The latest research progress on the relationship between obstructive sleep apnea–hypopnea syndrome and metabolic syndrome

Abstract

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is the most common subtype of sleep-disordered breathing, characterized by symptoms such as snoring, nocturnal sleep disturbances, and excessive daytime sleepiness. OSAHS is defined by recurrent upper airway collapses during sleep, leading to apneas or hypopneas. These episodes result in intermittent nocturnal hypoxia and sleep fragmentation, which provoke sympathetic activation, oxidative stress, and systemic inflammation, ultimately causing chronic damage across multiple bodily systems. OSAHS significantly increases the risk of various cardiovascular and metabolic disorders, including atherosclerosis, hypertension, obesity, insulin resistance, and dyslipidemia. In China, approximately 176 million individuals are estimated to have OSAHS, with about 60 million experiencing moderate to severe forms of the condition. This paper reviews the epidemiological characteristics of OSAHS, the evolution of diagnostic criteria, and the association between OSAHS and metabolic syndrome (MetS), emphasizing the high prevalence of MetS among OSAHS patients. Through cross-sectional analysis, cohort studies, and interventional studies, the complex interactions between OSAHS and MetS are examined, proposing therapeutic strategies to improve these metabolic anomalies, including continuous positive airway pressure therapy and weight management.

Keywords

epidemiology / metabolic syndrome (MetS) / obstructive sleep apnea–hypopnea syndrome (OSAHS)

References

[1] Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687-698.

[2] Malhotra A, Ayappa I, Ayas N, et al. Metrics of sleep apnea severity: beyond the apnea-hypopnea index. Sleep. 2021;44(7).

[3] Azarbarzin A, Sands SA, Taranto-Montemurro L, et al. The sleep apnea-specific hypoxic burden predicts incident heart failure. Chest. 2020;158(2):739-750.

[4] Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997;20(9):705-706.

[5] Kapur V, Strohl KP, Redline S, Iber C, O’connor G, Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath. 2002;6(2):49-54.

[6] Hong PC, Ou Q, Pan MX, et al. [Investigation on the awareness of snoring hazard and prevalence of obstructive sleep apnea among civil servants]. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(7):553-556. Chinese. https://doi.org/10.3760/cma.j.cn112147-20191013-00682

[7] Silva DVE, Alves D, Nóbrega M, et al. Obstructive sleep apnea screening in different age groups: performance of the Berlin, STOP-Bang questionnaires and Epworth Sleepiness Scale. Braz J Otorhinolaryngol. 2023;89(4):101283.

[8] Chiang AA, Khosla S. Consumer wearable sleep trackers: are they ready for clinical use? Sleep Med Clin.. 2023;18(3):311-330.

[9] Xu X, Zeng J, Yang W, et al. Prevalence of metabolic syndrome among the adult population in western China and the association with socioeconomic and individual factors: four cross-sectional studies. BMJ Open. 2022;12(4):e052457.

[10] Lee BJ, Kim JY. Identification of metabolic syndrome using phenotypes consisting of triglyceride levels with anthropometric indices in Korean adults. BMC Endocr Disord. 2020;20(1):29.

[11] Krishnamoorthy Y, Rajaa S, Murali S, Rehman T, Sahoo J, Kar SS. Prevalence of metabolic syndrome among adult population in India: a systematic review and meta-analysis. PLoS One. 2020;15(10):e0240971.

[12] El Bilbeisi AH, Shab-Bidar S, Jackson D, Djafarian K. The prevalence of metabolic syndrome and its related factors among adults in Palestine: a meta-analysis. Ethiop J Health Sci. 2017;27(1):77-84.

[13] Scuteri A, Laurent S, Cucca F, et al. Metabolic syndrome across Europe: different clusters of risk factors. Eur J Prev Cardiol. 2015;22(4):486-491.

[14] Farmanfarma KK, Kaykhaei MA, Mohammadi M, Adineh HA, Ansari-Moghaddam A. The prevalence and trend of metabolic syndrome in the South-East of Iran. J Med Life. 2020;13(4):587-599.

