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

Endocrinology and Metabolism Clinics of North America

Volumn 38, Issue 3, 2009, Pages 549-563

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

^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

ADIPONECTIN; C REACTIVE PROTEIN; CHOLESTEROL; FATTY ACID; GLUCOSE; GROWTH HORMONE; HIGH DENSITY LIPOPROTEIN; INSULIN; INTERLEUKIN 6; LIPID; LOW DENSITY LIPOPROTEIN; SOMATOMEDIN C; TRANSCRIPTION FACTOR FOXO; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; VERY LOW DENSITY LIPOPROTEIN;

ANTHROPOMETRY; ATHEROSCLEROSIS; BODY MASS; CARDIOVASCULAR RISK; CHILD; CHILD HEALTH CARE; DISEASE ASSOCIATION; DYSLIPIDEMIA; FATTY LIVER; GENETIC PREDISPOSITION; HERITABILITY; HUMAN; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PRIORITY JOURNAL; REVIEW; WAIST CIRCUMFERENCE;

CHILD; DIABETES MELLITUS, TYPE 2; HUMANS; INSULIN RESISTANCE; METABOLIC SYNDROME X;

EID: 69249183408     PISSN: 08898529     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ecl.2009.06.002     Document Type: Review

References (103)

1. Reaven G.M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37 (1988) 1595-1607
2. McGarry J.D. Banting lecture 2001: Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51 (2002) 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 8 (2007) 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 157 (2003) 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 350 (2004) 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 89 (2004) 108-113
7. Ford E.S., Ajani U.A., Mokdad A.H., and National Health and Nutrition Examination. The metabolic syndrome and concentrations of C-reactive protein among U.S. youth. Diabetes Care 28 (2005) 878-881
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 110 (2004) 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 145 (2004) 445-451
10. Batey L.S., Goff Jr. 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 96 (1997) 4319-4325
11. Arslanian S., Suprasongsin C., and Janosky J.E. Insulin secretion and sensitivity in black versus white prepubertal healthy children. J Clin Endocrinol Metab 82 (1997) 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 41 (1992) 313-317
13. Arslanian S., and Suprasongsin C. Differences in the in vivo insulin secretion and sensitivity of healthy black versus white adolescents. J Pediatr 129 (1996) 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 31 (2008) 2044-2049
15. World Health Organization. Obesity. Preventing and managing the global epidemic. Publication WHO/NUT/NCD/98.1.1998 (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 6 (1998) 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 320 (2000) 1240-1243
18. Himes J.H., and 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 59 (1994) 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 11 246 (2002) 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 145 (2004) 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 115 (2005) 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 73 (1994) 460-468
23. Katzmarzyk P.T. Waist circumference percentiles for Canadian youth 11-18 y of age. Eur J Clin Nutr 58 (2004) 1011-1015
24. Zannolli R., and Morgese G. Waist percentiles: a simple test for atherogenic disease?. Acta Paediatr 85 (1996) 1368-1369
25. McCarthy H.D., Jarrett K.V., and Crawley H.F. The development of waist circumference percentiles in British children aged 5.0-16.9 y. Eur J Clin Nutr 55 (2001) 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 25 (2001) 652-661
27. Janssen I., Katzmarzyk P.T., and Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med 162 (2002) 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 75 (2002) 683-688
29. Thompson C.J., Ryu J.E., Craven T.E., et al. Central adipose distribution is related to coronary atherosclerosis. Arterioscler Thromb 11 (1991) 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 25 (2001) 1183-1188
31. Maffeis C., Pietrobelli A., Grezzani A., et al. Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res 9 (2001) 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 69 (1999) 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 24 (2000) 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 30 (1997) 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 22 (1999) 1808-1812
36. O'Shaughnessy I.M., Myers T.J., Stepniakowski K., et al. Glucose metabolism in abdominally obese hypertensive and normotensive subjects. Hypertension 26 (1995) 186-192
37. Björntorp P. Portal adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10 (1990) 493-496
38. Williamson J.R., Kreisberg R.A., and Felts P.W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A 56 (1966) 247-254
39. Steppan C.M., Bailey S.T., Bhat S., et al. The hormone resistin links obesity to diabetes. Nature 409 (2001) 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 271 (1996) 665-668
41. Barzilai N., She L., Liu B.Q., et al. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 48 (1999) 94-98
42. Kim Y.W., Kim J.Y., and 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 14 (1999) 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 51 (2002) 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 285 (2001) 2486-2497
