep apnea (OSA) results in increased carotid intima-media thickness (IMT) and arterial stiffness; however, the association between adipocytokines and IMT/arterial stiffness in OSA patients is unclear. Methods: We enrolled 95 normal weight and overweight, not obese, participants from May 2018 to December 2018 in this study. All subjects underwent a carotid artery ultrasound examination and polysomnography. Blood samples were used to determine serum chemerin, adiponectin, SFRP5, and apelin levels. Correlations between two quantitative variables were assessed using the Pearson or Spearman coefficient. Stepwise models of multiple linear regression analysis were performed to assess the independent relationships. Result: IMT in OSA patients was significantly higher than in the non-snorers. There were significant differences in the arterial stiffness parameters such as distensibility coefficient (DC), compliance coefficient (CC), and pulse wave velocity (PWV). SFRP5 level was lower in OSA patients than in non-snorers. Adiponectin correlated with CC, DC, and PWV among OSA patients; however, the relationship disappeared after a multivariable adjustment. Age was independently associated with all quantitative IMT and stiffness indices. AHI and minimum oxygen saturation (Mini SaO2) were independently related to arterial stiffness. Conclusion: The quantitative IMT and carotid arterial elasticity were significantly worse among OSA patients. Age was the main independent factor correlated with quantitative IMT and arterial stiffness, and AHI and mini SaO2 were associated factors. There were no relationships between aforementioned adipocytokines and quantitative IMT/carotid arterial stiffness.

The objective of our study was to evaluate the effects of upper-airway surgery on improvement of endothelial function-related markers in patients with obstructive sleep apnea (OSA). Subjects with moderate to severe OSA who underwent upper-airway surgery, with a follow-up duration of at least 6 months, were included. Pre- and postoperative polysomnographic variables and endothelial function-related markers were compared. Subgroup and correlation analyses were conducted to find possible indicators for better endothelial function-related markers after upper-airway surgery. In total, 44 patients with OSA were included. The mean follow-up duration was 1.72 ± 0.92 years. Serum VEGFA [-20.29 (CI: -35.27, -5.31), p < 0.05], Ang2 [-0.06 (CI: -0.16, 0.03), p < 0.05], E-selectin [-7.21 (CI: -11.01, -3.41), p < 0.001], VWF [-58.83 (CI: -103.93, -13.73), p < 0.05], VWFCP [-33.52 (CI: -66.34, -0.70), p < 0.05], and TM [-0.06 (CI: -0.09, -0.03), p < 0.05] were significantly lower after upper-airway surgery. However, other risk markers of endothelial function, such as Ang1, ICAM1, VEGFR1, and VCAM, did not change significantly. Correlations between improved endothelial function-related markers and ameliorated oxyhemoglobin saturation and glucolipid metabolism were established. Upper-airway surgery might be associated with an improvement in endothelial function in patients with OSA. These changes may be associated with improved oxygen saturation after upper-airway surgery.

Slow-wave sleep (SWS) and obstructive sleep apnea (OSA) have attracted recent research attention. However, their joint effects on insulin resistance (IR) remain unclear. This study explored whether SWS influences the relationship between OSA and IR.

Obesity is strongly correlated with obstructive sleep apnea (OSA), and bariatric surgery can effectively treat obesity and alleviate OSA. However, the contributing factors are still unclear. We aimed to explore the relationship between betatrophin and OSA in patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. Our study consisted of thirty-seven individuals with OSA and type 2 diabetes (16 males, 21 females) undergoing RYGB surgery. The polysomnography test, anthropometric results, serum betatrophin, and abdominal magnetic resonance images were evaluated both before and 1 year after RYGB surgery. Factors that may correlate with the alleviation of OSA were investigated. In our study, RYGB surgery significantly decreased apnea hypopnea index (AHI) and serum betatrophin concentration (p < 0.001). The abdominal visceral fat area, subcutaneous fat area and HOMA-IR were also significantly decreased (p < 0.001). The preoperative AHI, postoperative AHI and the change in AHI were significantly correlated with the preoperative betatrophin, postoperative betatrophin and the change in betatrophin, respectively (p < 0.05). These correlations were still significant after adjustment for other risk factors. The change in betatrophin was also independently associated with the change in minimum oxygen saturation (p < 0.001). Our data might indicate that serum betatrophin was significantly independently correlated with the improvement of OSA after bariatric surgery.

