Sleep and Breathing

, Volume 23, Issue 1, pp 117–123 | Cite as

Oxidative stress in obese children and adolescents with and without type 2 diabetes mellitus is not associated with obstructive sleep apnea

  • Riva TaumanEmail author
  • Shlomit Shalitin
  • Lena Lavie
Sleep Breathing Physiology and Disorders • Original Article



Obesity, obstructive sleep apnea (OSA), and type 2 diabetes mellitus (T2DM) are associated with chronic low-grade inflammation and oxidative stress. In adults, increased lipid peroxidation, a marker of oxidative stress, was found in both metabolic syndrome and OSA. Studies on oxidative stress in children with T2DM and OSA are scarce.


Plasma oxidized low-density lipoprotein (Ox-LDL) levels were evaluated in obese children and adolescents with/without T2DM, and the contribution of OSA to oxidative stress was investigated.


Ten patients with T2DM, 8 with impaired glucose tolerance (IGT), and 20 body mass index-standard deviation score (BMI-SDS)-matched non-diabetic children (controls) were studied. They all underwent overnight polysomnography. Fasting plasma concentrations of Ox-LDL were measured and compared to the glycemic status and to the presence of OSA. Fourteen patients (36%) were diagnosed with OSA and 21 (55%) with hypertension. There were no significant group differences in plasma Ox-LDL levels or between patients with/without OSA. Plasma Ox-LDL levels were significantly higher among patients with hypertension compared to controls (P = 0.01), while they correlated with homeostasis model assessment (P = 0.02), BMI-SDS (P = 0.049), and systolic blood pressure (P = 0.002).


The findings of this pilot study suggest that increased lipid peroxidation is associated with insulin resistance and hypertension in obese children and adolescents, while OSA has most likely minor influence.