45. Terán-García M., and Bouchard C. Genetics of metabolic syndrome. Appl Physiol Nutr Metab 32 (2007) 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 18 (2005) 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 119 (2009) 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 9 (1996) 194-199
50. Bao W., Scrinivansan S.R., and 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 93 (1996) 54-59
51. Landsberg L. Hyperinsulinemia: possible role in obesity-induced hypertension. Hypertension 19 (1992) 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 55 (1975) 845-855
53. Stout R.W., Bierman E.L., and Ross R. Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. Circ Res 36 (1975) 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 44 (1995) 228-233
55. Kamagate A., and Dong H.H. FoxO1 integrates insulin signaling to VLDL production. Cell Cycle 7 (2008) 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 114 (1989) 963-967
57. Moran A., Steffen L.M., Jacobs Jr. D.R., et al. Relation of C-reactive protein to insulin resistance and cardiovascular risk factors in youth. Diabetes Care 28 (2005) 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 50 (2004) 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 26 (2003) 541-546
60. Körner A., Kratzsch J., Gausche R., et al. New predictors of the metabolic syndrome in children-role of adipocytokines. Pediatr Res 61 (2007) 640-645
61. Nemet D., Wang P., Funahashi T., et al. Adipocytokines, body composition, and fitness in children. Pediatr Res 53 (2003) 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 58 (2004) 696-699
63. Ruan H., and Lodish H.F. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14 (2003) 447-455
64. Maffeis C., Silvagni D., Bonadonna R., et al. Fat cell size, insulin sensitivity, and inflammation in obese children. J Pediatr 151 (2007) 647-652
65. Hara K., Yamauchi T., and Kadowaki T. Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep 5 (2005) 136-140
66. Kadowaki T., and Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 26 (2005) 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 89 (2004) 4053-4061
68. Reinehr T., Roth C., Menke T., et al. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab 89 (2004) 3790-3794
69. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 31 (2008) S55-S60
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 29 (2006) 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 297 (2007) 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 346 (2002) 802-810
73. Invitti C., Gilardini L., and Viberti G. Impaired glucose tolerance in obese children and adolescents. N Engl J Med 347 (2002) 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 149 (2006) 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 359 (2008) 2220-2232
76. Weiss R., and Caprio S. The metabolic consequences of childhood obesity. Best Pract Res Clin Endocrinol Metab 19 (2005) 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 32 (2009) 456-461
78. Gungor N., and Arslanian S. Progressive beta cell failure in type 2 diabetes mellitus of youth. J Pediatr 44 (2004) 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 32 (2009) 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 91 (2006) 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) 32 (2008) 381-387
82. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 346 (2002) 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 31 (2008) 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 40 (1995) 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 42 (1997) 1428-1432
86. Schwimmer J.B., Deutsch R., Kahen T., et al. Prevalence of fatty liver in children and adolescents. Pediatrics 118 (2006) 1388-1393
87. Strauss R.S., Barlow S.E., and Dietz W.H. Prevalence of abnormal serum amino transferase values in overweight and obese adolescents. J Pediatr Gastroenterol Nutr 136 (2000) 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 44 (2006) 865-873
89. Molleston J.P., White F., Teckman J., et al. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 97 (2002) 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 3 (1984) 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 18 (2003) 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 90 (2005) 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 147 (2005) 62-66
94. Day C.P., and James O.F.W. Steatohepatitis: a tale of two "hits". Gastroenterology 114 (1998) 842-845
95. Browning J.D., and Horton J.D. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114 (2004) 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 114 (1998) 764-774
97. Lavine J.E. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 136 (2000) 734-738
98. Pietrangelo A. Metals. Oxidative stress and hepatic fibrogenesis. Semin Liver Dis 16 (1996) 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 118 (2008) 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 49 (2009) 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 53 (2004) 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 57 (2008) 367-371
103. Cali A.M.G., and Caprio S. Ectopic fat deposition and the metabolic syndrome in obese children and adolescents. Horm Res 71 (2009) 2-7