Abstract
Introduction:
Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea.
Objective:
To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients.
Methods:
Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5.
Results:
Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance.
Conclusion:
Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.
Keywords
Obstructive sleep apnea; Secreted frizzled-related protein 5; Adipokine; Insulin sensitivity
Resumo
Introdução:
A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono.
Objetivo:
Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada.
Método:
Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5.
Resultados:
Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina.
Conclusões:
A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.
Palavras-chave
Apneia obstrutiva do sono; Proteína secretada relacionada ao receptor frizzled 5; Adipocina; Sensibilidade à insulina
Introduction
Obstructive sleep apnea (OSA) is a common breathing disorder. Its prevalence is high with a mean of 22% in men and 17% in women.11 Franklin KA, Lindberg E. Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thor Dis. 2015;7:1311-1322. OSA is characterized by the repetitive cessation of breathing due to airway obstruction during sleep, leading to hypoxemia and sleep disruptions.22. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999;22:667-689. Studies showed OSA was associated with metabolic disorders, such as insulin resistance (IR), type 2 diabetes (T2DM).33 Fernandes JF, Klein MR, Sanjuliani AF. Obstructive sleep apnea is independently associated with inflammation and insulin resistance, but not with blood pressure, plasma catecholamines, and endothelial function in obese subjects. Nutrition. 2015;31:1351-1357.–55 Rajan P, Greenberg H. Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus. Nat Sci Sleep. 2015;7:113-125. The exact mechanisms underlying this association remain unclear. However, adipose tissue is considered to play an important role in the development of IR and T2DM in OSA.66 Bonsignore MR, McNicholas WT, Montserrat JM, Eckel J. Adipose tissue in obesity and obstructive sleep apnoea. Eur Respir J. 2012;39:746-767.
Adipose tissue is not only an energy storage tissue but also an endocrine organ that secretes various adipokines.77 Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316:129-139. Increasing evidence shows that adipokine abnormalities are involved in OSA.88 Lam DC, Lam KS, Ip MS. Obstructive sleep apnoea, insulin resistance and adipocytokines. Clin Endocrinol (Oxf). 2015;82:165-177.–1010 Yosunkaya S, Okur HK, Can U, Zamani A, Kutlu R. Impact of continuous positive airway pressure treatment on leptin levels in patients with obstructive sleep apnea syndrome. Metab Syndr Relat Disord. 2015;13:272-277. As an adipokine, secreted frizzled-related protein 5 (Sfrp5) is highly expressed in white adipose tissue.1111 Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329:454-457.–1414 Hu W, Li L, Yang M, Luo X, Ran W, Liu D, et al. Circulating Sfrp5 is a signature of obesity-related metabolic disorders and is regulated by glucose and liraglutide in humans. J Clin Endocrinol Metab. 2013;98:290-298. Sfrp5 is associated with IR, T2DM and coronary artery diseases, and even represents a potential therapeutic target for abnormal glucose homeostasis.1111 Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329:454-457.,1515 Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99:391-395.–1818 Cheng L, Zhang D, Chen B. Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults. Pak J Med Sci. 2015;31:602-605. In addition, Sfrp5 expression is down-regulated under conditions of oxidative stress,1919 Nakamura K, Sano S, Fuster JJ, Kikuchi R, Shimizu I, Ohshima K, et al. Secreted frizzled-related protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury. J Biol Chem. 2016;291:2566-2575. which are frequently present in OSA during sleeping because of intermittent hypoxia.2020 Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008;117:2270-2278. Thus, we speculated the changes in Sfrp5 might be involved in OSA and be associated with IR in OSA. Assessing this association might contribute to identifying the mechanisms of IR in OSA and is thus crucial for the preventing from risks of IR and T2DM in OSA.
Methods
Subjects
All subjects were recruited from the Sleep Laboratory of the Department of Respiratory Medicine, the Department of Otolaryngological Medicine or the Health Examination Center of Beijing Friendship Hospital from 2016.03 to 2017.04. The inclusion criterion was being age from 18 to 70 years old. The exclusion criteria were having metabolic, allergic, cardiovascular, cerebrovascular, renal, or liver diseases, psychiatric disorders, having infectious diseases of the lungs, sleep disorders other than OSA, being pregnant, and having been previously treated for OSA. The study was approved by the Ethics Committee of Beijing Friendship Hospital and informed consent was obtained from all participants. The ethics code number: 2016-P2-003-02.
All subjects underwent a thorough physical examination before undergoing polysomnography (PSG). neck circumference (NC), waist circumference (WC), waist-to-hip ratio (WHR), and body mass index [BMI, weight (height)2] were measured. In addition, subjects were classified as obese, non-obese.2121. Predictive values of body mass index with waist circumference to risk factors of related diseases in Chinese adult population. Chin J Epidemiol. 2002;23:5-10. The Epworth Sleepiness Score (ESS) was collected to assess the level of daytime sleepiness.
