Sleep and Breathing

, Volume 17, Issue 1, pp 403–409 | Cite as

Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea

  • Trent A. Hargens
  • Stephen G. Guill
  • Anthony S. Kaleth
  • Sharon M. Nickols-Richardson
  • Larry E. Miller
  • Donald Zedalis
  • John M. Gregg
  • Frank Gwazdauskas
  • William G. Herbert
Original Article



Obstructive sleep apnea (OSA) increases the risk for insulin resistance (IR). The mechanisms that link the two are not clear and are frequently confounded by obesity. OSA is associated with alterations in adipose-derived hormones (adipokines) that increase IR; however, previous studies have focused on middle-aged and older adults. The objective of this study was to determine if IR and alterations in adipokines exist in young men with OSA, independent of obesity.


Subjects were assigned into the following groups based on body mass index and presence of OSA: obese with OSA (OSA, n = 12), obese without OSA (NOSA, n = 18), and normal weight without OSA (CON, n = 15). Fasting blood was obtained for batch analysis of biomarkers of IR. The homeostasis model assessment (HOMA) method was used to assess IR.


HOMA and leptin were higher in the OSA group than the CON group. There were no differences in insulin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) between the OSA and NOSA groups. Adiponectin was lower in the OSA group vs. NOSA and CON; however, when controlled for central abdominal fat (CAF), the difference was nullified. When controlled for total body adiposity, however, CAF was 24 % higher in the subjects with OSA vs. subjects without OSA.


These findings suggest that excess CAF in young men with OSA may contribute to risk for type 2 diabetes indirectly by a degree that would otherwise not be reached through obesity, although further research is needed.


Obstructive sleep apnea Insulin resistance Adiponectin Leptin Obesity 



This research was supported, in part, by a grant from the ResMed Corporation in San Diego, CA and the ResMed Foundation in Yorba Linda, CA.


