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The Relationship Between Pediatric Nonalcoholic Fatty Liver Disease and Cardiovascular Risk Factors and Increased Risk of Atherosclerosis in Obese Children

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Abstract

To investigate the relationship between nonalcoholic fatty liver disease and cardiovascular risk factors and increased risk of atherosclerosis in obese children. The study included 80 consecutive obese children who were stratified into group 1 [ultrasonographically diagnosed with NAFLD (n = 50)] and group 2 [not diagnosed with NAFLD (n = 30)]. The control group included 30 healthy children. The groups were compared in terms of clinical cardiovascular risk factors and carotid intimal medial thickness (CIMT) (as a marker of atherosclerosis) measured using B-mode ultrasound. Mean body mass index (BMI) and blood pressure (BP), as well as the frequency of dyslipidemia, metabolic syndrome (MetS), and insulin resistance (IR), were similar in groups 1 and 2. Mean BMI and triglyceride (TG) levels, and the frequency of IR and MetS, increased significantly as the grade of steatosis increased. Mean CIMT in group 1 was significantly greater than that in the control group (P < 0.01). There was a positive correlation between CIMT and age, BP, and BMI in groups 1 and 2. In addition, CIMT was correlated with TG, low high-density lipoprotein (HDL) cholesterol, MetS, and IR only in group 1. Linear regression analysis between CIMT and age, BP, BMI, TG level, HDL cholesterol level, IR, MetS, and grade of steatosis yielded a significant difference only for grade of steatosis. Cardiovascular risk factors are more impressive and CIMT was significantly higher in group 1 than in group 2 and the control group, indicating that they are associated with greater risk of atherosclerosis and future adverse cardiovascular events.

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References

  1. Barlow SE (2007) Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 120:164–192

    Article  Google Scholar 

  2. Bedossa P, Poynard T (1996) An algorithm for the grading of activity in chronic hepatitis C. The METAVIR cooperative study group. Hepatology 24:289–293

    Article  PubMed  CAS  Google Scholar 

  3. Botton J, Heude B, Kettaneh A, Borys JM, Lommez A, Bresson JL et al (2007) Cardiovascular risk factor levels and their relationship with overweight and fat distribution in children: The Fleurbaix Laventie Ville Sante II study. Metabolism 56:614–622

    Article  PubMed  CAS  Google Scholar 

  4. Bravo AA, Sheth SG, Chopra S (2001) Liver biopsy. N Engl J Med 344:495–500

    Article  PubMed  CAS  Google Scholar 

  5. Caserta CA, Pendino GM, Alicante S, Amante A, Amato F, Fiorillo M et al (2010) Body mass index, cardiovascular risk factors, and carotid intima-media thickness in a pediatric population in southern Italy. J Pediatr Gastroenterol Nutr 51:216–220

    Article  PubMed  Google Scholar 

  6. Caserta CA, Pendino MG, Amante A, Vacalebre C, Fiorillo MT, Surace P et al (2010) Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol 171:1195–1202

    Article  PubMed  Google Scholar 

  7. Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK et al (2004) Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord 28:1257–1263

    Article  PubMed  CAS  Google Scholar 

  8. Colloredo G, Guido M, Sonzogni A, Leandro G (2003) Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 39:239–244

    Article  PubMed  Google Scholar 

  9. Demircioğlu F, Koçyiğit A, Arslan N, Cakmakçi H, Hizli S, Sedat AT (2008) Intima-media thickness of carotid artery and susceptibility to atherosclerosis in obese children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 47:68–75

    Article  PubMed  Google Scholar 

  10. Denney-Wilson E, Hardy LL, Dobbins T, Okely AD, Baur LA (2008) Body mass index, waist circumference, and disease risk factors in Australian adolescents. Arch Pediatr Adolesc Med 162:566–573

    Article  PubMed  Google Scholar 

  11. Dienstag J (2002) The role of liver biopsy in chronic hepatitis C. Hepatology 36:152–160

    Article  Google Scholar 

  12. Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G et al (2006) Long-term follow-up of patients with NAFLD and increased liver enzymes. Hepatology 44:865–873