Background: Obstructive sleep apnea (OSA) is the most common type of sleep apnea that impacts the development or progression of many other disorders. Abnormal expression of N6-methyladenosine (m6A) RNA modification regulators have been found relating to a variety of human diseases. However, it is not yet known if m6A regulators are involved in the occurrence and development of OSA. Herein, we aim to explore the impact of m6A modification in severe OSA. Methods: We detected the differentially expressed m6A regulators in severe OSA microarray dataset GSE135917. The least absolute shrinkage and selection operator (LASSO) and support vector machines (SVM) were used to identify the severe OSA-related m6A regulators. Receiver operating characteristic (ROC) curves were performed to screen and verify the diagnostic markers. Consensus clustering algorithm was used to identify m6A patterns. And then, we explored the character of immune microenvironment, molecular functionals, protein-protein interaction networks and miRNA-TF coregulatory networks for each subcluster. Finally, the Connectivity Map (CMap) tools were used to tailor customized treatment strategies for different severe OSA subclusters. An independent dataset GSE38792 was used for validation. Results: We found that HNRNPA2B1, KIAA1429, ALKBH5, YTHDF2, FMR1, IGF2BP1 and IGF2BP3 were dysregulated in severe OSA patients. Among them, IGF2BP3 has a high diagnostic value in both independent datasets. Furthermore, severe OSA patients can be accurately classified into three m6A patterns (subcluster1, subcluster2, subcluster3). The immune response in subcluster3 was more active because it has high M0 Macrophages and M2 Macrophages infiltration and up-regulated human leukocyte antigens (HLAs) expression. Functional analysis showed that representative genes for each subcluster in severe OSA were assigned to histone methyltransferase, ATP synthesis coupled electron transport, virus replication, RNA catabolic, multiple neurodegeneration diseases pathway, et al. Moreover, our finding demonstrated cyclooxygenase inhibitors, several of adrenergic receptor antagonists and histamine receptor antagonists might have a therapeutic effect on severe OSA. Conclusion: Our study presents an overview of the expression pattern and crucial role of m6A regulators in severe OSA, which may provide critical insights for future research and help guide appropriate prevention and treatment options.

Both short sleep duration and obstructive sleep apnea (OSA) seem to be associated with insulin resistance. We aimed to explore whether short sleep duration modifies the relationship between OSA and insulin resistance.

Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear.

Immune and inflammatory factors have emerged as key pathophysiological mechanisms in the progression of diabetic renal injury. Noncanonical Wnt5a signaling plays an essential role in obesity- or diabetes-induced metabolic dysfunction and inflammation, but its explicit molecular mechanisms and biological function in diabetic nephropathy (DN) remain unknown. In this study, we found that the expression of Wnt5a and CD146 in the kidney and the level of soluble form of CD146 (sCD146) in serum and urine samples were upregulated in DN patients compared to controls, and this alteration was correlated with the inflammatory process and progression of renal impairment. Blocking the activation of Wnt5a signaling with the Wnt5a antagonist Box5 prevented JNK phosphorylation and high glucose-induced inflammatory responses in db/db mice and high glucose-treated HK-2 cells. Similar effects were observed by silencing Wnt5a with small-interfering RNA (siRNA) in cultured HK-2 cells. Knockdown of CD146 blocked Wnt5a-induced expression of proinflammatory cytokines and activation of JNK, which suggests that CD146 is essential for the activation of the Wnt5a pathway. Finally, we confirmed that Wnt5a directly interacted with CD146 to activate noncanonical Wnt signaling in HK-2 cells. Taken together, our findings suggest that by directly binding to CD146, Wnt5a-induced noncanonical signaling is a contributing mechanism for renal tubular inflammation in diabetic nephropathy. The concentration of sCD146 in serum and urine could be a potential biomarker to predict renal outcomes in DN patients.

Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.