Abstract

Background. We aimed to evaluate how the parameters used in the diagnosis of metabolic syndrome (MetS) and parameters such as epicardial adipose tissue (EAT) thickness, insulin resistance (IR), and serum uric acid (SUA) are affected according to the severity of obesity.

Methods. A total of 120 obese patients aged 10-18 years were classified as class 1-2-3 according to their body mass index (BMI) score. SUA was measured and oral glucose tolerance tests were performed on all patients. MetS components were determined according to the International Diabetes Federation 2007 criteria. IR was calculated using homeostatic model assessment for insulin resistance (HOMA-IR) and whole body insulin sensitivity index (WBISI).

Results. HOMA-IR was higher in the class 3 group than in the class 1 (p<0.001) and class 2 groups (p<0.01). WBISI was lower in the class 3 group than in the class 1 (p=0.015) and class 2 groups (p<0.01). EAT thickness was higher in the class 3 group than in the class 1 (p<0.01) and class 2 groups (p<0.01). No significant difference was found between class 1 and 2 groups for HOMA-IR, WBISI, and EAT thickness variables. The frequency of the MetS components was similar between the class of obesity groups (p=0.702). SUA and EAT thickness were significantly higher in the group with 2 and/or more MetS components than in the group with no MetS component. EAT thickness was positively and moderately correlated with SUA levels (Rho=0.319, p<0.001).

Conclusions. A more significant increase in cardiovascular disease risk factors, especially after class 2 obesity suggests that obese people should be followed closely and necessary interventions made for the prevention and progression of obesity. SUA and EAT thickness, an important risk factor affecting the obesity-related comorbidities, are positively correlated with each other and can be used in the follow-up of obese children.

Keywords: obesity, epicardial adipose tissue, uric acid, metabolic syndrome, insulin resistance

Copyright and license

How to cite

1.
Büyükyılmaz G, Özdemir Şahan Y. Evaluation of metabolic syndrome components, serum uric acid levels and epicardial adipose tissue thickness in pubertal children by severity of obesity. Turk J Pediatr 2024; 66: 690-702. https://doi.org/10.24953/turkjpediatr.2024.4558