[15] De Siqueira Valadares LT, De Souza LSB, Salgado Júnior VA, de Freitas Bonomo L, de Macedo LR, Silva M. Prevalence of metabolic syndrome in Brazilian adults in the last 10 years: a systematic review and meta-analysis. BMC Publ Health. 2022;22(1):327.

[16] O’Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D. Trends and disparities in cardiometabolic health among U.S. adults, 1999-2018. J Am Coll Cardiol. 2022;80(2):138-151.

[17] Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Global, regional, and country estimates of metabolic syndrome burden in children and adolescents in 2020: a systematic review and modelling analysis. Lancet Child Adolesc Health. 2022;6(3):158-170.

[18] Coughlin SR, Mawdsley L, Mugarza JA, et al. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J. 2004;25(9):735-741.

[19] Chaudhary P, Goyal A, Goel SK, et al. Women with OSA have higher chances of having metabolic syndrome than men: effect of gender on syndrome Z in cross sectional study. Sleep Med. 2021;79:83-87.

[20] Wu WT, Tsai SS, Shih TS, et al. The association between obstructive sleep apnea and metabolic markers and lipid profiles. PLoS One. 2015;10(6):e0130279.

[21] Guo W, Liu Y, Huajun X, et al. Obstructive sleep apnea and metabolic syndrome: a correlation study based on a large clinical database. Chin J Otorhinolaryngol Head Neck Surg. 2021;56(12):1263-1269.

[22] Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med. 2007;3(5):467-472.

[23] Fietze I, Laharnar N, Obst A, et al. Prevalence and association analysis of obstructive sleep apnea with gender and age differences -Results of SHIP-Trend. J Sleep Res. 2019;28(5):e12770.

[24] Drager LF, Lopes HF, Maki-Nunes C, et al. The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One. 2010;5(8):e12065.

[25] Hirotsu C, Haba-Rubio J, Togeiro SM, et al. Obstructive sleep apnoea as a risk factor for incident metabolic syndrome: a joined Episono and HypnoLaus prospective cohorts study. Eur Respir J. 2018;52(5):1801150.

[26] Zhuo Q, Zheng F, Su K, et al. Sleep apnea syndrome increases the risk of metabolic syndrome. Northwest Def Med J. 2016;37(09):568-570.

[27] Monneret D, Barthélémy JC, Hupin D, et al. Serum lipid profile, sleep-disordered breathing and blood pressure in the elderly: a 10-year follow-up of the PROOF-SYNAPSE cohort. Sleep Med. 2017;39:14-22.

[28] Kim DH, Kim B, Han K, Kim SW. The relationship between metabolic syndrome and obstructive sleep apnea syndrome: a nationwide population-based study. Sci Rep. 2021;11(1):8751.

[29] Cattazzo F, Pengo MF, Giontella A, et al. Effect of continuous positive airway pressure on glucose and lipid profiles in patients with obstructive sleep apnoea: a systematic review and meta-analysis of randomized controlled trials. Arch Bronconeumol. 2023;59(6):370-376.

[30] Oyama J, Yamamoto H, Maeda T, Ito A, Node K, Makino N. Continuous positive airway pressure therapy improves vascular dysfunction and decreases oxidative stress in patients with the metabolic syndrome and obstructive sleep apnea syndrome. Clin Cardiol. 2012;35(4):231-236.

[31] Oktay B, Akbal E, Firat H, Ardiç S, Kizilgun M. CPAP treatment in the coexistence of obstructive sleep apnea syndrome and metabolic syndrome, results of one year follow up. Acta Clin Belg. 2009;64(4):329-334.

[32] Hoyos CM, Sullivan DR, Liu PY. Effect of CPAP on the metabolic syndrome: a randomised sham-controlled study. Thorax. 2013;68(6):588-589.

[33] Giampá SQC, Furlan SF, Freitas LS, et al. Effects of CPAP on metabolic syndrome in patients with OSA: a randomized trial. Chest. 2022;161(5):1370-1381.

[34] Hoyos CM, Killick R, Yee BJ, Phillips CL, Grunstein RR, Liu PY. The relationship between excessive daytime cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study. Thorax. 2012;67(12):1081-1089.

[35] Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014;370(24):2265-2275.

