Identification and treatment of metabolic complications in pediatric obesity

Reviews in Endocrine and Metabolic Disorders

Volumn 10, Issue 3, 2009, Pages 167-188

  Ode, Katie Larson ^a   Frohnert, Brigitte I ^a   Nathan, Brandon M ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Fatty liver disease; Insulin resistance; Metabolic syndrome; Polycystic ovary disease; Type 2 diabetes mellitus

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALPHA GLUCOSIDASE INHIBITOR; ALPHA TOCOPHEROL; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIANDROGEN; ANTIDIABETIC AGENT; ASCORBIC ACID; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DECAPENTAPLEGIC PROTEIN INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; GLIMEPIRIDE; GLITINIDE; GLUCAGON LIKE PEPTIDE 1 AGONIST; INSULIN; INSULIN SENSITIZING AGENT; METFORMIN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; ORAL CONTRACEPTIVE AGENT; PENTOXIFYLLINE; PIOGLITAZONE; PLACEBO; RETINOL BINDING PROTEIN 4; ROSIGLITAZONE; SALICYLIC ACID; SULFONYLUREA; TROGLITAZONE; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

BODY MASS; CARDIOVASCULAR RISK; CHILDHOOD DISEASE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DIET THERAPY; DRUG PROTEIN BINDING; GLUCOSE TOLERANCE; HUMAN; HYPERANDROGENISM; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERTENSION; INFERTILITY; INFLAMMATION; INSULIN RESISTANCE; KINESIOTHERAPY; LIFESTYLE MODIFICATION; LIVER TOXICITY; MENSTRUAL IRREGULARITY; METABOLIC DISORDER; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; OBESITY; OVARY POLYCYSTIC DISEASE; PREVALENCE; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; REVIEW; SCREENING TEST;

CHILD; DIABETES MELLITUS, TYPE 2; FATTY LIVER; FEMALE; HUMANS; INSULIN RESISTANCE; MALE; METABOLIC SYNDROME X; MODELS, THEORETICAL; OBESITY; POLYCYSTIC OVARY SYNDROME;

EID: 70350200840     PISSN: 13899155     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11154-009-9115-7     Document Type: Review

References (210)

