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Obesity as a mediator linking sleep-disordered breathing to both impaired fasting glucose and type 2 diabetes

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Purpose

To examine whether or not associations between sleep-disordered breathing (SDB) and impaired fasting glucose and type 2 diabetes are mediated by obesity.

Methods

We used cross-sectional data including participants from the Multi-Ethnic Study of Atherosclerosis (MESA). SDB, including obstructive sleep apnea (OSA), hypoxia and sleep fragmentation, was evaluated by polysomnography. Further, five obesity measures related to overall obesity and central obesity were assessed. Mediation analysis was conducted to explore the mediating effect of obesity on these relationships between SDB and impaired fasting glucose and type 2 diabetes.

Results

Among 1615 participants, OSA and hypoxia, including apnea hypopnea index (AHI) ≥ 15, percent of total sleep time (TST) with SaO2 < 90% (TST90), oxygen desaturation index (ODI), and lowest oxygen saturation (SaO2), were significantly associated with impaired fasting glucose and type 2 diabetes. In addition, mean SaO2 was also associated with impaired fasting glucose. Mediation analysis showed that these relationships were significantly mediated by all five obesity measures, where central obesity had greater mediating effect than overall obesity. Proportion of mediation of obesity ranged from 21.5 to 62.5% for impaired fasting glucose and 25.85 to 71.6% for type 2 diabetes, with substantial differences found in the subgroup analysis by gender or race/ethnicity. The consistency of the mediating effect was demonstrated across multiple measures of SDB, obesity, and glucose metabolism.

Conclusion

Obesity, especially central obesity, may play a critical role in the pathway where SDB, including OSA and hypoxia, increases the occurrence of impaired fasting glucose and type 2 diabetes. Weight management is important for patients with SDB to prevent type 2 diabetes.

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Data availability

The data that support the findings of this study are available from the National Heart, Lung, and Blood Institute (NHLBI) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of NHLBI.

References

  1. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL (2002) Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 165:677–682. https://doi.org/10.1164/ajrccm.165.5.2104087

    Article  PubMed  Google Scholar 

  2. Seetho IW, Wilding JP (2014) Sleep-disordered breathing, type 2 diabetes and the metabolic syndrome. Chron Respir Dis 11:257–275. https://doi.org/10.1177/1479972314552806

    Article  PubMed  Google Scholar 

  3. Ip MS, Lam KS, Ho C, Tsang KW, Lam W (2000) Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 118:580–586. https://doi.org/10.1378/chest.118.3.580

    Article  CAS  PubMed  Google Scholar 

  4. Markwald RR, Melanson EL, Smith MR, Higgins J, Perreault L, Eckel RH, Wright KP Jr (2013) Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain. Proc Natl Acad Sci U S A 110:5695–5700. https://doi.org/10.1073/pnas.1216951110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee EJ, Alonso LC, Stefanovski D, Strollo HC, Romano LC, Zou B, Singamsetty S, Yester KA, McGaffin KR, Garcia-Ocana A, O’Donnell CP (2013) Time-dependent changes in glucose and insulin regulation during intermittent hypoxia and continuous hypoxia. Eur J Appl Physiol 113:467–478. https://doi.org/10.1007/s00421-012-2452-3

    Article  CAS  PubMed  Google Scholar 

  6. Drager LF, Li J, Reinke C, Bevans-Fonti S, Jun JC, Polotsky VY (2011) Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity. Obesity (Silver Spring) 19:2167–2174. https://doi.org/10.1038/oby.2011.240

    Article  CAS  PubMed  Google Scholar 

  7. Reutrakul S, Mokhlesi B (2017) Obstructive sleep apnea and diabetes: a state of the art review. Chest 152:1070–1086. https://doi.org/10.1016/j.chest.2017.05.009

    Article  PubMed  PubMed Central  Google Scholar 

  8. Martinez-Ceron E, Fernandez-Navarro I, Garcia-Rio F (2016) Effects of continuous positive airway pressure treatment on glucose metabolism in patients with obstructive sleep apnea. Sleep Med Rev 25:121–130. https://doi.org/10.1016/j.smrv.2015.03.002

    Article  PubMed  Google Scholar 

  9. Seicean S, Kirchner HL, Gottlieb DJ, Punjabi NM, Resnick H, Sanders M, Budhiraja R, Singer M, Redline S (2008) Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: the Sleep Heart Health Study. Diabetes Care 31:1001–1006. https://doi.org/10.2337/dc07-2003

    Article  PubMed  Google Scholar 

  10. Wilson ML (2017) Prediabetes: Beyond the Borderline. Nurs Clin North Am 52:665–677. https://doi.org/10.1016/j.cnur.2017.07.011

    Article  PubMed  Google Scholar 

  11. Wolk R, Shamsuzzaman AS, Somers VK (2003) Obesity, sleep apnea, and hypertension. Hypertension 42:1067–1074. https://doi.org/10.1161/01.HYP.0000101686.98973.A3