PSG
All subjects underwent overnight PSG using a sleep data-acquisition system (Homlogic N7000, Australia). Briefly, the recorded parameters were electroencephalograms from leads applied at C4-M1, C3-M2, O2-M1, O1-M2, F4-M1, and F3-M2, respiratory airflow detected by a flow pressure receptor, respiratory movements detected by thoracic and abdominal bands, oxygen saturation detected by a pulse oximeter, electrooculograms, as well as chin and anterior tibial electromyograms. Apnea was defined as an amplitude reduction >90% of nasal airflow for at least 10s. Hypopnea was defined as an airflow amplitude reduction >30% associated with oxyhemoglobin desaturation of 3% or more or associated with arousal. All PSG records were analyzed by two specialists. Normal subjects were defined as those having an Apnea/Hypopnea Index (AHI) < 5, and subjects with OSA were defined as those having an AHI ≥ 5.
Blood assay
Venous blood samples were obtained from all subjects in the morning after PSG and after having fasting overnight. The plasma was extracted by centrifugation at 1000 g/min for 20 min and stored at −80 °C until measurement. Plasma Sfrp5 was assessed using an ELISA kit (ShinnyBIO, Shanghai, China). All other blood tests (triglyceride [TG], total cholesterol [TC], low density lipoprotein [LDL], high density lipoprotein [HDL], high-sensitivity C-reactive protein [HS-CRP], fasting blood glucose, Fasting insulin) were completed by the Beijing Friendship Hospital. Insulin sensitivities were assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) = (fasting glucose [mmoL/L] * fasting insulin [lU/mL])/22.5.2222 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419.
Statistical analysis
Data are presented as the mean ± Standard Derivation for continuous variables and the number for categorical variables. One-sample Kolmogorov–Smirnov tests were performed to determine whether the independent variables were normally distributed. Comparisons of independent groups were performed with the independent-samples Student's t-test or the Mann–Whitney U-test based on the normality distribution. Categorical variables were compared with the Chi-square test. Linear correlations were analyzed by Spearson's correlation coefficient. A multiple linear regression analysis with stepwise selection was used to determine associations between various factors and Sfrp5. p-value <0.05 was considered to indicate significance. The statistical analyses of the data were conducted using SPSS 17.0.
Results
109 subjects were divided into two groups: the OSA group (n = 76; age: 46.13 ± 11.61 years; male/female: 56/20) and the control group (n = 33; age: 42.21 ± 11.22 years; male/female: 20/13). According to AHI, the OSA groups were divided into three subgroup: mild OSA (5 ≤ AHI < 15), moderate OSA (15 ≤ AHI < 30), severe OSA (AHI ≥ 30). All baseline characteristics and blood testing results of the subjects are presented in Tables 1 and 2.
Baseline demographics, sleep profiles and blood measurements of the control and OSA subgroups.
There was significant difference in Sfrp5 levels between the control and OSA groups (OSA group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). The concentrations of Sfrp5 were significantly lower in severe OSA group than control group (Table 2).
Fig. 1 showed the Sfrp5 level in control group was significantly lower in obese subjects than in non-obese subjects. In addition, there was no difference in Sfrp5 levels between males and females in control group (Fig. 2).
Comparison of Sfrp5 levels between non-obese and obese in the control and OSA groups. OSA, obstructive sleep apnea; Sfrp5, secreted frizzled-related protein 5.
Comparison of Sfrp5 levels between different genders in the control and OSA groups. OSA, obstructive sleep apnea; Sfrp5, secreted frizzled-related protein 5.
The correlation analysis showed that the Sfrp5 level was negatively correlated with BMI, ESS HS-CRP, HOMA-IR but positively correlated with the lowest and mean oxygen saturation levels. Adjusting for age, gender, BMI, NC, WC, and WHR, Sfrp5 was still negatively correlated with HOMA-IR and ESS (Table 3). The multiple linear regression analysis showed there was an independent negative correction between HOMA-IR and Sfrp5 in the OSA group (Table 4).
