This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200302-206OCv1 200302-206OCv2 169/2/156    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harsch, I. A. Articles by Ficker, J. H. Search for Related Content PubMed PubMed Citation Articles by Harsch, I. A. Articles by Ficker, J. H.

Continuous Positive Airway Pressure Treatment Rapidly Improves Insulin Sensitivity in Patients with Obstructive Sleep Apnea Syndrome

Department of Medicine I; Department of Medical Informatics, Biometrics, and Epidemiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen; Department of Medicine 3, Klinikum Nürnberg, Nuremberg, Germany

Correspondence and requests for reprints should be addressed to Igor Alexander Harsch, M.D., Department of Medicine I, Friedrich-Alexander University, Division of Respiratory Medicine and Division of Endocrinology and Metabolism, Ulmenweg 18, 91054 Erlangen, Germany. E-mail: igor.harsch{at}med1.imed.uni-erlangen.de

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea–hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 ± 4.20 baseline versus 6.79 ± 4.91 µmol/kg · min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m² than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.

Key Words: obstructive sleep apnea syndrome • continuous positive airway pressure treatment • insulin sensitivity • obesity • leptin

This article has been cited by other articles:

				P. Levy From the author: Eur. Respir. J., November 1, 2009; 34(5): 1210 - 1211. [Full Text] [PDF]

				D. E Henley, F. Buchanan, R. Gibson, J. A Douthwaite, S. A Wood, W. W Woltersdorf, J. R Catterall, and S. L Lightman Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy J. Endocrinol., October 1, 2009; 203(1): 181 - 188. [Abstract] [Full Text] [PDF]

				P. Levy, M. R. Bonsignore, and J. Eckel Sleep, sleep-disordered breathing and metabolic consequences Eur. Respir. J., July 1, 2009; 34(1): 243 - 260. [Abstract] [Full Text] [PDF]

				M. R. Bonsignore and J. Eckel Metabolic aspects of obstructive sleep apnoea syndrome Eur. Respir. Rev., June 1, 2009; 18(112): 113 - 124. [Abstract] [Full Text] [PDF]

				V. Y. Polotsky, S. P. Patil, V. Savransky, A. Laffan, S. Fonti, L. A. Frame, K. E. Steele, M. A. Schweizter, J. M. Clark, M. S. Torbenson, et al. Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity Am. J. Respir. Crit. Care Med., February 1, 2009; 179(3): 228 - 234. [Abstract] [Full Text] [PDF]

				R. D. Vorona Sleep, Sleep Disorders, and the Endocrine System ACCP Sleep Med Brd Rev, January 1, 2009; 4(0): 163 - 184. [Full Text] [PDF]

				A Barcelo, F Barbe, M de la Pena, P Martinez, J B Soriano, J Pierola, and A G N Agusti Insulin resistance and daytime sleepiness in patients with sleep apnoea Thorax, November 1, 2008; 63(11): 946 - 950. [Abstract] [Full Text] [PDF]

				P. Levy, J-L. Pepin, C. Arnaud, R. Tamisier, J-C. Borel, M. Dematteis, D. Godin-Ribuot, and C. Ribuot Intermittent hypoxia and sleep-disordered breathing: current concepts and perspectives Eur. Respir. J., October 1, 2008; 32(4): 1082 - 1095. [Abstract] [Full Text] [PDF]

				Z. Dorkova, D. Petrasova, A. Molcanyiova, M. Popovnakova, and R. Tkacova Effects of Continuous Positive Airway Pressure on Cardiovascular Risk Profile in Patients With Severe Obstructive Sleep Apnea and Metabolic Syndrome Chest, October 1, 2008; 134(4): 686 - 692. [Abstract] [Full Text] [PDF]

				E. Tasali, E. Van Cauter, L. Hoffman, and D. A. Ehrmann Impact of Obstructive Sleep Apnea on Insulin Resistance and Glucose Tolerance in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3878 - 3884. [Abstract] [Full Text] [PDF]