References

  1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc 2017; 92: 251-265. https://doi.org/10.1016/j.mayocp.2016.09.017
  2. Molnár D. The prevalence of the metabolic syndrome and type 2 diabetes mellitus in children and adolescents. Int J Obes Relat Metab Disord 2004; 28(Suppl 3): S70-S74. https://doi.org/10.1038/sj.ijo.0802811
  3. Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox. Mayo Clin Proc 2017; 92: 266-279. https://doi.org/10.1016/j.mayocp.2016.11.001
  4. Ortega FB, Sui X, Lavie CJ, Blair SN. Body mass index, the most widely used but also widely criticized index: would a criterion standard measure of total body fat be a better predictor of cardiovascular disease mortality? Mayo Clin Proc 2016; 91: 443-455. https://doi.org/10.1016/j.mayocp.2016.01.008
  5. Iacobellis G. Epicardial fat links obesity to cardiovascular diseases. Prog Cardiovasc Dis 2023; 78: 27-33. https://doi.org/10.1016/j.pcad.2023.04.006
  6. Sironi AM, Petz R, De Marchi D, et al. Impact of increased visceral and cardiac fat on cardiometabolic risk and disease. Diabet Med 2012; 29: 622-627. https://doi.org/10.1111/j.1464-5491.2011.03503.x
  7. Gastaldelli A, Morales MA, Marraccini P, Sicari R. The role of cardiac fat in insulin resistance. Curr Opin Clin Nutr Metab Care 2012; 15: 523-528. https://doi.org/10.1097/MCO.0b013e328358be7b
  8. Ansaldo AM, Montecucco F, Sahebkar A, Dallegri F, Carbone F. Epicardial adipose tissue and cardiovascular diseases. Int J Cardiol 2019; 278: 254-260. https://doi.org/10.1016/j.ijcard.2018.09.089
  9. Rabkin SW. Epicardial fat: properties, function and relationship to obesity. Obes Rev 2007; 8: 253-261. https://doi.org/10.1111/j.1467-789X.2006.00293.x
  10. Iacobellis G, Assael F, Ribaudo MC, et al. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes Res 2003; 11: 304-310. https://doi.org/10.1038/oby.2003.45
  11. Iacobellis G, Ribaudo MC, Assael F, et al. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab 2003; 88: 5163-5168. https://doi.org/10.1210/jc.2003-030698
  12. Xu Y, Cheng X, Hong K, Huang C, Wan L. How to interpret epicardial adipose tissue as a cause of coronary artery disease: a meta-analysis. Coron Artery Dis 2012; 23: 227-233. https://doi.org/10.1097/MCA.0b013e328351ab2c
  13. Pierdomenico SD, Pierdomenico AM, Cuccurullo F, Iacobellis G. Meta-analysis of the relation of echocardiographic epicardial adipose tissue thickness and the metabolic syndrome. Am J Cardiol 2013; 111: 73-78. https://doi.org/10.1016/j.amjcard.2012.08.044
  14. Jeong J, Suh YJ. Association between serum uric acid and metabolic syndrome in Koreans. J Korean Med Sci 2019; 34: e307. https://doi.org/10.3346/jkms.2019.34.e307
  15. Shah AS, Zeitler PS, Wong J, et al. ISPAD Clinical Practice Consensus Guidelines 2022: type 2 diabetes in children and adolescents. Pediatr Diabetes 2022; 23: 872-902. https://doi.org/10.1111/pedi.13409
  16. Bianchi C, Miccoli R, Trombetta M, et al. Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study. J Clin Endocrinol Metab 2013; 98: 2100-2105. https://doi.org/10.1210/jc.2012-3971
  17. Kelly LA, Lane CJ, Weigensberg MJ, Toledo-Corral CM, Goran MI. Pubertal changes of insulin sensitivity, acute insulin response, and β-cell function in overweight Latino youth. J Pediatr 2011; 158: 442-446. https://doi.org/10.1016/j.jpeds.2010.08.046
  18. Hampl SE, Hassink SG, Skinner AC, et al. Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics 2023; 151: e2022060640. https://doi.org/10.1542/peds.2022-060640
  19. Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic risks and severity of obesity in children and young adults. N Engl J Med 2015; 373: 1307-1317. https://doi.org/10.1056/NEJMoa1502821
  20. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114(2 Suppl 4th Report): 555-576. https://doi.org/10.1542/peds.114.2.S2.555
  21. Zimmet P, Alberti KG, Kaufman F, et al. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes 2007; 8: 299-306. https://doi.org/10.1111/j.1399-5448.2007.00271.x
  22. American Diabetes Association. 2. classification and diagnosis of diabetes. Diabetes Care 2017; 40: S11-S24. https://doi.org/10.2337/dc17-S005
  23. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470. https://doi.org/10.2337/diacare.22.9.1462
  24. Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2021; 143: e984-e1010. https://doi.org/10.1161/CIR.0000000000000973
  25. Tskhvedadze N, Giorgadze E, Janjgava S. The impact of the degree of obesity on metabolic parameters in children and adolescents. Georgian Med News 2018; (285): 51-56.
