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Published in: Diabetes Therapy 4/2019

Open Access 01-08-2019 | Sleep Apnea | Original Research

Association of OSAHS Hypoxia Indicators with Early Renal Injury and Serum Fibroblast Growth Factor 21 in Obese Type 2 Diabetic Patients

Authors: Weinan Yu, Xiaoqing Wang, Yaojun Ni, De Huai, Hairong Hao, Qingjun Li, Ziyu Liu, Surong Wen, Liang Cheng, Wen Hu

Published in: Diabetes Therapy | Issue 4/2019

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Abstract

Objective

This study aimed to explore the association of obstructive sleep apnea-hypopnea syndrome (OSAHS) hypoxia indicators with early renal injury and serum fibroblast growth factor 21 (FGF21) in obese type 2 diabetic patients.

Methods

A total of 109 obese patients with type 2 diabetes mellitus (T2DM) were recruited, including 70 males and 39 females, with an average age of 52.77 ± 13.57 years and average BMI of 29.08 ± 4.36 kg/m2. Overnight sleep monitoring was performed with a portable monitor to record respiratory parameters [apnea-hypopnea index (AHI), oxygen desaturation index (ODI), lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2/MPO2) and cumulative time of oxygen saturation < 90% (CT < 90%)]. Ultrasonography was done to detect the quantitative liver fat content (LFC). The urine microalbumin and creatinine ratio (ACR) were determined by immunoturbidimetry. FGF21 was measured at baseline by enzyme-linked immunosorbent assay. Patients were divided into the proteinuria group (n = 42) and non-proteinuria group (n = 67). Correlation analysis and multivariate linear regression analysis were used to analyze the related data. In addition, patients were divided into the T2DM without OSAHS group (n = 16) and T2DM with OSAHS group (n = 93) according to the AHI value. The correlation analysis was used to assess the relationship between FGF21 and clinical variables.

Results

(1) ACR positively correlated with waist circumference (WC), AHI, ODI, CT < 90% and LFC, but negatively with MSaO2 and LSaO2. (2) AHI, ODI, CT < 90% and LFC were independent risk factors for ACR, LSaO2 and MSaO2 was a protective factor. (3) Serum FGF21 decreased in the OSAHS group compared with the non-OSAHS group. After adjustment for age, WC and TG, FGF21 correlated negatively with AHI, but positively with MSaO2.

Conclusions

AHI, ODI, CT < 90% and LFC are independent risk factors for ACR. FGF21 is associated with hypoxia indicators, and improving OSAHS status and reducing liver fat content may be helpful for the prevention and treatment of early diabetic nephropathy (DN).

