Nonalcoholic Fatty Liver Disease and Continuous Metabolic Syndrome in Adolescents with Overweight/Obesity
DOI:
https://doi.org/10.20344/amp.19834Keywords:
Adolescent, Metabolic Syndrome, Non-alcoholic Fatty Liver Disease, Obesity, OverweightAbstract
Introduction: Nonalcoholic fatty liver disease is the leading cause of pediatric chronic liver disease. Although nonalcoholic fatty liver disease is closely associated with obesity, its relationship with metabolic syndrome in children is not fully understood. The main aim of this study was to evaluate the association between nonalcoholic fatty liver disease and a combination of cardiometabolic risk factors in adolescents with overweight/obesity, using a pediatric metabolic syndrome score (PsiMS) to predict metabolic syndrome.
Methods: A retrospective cohort study was conducted. Subjects with overweight/obesity aged 10 to 17 followed at two clinical centers in Portugal (2018 - 2021) were enrolled. The independent association of nonalcoholic fatty liver disease with PsiMS, and of other potential predictors, was tested through multiple regression analyses. Receiver operator characteristic curve analysis was performed to estimate the optimal cutoff of PsiMS to discriminate metabolic syndrome.
Results: Eighty-four subjects were included (median age at baseline 11.5 years). The prevalence rate of nonalcoholic fatty liver disease was 51% and the prevalence rate of metabolic syndrome was 7%. The mean PsiMS was 2.05 ± 0.48 at the first evaluation, and 2.11 ± 0.52 at the last evaluation (mean follow-up time was 15 months). The nonalcoholic fatty liver disease group had significantly (p < 0.05) higher weight and body mass index z-scores, higher rate of severe obesity and higher waist circumference percentile. PsiMS was highly accurate in predicting metabolic syndrome (area under the curve = 0.96), with an optimal cutoff of 2.46 (sensitivity 100%, specificity 89%). In the univariate analysis, no statistically significant association was observed between nonalcoholic fatty liver disease and PsiMS. In the multiple regression analysis, female sex had a negative association with PsiMS (first and last evaluation). Independent predictors of a higher PsiMS at first evaluation were: ≥ 2 metabolic syndrome criteria, body mass index z-score, insulin resistance and dyslipidemia. At the last evaluation, independent predictors of a higher PsiMS were: nonalcoholic fatty liver disease, baseline PsiMS and body mass index increase from baseline.
Conclusion: The results suggest a good performance of the PsiMS to assess metabolic syndrome and that nonalcoholic fatty liver disease is associated with PsiMS at follow-up.
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Magge SN, Goodman E, Armstrong SC, Daniels S, Corkins M, De Ferranti S, et al. The metabolic syndrome in children and adolescents: Shifting the focus to cardiometabolic risk factor clustering. Pediatrics. 2017;140:e20171603. DOI: https://doi.org/10.1542/peds.2017-1603
Zimmet P, Alberti GK, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes. 2007;8:299-306. DOI: https://doi.org/10.1111/j.1399-5448.2007.00271.x
Eisenmann JC. On the use of a continuous metabolic syndrome score in pediatric research. Cardiovasc Diabetol. 2008;7:1-6. DOI: https://doi.org/10.1186/1475-2840-7-17
Vukovic R, Milenkovic T, Stojan G, Vukovic A, Mitrovic K, Todorovic S, et al. Pediatric siMS score: a new, simple and accurate continuous metabolic syndrome score for everyday use in pediatrics. PLoS One. 2017;12:1-10. DOI: https://doi.org/10.1371/journal.pone.0189232
Villa JK, E Silva AR, Santos TS, Ribeiro AQ, Sant’Ana LF. Metabolic syndrome risk assessment in children: use of a single score. Rev Paul Pediatr. 2015;33:187-93. DOI: https://doi.org/10.1016/S2359-3482(15)30050-6
Peterson MD, Saltarelli WA, Visich PS, Gordon PM. Strength capacity and cardiometabolic risk clustering in adolescents. Pediatrics. 2014;133:e896-903. DOI: https://doi.org/10.1542/peds.2013-3169
Shafiee G, Kelishadi R, Heshmat R, Qorbani M, Motlagh ME, Aminaee T, et al. First report on the validity of a continuous Metabolic Syndrome score as an indicator for Metabolic Syndrome in a national sample of paediatric population - The CASPIAN-III study. Endokrynol Pol. 2013;64:278-84. DOI: https://doi.org/10.5603/EP.2013.0006
Peterson MD, Liu D, Iglay Reger HB, Saltarelli WA, Visich PS, Gordon PM. Principal component analysis reveals gender-specific predictors of cardiometabolic risk in 6th graders. Cardiovasc Diabetol. 2012;11:146. DOI: https://doi.org/10.1186/1475-2840-11-146
Kelishadi R, Heshmat R, Mansourian M, Motlagh ME, Ziaodini H, Taheri M, et al. Association of dietary patterns with continuous metabolic syndrome in children and adolescents; A nationwide propensity score-matched analysis: The CASPIAN-V study. Diabetol Metab Syndr. 2018;10:52. DOI: https://doi.org/10.1186/s13098-018-0352-3
Heshmat R, Heidari M, Ejtahed HS, Motlagh ME, Mahdavi-Gorab A, Ziaodini H, et al. Validity of a continuous metabolic syndrome score as an index for modeling metabolic syndrome in children and adolescents: The CASPIAN-V study. Diabetol Metab Syndr. 2017;9:89. DOI: https://doi.org/10.1186/s13098-017-0291-4
Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289-304. DOI: https://doi.org/10.2337/diacare.28.9.2289
Lee YJ, Seo MY, Kim SH, Park MJ. Validity of the pediatric simple metabolic syndrome score. Obes Res Clin Pract. 2020;14:508-13. DOI: https://doi.org/10.1016/j.orcp.2020.09.009
Ko JS. New perspectives in pediatric nonalcoholic fatty liver disease: epidemiology, genetics, diagnosis, and natural history. Pediatr Gastroenterol Hepatol Nutr. 2019;22:501-10. DOI: https://doi.org/10.5223/pghn.2019.22.6.501
Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the expert committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64:319-34. DOI: https://doi.org/10.1097/MPG.0000000000001482
Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol. 2011;17:3082-91.
Schwimmer J. Clinical advances in pediatric nonalcoholic fatty liver disease. Hepatology. 2016;63:1718-25. DOI: https://doi.org/10.1002/hep.28441
Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One. 2015;10:e0140908. DOI: https://doi.org/10.1371/journal.pone.0140908
Martins E, Oliveira A. NAFLD and cardiovascular disease. Porto Biomed J. 2018;3:e2. DOI: https://doi.org/10.1016/j.pbj.0000000000000002
Motamed N, Rabiee B, Poustchi H, Dehestani B, Hemasi GR, Khonsari MR, et al. Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clin Res Hepatol Gastroenterol. 2017;41:31-8. DOI: https://doi.org/10.1016/j.clinre.2016.07.005
Motamed N, Ajdarkosh H, Ahmadi M, Perumal D, Ashrafi GH, Nikkhah M, et al. Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event: a cohort study. World J Hepatol. 2020;12:323–31. DOI: https://doi.org/10.4254/wjh.v12.i6.323
Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007;24:1-6. DOI: https://doi.org/10.1111/j.1464-5491.2007.02025.x
Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341-50. DOI: https://doi.org/10.1056/NEJMra0912063
Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017;66:1138-53. DOI: https://doi.org/10.1136/gutjnl-2017-313884
Loureiro C, Martínez-Aguayo A, Campino C, Carvajal C, Fardella C, García H. Esteatosis Hepática: ¿Preludio de diabetes tipo 2 en población pediátrica? Nutr Hosp. 2014;29:350-8.
Manco M, Marcellini M, DeVito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes. 2008;32:381-7. DOI: https://doi.org/10.1038/sj.ijo.0803711
Patton HM, Yates K, Unalp-Arida A, Behling CA, Huang TT, Rosenthal P, et al. Association between metabolic syndrome and liver histology among children with nonalcoholic fatty liver disease. Am J Gastroenterol. 2010;105:2093-102. DOI: https://doi.org/10.1038/ajg.2010.152
Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008;118:277-83. DOI: https://doi.org/10.1161/CIRCULATIONAHA.107.739920
Guerra A. As curvas de crescimento da Organização Mundial de Saúde. Acta Pediatr Port. 2009;40:41-5.