Discussion
The present study showed that the Sfrp5 concentrations were significantly decreased in OSA. In addition, the Sfrp5 was positively correlated with the lowest and mean oxygen saturations with or without adjustments for age, gender, BMI, NC, WC and WHR. These results suggest that Sfrp5 might be involved in the pathophysiological process of OSA. Previous studies have reported that hypoxia could induce necrosis in 3T3-L1 adipocytes2323 Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab. 2009;296:E333-E342. and increase adipocytes death in the adipose tissue of obese subjects.2424 Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347-2355. Most importantly, the expression of Sfrp5 was down-regulated under the conditions of oxidative stress.1919 Nakamura K, Sano S, Fuster JJ, Kikuchi R, Shimizu I, Ohshima K, et al. Secreted frizzled-related protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury. J Biol Chem. 2016;291:2566-2575. Undoubtedly, hypoxia followed by oxidative stress occurs frequently during sleep2525 Pialoux V, Hanly PJ, Foster GE, Brugniaux JV, Beaudin AE, Hartmann SE, et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am J Respir Crit Care Med. 2009;180:1002-1009. in OSA. It seems that the reduction in circulating Sfrp5 may be a result of the adipocyte death and oxidative stress caused by hypoxia in OSA. However, Zhang DM2626 Zhang DM, Huang R, Xiao Y, Gong FG, Zhong X, Luo JM. Secreted frizzled-related protein 5 (SFRP5) in patients with obstructive sleep apnea. Chin Med Sci J. 2017;32:211-217. suggested that the Sfrp5 levels of OSA patients did not differ from that of non-OSA individuals. In the study of Zhang DM, the subjects were severe OSA individuals whose AHI were lower than that of severe OSA in present study. Importantly, Zhang DM's study, unlike the present study, did not include females. In addition, the present study showed the Sfrp5 concentrations of females were lower than that of males in OSA group (Fig. 2). To some extent, the discrepancies among these studies might lie in the different clinical characteristics of the studies.
One study showed that Sfrp5 expression was decreased in the adipose tissue of obese mice.1111 Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329:454-457. Studies1414 Hu W, Li L, Yang M, Luo X, Ran W, Liu D, et al. Circulating Sfrp5 is a signature of obesity-related metabolic disorders and is regulated by glucose and liraglutide in humans. J Clin Endocrinol Metab. 2013;98:290-298.,1515 Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99:391-395.,2727 Lu YC, Wang CP, Hsu CC, Chiu CA, Yu TH, Hung WC, et al. Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2013;29:551-556. suggested that there was a significantly lower circulating Sfrp5 concentration under conditions of obesity than under conditions of normal weight. In the present study, plasma Sfrp5 levels were significantly lower in obese subjects than in normal weight subjects, and Sfrp5 was negatively correlated with BMI. Furthermore, the multiple linear regression analysis showed that the BMI independently predicted the Sfrp5 level in control group. We speculated that the Sfrp5 expression might be reduced in obese humans, although this hypothesis needs to be verified in future studies.
As an anti-inflammatory adipokine, Sfrp5 inhibits the accumulation of activated macrophages in adipose tissue via noncanonical regulation of the JNK signaling pathway to ameliorate glucose intolerance in mouse models of obesity and T2DM.1111 Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329:454-457. Studies have reported that Sfrp5 is inversely correlated with HOMA-IR in obese subjects with normal glucose tolerance or T2DM.1212 Schulte DM, Muller N, Neumann K, Oberhauser F, Faust M, Gudelhofer H, et al. Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects. PLOS ONE. 2012;7:e32437.,1515 Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99:391-395.,1818 Cheng L, Zhang D, Chen B. Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults. Pak J Med Sci. 2015;31:602-605. We also found a significantly negative correlation even when the confounding factors of age, gender, BMI, NC and WHR were eliminated. Most importantly, the multiple linear regression analysis showed the negative association independently between Sfrp5 and IR in the OSA group. We speculated the reason for the negative correlation was that the decrease in Sfrp5 might attenuate its anti-inflammatory effects in adipose tissue in OSA.
Some studies suggested that adipokine levels might be correlated with gender.2828 Miyoshi T, Onoue G, Hirohata A, Hirohata S, Usui S, Hina K, et al. Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound. Atherosclerosis. 2010;211:164-169.,2929 Bottner A, Kratzsch J, Muller G, Kapellen TM, Bluher S, Keller E, et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab. 2004;89:4053-4061. However, we found no differences in the plasma Sfrp5 level between women and men in control group. In agreement with our finding, previous studies have also failed to find an association between the serum Sfrp5 levels and the sex of the subjects.1515 Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99:391-395.–1717 Carstensen M, Herder C, Kempf K, Erlund I, Martin S, Koenig W, et al. Sfrp5 correlates with insulin resistance and oxidative stress. Eur J Clin Invest. 2013;43:350-357.
The main limitation of present study was that the study was followed a case-control design without randomization, blinding or a placebo control.
Conclusions
In conclusion, Sfrp5 was involved in OSA and the decrease in Sfrp5 was directly proportional to the severity of OSA. There was an independent negative correlation between HOMA-IR and Sfrp5 in the OSA group. Sfrp5 might be a therapeutic target for IR in OSA.
