Metabolic Syndrome in Pediatrics: Old Concepts Revised, New Concepts Discussed

Pediatric Clinics of North America

Volumn 58, Issue 5, 2011, Pages 1241-1255

  D'Adamo, Ebe ^a,b   Santoro, Nicola ^a   Caprio, Sonia ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CHIETI   (Italy)

Author keywords

Children; Insulin resistance; Metabolic syndrome; Obesity; Type 2 diabetes

Indexed keywords

INSULIN;

BODY MASS; CARBOHYDRATE METABOLISM; CHILD; CHILDHOOD OBESITY; CORONARY RISK; DIAGNOSTIC TEST; DISEASE ASSOCIATION; HUMAN; HYPERINSULINEMIA; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; OBESITY; PATHOGENESIS; REVIEW;

ADOLESCENT; BLOOD GLUCOSE; CHILD; DIABETES MELLITUS, TYPE 2; FATTY LIVER; HUMANS; INSULIN RESISTANCE; METABOLIC SYNDROME X; PEDIATRICS; PHENOTYPE;

EID: 80053608161     PISSN: 00313955     EISSN: 15578240     Source Type: Journal    
DOI: 10.1016/j.pcl.2011.07.005     Document Type: Review

References (103)

1. Reaven G.M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988, 37:1595-1607.
2. McGarry J.D. Banting lecture 2001: Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002, 51:7-18.
3. Zimmet P., Alberti K.G., Kaufman F., et al. IDF Consensus Group. The metabolic syndrome in children and adolescents-an IDF consensus report. Pediatr Diabetes 2007, 8:299-306.
4. Cook S., Weitzman M., Auinger P., et al. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003, 157:821-827.
5. Weiss R., Dziura J., Burgert T.S., et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004, 350:2362-2374.
6. Cruz M.L., Weigensberg M.J., Huang T.T., et al. The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab 2004, 89:108-113.
7. Ford E.S., Ajani U.A., Mokdad A.H. The metabolic syndrome and concentrations of C-reactive protein among U.S. youth. Diabetes Care 2005, 28:878-881. National Health and Nutrition Examination.
8. de Ferranti S.D., Gauvreau K., Ludwig D.S., et al. Prevalence of the metabolic syndrome in American adolescents: findings from the third national health and nutrition examination survey. Circulation 2004, 110:2494-2497.
9. Goodman E., Daniels S.R., Morrison J.A., et al. Contrasting prevalence of and demographic disparities in the World Health Organization and National Cholesterol Education Program Adult Treatment Panel III definitions of metabolic syndrome among adolescents. J Pediatr 2004, 145:445-451.
10. Batey L.S., Goff D.C., Tortolero S.R., et al. Summary measures of the insulin resistance syndrome are adverse among Mexican-American versus non-Hispanic white children: the Corpus Christi Child Heart Study. Circulation 1997, 96:4319-4325.
11. Arslanian S., Suprasongsin C., Janosky J.E. Insulin secretion and sensitivity in black versus white prepubertal healthy children. J Clin Endocrinol Metab 1997, 82:1923-1927.
12. Svec F., Nastasi K., Hilton C., et al. Black-white contrasts in insulin levels during pubertal development. The Bogalusa Heart Study. Diabetes 1992, 41:313-317.
13. Arslanian S., Suprasongsin C. Differences in the in vivo insulin secretion and sensitivity of healthy black versus white adolescents. J Pediatr 1996, 129:440-443.
14. Nguyen Q.M., Srinivasan S.R., Xu J.H., et al. Changes in risk variables of metabolic syndrome since childhood in pre-diabetic and type 2 diabetic subjects: the Bogalusa Heart Study. Diabetes Care 2008, 31:2044-2049.
15. World Health Organization Obesity. Preventing and managing the global epidemic 1998, Publication WHO/NUT/NCD/98.1.1998, World Health Organization, Geneva, Switzerland.
16. National Heart, Lung and Blood Institute Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes Res 1998, 6:S51-S210.
17. Cole T.J., Bellizzi M.C., Flegal K.M., et al. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000, 320:1240-1243.
18. Himes J.H., Dietz W.H. Guidelines for overweight in adolescent preventive services: recommendations from an expert committee. The Expert Committee on Clinical Guidelines for Overweight in Adolescent Preventive Services. Am J Clin Nutr 1994, 59:307-316.
19. Kuczmarski R.J., Ogden C.L., Guo S.S., et al. + 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11 2002, 246:1-190.