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Rimm EB, Stampfer MJ, Willett WC, Hu FB (2005) Comparison of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes among men. Am J Clin Nutr 81:555–563. https://doi.org/10.1093/ajcn/81.3.555

    Article  CAS  PubMed  Google Scholar 

  13. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacob DR Jr, Kronmal R, Liu K, Nelson JC, O’Leary D, Saad MF, Shea S, Szklo M, Tracy RP (2002) Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol 156:871–881. https://doi.org/10.1093/aje/kwf113

    Article  PubMed  Google Scholar 

  14. Chen X, Wang R, Zee P, Lutsey PL, Javaheri S, Alcantara C, Jackson CL, Williams MA, Redline S (2015) Racial/ethnic differences in sleep disturbances: the Multi-Ethnic Study of Atherosclerosis (MESA). Sleep 38:877–888. https://doi.org/10.5665/sleep.4732

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ruehland WR, Rochford PD, O’Donoghue FJ, Pierce RJ, Singh P, Thornton AT (2009) The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index. Sleep 32:150–157. https://doi.org/10.1093/sleep/32.2.150

    Article  PubMed  PubMed Central  Google Scholar 

  16. Malhotra A, Ayappa I, Ayas N, Collop N, Kirsch D, McArdle N, Mehra R, Pack AI, Punjabi N, White DP, Gottlieb DJ (2021) Metrics of sleep apnea severity: beyond the apnea-hypopnea index. Sleep 44(7):zsab030. https://doi.org/10.1093/sleep/zsab030

  17. Sun K, Lin D, Feng Q, Li F, Qi Y, Feng W, Yang C, Yan L, Ren M, Liu D (2019) Assessment of adiposity distribution and its association with diabetes and insulin resistance: a population-based study. Diabetol Metab Syndr 11:51. https://doi.org/10.1186/s13098-019-0450-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomilehto J, Zimmet P, Expert Committee on the D Classification of Diabetes M (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–167. https://doi.org/10.2337/diacare.26.11.3160

    Article  PubMed  Google Scholar 

  19. Kendzerska T, Gershon AS, Hawker G, Tomlinson G, Leung RS (2014) Obstructive sleep apnea and incident diabetes. A historical cohort study. Am J Respir Crit Care Med 190:218–225. https://doi.org/10.1164/rccm.201312-2209OC

    Article  PubMed  Google Scholar 

  20. VanderWeele TJ (2016) Mediation Analysis: A Practitioner’s Guide. Annu Rev Public Health 37:17–32. https://doi.org/10.1146/annurev-publhealth-032315-021402

    Article  PubMed  Google Scholar 

  21. Shaw JE, Punjabi NM, Wilding JP, Alberti KG, Zimmet PZ, International Diabetes Federation Taskforce on E Prevention (2008) Sleep-disordered breathing and type 2 diabetes: a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Res Clin Pract 81:2–12. https://doi.org/10.1016/j.diabres.2008.04.025

    Article  PubMed  Google Scholar 

  22. Matsumoto T, Murase K, Tabara Y, Gozal D, Smith D, Minami T, Tachikawa R, Tanizawa K, Oga T, Nagashima S, Wakamura T, Komenami N, Setoh K, Kawaguchi T, Tsutsumi T, Takahashi Y, Nakayama T, Hirai T, Matsuda F, Chin K (2018) Impact of sleep characteristics and obesity on diabetes and hypertension across genders and menopausal status: the Nagahama study. Sleep 41(7):zsy071. https://doi.org/10.1093/sleep/zsy071

  23. Wilson NRC, Veatch OJ, Johnson SM (2022) On the relationship between diabetes and obstructive sleep apnea: evolution and epigenetics. Biomedicines 10(3):668. https://doi.org/10.3390/biomedicines10030668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rodrigues GD, Fiorelli EM, Furlan L, Montano N, Tobaldini E (2021) Obesity and sleep disturbances: The “chicken or the egg” question. Eur J Intern Med. 92:11–16. https://doi.org/10.1016/j.ejim.2021.04.017

    Article  PubMed  Google Scholar 

  25. Muraki I, Wada H, Tanigawa T (2018) Sleep apnea and type 2 diabetes. J Diabetes Investig 9(5):991–997. https://doi.org/10.1111/jdi.12823

    Article  PubMed  PubMed Central  Google Scholar 

  26. Garcia JM, Sharafkhaneh H, Hirshkowitz M, Elkhatib R, Sharafkhaneh A (2011) Weight and metabolic effects of CPAP in obstructive sleep apnea patients with obesity. Respir Res 12(1):80. https://doi.org/10.1186/1465-9921-12-80

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sabanayagam C, Teppala S, Shankar A (2012) Markers of sleep disordered breathing and diabetes mellitus in a multiethnic sample of us adults: results from the national health and nutrition examination survey (2005-2008). Int J Endocrinol 2012:879134. https://doi.org/10.1155/2012/879134

