Effects of Nasal CPAP Treatment on Insulin Resistance, Lipid Profile, and Plasma Leptin in Sleep Apnea



Obstructive sleep apnea has been linked with metabolic syndrome characterized by dyslipidemia, dyscoagulation, hypertension, and diabetes mellitus type 2 and their cardiovascular consequences. This study was designed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on insulin resistance, glucose, and lipid profile, and the relationship between leptin and insulin-resistance parameters in patients with moderate-to-severe obstructive sleep apnea.


In 44 patients, serum cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, leptin, and insulin parameters were measured at baseline and after 8 weeks of CPAP. Insulin resistance index was based on the homeostasis model assessment (HOMA-IR) method. Insulin sensitivity (HOMA-S) and insulin secretion capacity (HOMA-β) also were calculated. Thirteen patients were excluded from statistical analyses due to noncompliant CPAP usage (<4 h night−1).


In 31 patients who used CPAP for ≥4 h night−1, CPAP therapy reduced total cholesterol (P < 0.05), low-density lipoprotein (P < 0.05), and leptin (P < 0.05). Circulating leptin levels showed significant correlation with both HOMA-S and HOMA-IR at baseline and follow-up (P = 0.03 for all). In addition, there was no correlation between HOMA-IR and the severity of sleep apnea, which was shown by apnea-hypopnea index.


In patients with moderate-to-severe obstructive sleep apnea, compliant CPAP usage may improve insulin secretion capacity, reduce leptin, total cholesterol, and low-density lipoprotein levels. Leptin showed significant relationship with insulin resistance, and this relationship remained after 8 weeks of CPAP therapy.

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  1. 1.

    Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235. doi:10.1056/NEJM199304293281704

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Olson LG, King MT, Hensley MJ, Saunders NA (1995) A community study of snoring and sleep-disordered breathing: prevalence. Am J Respir Crit Care Med 152:711–716

    PubMed  CAS  Google Scholar 

  3. 3.

    Vgontzas AN, Bixler EO, Chrousos GP (2003) Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. J Intern Med 254:32–44. doi:10.1046/j.1365-2796.2003.01177.x

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Vgontzas AN, Bixler EO, Chrousos GP (2005) Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 9:211–224. doi:10.1016/j.smrv.2005.01.006

    PubMed  Article  Google Scholar 

  5. 5.

    Ünal M, Öztürk L (2005) The effect of body mass index on the severity of obstructive sleep apnea. In: Ferrera LA (ed) Body mass index and health. Nova Science Publishers, New York, pp 81–96

    Google Scholar 

  6. 6.

    Dancey DR, Hanly PJ, Soong C, Lee B, Shepard J, Hoffstein V (2003) Gender differences in sleep apnea: the role of neck circumference. Chest 123:1544–1550. doi:10.1378/chest.123.5.1544

    PubMed  Article  Google Scholar 

  7. 7.

    Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, Kales A, Chrousos GP (2000) Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 85:1151–1158. doi:10.1210/jc.85.3.1151

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    American Diabetes Association (1998) Consensus development conference on insulin resistance. Diabetes Care 21:1–5

    Google Scholar 

  9. 9.

    Reaven GM (1988) Role of insulin resistance in human disease. Banting Lecture 1988. Diabetes 37:1595–1607. doi:10.2337/diabetes.37.12.1595

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ (1996) Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 334:952–957. doi:10.1056/NEJM199604113341504

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432. doi:10.1038/372425a0

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Frühbeck G, Jebb SA, Prentice AM (1998) Leptin: physiology and pathophysiology. Clin Physiol 18:399–419. doi:10.1046/j.1365-2281.1998.00129.x

    PubMed  Article  Google Scholar 

  13. 13.

    Öztürk L, Ünal M, Tamer L, Çelikoğlu F (2003) The association of the severity of obstructive sleep apnea with plasma leptin levels. Arch Otolaryngol Head Neck Surg 129:538–540. doi:10.1001/archotol.129.5.538

    PubMed  Article  Google Scholar 

  14. 14.

    Kapsimalis F, Varouchakis G, Manousaki A et al (2008) Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea. Lung 186:209–217. doi:10.1007/s00408-008-9082-x

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Chin K, Shimizu K, Nakamura T, Narai N, Masuzaki H, Ogawa Y, Mishima M, Nakamura T, Nakao K, Ohi M (1999) Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation 100:706–712

    PubMed  CAS  Google Scholar 

  16. 16.

    Saarelainen S, Lahtela J, Kallonen E (1997) Effect of nasal CPAP treatment on insulin sensitivity and plasma leptin. J Sleep Res 6:146–147

    PubMed  CAS  Google Scholar 

  17. 17.