Insulin resistance Type 2 diabetes mellitus Obesity Obstructive sleep apnea  Ox-LDL 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional research committee (Schneider Children’s Medical Center of Israel and the Tel Aviv Souraski Medical Center) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Deckelbaum RJ, Williams CL (2001) Childhood obesity: the health issue. Obesity Research 9(suppl 4):239S–243SCrossRefGoogle Scholar
  2. 2.
    Vivian EM (2006) Type 2 diabetes in children and adolescents-the next epidemic? Curr Med Res Opin 22:297–306CrossRefGoogle Scholar
  3. 3.
    Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G (1999) Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med 159:1527–1532CrossRefGoogle Scholar
  4. 4.
    Singer K, Eng DS, Lumeng CN, Gebremariam A, M Lee J (2014) The relationship between body fat mass percentiles and inflammation in children. Obesity 22(5):1332–1336Google Scholar
  5. 5.
    Gozal D (2009) Sleep, sleep disorders and inflammation in children. Sleep Med Suppl 1:S12–S16CrossRefGoogle Scholar
  6. 6.
    Valle M, Martos R, Gascón F, Cañete R, Zafra MA, Morales R (2005) Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome. Diabetes Metab 31(1):55–62CrossRefGoogle Scholar
  7. 7.
    Tan HL, Gozal D, Kheirandish-Gozal L (2013) Obstructive sleep apnea in children: a critical update. Nat Sci Sleep 25(5):109–123Google Scholar
  8. 8.
    Lavie L (2009) Oxidative stress—a unifying paradigm in obstructive sleep apnea and comorbidities. Prog Cardiovasc Dis 51(4):303–312CrossRefGoogle Scholar
  9. 9.
    Sedeek MH, Llinas MT, Drummond H, Fortepiani L, Abram SR, Alexander BT, Reckelhoff JF, Granger JP (2003) Role of reactive oxygen species in endothelin-induced hypertension. Hypertension 42:806–810CrossRefGoogle Scholar
  10. 10.
    Lavie L, Lavie P (2009) Molecular mechanisms of cardiovascular disease in ISAHS: the oxidative stress link. Eur Respir J 33(6):1467–1484CrossRefGoogle Scholar
  11. 11.
    Lavie L, Vishnevsky A, Lavie P (2004) Evidence for lipid peroxidation in obstructive sleep apnea. Sleep 27(1):123–128Google Scholar
  12. 12.
    Barcelo A, Miralles C, Barbe F, Vila M, Pons S, Agusti AG (2000) Abnormal lipid peroxidation in patients with sleep apnoea. Eur Respir J 16:644–647CrossRefGoogle Scholar
  13. 13.
    Barcelo A, Barbé F, de la Peña M, Vila M, Pérez G, Piérola J, Durán J, Agustí AG (2006) Antioxidant status in patients with sleep apnea and impact of continuous positive airway pressure treatment. Eur Respir J 27:756–760CrossRefGoogle Scholar
  14. 14.
    Vatansever E, Surmen-Gur E, Ursavas A, Karadag M (2011) Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels. Sleep Breath 15:275–282CrossRefGoogle Scholar
  15. 15.
    Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939CrossRefGoogle Scholar
  16. 16.
    Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2003) Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52:1–8CrossRefGoogle Scholar
  17. 17.
    Ceriello A, Motz E (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes and cardiovascular disease? The common soil hypothesis revisited. Artherioscler Thromb Vasc Biol 24:816–823CrossRefGoogle Scholar
  18. 18.
    Weinbrenner T, Schroder H, Escurriol V, Fito M, Elosua R, Vila J et al (2006) Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women. Am J Clin Nutr 83(1):30–35CrossRefGoogle Scholar
  19. 19.
    Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR Jr. (2008) Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA 299(19):2287–2293Google Scholar
  20. 20.
    Holvoet P, Jenny NS, Schreiner PJ, Tracy RP, Jacobs DR (2007) The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 194(1):245–252CrossRefGoogle Scholar
  21. 21.
    Norris AL1, Steinberger J, Steffen LM, Metzig AM, Schwarzenberg SJ, Kelly AS (2011). Circulating oxidized LDL and inflammation in extreme pediatric obesity. Obesity 19(7):1415–1419Google Scholar
  22. 22.
    Kelly AS, Jacobs DR, Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J (2010) Relation of circulating oxidized LDL to obesity and insulin resistance in children. Pediatr Diabetes11(8):552–555Google Scholar
  23. 23.
    Tauman R, Lavie L, Greenfeld M, Sivan Y (2014) Oxidative stress in children with obstructive sleep apnea syndrome. J Clin Sleep Med 10(6):677–681Google Scholar
  24. 24.
    Shalitin S, Tauman R, Meyerovitch J, Sivan Y (2014) Are frequency and severity of sleep-disordered breathing in obese children and youth with and without type 2 diabetes mellitus different? Acta Diabetol 51(5):757–764CrossRefGoogle Scholar
  25. 25.
    Shalitin S, Deutsch V, Tauman R (2018) Hepcidine, soluble transferrin receptor and IL-6 levels in obese children and adolescents with and without type 2 diabetes mellitus/impaired glucose tolerance and their association with obstructive sleep apnea. J Endocrinol Invest (pubmed ahead of print)Google Scholar
  26. 26.
    Quon MJ (2001) Limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity. J Clin Endocrinol Metab 86:4615–4617CrossRefGoogle Scholar
  27. 27.
    Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG (2006) Prevalence and determinants of insulin resistance among U.S. adolescents: a population- based study. Diabetes Care 29(11):2427–2432CrossRefGoogle Scholar
  28. 28.
    Iber C, Ancoli-Israel S, Chesson A, Quan SF (2007) For the American Academy of sleep medicine rules, terminology and technical specifications, 1st edn. American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events, Westchester ILGoogle Scholar
  29. 29.
    National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRefGoogle Scholar
  30. 30.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (2014) Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311:507–520CrossRefGoogle Scholar
  31. 31.
    Manna P, Jain SK (2015) Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord 13(10):423–444CrossRefGoogle Scholar
  32. 32.
    Wirix AJ, Kaspers PJ, Nauta J, Chinapaw MJ, Kist-van Holthe JE (2015) Pathophysiology of hypertension in obese children: a systemic review. Obes Rev 16(10):831–842CrossRefGoogle Scholar
  33. 33.
    Reddy KJ, Singh M, Bangit JR, Batsell RR (2010) The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review. J Cardiovasc Med 11(9):633–647CrossRefGoogle Scholar
  34. 34.
    Ostrow V, Wu S, Aguilar A, Bonner R Jr, Suarez E, De Luca F (2011) Association between oxidative stress and masked hypertension in a multi-ethnic population of obese children and adolescents. J Pediatr 158(4):628–633CrossRefGoogle Scholar
  35. 35.
    Drozdz D, Kwinta P, Sztefko K et al (2016) Oxidative stress biomarkers and left ventricular hypertrophy in children with chronic kidney disease. Oxidative Med Cell Longev 2016:7520231CrossRefGoogle Scholar
  36. 36.
    Sinaiko AR, Steinberger J, Moran A, Prineas RJ, Vessby B, Basu S, Tracy R, Jacobs DR Jr (2005) Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation 111:1985–1991CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Sleep Disorders CenterTel Aviv Medical CenterTel AvivIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.The Jesse Z. and Lea Shafer Institute of Endocrinology and DiabetesSchneider Children’s Medical Center of IsraelPetach TikvaIsrael
  4. 4.Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of MedicineTechnion - Israel Institute of TechnologyHaifaIsrael

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