20. Fernández J.R., Redden D.T., Pietrobelli A., et al. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 2004, 145:439-444.
21. Janssen I., Katzmarzyk P.T., Srinivasan S.R., et al. Combined influence of body mass index and waist circumference on coronary artery disease risk factors among children and adolescents. Pediatrics 2005, 115:1623-1630.
22. Pouliot M.C., Després J.P., Lemieux S., et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994, 73:460-468.
23. Katzmarzyk P.T. Waist circumference percentiles for Canadian youth 11-18 y of age. Eur J Clin Nutr 2004, 58:1011-1015.
24. Zannolli R., Morgese G. Waist percentiles: a simple test for atherogenic disease?. Acta Paediatr 1996, 85:1368-1369.
25. McCarthy H.D., Jarrett K.V., Crawley H.F. The development of waist circumference percentiles in British children aged 5.0-16.9 y. Eur J Clin Nutr 2001, 55:902-907.
26. Dobbelsteyn C.J., Joffres M.R., MacLean D.R., et al. A comparative evaluation of waist circumference, waist-to-hip ratio and body mass index as indicators of cardiovascular risk factors. The Canadian Heart Health Surveys. Int J Obes Relat Metab Disord 2001, 25:652-661.
27. Janssen I., Katzmarzyk P.T., Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med 2002, 162:2074-2079.
28. Janssen I., Heymsfield S.B., Allison D.B., et al. Body mass index and waist circumference independently contribute to the prediction of nonabdominal, abdominal subcutaneous, and visceral fat. Am J Clin Nutr 2002, 75:683-688.
29. Thompson C.J., Ryu J.E., Craven T.E., et al. Central adipose distribution is related to coronary atherosclerosis. Arterioscler Thromb 1991, 11:327-333.
30. Van Pelt R.E., Evans E.M., Schechtman K.B., et al. Waist circumference vs body mass index for prediction of disease risk in postmenopausal women. Int J Obes Relat Metab Disord 2001, 25:1183-1188.
31. Maffeis C., Pietrobelli A., Grezzani A., et al. Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res 2001, 9:179-187.
32. Freedman D.S., Serdula M.K., Srinivasan S.R., et al. Relation of circumferences and skinfold thicknesses to lipid and insulin concentrations in children and adolescents: the Bogalusa Heart Study. Am J Clin Nutr 1999, 69:308-317.
33. Savva S.C., Tornaritis M., Savva M.E., et al. Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat Metab Disord 2000, 24:1453-1458.
34. Ferrannini E., Natali A., Capaldo B., et al. Insulin resistance, hyperinsulinemia, and blood pressure: role of age and obesity. European Group for the Study of Insulin Resistance (EGIR). Hypertension 1997, 30:1144-1149.
35. Fujimoto W.Y., Bergstrom R.W., Boyko E.J., et al. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study. Diabetes Care 1999, 22:1808-1812.
36. O'Shaughnessy I.M., Myers T.J., Stepniakowski K., et al. Glucose metabolism in abdominally obese hypertensive and normotensive subjects. Hypertension 1995, 26:186-192.
37. Björntorp P. Portal adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990, 10:493-496.
38. Williamson J.R., Kreisberg R.A., Felts P.W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A 1966, 56:247-254.
39. Steppan C.M., Bailey S.T., Bhat S., et al. The hormone resistin links obesity to diabetes. Nature 2001, 409:307-312.
40. Hotamisligil G.S., Peraldi P., Budavari A., et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 1996, 271:665-668.
41. Barzilai N., She L., Liu B.Q., et al. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 1999, 48:94-98.
42. Kim Y.W., Kim J.Y., Lee S.K. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats. J Korean Med Sci 1999, 14:539-545.
43. Gabriely I., Ma X.H., Yang X.M., et al. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?. Diabetes 2002, 51:2951-2958.
44. 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 2001, 285:2486-2497.
45. Terán-García M., Bouchard C. Genetics of metabolic syndrome. Appl Physiol Nutr Metab 2007, 32:89-114.
46. Kraja A.T., Hunt S.C., Pankow J.S., et al. An evaluation of the metabolic syndrome in the HyperGEN study. Nutr Metab 2005, 18:2.
47. Weiss R, Shaw M, Savoy M, et al. Obesity dynamics and cardio-vascular risk factor stability in obese adolescents. Pediatr Diabetes, in press.
