Resistin - the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea



Resistin is an adipocytokine, associated with obesity and inflammation. Its exact role in insulin resistance and diabetes in the general population is still controversial. The relation between resistin plasma levels, insulin resistance and risk of impaired glucose metabolism in OSA patients has not been investigated.

Materials and methods

Plasma levels of resistin were measured in 67 patients with OSA and impaired glucose metabolism. 34,7% (23/67) had diabetes; 40% (27/67) patients had impаired glucose tolerance(IGT); 25,3%(17/67) had normal glucose metabolism (NGM). The association between resistin, BMI, obesity, markers of insulin resistance, oxidative stress and sleep study characteristics was analysed. The different groups of patients were compared in regards to glucometabolic parameters and biomarkers of oxidative stress – isoprostanes and insulin resistance – free fatty acids (FFA).


Plasma levels of resistin were higher in patients with diabetes (6,12 ±5,93ng/ml), compared to those with IGT (3,85±2,81ng/ml, p-0,021) and NGM (3,77±3,23, p-0,043). Resistin did not differ between patients with IGT and NGM (p-0,954). In OSA patients with BMI>40 resistin plasma levels correlated neither to the clinical parameters (BMI, IRI, HOMA-I, HbA1C, AHI, desaturation index), nor to the biomarkers of oxidative stress and insulin resistance. Free fatty acids (0,232>0,177mmol/l, p-0,037) were higher in diabetics in comparison to NGM.


Plasma resistin levels in OSA patients with BMI>40 are independent of insulin resistance and are not associated with the parameters, characterising the oxidative stress or severity of OSA. Resistin could be used in a multiple panel of clinical and biomarkers to discern patients with diabetes from those with IGT; in OSA patients with BMI >40 resistin together with HbA1C could discern patients with diabetes from those with NGM. In OSA patients with BMI >40 FFA and HbA1C are useful clinical markers in assessing the risk of dysglycaemia among patients with normal and IGT.

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Figure 1
Figure 2
Figure 3



Obstructive Sleep Apnea


Apnea+Hypopnea Index


Bilevel Positive Airway Pressure


Body Mass Index


Homeostasis Model Assessment Index


Immuno Reactive Insulin


Oral Glucose Tolerance Test


Riva Rocchi


Free Fatty Acids


Impaired Glucose Tolerance


Normal Glucose Metabolism.


  1. 1.

    Hatipoglu U, Rubinstein I: Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 2003, 70: 665–671. 10.1159/000075218

    PubMed  Google Scholar 

  2. 2.

    Tanriverdi H, Evrengul H, Kara CO, Kuru O, Tanriverdi S, Ozkurt S, Kaftan A, Kilic M: Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis. Respiration 2006, 73: 741–750. 10.1159/000093531

    PubMed  Google Scholar 

  3. 3.

    Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Tanaka A, Oda N, Okada S, Ohta S, Naito H, Adachi M: Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 2005, 172: 625–630. 10.1164/rccm.200412-1652OC

    PubMed  Google Scholar 

  4. 4.

    Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS: Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002, 165: 670–676.

    PubMed  Google Scholar 

  5. 5.

    Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE: Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 2004, 160: 521–530. 10.1093/aje/kwh261

    PubMed  Google Scholar 

  6. 6.

    McArdle N, Hillman D, Beilin L, Watts G: Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Am J Respir Crit Care Med 2007, 175: 190–195.

    CAS  Google Scholar 

  7. 7.

    Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP: Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004, 25: 735–741. 10.1016/j.ehj.2004.02.021

    PubMed  Google Scholar 

  8. 8.

    Lam JC, Lam B, Lam CL, Fong D, Wang JK, Tse HF, Lam KS, Ip MS: Obstructive sleep apnea and the metabolic syndrome in community- based Chinese adults in Hong Kong. Respir Med 2006, 100: 980–987. 10.1016/j.rmed.2005.10.003

    PubMed  Google Scholar 

  9. 9.

    Yannakoulia M, Yiannakouris N, Bluher S, Matalas AL, Klimis-Zacas D, Mantzoros CS: Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 2003, 88: 1730–1736. 10.1210/jc.2002-021604

    CAS  PubMed  Google Scholar 

  10. 10.

