Ewha Med J.  2022 Oct;45(4):e13. 10.12771/emj.2022.e13.

Metabolic Syndrome in Children and Adolescents

• Chung YL
• Rhie YJ

• KMID: 2534732
• DOI: http://doi.org/10.12771/emj.2022.e13

Abstract

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that include hypertension, altered glucose metabolism, dyslipidemia, and abdominal obesity and is strongly associated with an increased risk for diabetes and cardiovascular disease onset in obese adults and children. A progressively greater number of children and adolescents are being affected by this syndrome due to the constant increase in the prevalence of obesity. Like obesity, childhood MetS highly tracks to adulthood. The pathogenesis of MetS includes the interaction between obesity, insulin resistance, and inflammation. Early diagnosis and intervention are important in order to conduct lifestyle modification. In this article, we review the definition and pathophysiology of MetS, the importance of screening, and prevention and treatment options for MetS in childhood.

Keyword

Metabolic syndrome; Cardiovascular disease; Obesity; Insulin resistance; Pediatrics

Reference

References

1. Wilson PWF, D’Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005; 112(20):3066–3072. DOI: 10.1161/CIRCULATIONAHA.105.539528. PMID: 16275870.

2. Yoo SE, Lee JH, Lee JW, Park HS, Lee HA, Kim HS. Increasing prevalence of fasting hyperglycemia in adolescents aged 10–18 years and its relationship with metabolic indicators: the Korea National Health and Nutrition Examination Study (KNHANES), 2007–2018. Ann Pediatr Endocrinol Metab. 2022; 27(1):60–68. DOI: 10.6065/apem.2142068.034. PMID: 33971707. PMCID: PMC8984745.

3. Seo MY, Kim SH, Park MJ. Changes in anthropometric indices among Korean school students based on the 2010 and 2018 Korea School Health Examination Surveys. Ann Pediatr Endocrinol Metab. 2021; 26(1):38–45. DOI: 10.6065/apem.2040100.050. PMID: 33819957. PMCID: PMC8026332.

4. Lee SE, Han K, Kang YM, Kim SO, Cho YK, Ko KS, et al. Trends in the prevalence of metabolic syndrome and its components in South Korea: findings from the Korean National Health Insurance Service Database (2009–2013). PLoS One. 2018; 13(3):e0194490. DOI: 10.1371/journal.pone.0194490. PMID: 29566051. PMCID: PMC5864027.

5. Lim S, Shin H, Song JH, Kwak SH, Kang SM, Yoon JW, et al. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998-2007. Diabetes Care. 2011; 34:1323–1328. DOI: 10.2337/dc10-2109. PMID: 21505206. PMCID: PMC3114326.

6. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004; 350(23):2362–2374. DOI: 10.1056/NEJMoa031049. PMID: 15175438.

7. Kim JH, Moon JS. Secular trends in pediatric overweight and obesity in Korea. J Obes Metab Syndr. 2020; 29(1):12–17. DOI: 10.7570/jomes20002. PMID: 32188238. PMCID: PMC7118001.

8. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic syndrome. Endocr Rev. 2008; 29(7):777–822. DOI: 10.1210/er.2008-0024. PMID: 18971485. PMCID: PMC5393149.

9. Cho MH, Kim YM, Yoon JH, Kim DH, Lim JS. Serum uric acid in Korean children and adolescents: reference percentiles and association with metabolic syndrome. Ann Pediatr Endocrinol Metab. 2020; 25(2):104–111. DOI: 10.6065/apem.1938156.078. PMID: 32615690. PMCID: PMC7336265.

10. Zimmet P, Alberti G, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents. Lancet. 2007; 369(9579):2059–2061. DOI: 10.1016/S0140-6736(07)60958-1.

11. Ahrens W, Moreno LA, Mårild S, Molnár D, Siani A, De Henauw S, et al. Metabolic syndrome in young children: definitions and results of the IDEFICS study. Int J Obes. 2014; 38:S4–S14. DOI: 10.1038/ijo.2014.130. PMID: 25376220.

12. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004; 110(10):1245–1250. DOI: 10.1161/01.CIR.0000140677.20606.0E. PMID: 15326067.

13. Stanley TL, Chen ML, Goodman E. The typology of metabolic syndrome in the transition to adulthood. J Clin Endocrinol Metab. 2014; 99(3):1044–1052. DOI: 10.1210/jc.2013-3531. PMID: 24423351. PMCID: PMC3942239.

14. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med. 1998; 338(23):1650–1656. DOI: 10.1056/NEJM199806043382302. PMID: 9614255.

15. Kelly AS, Steinberger J, Jacobs DR Jr, Hong CP, Moran A, Sinaiko AR. Predicting cardiovascular risk in young adulthood from the metabolic syndrome, its component risk factors, and a cluster score in childhood. Int J Pediatr Obes. 2011; 6(2-2):e283–289. DOI: 10.3109/17477166.2010.528765. PMID: 21070100. PMCID: PMC3684392.

16. Matsumoto M, Han S, Kitamura T, Accili D. Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. J Clin Invest. 2006; 116(9):2464–2472. DOI: 10.1172/JCI27047. PMID: 16906224. PMCID: PMC1533874.

17. Lewis GF, Uffelman KD, Szeto LW, Steiner G. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes. 1993; 42(6):833–842. DOI: 10.2337/diab.42.6.833. PMID: 8495807.

18. Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab. 2008; 7(2):95–96. DOI: 10.1016/j.cmet.2007.12.009. PMID: 18249166.

19. Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res. 2005; 36(3):232–240. DOI: 10.1016/j.arcmed.2005.01.005. PMID: 15925013.

20. Large V, Arner P. Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab. 1998; 24(5):409–418.

21. Heilbronn LK, Campbell LV. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des. 2008; 14(12):1225–1230. DOI: 10.2174/138161208784246153. PMID: 18473870.

22. Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci USA. 2007; 104(31):12587–12594. DOI: 10.1073/pnas.0705408104. PMID: 17640906. PMCID: PMC1924794.

23. Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010; 375(9733):2267–2277. DOI: 10.1016/S0140-6736(10)60408-4.

24. Unger RH. The hyperleptinemia of obesity—regulator of caloric surpluses. Cell. 2004; 117(2):145–146. DOI: 10.1016/S0092-8674(04)00339-3.

25. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002; 51(7):2325–2328. DOI: 10.2337/diabetes.51.7.2325. PMID: 12086969.

26. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway. Circulation. 2000; 102(11):1296–1301. DOI: 10.1161/01.CIR.102.11.1296. PMID: 10982546.

27. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112(12):1796–1808. DOI: 10.1172/JCI200319246. PMID: 14679176. PMCID: PMC296995.

28. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000; 148(2):209–214. DOI: 10.1016/S0021-9150(99)00463-3.

29. Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149(1):139–150. DOI: 10.1016/S0021-9150(99)00312-3.

30. Winer JC, Zern TL, Taksali SE, Dziura J, Cali AMG, Wollschlager M, et al. Adiponectin in childhood and adolescent obesity and its association with inflammatory markers and components of the metabolic syndrome. J Clin Endocrinol Metab. 2006; 91(11):4415–4423. DOI: 10.1210/jc.2006-0733. PMID: 16926246.

31. Leyva F, Godsland IF, Ghatei M, Proudler AJ, Aldis S, Walton C, et al. Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler Thromb Vasc Biol. 1998; 18(6):928–933. DOI: 10.1161/01.ATV.18.6.928. PMID: 9633933.

32. Barlow SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007; 120:S164–S192. DOI: 10.1542/peds.2007-2329C. PMID: 18055651.

33. Temple JL, Cordero P, Li J, Nguyen V, Oben JA. A guide to non-alcoholic fatty liver disease in childhood and adolescence. Int J Mol Sci. 2016; 17(6):947. DOI: 10.3390/ijms17060947. PMID: 27314342. PMCID: PMC4926480.

34. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2022. Diabetes Care. 2021; 45:S17–S38. DOI: 10.2337/dc22-S002. PMID: 34964875.

35. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011; 128:S213–S256. DOI: 10.1542/peds.2009-2107C. PMID: 22084329. PMCID: PMC4536582.

36. Styne DM, Arslanian SA, Connor EL, Farooqi IS, Hassan Murad M, Silverstein JH, et al. Pediatric obesity—assessment, treatment, and prevention: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017; 102(3):709–757. DOI: 10.1210/jc.2016-2573. PMID: 28359099. PMCID: PMC6283429.