Onis M. World Health Organization Reference Curves. The free obesity ebook. 2014. [cited 2023 Feb 13]. Available from: https://ebook.ecog-obesity.eu/wp-content/uploads/2015/02/ECOG-Obesity-eBook-World-Health-Organization-Reference-Curves.pdf.
Green Corkins K, Teague EE. Pediatric nutrition assessment: anthropometrics to zinc. Nutr Clin Pract. 2017;32:40-51. DOI: https://doi.org/10.1177/0884533616679639
Sharma AK, Metzger DL, Daymont C, Hadjiyannakis S, Rodd CJ. LMS tables for waist-circumference and waist-height ratio z-scores in children aged 5-19 y in NHANES III: association with cardio-metabolic risks. Pediatr Res. 2015;78:723-9. DOI: https://doi.org/10.1038/pr.2015.160
Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140:e20171904. DOI: https://doi.org/10.1542/peds.2017-1904
Conwell LS, Trost SG, Brown WJ, Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care. 2004;27:314-9. DOI: https://doi.org/10.2337/diacare.27.2.314
Mohamed RZ, Jalaludin MY, Anuar Zaini A. Predictors of non-alcoholic fatty liver disease (NAFLD) among children with obesity. J Pediatr Endocrinol Metab. 2020;33:247-53. DOI: https://doi.org/10.1515/jpem-2019-0403
Sartorio A, Del Col A, Agosti F, Mazzilli G, Bellentani S, Tiribelli C, et al. Predictors of non-alcoholic fatty liver disease in obese children. Eur J Clin Nutr. 2007;61:877-83. DOI: https://doi.org/10.1038/sj.ejcn.1602588
Mosca A, Nobili V, De Vito R, Crudele A, Scorletti E, Villani A, et al. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. J Hepatol. 2017;66:1031-6. DOI: https://doi.org/10.1016/j.jhep.2016.12.025
Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr. 2011;53:190-5. DOI: https://doi.org/10.1097/MPG.0b013e31821b4b61
Ezaizi Y, Kabbany MN, Conjeevaram Selvakumar PK, Sarmini MT, Singh A, Lopez R, et al. Comparison between non-alcoholic fatty liver disease screening guidelines in children and adolescents. JHEP Rep. 2019;1:259-64. DOI: https://doi.org/10.1016/j.jhepr.2019.06.005
Reisinger C, Nkeh-Chungag BN, Fredriksen PM, Goswami N. The prevalence of pediatric metabolic syndrome—a critical look on the discrepancies between definitions and its clinical importance. Int J Obes. 2021;45:12-24. DOI: https://doi.org/10.1038/s41366-020-00713-1
Moniz M, Marques T, Cabral M, Nizarali Z, Coelho R, Monteiro A, et al. Factores de risco cardiovascular e obesidade infantil. Acta Med Port. 2011;24:327-32.
Silva F, Ferreira E, Gonçalves R, Cavaco A. Obesidade pediátrica: a realidade de uma consulta. Acta Med Port. 2012;25:91-6.
Barstad LH, Júlíusson PB, Johnson LK, Hertel JK, Lekhal S, Hjelmesæth J. Gender-related differences in cardiometabolic risk factors and lifestyle behaviors in treatment-seeking adolescents with severe obesity. BMC Pediatr. 2018;18:1-8. DOI: https://doi.org/10.1186/s12887-018-1057-3
Lafortuna CL, Adorni F, Agosti F, De Col A, Sievert K, Siegfried W, et al. Prevalence of the metabolic syndrome among extremely obese adolescents in Italy and Germany. Diabetes Res Clin Pract. 2010;88:14-21. DOI: https://doi.org/10.1016/j.diabres.2010.01.008
Jankowska A, Brzeziński M, Romanowicz-Sołtyszewska A, Sidorkiewicz AS. Metabolic syndrome in obese children-clinical prevalence and risk factors. Int J Environ Res Public Health. 2021;18:1-11. DOI: https://doi.org/10.3390/ijerph18031060
Thomas NE, Rowe DA, Murtagh EM, Stephens JW, Williams R. Associations between metabolic syndrome components and markers of inflammation in Welsh school children. Eur J Pediatr. 2018;177:409-17. DOI: https://doi.org/10.1007/s00431-017-3065-y
De Jesus JM. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics. 2011;128:213-56. DOI: https://doi.org/10.1542/peds.2009-2107C
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