    Vozarova de Courten B, Degawa-Yamauchi M, Considine RV, Tataranni PA: High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians. Diabetes 2004, 53: 1279–1284. 10.2337/diabetes.53.5.1279

    CAS  PubMed  Google Scholar 

  11. 11.

    Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV: Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003, 88: 5452–5455. 10.1210/jc.2002-021808

    CAS  PubMed  Google Scholar 

  12. 12.

    McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S: Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 2002, 87: 2407–2411. 10.1210/jc.87.5.2407

    CAS  PubMed  Google Scholar 

  13. 13.

    McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S: Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 2003, 88: 6098–6106. 10.1210/jc.2003-030898

    CAS  PubMed  Google Scholar 

  14. 14.

    Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003, 149: 331–335. 10.1530/eje.0.1490331

    CAS  PubMed  Google Scholar 

  15. 15.

    Szapary PO, Bloedon LT, Samaha FF, Duffy D, Wolfe ML, Soffer D, Reilly MP, Chittams J, Rader DJ: Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome. Arterioscler Thromb Vasc Biol 2006, 26: 182–188. 10.1161/01.ATV.0000195790.24531.4f

    CAS  PubMed  Google Scholar 

  16. 16.

    Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA: An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 2004,2(1):161–168.

    Google Scholar 

  17. 17.

    Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A: Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005, 174: 5789–5795.

    CAS  PubMed  Google Scholar 

  18. 18.

    Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA: Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 2003, 108: 736–740. 10.1161/01.CIR.0000084503.91330.49

    CAS  PubMed  Google Scholar 

  19. 19.

    Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ: Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005, 111: 932–939. 10.1161/01.CIR.0000155620.10387.43

    CAS  PubMed  Google Scholar 

  20. 20.

    Blaak EE: Fatty acid metabolism in obesity and type 2 diabetes mellitus. Proc Nutr Soc 2003, 62: 753–760. 10.1079/PNS2003290

    CAS  PubMed  Google Scholar 

  21. 21.

    Sarafidis PA, Bakris GL: Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance? J Hum Hypertens 2007, 21: 12–19. 10.1038/sj.jhh.1002103

    CAS  PubMed  Google Scholar 

  22. 22.

    Nourooz-Zadeh J: Key issues in F2-isoprostane analysis. Biochem Soc Trans 2008, 36: 1060–1065. 10.1042/BST0361060

    CAS  PubMed  Google Scholar 

  23. 23.

    Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ: А series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 1990, 87: 9383–9387. 10.1073/pnas.87.23.9383

    CAS  PubMed  Google Scholar 

  24. 24.

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and_ -cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–419. 10.1007/BF00280883

    CAS  PubMed  Google Scholar 

  25. 25.

    Committee E: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997, 20: 1183–1189.

    Google Scholar 

  26. 26.

    Phillips LK, Prins JB: The link between abdominal obesity and the metabolic syndrome. Curr Hypertens Rep 2008,2008(10):156–164.

    Google Scholar 

  27. 27.

    Pittas AG, Joseph NA, Greenberg AS: Adipocytokines and insulin resistance. J Clin Endocrinol Metab 2004, 89: 447–452. 10.1210/jc.2003-031005

    CAS  PubMed  Google Scholar 

  28. 28.

    Beltowski J: Adiponectin and resistin—new hormones of white adipose tissue. Med Sci Monit. 2003,9(2):55–61.

    Google Scholar 

  29. 29.

    Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001, 409: 307–312. 10.1038/35053000

    CAS  PubMed  Google Scholar 

  30. 30.

    Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA: Regulation of fasted blood glucose by resistin. Science 2004, 303: 1195–1198. 10.1126/science.1092341

    CAS  PubMed  Google Scholar 

  31. 31.

    Rajala MW, Obici S, Scherer PE, Rossetti L: Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest 2003, 111: 225–230.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, Lazar MA: Abnormal Glucose Homeostasis due to Chronic Hyperresistinemia. Diabetes 2004, 53: 1937–1941. 10.2337/diabetes.53.8.1937

    CAS  PubMed  Google Scholar 

  33. 33.

