, Volume 187, Issue 2, pp 75–81 | Cite as

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

  • Çağlar ÇuhadaroğluEmail author
  • Ayfer Utkusavaş
  • Levent Öztürk
  • Serpil Salman
  • Turhan Ece



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.


Sleep apnea Leptin Insulin resistance Continuous positive airway pressure Lipid 


  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 PubMedCrossRefGoogle 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 152:711–716PubMedGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 81–96Google 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle Scholar
  8. 8.
    American Diabetes Association (1998) Consensus development conference on insulin resistance. Diabetes Care 21:1–5Google 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 100:706–712PubMedGoogle Scholar
  16. 16.
    Saarelainen S, Lahtela J, Kallonen E (1997) Effect of nasal CPAP treatment on insulin sensitivity and plasma leptin. J Sleep Res 6:146–147PubMedGoogle 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 PubMedCrossRefGoogle 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 108:1533–1540PubMedGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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, DCGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle Scholar
  35. 35.
    Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 21:568–576Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Çağlar Çuhadaroğlu
    • 1
    Email author
  • Ayfer Utkusavaş
    • 1
  • Levent Öztürk
    • 2
  • Serpil Salman
    • 3
  • Turhan Ece
    • 1
  1. 1.Department of Chest Diseases, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of PhysiologyTrakya University Faculty of MedicineEdirneTurkey
  3. 3.Department of Endocrinology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations