Obstructive sleep apnea (OSA) is a global public health concern characterized by repeated upper airway collapse during sleep. Research indicates that OSA is a risk factor for the development of various diseases, including cardiovascular disease, metabolic disorders, respiratory diseases, neurodegenerative diseases, and cancer. Exosomes, extracellular vesicles released by most cell types, play a key role in intercellular communication by transporting their contents-such as microRNA, messenger RNA, DNA, proteins, and lipids-to target cells. Intermittent hypoxia associated with OSA alters circulating exosomes and promotes a range of cellular structural and functional disturbances involved in the pathogenesis of OSA-related diseases. This review discusses the potential roles of exosomes and exosome-derived molecules in the onset and progression of OSA-associated diseases, explores the possible underlying mechanisms, and highlights novel strategies for developing exosome-based therapies for these conditions.
Humans ; Exosomes/physiology* ; Sleep Apnea, Obstructive/metabolism* ; Animals ; MicroRNAs/metabolism*

Background: Obstructive sleep apnea syndrome (OSAS) is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers. Methods: A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density (BMD) and the serum levels of total procollagen type 1 N-terminal propeptide (t-P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), vitamin D (VD), and parathyroid hormone (PTH) were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses. Results: No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels of t-P1NP and β-CTX in the severe OSAS group were significantly higher than those in the obesity group (48.42 ± 23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P < 0.001; 0.53 ± 0.24 ng/ml vs. 0.41 ± 0.13 ng/ml, P = 0.011, respectively). The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups (both P < 0.001), and decreased as the severity of OSAS increased (P < 0.001). The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups (both P < 0.001). The results of correlation analysis indicated that the level of apnea-hypopnea index (AHI) was correlated with the levels of t-P1NP (r = 0.396, P < 0.001), VD (r = -0.404, P < 0.001), and PTH (r = 0.400, P < 0.001), whereas the level of minimum Osaturation (SaOmin) was correlated with the levels of VD (r = 0.258, P = 0.016) and PTH (r = -0.376, P < 0.001). Conclusions The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.
Biomarkers ; blood ; Bone Density ; Bone and Bones ; metabolism ; Humans ; Male ; Middle Aged ; Obesity ; complications ; Parathyroid Hormone ; Polysomnography ; Sleep Apnea, Obstructive ; complications

Sleep is a physiologic state of decreased metabolism and serves a reparative role, marked by increased glycogen stores and peptide synthesis. Normal sleep is characterized by reduced glucose turnover by the brain and other metabolically active tissues, particularly during non-rapid eye movement sleep. Circadian and sleep-related changes in glucose tolerance occur in normal subjects. Sleep duration has decreased over the last several decades, and with this have come cross-sectional and longitudinal data suggesting a link between short sleep duration and the prevalence of type 2 diabetes. Forced decreased sleep duration in healthy individuals has linked to impaired glucose homeostasis. Moreover, short sleep duration has been associated with obesity. Obstructive sleep apnea syndrome is characterized by diminished or abrogated airflow, which results in intermittent hypoxia and sleep fragmentation. This disorder appears to be associated with impaired glucose tolerance. Thus, the quality and quantity of sleep may have a profound effect on type 2 diabetes; therefore, these relationships should be carefully assessed in primary and endocrinology clinics.
Anoxia ; Brain ; Diabetes Mellitus ; Endocrinology ; Eye Movements ; Glucose ; Glycogen ; Homeostasis ; Metabolism ; Obesity ; Prevalence ; Sleep Apnea, Obstructive ; Sleep Deprivation

BACKGROUNDThe mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves.

METHODSEight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.

RESULTSThe P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits.

CONCLUSIONSThe P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

Animals ; Disease Models, Animal ; Hypoxia ; Male ; Metabolic Networks and Pathways ; Mice ; Mice, Inbred C57BL ; Purinergic P2 Receptor Antagonists ; pharmacology ; Receptors, Purinergic P2X7 ; analysis ; physiology ; Rosaniline Dyes ; pharmacology ; Sleep Apnea, Obstructive ; metabolism

BACKGROUNDStudies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels).

METHODSWe used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels.

RESULTSThe study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders.

CONCLUSIONSSleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control.

Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; blood ; complications ; Sleep Wake Disorders ; blood ; complications

BACKGROUNDObstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients.

METHODSAll patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5-14 events/h, 15-29 events/h, and ≥30 events/h.

RESULTSA total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO 2 ), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation.

CONCLUSIONSOur data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS.

Adult ; Aged ; Alanine Transaminase ; blood ; metabolism ; Aspartate Aminotransferases ; blood ; metabolism ; Cholesterol ; blood ; Female ; Humans ; Liver ; enzymology ; Male ; Middle Aged ; Polysomnography ; Risk Factors ; Sleep Apnea, Obstructive ; blood ; enzymology ; Triglycerides ; blood ; gamma-Glutamyltransferase ; blood ; metabolism

OBJECTIVE: To research the serum levels of BDNF, H2S and S-100β as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD: Forty-four randomly selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100β levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT: (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100β levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100β level was positively correlated with AHI index, and S-100β levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100β levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100β levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100β) (R2 = 0.461). CONCLUSION OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100β levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients.
Brain-Derived Neurotrophic Factor ; metabolism ; Cerebral Cortex ; physiopathology ; Cognition Disorders ; complications ; Hippocampus ; physiopathology ; Humans ; Hypoxia ; Memory ; Metabolic Diseases ; physiopathology ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Sleep Apnea, Obstructive ; complications

BACKGROUNDObstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides from the same source but have opposite roles. Both of them can affect feeding and regulate vascular tune. The aim of this study was to investigate the relationship between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.