				N. Nakra, S. Bhargava, J. Dzuira, S. Caprio, and A. Bazzy-Asaad Sleep-Disordered Breathing in Children With Metabolic Syndrome: The Role of Leptin and Sympathetic Nervous System Activity and the Effect of Continuous Positive Airway Pressure Pediatrics, September 1, 2008; 122(3): e634 - e642. [Abstract] [Full Text] [PDF]

				J. Theorell-Haglow, C. Berne, C. Janson, and E. Lindberg Obstructive sleep apnoea is associated with decreased insulin sensitivity in females Eur. Respir. J., May 1, 2008; 31(5): 1054 - 1060. [Abstract] [Full Text] [PDF]

				S. Seicean, H. L. Kirchner, D. J. Gottlieb, N. M. Punjabi, H. Resnick, M. Sanders, R. Budhiraja, M. Singer, and S. Redline Sleep-Disordered Breathing and Impaired Glucose Metabolism in Normal-Weight and Overweight/Obese Individuals: The Sleep Heart Health Study Diabetes Care, May 1, 2008; 31(5): 1001 - 1006. [Abstract] [Full Text] [PDF]

				I A Harsch, E G Hahn, and S Pour Schahin Effect of CPAP on insulin resistance in patients with obstructive sleep apnoea and type 2 diabetes Thorax, April 1, 2008; 63(4): 384 - 385. [Full Text] [PDF]

				J. M. Golbin, V. K. Somers, and S. M. Caples Obstructive Sleep Apnea, Cardiovascular Disease, and Pulmonary Hypertension Proceedings of the ATS, February 15, 2008; 5(2): 200 - 206. [Abstract] [Full Text] [PDF]

				E. Tasali and M. S. M. Ip Obstructive Sleep Apnea and Metabolic Syndrome: Alterations in Glucose Metabolism and Inflammation Proceedings of the ATS, February 15, 2008; 5(2): 207 - 217. [Abstract] [Full Text] [PDF]

				E. Tasali, B. Mokhlesi, and E. Van Cauter Obstructive Sleep Apnea and Type 2 Diabetes*: Interacting Epidemics Chest, February 1, 2008; 133(2): 496 - 506. [Abstract] [Full Text] [PDF]

				T. Yokoe, L. C. Alonso, L. C. Romano, T. C. Rosa, Robert. M. O'Doherty, A. Garcia-Ocana, K. Minoguchi, and C. P. O'Donnell Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic {beta}-cell replication in mice J. Physiol., February 1, 2008; 586(3): 899 - 911. [Abstract] [Full Text] [PDF]

				G. Pillar and N. Shehadeh Abdominal Fat and Sleep Apnea: The chicken or the egg? Diabetes Care, February 1, 2008; 31(Supplement_2): S303 - S309. [Abstract] [Full Text] [PDF]

				I. A. Harsch Metabolic disturbances in patients with obstructive sleep apnoea syndrome Eur. Respir. Rev., December 1, 2007; 16(106): 196 - 202. [Abstract] [Full Text] [PDF]

				S. D West, D. J Nicoll, T. M Wallace, D. R Matthews, and J. R Stradling Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes Thorax, November 1, 2007; 62(11): 969 - 974. [Abstract] [Full Text] [PDF]

				L. F. Drager, L. A. Bortolotto, A. C. Figueiredo, E. M. Krieger, and G. Lorenzi-Filho Effects of Continuous Positive Airway Pressure on Early Signs of Atherosclerosis in Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., October 1, 2007; 176(7): 706 - 712. [Abstract] [Full Text] [PDF]

				W. T. McNicholas Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1666 - R1670. [Abstract] [Full Text] [PDF]

				G. Parati, C. Lombardi, and K. Narkiewicz Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1671 - R1683. [Abstract] [Full Text] [PDF]

				S. Redline, A. Storfer-Isser, C. L. Rosen, N. L. Johnson, H. L. Kirchner, J. Emancipator, and A. M. Kibler Association between Metabolic Syndrome and Sleep-disordered Breathing in Adolescents Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 401 - 408. [Abstract] [Full Text] [PDF]