    Aizawa-Abe M, Ogawa Y, Masuzaki H, Ebihara K, Satoh N, Iwai H, Matsuoka N, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Nakao K (2000) Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest 105:1243–1252. doi:10.1172/JCI8341

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Konstantinides S, Schafer K, Koschnick S, Loskutoff DJ (2001) Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest 108:1533–1540

    PubMed  CAS  Google Scholar 

  19. 19.

    Murakami T, Iida M, Shima K (1995) Dexamethasone regulates obese expression in isolated rat adipocytes. Biochem Biophys Res Commun 214:1260–1267. doi:10.1006/bbrc.1995.2422

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Wabitsch M, Jensen PB, Blum WF et al (1996) Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 45:1435–1438. doi:10.2337/diabetes.45.10.1435

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Rechtschaffen A, Kales AA (1968) A manual of standardized terminology, techniques and scoring for sleep stages of human subjects. National Institutes of Health publication No.204. Government Printing Office, Washington, DC

    Google Scholar 

  22. 22.

    Gokcel A, Baltali M, Tarim E, Bagis T, Gumurdulu Y, Karakose H, Yalcin F, Akbaba M, Guvener N (2003) Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes Obes Metab 5:126–130. doi:10.1046/j.1463-1326.2003.00253.x

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Wallace TM, Matthews DR (2002) The assessment of insulin resistance in man. Diabet Med 19:527–534. doi:10.1046/j.1464-5491.2002.00745.x

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Ascaso JF, Romero P, Real JT, Lorente RI, Martinez-Valls J, Carmena R (2003) Abdominal obesity, insulin resistance and metabolic syndrome in a southern European population. Eur J Intern Med 14:101–106. doi:10.1016/S0953-6205(03)00022-0

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Segal KR, Landt M, Klein S (1996) Relationship between insulin sensitivity and plasma leptin concentrations in lean and obese males. Diabetes 45:988–991. doi:10.2337/diabetes.45.7.988

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Dorkova Z, Petrasova D, Molcanyiova A, Popovnakova M, Tkacova R (2008) Effects of CPAP on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest 134:686–692. doi:10.1378/chest.08-0556

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Harsch IA, Schahin SP, Radespiel-Troger M et al (2004) Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 169:156–162. doi:10.1164/rccm.200302-206OC

    PubMed  Article  Google Scholar 

  28. 28.

    Comondore VR, Cheema R, Fox J et al (2008) The impact of CPAP on cardiovascular biomarkers in minimally symptomatic patients with obstructive sleep apnea: a pilot feasibility randomized crossover trial. Lung 186:209–217. doi:10.1007/s00408-008-9082-x

    Article  Google Scholar 

  29. 29.

    Ostlund RE, Yang JW, Klein S et al (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 81:3909–3913. doi:10.1210/jc.81.11.3909

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Harsch IA, Konturek PC, Koebnick C, Kuehlein PP, Fuchs FS, Schahin SP, Wiest GH, Hahn EG, Lohmann T, Ficker JH (2003) Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment. Eur Respir J 22:251–257. doi:10.1183/09031936.03.00010103

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Kieffer TJ, Heller RS, Habener JF et al (1996) Leptin receptors expressed on pancreatic beta-cells. Biochem Biophys Res Commun 224:522–527. doi:10.1006/bbrc.1996.1059

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Kolaczynski JW, Nyce MR, Considine TV et al (1996) Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes 45:699–701. doi:10.2337/diabetes.45.5.699

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Buechner NJ, Zidek W, Esser M, Haske M, Sanner BM (2001) Obstructive sleep apnea syndrome. Effects of therapy on dyslipidemia. Somnologie 5:97–102. doi:10.1046/j.1439-054X.2001.01159.x

    Article  Google Scholar 

  34. 34.

    Mazzone T, Foster D, Chait A (1984) In vivo stimulation of low-density lipoprotein degradation by insulin. Diabetes 33:333–338. doi:10.2337/diabetes.33.4.333

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 21:568–576

    CAS  Google Scholar 

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Correspondence to Çağlar Çuhadaroğlu.

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Çuhadaroğlu, Ç., Utkusavaş, A., Öztürk, L. et al. Effects of Nasal CPAP Treatment on Insulin Resistance, Lipid Profile, and Plasma Leptin in Sleep Apnea. Lung 187, 75–81 (2009). https://doi.org/10.1007/s00408-008-9131-5

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  • Sleep apnea
  • Leptin
  • Insulin resistance
  • Continuous positive airway pressure
  • Lipid