Clinical Trial Registration Number

ChiCTR-IOR-15006225.
Literature
1.
go back to reference Bakris GL. Recognition, pathogenesis, and treatment of different stages of nephropathy in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2011;86:444–56.CrossRef Bakris GL. Recognition, pathogenesis, and treatment of different stages of nephropathy in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2011;86:444–56.CrossRef
2.
go back to reference Afghahi H, Cederholm J, Eliasson B, et al. Risk factors for the development of albuminuria and renal impairment in type 2 diabetesdthe Swedish National Diabetes Register (NDR). Nephrol Dial Transplant. 2011;26:1236–43.CrossRef Afghahi H, Cederholm J, Eliasson B, et al. Risk factors for the development of albuminuria and renal impairment in type 2 diabetesdthe Swedish National Diabetes Register (NDR). Nephrol Dial Transplant. 2011;26:1236–43.CrossRef
3.
go back to reference Caliskan Y, Kiryluk K. Novel biomarkers in glomerular disease. Adv Chronic Kidney Dis. 2014;21:205–16.CrossRef Caliskan Y, Kiryluk K. Novel biomarkers in glomerular disease. Adv Chronic Kidney Dis. 2014;21:205–16.CrossRef
4.
go back to reference Crawford JA, Montevecchi F, Vicini C, Magnuson JS. Transoral robotic sleep surgery: the obstructive sleep apnea-hypopnea syndrome. Otolaryngol Clin North Am. 2014;47(3):397–406.CrossRef Crawford JA, Montevecchi F, Vicini C, Magnuson JS. Transoral robotic sleep surgery: the obstructive sleep apnea-hypopnea syndrome. Otolaryngol Clin North Am. 2014;47(3):397–406.CrossRef
5.
go back to reference He Quanzhen, Chen Baoyuan. Interpretation of the guidelines for the diagnosis and treatment of obstructive sleep apnea hypopnea syndrome (2011 revised edition) [J]. Chin J Tuberc Respir Dis. 2012;35(1):7–8. He Quanzhen, Chen Baoyuan. Interpretation of the guidelines for the diagnosis and treatment of obstructive sleep apnea hypopnea syndrome (2011 revised edition) [J]. Chin J Tuberc Respir Dis. 2012;35(1):7–8.
6.
go back to reference Zhang P, Zhang R, Zhao F, et al. The prevalence and characteristics of obstructive sleep apnea in hospitalized patients with type 2 diabetes in China[J]. J Sleep Res. 2016;25(1):39–46.CrossRef Zhang P, Zhang R, Zhao F, et al. The prevalence and characteristics of obstructive sleep apnea in hospitalized patients with type 2 diabetes in China[J]. J Sleep Res. 2016;25(1):39–46.CrossRef
7.
go back to reference Resnick HE, Redline S, Shahar E, et al. Diabetes and sleep disturbances: findings from the Sleep Heart Health Study. Diabetes Care. 2003;26:702–9.CrossRef Resnick HE, Redline S, Shahar E, et al. Diabetes and sleep disturbances: findings from the Sleep Heart Health Study. Diabetes Care. 2003;26:702–9.CrossRef
8.
go back to reference Aronsohn RS, Whitmore H, Van Cauter E, Tasali E. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med. 2010;181:507–13.CrossRef Aronsohn RS, Whitmore H, Van Cauter E, Tasali E. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med. 2010;181:507–13.CrossRef
9.
go back to reference He Q, Yang Q, Zhou Q, et al. Effects of varying degrees of intermittent hypoxia on proinflammatory cytokines and adipokines in rats and 3T3-L1 adipocytes. PLoS One. 2014;9(1):e86326.CrossRef He Q, Yang Q, Zhou Q, et al. Effects of varying degrees of intermittent hypoxia on proinflammatory cytokines and adipokines in rats and 3T3-L1 adipocytes. PLoS One. 2014;9(1):e86326.CrossRef
10.
go back to reference Kim HW, Lee JE, Cha JJ, et al. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology. 2013;154:3366–76.CrossRef Kim HW, Lee JE, Cha JJ, et al. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology. 2013;154:3366–76.CrossRef
11.
go back to reference Campos I, Chan L, Zhang H, et al. Intradialytic hypoxemia in chronic hemodialysis patients. Blood Purif. 2016;41(1–3):177–87.CrossRef Campos I, Chan L, Zhang H, et al. Intradialytic hypoxemia in chronic hemodialysis patients. Blood Purif. 2016;41(1–3):177–87.CrossRef
12.
go back to reference Jian WX, Peng WH, Jin J, et al. Association between serum fibroblast growth factor 21 and diabetic nephropathy. Metab Clin Exp. 2012;61:853–9.CrossRef Jian WX, Peng WH, Jin J, et al. Association between serum fibroblast growth factor 21 and diabetic nephropathy. Metab Clin Exp. 2012;61:853–9.CrossRef
13.
go back to reference Chinese Medical Association Diabetes Branch. China guidelines for type 2 diabetes prevention (2017 edition). Chin J Diabetes. 2018;10(1):4–67.CrossRef Chinese Medical Association Diabetes Branch. China guidelines for type 2 diabetes prevention (2017 edition). Chin J Diabetes. 2018;10(1):4–67.CrossRef
14.
go back to reference Working Group on Obesity in China. Guidelines for prevention and control of overweight and obesity in adults in China. J Nutr. 2004;26(1):1–4. Working Group on Obesity in China. Guidelines for prevention and control of overweight and obesity in adults in China. J Nutr. 2004;26(1):1–4.
15.
go back to reference Microvascular Complications Group of Diabetes Branch of Chinese Medical Association. Expert consensus on prevention and treatment of diabetic nephropathy (2014 edition). Chin J Diabetes Mellitus. 2014;6(11):792–801. Microvascular Complications Group of Diabetes Branch of Chinese Medical Association. Expert consensus on prevention and treatment of diabetic nephropathy (2014 edition). Chin J Diabetes Mellitus. 2014;6(11):792–801.
16.
go back to reference Mather K, Kim C, Christophi C, et al. Steroid sex hormones, sex hormone binding globulin and diabetes incidence in the Diabetes Prevention Program. J Clin Endocrinol Metabol. 2015;2015:jc.2015–328. Mather K, Kim C, Christophi C, et al. Steroid sex hormones, sex hormone binding globulin and diabetes incidence in the Diabetes Prevention Program. J Clin Endocrinol Metabol. 2015;2015:jc.2015–328.