    Article  PubMed  CAS  Google Scholar 

  13. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel On Detection, Evaluation, And Treatment Of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285:2486–2497

    Article  Google Scholar 

  14. Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC et al (1997) Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 42:1428–1432

    Article  PubMed  CAS  Google Scholar 

  15. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R et al (2003) The expert committee on the diagnosis and classification of diabetes mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167

    Article  PubMed  Google Scholar 

  16. Giordano M, Colella V, Dammacco A, Torelli C, Grandaliano G, Teutonico A et al (2006) A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant. J Endocrinol Invest 29:330–336

    PubMed  CAS  Google Scholar 

  17. Guzzaloni G, Grugni G, Minocci A, Moro D, Morabito F (2000) Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test. Int J Obes Relat Metab Disord 24:772–776

    Article  PubMed  CAS  Google Scholar 

  18. Kelishadi R, Cook SR, Amra B, Adibi A (2009) Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis 204:538–543

    Article  PubMed  CAS  Google Scholar 

  19. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazıcı C (2005) Homeostasis model assessment is more reliable than the fasting glucose /insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:500–503

    Article  Google Scholar 

  20. Kim SH, Lee JM, Kim JH, Kim KG, Han JK, Lee KH et al (2005) Appropriateness of a donor liver with respect to macrosteatosis: application of artificial neural networks to US images—initial experience. Radiology 234:793–803

    Article  PubMed  Google Scholar 

  21. Kotronen A, Yki-Jarvinen H (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28:27–38

    Article  PubMed  CAS  Google Scholar 

  22. Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H (2007) Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 92:3490–3497

    Article  PubMed  CAS  Google Scholar 

  23. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R et al (2000) CDC growth charts: United States. Adv Data 314:1–27

    PubMed  Google Scholar 

  24. Lambert M, Delvin EE, Levy E, O’Loughlin J, Paradis G, Barnett T et al (2008) Prevalence of cardiometabolic risk factors by weight status in a population-based sample of Quebec children and adolescents. Can J Cardiol 24:575–583

    Article  PubMed  Google Scholar 

  25. Manco M, Bedogni C, Monti L, Morino G, Natali G, Nobili V (2010) Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease. Atherosclerosis 209:463–468

    Article  PubMed  CAS  Google Scholar 

  26. 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 28:412–419

    Article  PubMed  CAS  Google Scholar 

  27. Nadeau KJ, Klingensmith G, Zeitler P (2005) Type 2 diabetes in children is frequently associated with increased alanine aminotransferase. J Pediatr Gastroenterol Nutr 41:94–98

    Article  PubMed  CAS  Google Scholar 

  28. Nail WA (2007) Disorders of lipoprotein metabolism and transport. In: Behrman RE, Kliegman RM (eds) Nelson textbook of pediatrics, 18th edn. Elsevier Science, Philadelphia, pp 580–593

    Google Scholar 

  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 114:555–576

    Article  Google Scholar 

  30. Nobili V, Alkhouri N, Bartuli A, Manco M, Lopez R, Alisi A et al (2010) Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatr Res 67:665–670

    Article  PubMed  CAS  Google Scholar 

  31. Pacifico L, Cantisani V, Ricci P, Osborn JF, Schiavo E, Anania C et al (2008) Nonalcoholic fatty liver disease and carotid atherosclerosis in children. Pediatr Res 63:423–427

    Article  PubMed  CAS  Google Scholar 

  32. Pacifico L, Anania C, Martino F, Cantisani V, Pascone R, Marcantonio A et al (2010) Functional and morphological vascular changes in pediatric nonalcoholic fatty liver disease. Hepatology 52:1643–1651

    Article  PubMed  Google Scholar 

  33. Pesce MA (2007) Reference ranges for laboratory tests and procedures. In: Behrman RE, Kliegman RM (eds) Nelson textbook of pediatrics, 18th edn. Elsevier Science, Philadelphia, pp 2939–3000

    Google Scholar 

  34. Poynard T, Ratziu V, Bedossa P (2000) Appropriateness of liver biopsy. Can J Gastroenterol 14:543–548

    PubMed  CAS  Google Scholar 

  35. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT et al (2002) Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 97:2614–2618