37. Kamath CC, Vickers KS, Ehrlich A, McGovern L, Johnson J, Singhal V, et al. Behavioral interventions to prevent childhood obesity: a systematic review and metaanalyses of randomized trials. J Clin Endocrinol Metab. 2008; 93(12):4606–4615. DOI: 10.1210/jc.2006-2411. PMID: 18782880.

38. Rajjo T, Mohammed K, Alsawas M, Ahmed AT, Farah W, Asi N, et al. Treatment of pediatric obesity: an umbrella systematic review. J Clin Endocrinol Metab. 2017; 102(3):763–775. DOI: 10.1210/jc.2016-2574. PMID: 28359101.

39. Bravata DM, Sanders L, Huang J, Krumholz HM, Olkin I, Gardner CD, et al. Efficacy and safety of low-carbohydrate diets: a systematic review. J Am Med Assoc. 2003; 289(14):1837–1850. DOI: 10.1001/jama.289.14.1837. PMID: 12684364.

40. Gudi SK. Eating speed and the risk of type 2 diabetes: explorations based on real-world evidence. Ann Pediatr Endocrinol Metab. 2020; 25(2):80–83. DOI: 10.6065/apem.2040028.014. PMID: 32615686. PMCID: PMC7336266.

41. Lobelo F, Muth ND, Hanson S, Nemeth BA, LaBella CR, Brooks MA, et al. Physical activity assessment and counseling in pediatric clinical settings. Pediatrics. 2020; 145(3):e20193992. DOI: 10.1542/peds.2019-3992. PMID: 32094289.

42. Bremer AA, Auinger P, Byrd RS. Relationship between insulin resistance–associated metabolic parameters and anthropometric measurements with sugar-sweetened beverage intake and physical activity levels in US adolescents: findings from the 1999–2004 National Health and Nutrition Examination Survey. Arch Pediatr Adolesc Med. 2009; 163(4):328–335. DOI: 10.1001/archpediatrics.2009.21. PMID: 19349561. PMCID: PMC4264593.

43. Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M. Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children. J Am Coll Cardiol. 2009; 54(25):2396–2406. DOI: 10.1016/j.jacc.2009.08.030. PMID: 20082930.

44. Wickham EP 3rd, DeBoer MD. Evaluation and treatment of severe obesity in childhood. Clin Pediatr. 2015; 54(10):929–940. DOI: 10.1177/0009922814565886. PMID: 25567296. PMCID: PMC5596453.

45. Maahs D, de Serna DG, Kolotkin RL, Ralston S, Sandate J, Qualls C, et al. Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocr Pract. 2006; 12(1):18–28. DOI: 10.4158/EP.12.1.18. PMID: 16524859.

46. Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med. 2020; 382(22):2117–2128. DOI: 10.1056/NEJMoa1916038. PMID: 32233338.

47. Zoicas F, Droste M, Mayr B, Buchfelder M, Schöfl C. GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. Eur J Endocrinol. 2013; 168(5):699–706. DOI: 10.1530/EJE-12-0997. PMID: 23392214.

48. Kim YM, Lee YJ, Kim SY, Cheon CK, Lim HH. Successful rapid weight reduction and the use of liraglutide for morbid obesity in adolescent Prader-Willi syndrome. Ann Pediatr Endocrinol Metab. 2020; 25(1):52–56. DOI: 10.6065/apem.2020.25.1.52. PMID: 32252218. PMCID: PMC7136503.

49. Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW, Filion KB. Efficacy and safety of metformin for obesity: a systematic review. Pediatrics. 2021; 147(3):e20201610. DOI: 10.1542/peds.2020-1610. PMID: 33608415.

50. Pratt JSA, Browne A, Browne NT, Bruzoni M, Cohen M, Desai A, et al. ASMBS pediatric metabolic and bariatric surgery guidelines, 2018. Surg Obes Relat Dis. 2018; 14(7):882–901. DOI: 10.1016/j.soard.2018.03.019. PMID: 30077361. PMCID: PMC6097871.

51. Inge TH, Krebs NF, Garcia VF, Skelton JA, Guice KS, Strauss RS, et al. Bariatric surgery for severely overweight adolescents: concerns and recommendations. Pediatrics. 2004; 114(1):217–223. DOI: 10.1542/peds.114.1.217. PMID: 15231931.

52. Kim JH, Yun S, Hwang S, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr. 2018; 61(5):135–149. DOI: 10.3345/kjp.2018.61.5.135. PMID: 29853938. PMCID: PMC5976563.