  1. 1.
    Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165(9):1217–1239PubMedCrossRefGoogle Scholar
  2. 2.
    Malhotra A, White DP (2002) Obstructive sleep apnoea. Lancet 360(9328):237–245PubMedCrossRefGoogle Scholar
  3. 3.
    Peppard PE, Young T, Palta M, Skatrud J (2000) Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 342(19):1378–1384PubMedCrossRefGoogle Scholar
  4. 4.
    Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE (2004) Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 160(6):521–530PubMedCrossRefGoogle Scholar
  5. 5.
    Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP (2004) Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 25(9):735–741PubMedCrossRefGoogle Scholar
  6. 6.
    Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS (2002) Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165(5):670–676PubMedGoogle Scholar
  7. 7.
    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(5):677–682PubMedGoogle Scholar
  8. 8.
    Kokturk O, Ciftci TU, Mollarecep E, Ciftci B (2005) Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Hear J 46(5):801–809CrossRefGoogle Scholar
  9. 9.
    Ciftci TU, Kokturk O, Bukan N, Bilgihan A (2004) The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome. Cytokine 28(2):87–91PubMedCrossRefGoogle Scholar
  10. 10.
    Ip MS, Lam KS, Ho C, Tsang KW, Lam W (2000) Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 118(3):580–586PubMedCrossRefGoogle Scholar
  11. 11.
    Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Investig 116(7):1784–1792PubMedCrossRefGoogle Scholar
  12. 12.
    Kanbay A, Kokturk O, Ciftci TU, Tavil Y, Bukan N (2008) Comparison of serum adiponectin and tumor necrosis factor-alpha levels between patients with and without obstructive sleep apnea syndrome. Respir Int Rev Thorac Dis 76(3):324–330Google Scholar
  13. 13.
    Zhang XL, Yin KS, Mao H, Wang H, Yang Y (2004) Serum adiponectin level in patients with obstructive sleep apnea hypopnea syndrome. Chin Med J (Engl) 117(11):1603–1606Google Scholar
  14. 14.
    Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2001) Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Lett 507(2):142–146PubMedCrossRefGoogle Scholar
  15. 15.
    Chasens ER, Weaver TE, Umlauf MG (2003) Insulin resistance and obstructive sleep apnea: is increased sympathetic stimulation the link? Biol Res Nurs 5(2):87–96PubMedCrossRefGoogle Scholar
  16. 16.
    Ievers-Landis CE, Redline S (2007) Pediatric sleep apnea: implications of the epidemic of childhood overweight. Am J Respir Crit Care Med 175(5):436–441PubMedCrossRefGoogle Scholar
  17. 17.
    Flegal KM, Carroll MD, Kit BK, Ogden CL (2012) Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 307(5):491–497PubMedCrossRefGoogle Scholar
  18. 18.
    Dingli K, Coleman EL, Vennelle M, Finch SP, Wraith PK, Mackay TW, Douglas NJ (2003) Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome. Eur Respir J 21(2):253–259PubMedCrossRefGoogle Scholar
  19. 19.
    Anonymous (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine Task Force. Sleep 22(5):667–689Google Scholar
  20. 20.
    Johns MW (1992) Reliability and factor analysis of the Epworth sleepiness scale. Sleep 15(4):376–381PubMedGoogle Scholar
  21. 21.
    Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545PubMedGoogle Scholar
  22. 22.
    American College of Sports Medicine, Thompson WR, Gordon NF, Pescatello LS (2010) ACSM’s guidelines for exercise testing and prescription, 8th edn. Lippincott, PhiladelphiaGoogle Scholar
  23. 23.
    Kamel EG, McNeill G, Van Wijk MC (2000) Usefulness of anthropometry and DXA in predicting intra-abdominal fat in obese men and women. Obes Res 8(1):36–42PubMedCrossRefGoogle Scholar
  24. 24.
    Miller LE, Nickols-Richardson SM, Wootten DF, Ramp WK, Herbert WG (2004) Relationships among bone mineral density, body composition, and isokinetic strength in young women. Calcif Tissue Int 74(3):229–235PubMedCrossRefGoogle Scholar
  25. 25.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419PubMedCrossRefGoogle Scholar
  26. 26.
    Steffes MW, Gross MD, Schreiner PJ, Yu X, Hilner JE, Gingerich R, Jacobs DR Jr (2004) Serum adiponectin in young adults—interactions with central adiposity, circulating levels of glucose, and insulin resistance: the CARDIA study. Ann Epidemiol 14(7):492–498PubMedCrossRefGoogle Scholar
  27. 27.
    Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Collins B, Basta M, Pejovic S, Chrousos GP (2008) Selective effects of CPAP on sleep apnoea-associated manifestations. Eur J Clin Investig 38(8):585–595CrossRefGoogle Scholar
  28. 28.
    Makino S, Handa H, Suzukawa K, Fujiwara M, Nakamura M, Muraoka S, Takasago I, Tanaka Y, Hashimoto K, Sugimoto T (2006) Obstructive sleep apnoea syndrome, plasma adiponectin levels, and insulin resistance. Clin Endocrinol 64(1):12–19CrossRefGoogle Scholar
  29. 29.
    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(3):1151–1158PubMedCrossRefGoogle Scholar
  30. 30.
    Ozturk L, Unal M, Tamer L, Celikoglu F (2003) The association of the severity of obstructive sleep apnea with plasma leptin levels. Arch Otolaryngol Head Neck Surg 129(5):538–540PubMedCrossRefGoogle Scholar
  31. 31.
    Harsch IA, Konturek PC, Koebnick C, Kuehnlein PP, Fuchs FS, Pour Schahin S, 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(2):251–257PubMedCrossRefGoogle Scholar
  32. 32.
    Phillips BG, Kato M, Narkiewicz K, Choe I, Somers VK (2000) Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol 279(1):H234–H237PubMedGoogle Scholar
  33. 33.
    Sanchez-de-la-Torre M, Mediano O, Barcelo A, Pierola J, de la Pena M, Esquinas C, Miro A, Duran-Cantolla J, Agusti AG, Capote F, Marin JM, Montserrat JM, Garcia-Rio F, Barbe F (2011) The influence of obesity and obstructive sleep apnea on metabolic hormones. Sleep Breath. doi: 10.1007/s11325-011-0552-7
  34. 34.
    Canapari CA, Hoppin AG, Kinane TB, Thomas BJ, Torriani M, Katz ES (2011) Relationship between sleep apnea, fat distribution, and insulin resistance in obese children. J Clin Sleep Med JCSM 7(3):268–273Google Scholar
  35. 35.
    Masserini B, Morpurgo PS, Donadio F, Baldessari C, Bossi R, Beck-Peccoz P, Orsi E (2006) Reduced levels of adiponectin in sleep apnea syndrome. J Endocrinol Investig 29(8):700–705Google Scholar
  36. 36.
    Lam JC, Xu A, Tam S, Khong PI, Yao TJ, Lam DC, Lai AY, Lam B, Lam KS, Mary SM (2008) Hypoadiponectinemia is related to sympathetic activation and severity of obstructive sleep apnea. Sleep 31(12):1721–1727PubMedGoogle Scholar
  37. 37.
    Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444(7121):840–846PubMedCrossRefGoogle Scholar
  38. 38.
    Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ (1996) Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 45(5):633–638PubMedCrossRefGoogle Scholar
  39. 39.
    Matsuzawa Y (2005) White adipose tissue and cardiovascular disease. Best Pract Res Clin Endocrinol Metabol 19(4):637–647CrossRefGoogle Scholar
  40. 40.
    Gottlieb DJ, Whitney CW, Bonekat WH, Iber C, James GD, Lebowitz M, Nieto FJ, Rosenberg CE (1999) Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. Am J Respir Crit Care Med 159(2):502–507PubMedGoogle Scholar
  41. 41.
    Johns MW (1994) Sleepiness in different situations measured by the Epworth sleepiness scale. Sleep 17(8):703–710PubMedGoogle Scholar
  42. 42.
    Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G (1984) Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed) 288(6428):1401–1404CrossRefGoogle Scholar
  43. 43.
    Despres JP, Couillard C, Gagnon J, Bergeron J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C (2000) Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. Arterioscler Thromb Vasc Biol 20(8):1932–1938PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Trent A. Hargens
    • 1
    • 2
  • Stephen G. Guill
    • 2
  • Anthony S. Kaleth
    • 3
  • Sharon M. Nickols-Richardson
    • 4
  • Larry E. Miller
    • 5
  • Donald Zedalis
    • 6
  • John M. Gregg
    • 7
  • Frank Gwazdauskas
    • 8
  • William G. Herbert
    • 2
    • 7
  1. 1.Department of KinesiologyJames Madison UniversityHarrisonburgUSA
  2. 2.Laboratory for Health and Exercise Sciences, Department of Human Nutrition, Foods and ExerciseVirginia Polytechnic Institute and State UniversityBlacksburgUSA
  3. 3.Department of KinesiologyIndiana University-Purdue UniversityIndianapolisUSA
  4. 4.Department of Nutritional SciencesThe Pennsylvania State UniversityUniversity ParkUSA
  5. 5.Miller Scientific Consulting, Inc.ArdenUSA
  6. 6.Edward Via Virginia College of Osteopathic MedicineBlacksburgUSA
  7. 7.Health Research Group, LLCRockbridge BathsUSA
  8. 8.Department of Dairy ScienceVirginia Polytechnic Institute and State UniversityBlacksburgUSA

Personalised recommendations