48. Steinberger J., Daniels S.R., Eckel R.H., et al. American Heart Association Atherosclerosis, Hypertension, and Obesity in the young committee of the council on cardiovascular disease in the young; council on cardiovascular nursing; and council on nutrition, physical activity, and metabolism. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the young committee of the council on cardiovascular disease in the young; council on cardiovascular nursing; and council on nutrition, physical activity, and metabolism. Circulation 2009, 119:628-647.
49. Taittonen L., Uhari M., Nuutinen M., et al. Insulin and blood pressure among healthy children. Cardiovascular risk in young Finns. Am J Hypertens 1996, 9:194-199.
50. Bao W., Scrinivansan S.R., Berenson G.S. Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults: the Bogalusa Heart Study. Circulation 1996, 93:54-59.
51. Landsberg L. Hyperinsulinemia: possible role in obesity-induced hypertension. Hypertension 1992, 19:I61-I66.
52. DeFronzo R.A., Cooke C.R., Andres R., et al. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975, 55:845-855.
53. Stout R.W., Bierman E.L., Ross R. Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. Circ Res 1975, 36:319-327.
54. Assimacopoulos-Jeannet F., Brichard S., Rencurel F., et al. In vivo effects of hyperinsulinemia on lipogenic enzymes and glucose transporter expression in rat liver and adipose tissues. Metabolism 1995, 44:228-233.
55. Kamagate A., Dong H.H. FoxO1 integrates insulin signaling to VLDL production. Cell Cycle 2008, 7:3162-3170.
56. Caprio S., Plewe G., Diamond M.P., et al. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr 1989, 114:963-967.
57. Moran A., Steffen L.M., Jacobs D.R., et al. Relation of C-reactive protein to insulin resistance and cardiovascular risk factors in youth. Diabetes Care 2005, 28:1763-1768.
58. Lambert M., Delvin E.E., Paradis G., et al. C-reactive protein and features of the metabolic syndrome in a population-based sample of children and adolescents. Clin Chem 2004, 50:1762-1768.
59. Hiura M., Kikuchi T., Nagasaki K., et al. Elevation of serum C-reactive protein levels is associated with obesity in boys. Hypertens Res 2003, 26:541-546.
60. Körner A., Kratzsch J., Gausche R., et al. New predictors of the metabolic syndrome in children-role of adipocytokines. Pediatr Res 2007, 61:640-645.
61. Nemet D., Wang P., Funahashi T., et al. Adipocytokines, body composition, and fitness in children. Pediatr Res 2003, 53:148-152.
62. Dixon D., Goldberg R., Schneiderman N., et al. Gender differences in TNF-alpha levels among obese vs nonobese Latino children. Eur J Clin Nutr 2004, 58:696-699.
63. Ruan H., Lodish H.F. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 2003, 14:447-455.
64. Maffeis C., Silvagni D., Bonadonna R., et al. Fat cell size, insulin sensitivity, and inflammation in obese children. J Pediatr 2007, 151:647-652.
65. Hara K., Yamauchi T., Kadowaki T. Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep 2005, 5:136-140.
66. Kadowaki T., Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005, 26:439-451.
67. Böttner A., Kratzsch J., Müller G., et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004, 89:4053-4061.
68. Reinehr T., Roth C., Menke T., et al. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab 2004, 89:3790-3794.
69. Diagnosis and classification of diabetes mellitus. Diabetes Care 2008, 31:S55-S60. American Diabetes Association.
70. Meyer C., Pimenta W., Woerle H.J., et al. Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans. Diabetes Care 2006, 29:1909-1914.
71. The Writing Group for the SEARCH for Diabetes in Youth Study Group Incidence of diabetes in youth in the United States. JAMA 2007, 297:2716-2724.
72. Sinha R., Fisch G., Teague B., et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002, 346:802-810.
73. Invitti C., Gilardini L., Viberti G. Impaired glucose tolerance in obese children and adolescents. N Engl J Med 2002, 347:290-292.
74. Gilardini L., Girola A., Morabito F., et al. Fasting glucose is not useful in identifying obese white children with impaired glucose tolerance. J Pediatr 2006, 149:282.