METHODSThis study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group). Polysomnography (PSG) was performed in the OSAS group and over-weight group. Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring. The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSPlasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P < 0.05). Plasma obestatin levels were lower in the over-weight group and OSAS group, but there was no significant difference among the three groups. The blood pressure in OSAS patients was higher, and there was a significant difference in all blood pressure parameters compared to the control group, and in the daytime average diastolic blood pressure (DBP), nocturnal average systolic blood pressure (SBP) and DBP, DBP variability values as compared to over-weight subjects. Furthermore, there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P < 0.01). Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters. In contrast, the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with the blood pressure variability values (P < 0.01). In multivariate analyses, AHI (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were independently related to DBP variability changes.

CONCLUSIONSOur data show plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity. Moreover, the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.

Adolescent ; Adult ; Aged ; Blood Pressure ; physiology ; Circadian Rhythm ; physiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ghrelin ; blood ; Humans ; Male ; Middle Aged ; Obesity ; blood ; physiopathology ; Pancreatic Neoplasms ; blood ; physiopathology ; Prognosis ; Repressor Proteins ; metabolism ; Sleep Apnea, Obstructive ; blood ; physiopathology ; Young Adult

OBJECTIVE: To detect the levels and effects of protective bioactive substances such as NO, SOD and GSH in patients with obstructive sleep apnea syndrome (OSAHS) combining hypertension. METHOD: To collect the data from 99 snoring patients, which were divided into control group, OSAHS group, and OSAHS combined with hypertension group. The serum levels of NO), SOD and GSH in these patients were detected perioperatively, correlation analysis were carried out between these parameters. RESULT: The levels of NO, SOD and GSH in control group, OSAHS group and OSAHS combined with hypertension group reduced in turn with statistically significance, and had inverse correlations with apnea hyponea index (AHDI) and lowest saturation of blood oxygen. After operation, the levels of NO), SOD and GSH were increased and the blood pressure was decreased. CONCLUSION The oxidative stress state is serious in patients with OSAHS. The oxidative stress process is more severe in patients with hypertension, which may play a role in the devolepment of hypertension in OSAHS patients.
Adult ; Case-Control Studies ; Glutathione ; blood ; Humans ; Hypertension ; etiology ; Male ; Middle Aged ; Nitric Oxide ; blood ; Oxidative Stress ; Sleep Apnea, Obstructive ; complications ; metabolism ; Snoring ; Superoxide Dismutase ; blood

BACKGROUNDIncreasingly, evidence from population, clinic-based and laboratory studies supports an independent association between obstructive sleep apnea syndrome (OSAS) and an increased risk of type 2 diabetes; however, this observation has yet to be replicated in China and the potential mechanisms that link these two conditions are not clear.

METHODSA total of 179 Han Chinese subjects were enrolled in this study. All subjects underwent polysomnography, the oral glucose tolerance-insulin releasing test (OGTT-IRT) and serum HbA(1)c measurement. Indexes including homeostasis model assessment-IR (HOMA-IR), Matsuda index, HOMA-β, early phase insulinogenic index (ΔI(30)/ΔG(30)), AUC-I(180) and oral disposition index (DIo) were calculated for the assessment of insulin resistance and pancreatic β-cell function.

RESULTSBased on OGTT, 25.4%, 44.6% and 54.5% subjects were diagnosed having glucose metabolic disorders respectively in control, mild to moderate and severe OSAS groups (P < 0.05). Serum HbA(1)c levels were highest in subjects with severe OSAS (P < 0.05). In contrast, compared with normal subjects, HOMA-β, ΔI(30)/Δ(G30) and DIO were lower in severe OSAS group (P < 0.05). In stepwise multiple linear regressions, 0-min glucose and HbA(1)c were positively correlated with the percentage of total sleep time below an oxyhemoglobin saturation of 90% (T90) (Beta = 0.215 and 0.368, P < 0.05); 30-min and 60-min glucose was negatively correlated with the lowest SpOO(2) (LSpO(2)) (Beta = -0.214 and -0.241, P < 0.05). HOMA-β and DI(O) were negatively correlated with T90 (Beta = -0.153 and -0.169, P < 0.05) while body mass index (BMI) was the only determinant of HOMA-IR and Matsuda index.

CONCLUSIONSOSAS is associated with impairment in glucose tolerance and pancreatic β-cell function in Han Chinese subjects while insulin sensitivity is mainly determined by obesity.

Adolescent ; Adult ; Aged ; Female ; Glucose ; metabolism ; Glucose Tolerance Test ; Glycated Hemoglobin A ; analysis ; Humans ; Insulin Resistance ; Insulin-Secreting Cells ; physiology ; Male ; Middle Aged ; Polysomnography ; Sleep Apnea, Obstructive ; metabolism