				E. Kelly, G. Cullen, and C. McGurk Obstructive sleep apnoea in patients with type 2 diabetes Thorax, July 1, 2007; 62(7): 651 - 651. [Full Text] [PDF]

				E. R. Chasens Obstructive Sleep Apnea, Daytime Sleepiness, and Type 2 Diabetes The Diabetes Educator, May 1, 2007; 33(3): 475 - 482. [Abstract] [Full Text] [PDF]

				M. Kono, K. Tatsumi, T. Saibara, A. Nakamura, N. Tanabe, Y. Takiguchi, and T. Kuriyama Obstructive Sleep Apnea Syndrome Is Associated With Some Components of Metabolic Syndrome Chest, May 1, 2007; 131(5): 1387 - 1392. [Abstract] [Full Text] [PDF]

				N. Iiyori, L. C. Alonso, J. Li, M. H. Sanders, A. Garcia-Ocana, R. M. O'Doherty, V. Y. Polotsky, and C. P. O'Donnell Intermittent Hypoxia Causes Insulin Resistance in Lean Mice Independent of Autonomic Activity Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 851 - 857. [Abstract] [Full Text] [PDF]

				S. R. Coughlin, L. Mawdsley, J. A. Mugarza, J. P. H. Wilding, and P. M. A. Calverley Cardiovascular and metabolic effects of CPAP in obese males with OSA Eur. Respir. J., April 1, 2007; 29(4): 720 - 727. [Abstract] [Full Text] [PDF]

				S. G. Kang, A. L. Brown, and J. H. Chung Oxygen Tension Regulates the Stability of Insulin Receptor Substrate-1 (IRS-1) through Caspase-mediated Cleavage J. Biol. Chem., March 2, 2007; 282(9): 6090 - 6097. [Abstract] [Full Text] [PDF]

				W. T. McNicholas, M. R. Bonsignore, and the Management Committee of EU COST ACTION B26 Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities Eur. Respir. J., January 1, 2007; 29(1): 156 - 178. [Abstract] [Full Text] [PDF]

				R. Wolk and V. K. Somers Sleep Apnoea & Hypertension: Physiological bases for a causal relation: Sleep and the metabolic syndrome Exp Physiol, January 1, 2007; 92(1): 67 - 78. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Third Annual World Congress on the Insulin Resistance Syndrome: Associated conditions. Diabetes Care, September 1, 2006; 29(9): 2165 - 2174. [Full Text] [PDF]

				N T Ayas, G B J Mancini, and J Fleetham Does CPAP delay the development of cardiovascular disease in patients with obstructive sleep apnoea hypopnoea? Thorax, June 1, 2006; 61(6): 459 - 460. [Full Text] [PDF]

				Investigate Sleep Profiles of Patients With Diabetes DOC News, March 1, 2006; 3(3): 5 - 5. [Full Text]

				E. Tasali, E. Van Cauter, and D. A. Ehrmann Relationships between Sleep Disordered Breathing and Glucose Metabolism in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 36 - 42. [Abstract] [Full Text] [PDF]

				A. I. Pack Advances in Sleep-disordered Breathing Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 7 - 15. [Abstract] [Full Text] [PDF]

				K. J. Reichmuth, D. Austin, J. B. Skatrud, and T. Young Association of Sleep Apnea and Type II Diabetes: A Population-based Study Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1590 - 1595. [Abstract] [Full Text] [PDF]

				M. Arzt, T. Young, L. Finn, J. B. Skatrud, and T. D. Bradley Association of Sleep-disordered Breathing and the Occurrence of Stroke Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1447 - 1451. [Abstract] [Full Text] [PDF]

				N. M. Punjabi and V. Y. Polotsky Disorders of glucose metabolism in sleep apnea J Appl Physiol, November 1, 2005; 99(5): 1998 - 2007. [Abstract] [Full Text] [PDF]