75. Lyssenko V., Jonsson A., Almgren P., et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 2008, 359:2220-2232.
76. Weiss R., Caprio S. The metabolic consequences of childhood obesity. Best Pract Res Clin Endocrinol Metab 2005, 19:405-419.
77. Cali A.M., Dalla Man C., Cobelli C., et al. Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents. Diabetes Care 2009, 32:456-461.
78. Gungor N., Arslanian S. Progressive beta cell failure in type 2 diabetes mellitus of youth. J Pediatr 2004, 44:656-659.
79. West N.A., Hamman R.F., Mayer-Davis E.J., et al. Cardiovascular risk factors among youth with and without type 2 diabetes: differences and possible mechanisms. Diabetes Care 2009, 32:175-180.
80. Burgert T.S., Taksali S.E., Dziura J., et al. Alanine aminotransferase levels fatty liver in childhood obesity: Associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 2006, 91:2487-2494.
81. Manco M., Marcellini M., Devito R., et al. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes (Lond) 2008, 32:381-387.
82. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002, 346:1221-1231.
83. Caprio S., Daniels S.R., Drewnowski A., et al. Influence of race, ethnicity, and culture on childhood obesity: implications for prevention and treatment: a consensus statement of Shaping America's Health and the Obesity Society. Diabetes Care 2008, 31:2211-2221.
84. Tominaga K., Kurata J.H., Chen Y.K., et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 1995, 40:2002-2009.
85. Franzese A., Vajro P., Argenziano A., et al. Liver involvement in obese children. Ultrasonography and liver enzymes levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997, 42:1428-1432.
86. Schwimmer J.B., Deutsch R., Kahen T., et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006, 118:1388-1393.
87. Strauss R.S., Barlow S.E., Dietz W.H. Prevalence of abnormal serum amino transferase values in overweight and obese adolescents. J Pediatr Gastroenterol Nutr 2000, 136:727-733.
88. Ekstedt M., Franzén L.E., Mathiesen U.L., et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006, 44:865-873.
89. Molleston J.P., White F., Teckman J., et al. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 2002, 97:2460-2462.
90. Kinugasa A., Tsunamoto K., Furukawa N., et al. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gastroenterol Nutr 1984, 3:408-414.
91. Angelico F., Del B.M., Conti R., et al. Non-alcoholic fatty liver syndrome: A hepatic consequence of common metabolic diseases. J Gastroenterol Hepatol 2003, 18:588-594.
92. Angelico F., Del B.M., Conti R., et al. Insulin resistance, the metabolic syndrome and non-alcoholic fatty liver disease. J Clin Endocrinol Metab 2005, 90:1578-1582.
93. Mandato C., Lucariello S., Licenziati M.R., et al. Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease. J Pediatr 2005, 147:62-66.
94. Day C.P., James O.F.W. Steatohepatitis: a tale of two " hits" Gastroenterology 1998, 114:842-845.
95. Browning J.D., Horton J.D. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004, 114:147-152.
96. Berson A., De B.V., Letteron P., et al. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 1998, 114:764-774.
97. Lavine J.E. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000, 136:734-738.
98. Pietrangelo A. Metals. Oxidative stress and hepatic fibrogenesis. Semin Liver Dis 1996, 16:13-30.
99. Schwimmer J.B., Pardee P.E., Lavine J.E., et al. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008, 118:277-283.
100. Cali A.M.G., De Oliveira A.M., Kim H., et al. Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link?. Hepatology 2009, 49:1896-1903.
101. Sattar N., Scherbakova O., Ford I., et al. West of Scotland Coronary Prevention Study Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes 2004, 53:2855-2860.
102. Taksali S.E., Caprio S., Dziura J., et al. High visceral and low abdominal subcutaneous fat stores in the obese adolescent. Diabetes 2008, 57:367-371.
103. Cali A.M.G., Caprio S. Ectopic fat deposition and the metabolic syndrome in obese children and adolescents. Horm Res 2009, 71:2-7.