1. CL Ogden MD Carroll LR Curtin MA McDowell CJ Tabak KM Flegal 2006 Prevalence of overweight and obesity in the United States, 1999-2004 JAMA 295 1549 55 16595758
2. D Dabelea RA Bell RB D'Agostino G Imperatore JM Johansen B Linder, et al. 2007 Incidence of diabetes in youth in the United States JAMA 297 2716 24 17595272
3. F Marra C Bertolani 2009 Adipokines in liver diseases Hepatology 50 957 69 19585655
4. F González NS Rote J Minium JP Kirwan 2009 Evidence of proatherogenic inflammation in polycystic ovary syndrome Metab Clin Exp 58 954 62 19375763
5. C Savoia EL Schiffrin 2007 Reduction of C-reactive protein and the use of anti-hypertensives Vasc Health Risk Manag 3 975 83 18200816
6. CF Rueda-Clausen P López-Jaramillo C Luengas M del Pilar Oubiña V Cachofeiro V Lahera 2009 Inflammation but not endothelial dysfunction is associated with the severity of coronary artery disease in dyslipidemic subjects Mediators Inflamm 2009 2009 469169
7. D Gozal L Kheirandish-Gozal 2008 Cardiovascular morbidity in obstructive sleep apnea:oxidative stress, inflammation, and much more Am J Respir Crit Care Med 177 369 75 17975198
8. N Rasouli PA Kern 2008 Adipocytokines and the metabolic complications of obesity J Clin Endocrinol Metab 93 S64 73 18987272
9. D Nemet P Wang T Funahashi Y Matsuzawa S Tanaka L Engelman, et al. 2003 Adipocytokines, body composition, and fitness in children Pediatr Res 53 148 52 12508095
10. R Anty S Bekri N Luciani M Saint-Paul M Dahman A Iannelli, et al. 2006 The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, type 2 diabetes, and NASH Am J Gastroenterol 101 1824 33 16790033
11. RJ Bisoendial RS Birjmohun F Akdim C Van 't Veer CA Spek D Hartman, et al. 2009 C-reactive protein elicits white blood cell activation in humans Am J Med 122 582.e1-9 19486722
12. PM Ridker 2007 C-reactive protein and the prediction of cardiovascular events among those at intermediate risk:moving an inflammatory hypothesis toward consensus J Am Coll Cardiol 49 2129 38 17531663
13. AA Venner ME Lyon PK Doyle-Baker 2006 Leptin:a potential biomarker for childhood obesity? Clin Biochem 39 1047 56 17005171
14. RS Ahima JS Flier 2000 Leptin Annu Rev Physiol 62 413 37 10845097
15. S Loffreda SQ Yang HZ Lin CL Karp ML Brengman DJ Wang, et al. 1998 Leptin regulates proinflammatory immune responses FASEB J 12 57 65 9438411
16. J Bastard M Maachi C Lagathu MJ Kim M Caron H Vidal, et al. 2006 Recent advances in the relationship between obesity, inflammation, and insulin resistance Eur Cytokine Netw 17 4 12 16613757
17. Plaisance EP, Grandjean PW, Judd RL, Jones KW, Taylor JK. The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations. Metab Clin Exp. 2009; doi: 10.1016/j.metabol.2009.04.038.
18. A Böttner J Kratzsch G Müller TM Kapellen S Blüher E Keller, et al. 2004 Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels J Clin Endocrinol Metab 89 4053 61 15292348
19. Q Yang TE Graham N Mody F Preitner OD Peroni JM Zabolotny, et al. 2005 Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes Nature 436 356 62 16034410
20. S Gavi S Qurashi LM Stuart R Lau MM Melendez DC Mynarcik, et al. 2008 Influence of age on the association of retinol-binding protein 4 with metabolic syndrome Obesity (Silver Spring) 16 893 5
21. A Fukuhara M Matsuda M Nishizawa K Segawa M Tanaka K Kishimoto, et al. 2005 Visfatin: a protein secreted by visceral fat that mimics the effects of insulin Science 307 426 30 15604363
22. JR Revollo A Körner KF Mills A Satoh T Wang A Garten, et al. 2007 Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme Cell Metab 6 363 75 17983582
23. SW Liu SB Qiao JS Yuan DQ Liu, et al. 2009 Association of plasma visfatin levels with inflammation, atherosclerosis, and acute coronary syndromes in humans Clin Endocrinol (Oxf) 71 202 7
24. MK Badman JS Flier 2007 The adipocyte as an active participant in energy balance and metabolism Gastroenterology 132 2103 15 17498506
25. V Vachharajani DN Granger 2009 Adipose tissue: a motor for the inflammation associated with obesity IUBMB Life 61 424 30 19319966
26. I Kowalska M Straczkowski A Nikolajuk A Adamska M Karczewska-Kupczewska E Otziomek, et al. 2008 Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome Metab Clin Exp 57 1539 44 18940391
27. ES Ford UA Ajani AH Mokdad 2005 The metabolic syndrome and concentrations of C-reactive protein among U.S. youth Diabetes Care 28 878 81 15793189
28. M Valle R Martos F Gascón R Cañete MA Zafra R Morales 2005 Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome Diabetes Metab 31 55 62 15803114
29. J Wärnberg A Marcos 2008 Low-grade inflammation and the metabolic syndrome in children and adolescents Curr Opin Lipidol 19 11 5 18196981
30. J Wärnberg E Nova J Romeo LA Moreno M Sjöström A Marcos 2007 Lifestyle-related determinants of inflammation in adolescence Br J Nutr 98 Suppl 1 S116 20 17922948