    Heilbronn LK, Rood J, Janderova L, Albu JB, Kelley DE, Ravussin E, Smith SR: Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects. J Clin Endocrinol Metab 2004, 89: 1844–1848. 10.1210/jc.2003-031410

    CAS  PubMed  Google Scholar 

  34. 34.

    Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros CS: Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 2003, 88: 4848–4856. 10.1210/jc.2003-030519

    CAS  PubMed  Google Scholar 

  35. 35.

    Vozarova de Courten B, Degawa-Yamauchi M, Considine RV, Tataranni PA: High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians. Diabetes 2004,2004(53):1279–1284.

    Google Scholar 

  36. 36.

    Hivert MF, Sullivan LM, Fox CS, Nathan DM, D’Agostino RB Sr, Wilson PW, Meigs JB: Associations of adiponectin, resistin, and tumor necrosis factor-_ with insulin resistance. J Clin Endocrinol Metab 2008, 93: 3165–3172. 10.1210/jc.2008-0425

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Yamamoto Y, Fujiuchi S, Hiramatsu M, Nishigaki Y, Takeda A, Fujita Y, Yamazaki Y: Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea. Respiration 2008, 76: 377–385. 10.1159/000141866

    CAS  PubMed  Google Scholar 

  38. 38.

    Wysocka E, Cofta S, Dziegielewska S, Gozdzik J, Torlinski L, Batura-Gabryel H: Adipocytokines in sleep apnea syndrome. Eur J Med Res. 2009,14(4):255–258. 10.1186/2047-783X-14-S4-255

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R, Bouloumie A: Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006, 49: 744–747. 10.1007/s00125-006-0173-z

    CAS  PubMed  Google Scholar 

  40. 40.

    Patel C, Macphee CH, Smith SA: Resistin is expressed in human macrophages and directly regulated by PPAR_ activators. Biochem Biophys Res Commun 2003, 300: 427–476.

    Google Scholar 

  41. 41.

    Li M, He XG, Qu SH, Zhan HM, Yang YB, Xu X, Si YF: Plasma resistin level in obstructive sleep apnea hypopnea syndrome. Zhonghua Yi Xue Za Zhi. 2008,88(34):2399–2402.

    CAS  PubMed  Google Scholar 

  42. 42.

    Wasilewska J, Kaczmarski M, Sawicka-Zukowska M, Serum resistin level in pediatric obstructive sleep apnea. Thematic Poster Session: Paediatric respiratory epidemiology I: primary ciliary dyskinesia, sleep-disordered breathing, exercise-induced symptoms and rare diseases. 2008. Tuesday, 07 October 2008

    Google Scholar 

  43. 43.

    Kunnari A, Ukkola O, Paivansalo M, Kesaniemi YA: High plasma resistin level is associated with enhanced highly sensitive C reactive protein and leukocytes. J Clin Endocrinol Metab 2006, 91: 2755–2760. 10.1210/jc.2005-2115

    CAS  PubMed  Google Scholar 

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This work is supported by the Scientific Grant of the Medical University of Sofia, 2011; Contract 42/ Project 51 with the kind collaboration of the Department of Medical Chemistry and Biochemistry, Laboratory of Synthesis and Analysis of Bioactive Substances and the Central Clinical Laboratory.

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Corresponding author

Correspondence to Radostina Vlaeva Cherneva.

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Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

RCh, OG, VM and DP participated in the design of the study and in writing the manuscript. RCh recruited the patients and collected the data. TM,OG performed the PSG studies. SSR and VL performed the HRAM analysis and free fatty acids measurements. AC performed the ELISA for resistin and the enzymatic determination of urinary creatinine levels. All reviewed and approved the final version of the manuscript.

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Cherneva, R.V., Georgiev, O.B., Petrova, D.S. et al. Resistin - the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea. J Diabetes Metab Disord 12, 5 (2013).

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  • Resistin
  • Insulin resistance
  • OSA
  • Diabetes
  • Normal glucose metabolism
  • Impaired glucose tolerance