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Funding
The study was funded by Natural Science Foundation of Beijing Municipality (CN) (No. 7142046), Teaching and Reform Program of Kunming Medical University (No. 2016-JY-Y-43), and Yunnan Provincial Department of Education (No. 2017zzx201). -
☆
Please cite this article as: Sun S, Zhai H, Zhu M, Wen P, He X, Wang H. Insulin resistance is associated with Sfrp5 in obstructive sleep apnea. Braz J Otorhinolaryngol. 2019;85:739–45.
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☆☆
Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.
References
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1Franklin KA, Lindberg E. Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thor Dis. 2015;7:1311-1322.
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2Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999;22:667-689.
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3Fernandes JF, Klein MR, Sanjuliani AF. Obstructive sleep apnea is independently associated with inflammation and insulin resistance, but not with blood pressure, plasma catecholamines, and endothelial function in obese subjects. Nutrition. 2015;31:1351-1357.
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5Rajan P, Greenberg H. Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus. Nat Sci Sleep. 2015;7:113-125.
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6Bonsignore MR, McNicholas WT, Montserrat JM, Eckel J. Adipose tissue in obesity and obstructive sleep apnoea. Eur Respir J. 2012;39:746-767.
-
7Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316:129-139.
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8Lam DC, Lam KS, Ip MS. Obstructive sleep apnoea, insulin resistance and adipocytokines. Clin Endocrinol (Oxf). 2015;82:165-177.
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9Zhuang X, Ni Y, Jiang D, Pu Y, Liu X, Chen S, et al. Vaspin as a risk factor of insulin resistance in obstructive sleep apnea-hypopnea syndrome in an animal model. Clin Lab. 2015;61:883-889.
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10Yosunkaya S, Okur HK, Can U, Zamani A, Kutlu R. Impact of continuous positive airway pressure treatment on leptin levels in patients with obstructive sleep apnea syndrome. Metab Syndr Relat Disord. 2015;13:272-277.
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11Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329:454-457.
-
12Schulte DM, Muller N, Neumann K, Oberhauser F, Faust M, Gudelhofer H, et al. Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects. PLOS ONE. 2012;7:e32437.
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13Jura M, Jaroslawska J, Chu DT, Kozak LP. Mest and Sfrp5 are biomarkers for healthy adipose tissue. Biochimie. 2016;124:124-133.
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14Hu W, Li L, Yang M, Luo X, Ran W, Liu D, et al. Circulating Sfrp5 is a signature of obesity-related metabolic disorders and is regulated by glucose and liraglutide in humans. J Clin Endocrinol Metab. 2013;98:290-298.
-
15Hu Z, Deng H, Qu H. Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance. Diabetes Res Clin Pract. 2013;99:391-395.
-
16Miyoshi T, Doi M, Usui S, Iwamoto M, Kajiya M, Takeda K, et al. Low serum level of secreted frizzled-related protein 5, an anti-inflammatory adipokine, is associated with coronary artery disease. Atherosclerosis. 2014;233:454-459.
-
17Carstensen M, Herder C, Kempf K, Erlund I, Martin S, Koenig W, et al. Sfrp5 correlates with insulin resistance and oxidative stress. Eur J Clin Invest. 2013;43:350-357.
-
18Cheng L, Zhang D, Chen B. Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults. Pak J Med Sci. 2015;31:602-605.
-
19Nakamura K, Sano S, Fuster JJ, Kikuchi R, Shimizu I, Ohshima K, et al. Secreted frizzled-related protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury. J Biol Chem. 2016;291:2566-2575.
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20Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008;117:2270-2278.
-
21Predictive values of body mass index with waist circumference to risk factors of related diseases in Chinese adult population. Chin J Epidemiol. 2002;23:5-10.
-
22Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419.
-
23Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab. 2009;296:E333-E342.
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24Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347-2355.
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25Pialoux V, Hanly PJ, Foster GE, Brugniaux JV, Beaudin AE, Hartmann SE, et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am J Respir Crit Care Med. 2009;180:1002-1009.
-
26Zhang DM, Huang R, Xiao Y, Gong FG, Zhong X, Luo JM. Secreted frizzled-related protein 5 (SFRP5) in patients with obstructive sleep apnea. Chin Med Sci J. 2017;32:211-217.
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27Lu YC, Wang CP, Hsu CC, Chiu CA, Yu TH, Hung WC, et al. Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2013;29:551-556.
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28Miyoshi T, Onoue G, Hirohata A, Hirohata S, Usui S, Hina K, et al. Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound. Atherosclerosis. 2010;211:164-169.
-
29Bottner A, Kratzsch J, Muller G, Kapellen TM, Bluher S, Keller E, et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab. 2004;89:4053-4061.
Publication Dates
-
Publication in this collection
13 Dec 2019 -
Date of issue
Nov-Dec 2019
History
-
Received
01 Jan 2018 -
Accepted
02 July 2018