    Article  PubMed  PubMed Central  Google Scholar 

  28. Valham F, Stegmayr B, Eriksson M, Hagg E, Lindberg E, Franklin KA (2009) Snoring and witnessed sleep apnea is related to diabetes mellitus in women. Sleep Med 10:112–117. https://doi.org/10.1016/j.sleep.2007.11.005

    Article  PubMed  Google Scholar 

  29. Vgontzas A, Chrousos G (2002) Sleep, the hypothalamic-pituitaryadrenal axis, and cytokines: Multiple interactions and disturbances in sleep disorders. Endocrinol Metabol Clinic N A 31:15–36. https://doi.org/10.1016/S0889-8529(01)00005-6

    Article  CAS  Google Scholar 

  30. Chen X, Wang R, Lutsey PL, Zee PC, Javaheri S, Alcántara C, Jackson CL, Szklo M, Punjabi N, Redline S, Williams MA (2016) Racial/ethnic differences in the associations between obesity measures and severity of sleep-disordered breathing: the Multi-Ethnic Study of Atherosclerosis. Sleep Med 26:46–53. https://doi.org/10.1016/j.sleep.2015.06.003

    Article  PubMed  Google Scholar 

  31. Ryan S (2017) Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction. J Physiol 595:2423–2430. https://doi.org/10.1113/JP273312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yilmaz Avci A, Avci S, Lakadamyali H, Can U (2017) Hypoxia and inflammation indicate significant differences in the severity of obstructive sleep apnea within similar apnea-hypopnea index groups. Sleep Breath 21:703–711. https://doi.org/10.1007/s11325-017-1486-5

    Article  PubMed  Google Scholar 

  33. Leinum CJ, Dopp JM, Morgan BJ (2009) Sleep-disordered breathing and obesity: pathophysiology, complications, and treatment. Nutr Clin Pract 24:675–687. https://doi.org/10.1177/0884533609351532

    Article  PubMed  PubMed Central  Google Scholar 

  34. Storz C, Heber SD, Rospleszcz S, Machann J, Sellner S, Nikolaou K, Lorbeer R, Gatidis S, Elser S, Peters A, Schlett CL, Bamberg F (2018) The role of visceral and subcutaneous adipose tissue measurements and their ratio by magnetic resonance imaging in subjects with prediabetes, diabetes and healthy controls from a general population without cardiovascular disease. Br J Radiol 91:20170808. https://doi.org/10.1259/bjr.20170808

    Article  PubMed  PubMed Central  Google Scholar 

  35. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830. https://doi.org/10.1172/JCI19451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kosseifi S, Bailey B, Price R, Roy TM, Byrd RP Jr, Peiris AN (2010) The association between obstructive sleep apnea syndrome and microvascular complications in well-controlled diabetic patients. Mil Med 175:913–916. https://doi.org/10.7205/milmed-d-10-00131

    Article  PubMed  Google Scholar 

  37. Brozyna-Tkaczyk K, Myslinski W, Mosiewicz J (2021) The Assessment of Endothelial Dysfunction among OSA Patients after CPAP Treatment. Medicina (Kaunas) 57(4):310. https://doi.org/10.3390/medicina57040310

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Acknowledgements

This manuscript was prepared using MESA Research Material obtained from the National Heart, Lung, and Blood Institute (NHLBI). The authors appreciate the contributions of the investigators, staff, and participants of the MESA study and NHLBI.

Funding

This project was supported by the National Natural Science Foundation of China (Grant numbers: 82073674 and 81872715).

Author information

Authors and Affiliations

  1. Department of Health Statistics, School of Public Health, Shanxi Medical University, No.56 Xinjian South Road, Taiyuan, 030001, China

    Shuting Chen, Jiale Wang, Juping Wang, Qian Gao & Tong Wang

  2. Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China

    Xiaotian Zhao

  3. Department of Health Promotion and Physical Education, Ithaca College, Ithaca, NY, 14850, USA

    Hongwei Guan

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  1. Shuting Chen
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Contributions

Tong Wang designed the study, provided statistical advice, and contributed to the data management, manuscript reviewing, and editing. Shuting Chen designed the study and contributed to the data analysis and interpretation, figures creation, and drafting, reviewing, and editing of the manuscript. Jiale Wang contributed to the data analysis, reviewing, and editing of the manuscript. Juping Wang and Qian Gao contributed to the critically reviewing and editing of the manuscript. Xiaotian Zhao contributed to the figures creation and manuscript reviewing. Hongwei Guan contributed to the manuscript polishing and reviewing. All authors have read and approved the final manuscript.

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Correspondence to Tong Wang.

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Chen, S., Wang, J., Wang, J. et al. Obesity as a mediator linking sleep-disordered breathing to both impaired fasting glucose and type 2 diabetes. Sleep Breath 27, 1067–1080 (2023). https://doi.org/10.1007/s11325-022-02705-z

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  • DOI: https://doi.org/10.1007/s11325-022-02705-z

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