				K. Spiegel, K. Knutson, R. Leproult, E. Tasali, and E. V. Cauter Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes J Appl Physiol, November 1, 2005; 99(5): 2008 - 2019. [Abstract] [Full Text] [PDF]

				S. M. Caples, A. S. Gami, and V. K. Somers Obstructive Sleep Apnea Focus, October 1, 2005; 3(4): 557 - 567. [Full Text] [PDF]

				L J Cormican and A Williams Sleep disordered breathing and its treatment in congestive heart failure Heart, October 1, 2005; 91(10): 1265 - 1270. [Abstract] [Full Text] [PDF]

				J. Li, L. N. Thorne, N. M. Punjabi, C.-K. Sun, A. R. Schwartz, P. L. Smith, R. L. Marino, A. Rodriguez, W. C. Hubbard, C. P. O'Donnell, et al. Intermittent Hypoxia Induces Hyperlipidemia in Lean Mice Circ. Res., September 30, 2005; 97(7): 698 - 706. [Abstract] [Full Text] [PDF]

				R. Tauman, L. M. O'Brien, A. Ivanenko, and D. Gozal Obesity Rather Than Severity of Sleep-Disordered Breathing as the Major Determinant of Insulin Resistance and Altered Lipidemia in Snoring Children Pediatrics, July 1, 2005; 116(1): e66 - e73. [Abstract] [Full Text] [PDF]

				T. D. Bradley, Y. E. Miller, F. J. Martinez, D. C. Angus, W. MacNee, and E. Abraham Interstitial Lung Disease, Lung Cancer, Lung Transplantation, Pulmonary Vascular Disorders, and Sleep-disordered Breathing in AJRCCM in 2004 Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 675 - 685. [Full Text] [PDF]

				S. Teramoto, H. Yamamoto, Y. Yamaguchi, R. Namba, and Y. Ouchi Obstructive Sleep Apnea Causes Systemic Inflammation and Metabolic Syndrome Chest, March 1, 2005; 127(3): 1074 - 1075. [Full Text] [PDF]

				A. R. Babu, J. Herdegen, L. Fogelfeld, S. Shott, and T. Mazzone Type 2 Diabetes, Glycemic Control, and Continuous Positive Airway Pressure in Obstructive Sleep Apnea Arch Intern Med, February 28, 2005; 165(4): 447 - 452. [Abstract] [Full Text] [PDF]

				S. M. Caples, A. S. Gami, and V. K. Somers Obstructive Sleep Apnea Ann Intern Med, February 1, 2005; 142(3): 187 - 197. [Full Text] [PDF]

				E. H. Schlenker, Y. Shi, J. Wipf, D. S. Martin, and C. K. Kost Jr. Fructose feeding and intermittent hypoxia affect ventilatory responsiveness to hypoxia and hypercapnia in rats J Appl Physiol, October 1, 2004; 97(4): 1387 - 1394. [Abstract] [Full Text] [PDF]

				I. A. Harsch, S. P. Schahin, and R. Wiedmann Multiple Symmetric Lipomatosis: A Paradigm of Metabolically Innocent Obesity?: Response to Haap et al. Diabetes Care, July 1, 2004; 27(7): 1849 - 1850. [Full Text] [PDF]

				M. Haap, C. Thamer, H.-U. Haring, R. M. Szeimies, and M. Stumvoll Multiple Symmetric Lipomatosis: A Paradigm of Metabolically Innocent Obesity?: Response to Harsch, Schahin, and Wiedmann Diabetes Care, July 1, 2004; 27(7): 1850 - 1850. [Full Text] [PDF]

				K. M. Oltmanns, H. Gehring, S. Rudolf, B. Schultes, S. Rook, U. Schweiger, J. Born, H. L. Fehm, and A. Peters Hypoxia Causes Glucose Intolerance in Humans Am. J. Respir. Crit. Care Med., June 1, 2004; 169(11): 1231 - 1237. [Abstract] [Full Text] [PDF]

				N. M. Punjabi Improvement of Metabolic Function in Sleep Apnea: The Power of Positive Pressure Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 139 - 140. [Full Text] [PDF]