  26. Toemen L, Santos S, Roest AAW, et al. Pericardial adipose tissue, cardiac structures, and cardiovascular risk factors in school-age children. Eur Heart J Cardiovasc Imaging 2021; 22: 307-313. https://doi.org/10.1093/ehjci/jeaa031
  27. Blancas Sánchez IM, Aristizábal-Duque CH, Fernández Cabeza J, et al. Role of obesity and blood pressure in epicardial adipose tissue thickness in children. Pediatr Res 2022; 92: 1681-1688. https://doi.org/10.1038/s41390-022-02022-x
  28. Ozdemir O, Hizli S, Abaci A, Agladioglu K, Aksoy S. Echocardiographic measurement of epicardial adipose tissue in obese children. Pediatr Cardiol 2010; 31: 853-860. https://doi.org/10.1007/s00246-010-9720-y
  29. Barbaro G, Piedimonte A, Podagrosi M, et al. Epicardial adipose tissue and signs of metabolic syndrome in children. Eat Weight Disord 2016; 21: 269-276. https://doi.org/10.1007/s40519-015-0221-0
  30. Blüher M. Metabolically healthy obesity. Endocr Rev 2020; 41: bnaa004. https://doi.org/10.1210/endrev/bnaa004
  31. Okyay K, Balcioglu AS, Tavil Y, Tacoy G, Turkoglu S, Abaci A. A relationship between echocardiographic subepicardial adipose tissue and metabolic syndrome. Int J Cardiovasc Imaging 2008; 24: 577-583. https://doi.org/10.1007/s10554-008-9295-3
  32. Mazur A, Ostański M, Telega G, Malecka-Tendera E. Is epicardial fat tissue a marker of metabolic syndrome in obese children? Atherosclerosis 2010; 211: 596-600. https://doi.org/10.1016/j.atherosclerosis.2010.02.036
  33. Eren E, Koca B, Ture M, Guzel B. Epicardial adiposity in children with obesity and metabolic syndrome. Iran J Pediatr 2014; 24: 411-417.
  34. Abacı A, Tascılar ME, Sarıtas T, et al. Threshold value of subepicardial adipose tissue to detect insulin resistance in obese children. Int J Obes (Lond) 2009; 33: 440-446. https://doi.org/10.1038/ijo.2009.1
  35. Akyol B, Boyraz M, Aysoy C. Relationship of epicardial adipose tissue thickness with early indicators of atherosclerosis and cardiac functional changes in obese adolescents with metabolic syndrome. J Clin Res Pediatr Endocrinol 2013; 5: 156-163. https://doi.org/10.4274/Jcrpe.1064
  36. Kim JK. Hyperinsulinemic-euglycemic clamp to assess insulin sensitivity in vivo. Methods Mol Biol 2009; 560: 221-238. https://doi.org/10.1007/978-1-59745-448-3_15
  37. Tagi VM, Giannini C, Chiarelli F. Insulin resistance in children. Front Endocrinol (Lausanne) 2019; 10: 342. https://doi.org/10.3389/fendo.2019.00342
  38. Yeckel CW, Weiss R, Dziura J, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004; 89: 1096-1101. https://doi.org/10.1210/jc.2003-031503
  39. Cohen M, Syme C, Deforest M, et al. Ectopic fat in youth: the contribution of hepatic and pancreatic fat to metabolic disturbances. Obesity (Silver Spring) 2014; 22: 1280-1286. https://doi.org/10.1002/oby.20674
  40. Lima WG, Martins-Santos ME, Chaves VE. Uric acid as a modulator of glucose and lipid metabolism. Biochimie 2015; 116: 17-23. https://doi.org/10.1016/j.biochi.2015.06.025
  41. Özalp Kızılay D, Şen S, Ersoy B. Associations between serum uric acid concentrations and cardiometabolic risk and renal injury in obese and overweight children. J Clin Res Pediatr Endocrinol 2019; 11: 262-269. https://doi.org/10.4274/jcrpe.galenos.2018.2019.0241
  42. Rubio-Guerra AF, Benítez-Maldonado DR, Lozano-Nuevo JJ, Arana-Pazos KC, Huerta-Ramirez S, Narváez-Rivera JL. Correlation between epicardial fat thickness and biochemical markers of metabolic risk. Med Clin (Barc) 2018; 151: 236-238. https://doi.org/10.1016/j.medcli.2018.01.019
  43. Schusterova I, Leenen FH, Jurko A, Sabol F, Takacova J. Epicardial adipose tissue and cardiometabolic risk factors in overweight and obese children and adolescents. Pediatr Obes 2014; 9: 63-70. https://doi.org/10.1111/j.2047-6310.2012.00134.x
  44. Kim HR, Han MA. Association between serum liver enzymes and metabolic syndrome in Korean adults. Int J Environ Res Public Health 2018; 15: 1658. https://doi.org/10.3390/ijerph15081658
  45. Wang J, Qu HQ, Huang K, et al. High prevalence of elevated serum liver enzymes in Chinese children suggests metabolic syndrome as a common risk factor. J Paediatr Child Health 2020; 56: 1590-1596. https://doi.org/10.1111/jpc.15038
  46. Lee DH, Jacobs DR, Gross M, et al. Gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clin Chem 2003; 49: 1358-1366. https://doi.org/10.1373/49.8.1358
  47. Ege MR, Guray U, Guray Y, Demirkan B, Kisacik H. Serum γ-glutamyltransferase levels correlate with epicardial adipose tissue thickness in patients with coronary artery disease. Angiology 2013; 64: 21-25. https://doi.org/10.1177/0003319711433197