[36] Fletcher EC. Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea. Sleep. 2003;26(1):15-19.

[37] Arnaud C, Beguin PC, Lantuejoul S, et al. The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition. Am J Respir Crit Care Med. 2011;184(6):724-731.

[38] Jelic S, Padeletti M, Kawut SM, et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008;117(17):2270-2278.

[39] Lee YS, Kim JW, Osborne O, et al. Increased adipocyte O₂ consumption triggers HIF-1α causing inflammation and insulin resistance in obesity. Cell. 2014;157(6):1339-1352.

[40] Drager LF, Li J, Shin MK, et al. Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea. Eur Heart J. 2012;33(6):783-790.

[41] Schödel J, Ratcliffe PJ. Mechanisms of hypoxia signalling: new implications for nephrology. Nat Rev Nephrol. 2019;15(10):641-659.

[42] Ntambi JM, Miyazaki M. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res. 2004;43(2):91-104.

[43] Barros D, GarcíA-Río F. Obstructive sleep apnea and dyslipidemia: from animal models to clinical evidence. Sleep. 2019;42(3).

[44] Polak J, Shimoda LA, Drager LF, et al. Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure. Sleep. 2013;36(10):1483-1490, 90a-90b.

[45] Murphy AM, Thomas A, Crinion SJ, et al. Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. Eur Respir J. 2017;49(4):1601731.

[46] Shao Y, Lv C, Yuan Q, Wang Q. Levels of serum 25(OH)VD3, HIF-1α VEGF, vWf, and IGF-1 and their correlation in type 2 diabetes patients with different urine albumin creatinine ratio. J Diabetes Res. 2016;2016:1925424.

[47] Nagao A, Kobayashi M, Koyasu S, Chow CCT, Harada H. HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int J Mol Sci. 2019;20(2):238.

[48] Ryan S, Arnaud C, Fitzpatrick SF, Gaucher J, Tamisier R, Pépin JL. Adipose tissue as a key player in obstructive sleep apnoea. Eur Respir Rev. 2019;28(152):190006.

[49] Takasawa S, Shobatake R, Itaya-Hironaka A, et al. Upregulation of IL-8, osteonectin, and myonectin mRNAs by intermittent hypoxia via OCT1-and NRF2-mediated mechanisms in skeletal muscle cells. J Cell Mol Med. 2022;26(24):6019-6031.

[50] Tang SS, Liang CH, Liu YL, et al. Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome. World J Gastroenterol. 2022;28(21):2320-2333.

[51] Abboud F, Kumar R. Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity. J Clin Invest. 2014;124(4):1454-1457.

[52] Takeda Y, Itaya-Hironaka A, Yamauchi A, et al. Intermittent hypoxia upregulates the renin and Cd38 mRNAs in renin-producing cells via the downregulation of miR-203. Int J Mol Sci. 2021;22(18):10127.

[53] Xiong J, Xia M, Yi F, Abais JM, Boini KM, Li PL. Regulation of renin release via cyclic ADP-ribose-mediated signaling: evidence from mice lacking CD38 gene. Cell Physiol Biochem. 2013;31(1):44-55.

[54] Vgontzas AN, Pejovic S, Zoumakis E, et al. Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy. J Clin Endocrinol Metab. 2007;92(11):4199-4207.

[55] Jalilolghadr S, Yazdi Z, Mahram M, et al. Sleep architecture and obstructive sleep apnea in obese children with and without metabolic syndrome: a case control study. Sleep Breath. 2016;20(2):845-851.

[56] Peppard PE, Young T, Palta M, et al. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23):3015-3021.

[57] Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol. 2005;99(4):1592-1599.

[58] Gileles-Hillel A, Almendros I, Khalyfa A, et al. Prolonged exposures to intermittent hypoxia promote visceral white adipose tissue inflammation in a murine model of severe sleep apnea: effect of normoxic recovery. Sleep. 2017;40(3).

[59] Poulain L, Thomas A, Rieusset J, et al. Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J. 2014;43(2):513-522.

RIGHTS & PERMISSIONS

2024 The Author(s). Sleep Research published by John Wiley & Sons Australia, Ltd on behalf of Chinese Sleep Research Society.