17.
go back to reference Hui-Ming S, Dan X, Jia LI, et al. Clinical value of ultrasonic quantitative detection of liver fat content in patients with type 2 diabetes mellitus. Chin J Diabetes. 2014;22(11):966–9. Hui-Ming S, Dan X, Jia LI, et al. Clinical value of ultrasonic quantitative detection of liver fat content in patients with type 2 diabetes mellitus. Chin J Diabetes. 2014;22(11):966–9.
18.
go back to reference Tahrani AA. Obstructive sleep apnoea in diabetes: does it matter? Diab Vasc Dis Res. 2017;7:1479164117714397. Tahrani AA. Obstructive sleep apnoea in diabetes: does it matter? Diab Vasc Dis Res. 2017;7:1479164117714397.
19.
go back to reference Mao S, Ren X, Zhang J. The emerging role of fibroblast growth factor 21 in diabetic nephropathy. J Recept Signal Transduct Res. 2016;36(6):1–7.CrossRef Mao S, Ren X, Zhang J. The emerging role of fibroblast growth factor 21 in diabetic nephropathy. J Recept Signal Transduct Res. 2016;36(6):1–7.CrossRef
20.
go back to reference Wen-Juan C, Yang LI, Lan M, et al. The value of urinary albumin-to-creatinine ratio in the early diagnosis of diabetic kidney disease. Chin J Lab Diagnosis. 2013;17(9):1650–3. Wen-Juan C, Yang LI, Lan M, et al. The value of urinary albumin-to-creatinine ratio in the early diagnosis of diabetic kidney disease. Chin J Lab Diagnosis. 2013;17(9):1650–3.
21.
go back to reference Kaplan MJ. Cardiovascular complications of rheumatoid arthritis: assessment, prevention, and treatment. Rheum Dis Clin N Am. 2010;36(2):405–26.CrossRef Kaplan MJ. Cardiovascular complications of rheumatoid arthritis: assessment, prevention, and treatment. Rheum Dis Clin N Am. 2010;36(2):405–26.CrossRef
22.
go back to reference Faulx MD, Storferisser A, Kirchner HL, et al. Obstructive sleep apnea is associated with increased urinary albumin excretion. Sleep. 2007;30(7):923.CrossRef Faulx MD, Storferisser A, Kirchner HL, et al. Obstructive sleep apnea is associated with increased urinary albumin excretion. Sleep. 2007;30(7):923.CrossRef
23.
go back to reference Buyukaydin B, Akkoyunlu ME, Kazancioglu R, et al. The effect of sleep apnea syndrome on the development of diabetic nephropathy in patients with type 2 diabetes. Diabetes Res Clin Pract. 2012;98:1.CrossRef Buyukaydin B, Akkoyunlu ME, Kazancioglu R, et al. The effect of sleep apnea syndrome on the development of diabetic nephropathy in patients with type 2 diabetes. Diabetes Res Clin Pract. 2012;98:1.CrossRef
24.
go back to reference Taleb N, Salti H, Al-Mokaddam M, et al. Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon. Ann Saudi Med. 2008;28(6):420–5.CrossRef Taleb N, Salti H, Al-Mokaddam M, et al. Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon. Ann Saudi Med. 2008;28(6):420–5.CrossRef
25.
go back to reference Zhang R, Guo X, Guo L, et al. Prevalence and associated factors of obstructive sleep apnea in hospitalized patients with type 2 diabetes in Beijing. China J Diabetes. 2015;7(1):16–23.CrossRef Zhang R, Guo X, Guo L, et al. Prevalence and associated factors of obstructive sleep apnea in hospitalized patients with type 2 diabetes in Beijing. China J Diabetes. 2015;7(1):16–23.CrossRef
26.
go back to reference Furukawa S, Saito I, Yamamoto S, et al. Nocturnal intermittent hypoxia as an associated risk factor for microalbuminuria in Japanese patients with type 2 diabetes mellitus. Eur J Endocrinol. 2013;169(2):239–46.CrossRef Furukawa S, Saito I, Yamamoto S, et al. Nocturnal intermittent hypoxia as an associated risk factor for microalbuminuria in Japanese patients with type 2 diabetes mellitus. Eur J Endocrinol. 2013;169(2):239–46.CrossRef
27.
go back to reference Sim JJ, Rasgon SA, Derose SF. Review article: managing sleep apnoea in kidney diseases. Nephrology. 2010;15(2):146–52.CrossRef Sim JJ, Rasgon SA, Derose SF. Review article: managing sleep apnoea in kidney diseases. Nephrology. 2010;15(2):146–52.CrossRef
28.
go back to reference Hall IE, Kashgarian M, Moeckel GW, et al. Resolution of proteinuria in a patient with focal segmental glomerulosclerosis following BiPAP initiation for obesity hypoventilation syndrome [J]. Clin Nephrol. 2012;77(1):62.CrossRef Hall IE, Kashgarian M, Moeckel GW, et al. Resolution of proteinuria in a patient with focal segmental glomerulosclerosis following BiPAP initiation for obesity hypoventilation syndrome [J]. Clin Nephrol. 2012;77(1):62.CrossRef
29.
go back to reference Lin Z, Zhou Z, Liu Y, et al. Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese. PLoS One. 2011;6:e18398.CrossRef Lin Z, Zhou Z, Liu Y, et al. Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese. PLoS One. 2011;6:e18398.CrossRef
30.
go back to reference Liu Y, Wang C, Wang Y, et al. Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells. Toxicol Appl Pharmacol. 2012;264(2):212–21.CrossRef Liu Y, Wang C, Wang Y, et al. Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells. Toxicol Appl Pharmacol. 2012;264(2):212–21.CrossRef
Metadata
Title
Association of OSAHS Hypoxia Indicators with Early Renal Injury and Serum Fibroblast Growth Factor 21 in Obese Type 2 Diabetic Patients
Authors
Weinan Yu
Xiaoqing Wang
Yaojun Ni
De Huai
Hairong Hao
Qingjun Li
Ziyu Liu
Surong Wen
Liang Cheng
Wen Hu
Publication date
01-08-2019
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 4/2019
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-019-0639-x

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