    Article  PubMed  Google Scholar 

  36. Roberts EA (2007) Pediatric nonalcoholic fatty liver disease (NAFLD): a “growing” problem? J Hepatol 46:1133–1142

    Article  PubMed  CAS  Google Scholar 

  37. Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE et al (2003) Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 143:500–505

    Article  PubMed  Google Scholar 

  38. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ et al (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42:641–649

    Article  PubMed  Google Scholar 

  39. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE (2005) Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 115:e561–e565

    Article  PubMed  Google Scholar 

  40. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C (2006) Prevalence of fatty liver in children and adolescents. Pediatrics 118:1388–1393

    Article  PubMed  Google Scholar 

  41. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S (2008) Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 118:277–283

    Article  PubMed  CAS  Google Scholar 

  42. Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R et al (2011) Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr 53:190–195

    Article  PubMed  Google Scholar 

  43. Speiser PW, Rudolf MC, Anhalt H, Camacho-Hubmer C, Chiarelli F, Eliakim A et al (2005) Childhood obesity. J Clin Endocrinol Metab 90:1787–1871

    Google Scholar 

  44. Tazawa Y, Noguchi H, Nishinomiya F, Takada G (1997) Serum alanine aminotransferase activity in obese children. Acta Pediatr 86:238–241

    Article  CAS  Google Scholar 

  45. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I et al (1995) Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 40:2002–2009

    Article  PubMed  CAS  Google Scholar 

  46. Wasastjerna C, Reissell P, Karjalainen J, Ekelund P (1972) Fatty liver in diabetes. A cytological study. Acta Med Scand 191:225–228

    PubMed  CAS  Google Scholar 

  47. Weghuber D, Roden M, Franz C, Chmelik M, Torabia S, Nowotny P et al (2011) Vascular function in obese children with non-alcoholic fatty liver disease. Int J Pediatr Obes 6:120–127

    Article  PubMed  Google Scholar 

  48. World Medical Association (2012) Declaration of Helsinki ethical principles for medical research involving human subjects. http://www.wma.net/en/30publications/10policies/b3/. Accessed 7 Jan 2004

  49. Rashid M, Roberts EA (2000) Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 30:48–53

    Google Scholar 

  50. Zhou YJ, Li YY, Nie YQ, Ma JX, Lu LG, Shi SL et al (2007) Prevalence of fatty liver disease and its risk factors in the population of South China. World J Gastroenterol 13(47):6419–6424

    Article  PubMed  Google Scholar 

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Acknowledgments

Thanks to Scott B. Evans for language edition.

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Authors and Affiliations

  1. Department of Pediatric Gastroenterology, Dr. Sami Ulus Obstetrics and Gynecology, Children’s Health and Disease Training and Research Hospital, 06080, Altındağ, Ankara, Turkey

    Selim Gökçe

  2. Department of Pediatrics, Dr. Sami Ulus Obstetrics and Gynecology, Children’s Health and Disease Training and Research Hospital, 06080, Altındağ, Ankara, Turkey

    Zehra Atbinici & Pelin Zorlu

  3. Department of Pediatric Endocrinology, Dr. Sami Ulus Obstetrics and Gynecology, Children’s Health and Disease Training and Research Hospital, 06080, Altındağ, Ankara, Turkey

    Zehra Aycan

  4. Department of Radiology, Dr. Sami Ulus Obstetrics and Gynecology, Children’s Health and Disease Training and Research Hospital, 06080, Altındağ, Ankara, Turkey

    Hasibe Gökçe Çınar

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  1. Selim Gökçe
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Correspondence to Selim Gökçe.

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Gökçe, S., Atbinici, Z., Aycan, Z. et al. The Relationship Between Pediatric Nonalcoholic Fatty Liver Disease and Cardiovascular Risk Factors and Increased Risk of Atherosclerosis in Obese Children. Pediatr Cardiol 34, 308–315 (2013). https://doi.org/10.1007/s00246-012-0447-9

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  • DOI: https://doi.org/10.1007/s00246-012-0447-9

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