31. Cizmecioglu F, Etiler N, Ergen A, Keser A, Hekim N, Hamzaoglu O, et al. Association of Adiponectin, Resistin and High Sensitive CRP Level with the Metabolic Syndrome in Childhood and Adolescence. Exp Clin Endocrinol Diabetes. 2009; doi: 10.1055/s-0028-1112151.
32. HC McGill CA McMahan 1998 Determinants of atherosclerosis in the young. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group Am J Cardiol 82 30T 6 9860371
33. GS Berenson SR Srinivasan W Bao WP Newman RE Tracy WA Wattigney 1998 Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study N Engl J Med 338 1650 6 9614255
34. A Guilherme JV Virbasius V Puri MP Czech 2008 Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes Nat Rev Mol Cell Biol 9 367 77 18401346
35. BB Kahn JS Flier 2000 Obesity and insulin resistance J Clin Invest 106 473 81 10953022
36. BM Nathan A Moran 2008 Metabolic complications of obesity in childhood and adolescence:more than just diabetes Curr Opin Endocrinol Diabetes Obes 15 21 9 18185059
37. MG Huerta JN Roemmich ML Kington VE Bovbjerg AL Weltman VF Holmes, et al. 2005 Magnesium deficiency is associated with insulin resistance in obese children Diabetes Care 28 1175 81 15855585
38. M Krekoukia GP Nassis G Psarra K Skenderi GP Chrousos LS Sidossis 2007 Elevated total and central adiposity and low physical activity are associated with insulin resistance in children Metab Clin Exp 56 206 13 17224334
39. B Schwartz DR Jacobs A Moran J Steinberger C Hong AR Sinaiko 2008 Measurement of Insulin Sensitivity in Children:Comparison Between the Euglycemic Hyperinsulinemic Clamp and Surrogate Measures Diabetes Care 31 783 8 18174496
40. F Eyzaguirre V Mericq 2009 Insulin resistance markers in children Horm Res 71 65 74 19129710
41. JM Lee MJ Okumura MM Davis WH Herman JG Gurney 2006 Prevalence and determinants of insulin resistance among U.S. adolescents:a population-based study Diabetes Care 29 2427 32 17065679
42. AR Sinaiko J Steinberger A Moran C Hong RJ Prineas DR Jacobs 2006 Influence of insulin resistance and body mass index at age 13 on systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19 Hypertension 48 730 6 16923995
43. AR Sinaiko DR Jacobs J Steinberger A Moran R Luepker AP Rocchini, et al. 2001 Insulin resistance syndrome in childhood:associations of the euglycemic insulin clamp and fasting insulin with fatness and other risk factors J Pediatr 139 700 7 11713450
44. DE Williams BL Cadwell YJ Cheng CC Cowie EW Gregg LS Geiss, et al. 2005 Prevalence of impaired fasting glucose and its relationship with cardiovascular disease risk factors in US adolescents, 1999-2000 Pediatrics 116 1122 6 16263998
45. AC Oliveira AM Oliveira LF Adan NF Oliveira AM Silva AM Ladeia 2008 C-reactive protein and metabolic syndrome in youth:a strong relationship? Obesity (Silver Spring) 16 1094 8
46. J Steinberger SR Daniels RH Eckel L Hayman RH Lustig B McCrindle, et al. 2009 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 119 628 47 19139390
47. AR Sinaiko J Steinberger A Moran RJ Prineas B Vessby S Basu, et al. 2005 Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence Circulation 111 1985 91 15837953
48. JA Morrison LA Friedman P Wang CJ Glueck 2008 Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later J. Pediatr 152 201 6 18206689
49. BH Sanders LM Lubsch DS West 2006 Prevalence and treatment of metabolic syndrome in adolescents with type 2 diabetes Ann Pharmacother 40 1517 21 16896016
50. JB Schwimmer PE Pardee JE Lavine AK Blumkin S Cook 2008 Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease Circulation 118 277 83 18591439
51. U Ekelund S Anderssen LB Andersen CJ Riddoch LB Sardinha J Luan, et al. 2009 Prevalence and correlates of the metabolic syndrome in a population-based sample of European youth Am J Clin Nutr 89 90 6 19056570
52. R Kelishadi EM Razaghi MM Gouya G Ardalan R Gheiratmand A Delavari, et al. 2007 Association of physical activity and the metabolic syndrome in children and adolescents: CASPIAN study Horm Res 67 46 52 17035710 (Pubitemid 46257007)
53. Y Pan CA Pratt 2008 Metabolic syndrome and its association with diet and physical activity in US adolescents J Am Diet Assoc 108 276 86 18237576 discussion 286
54. S Cook P Auinger C Li ES Ford 2008 Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999-2002 J Pediatr 152 165 70 18206683
55. R Jago T Baranowski J Buse S Edelstein P Galassetti J Harrell, et al. 2008 Prevalence of the metabolic syndrome among a racially/ethnically diverse group of U.S. eighth-grade adolescents and associations with fasting insulin and homeostasis model assessment of insulin resistance levels: Studies to Treat or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Prevention Study Group Diabetes Care 31 10 2020 5
56. R Monzavi D Dreimane ME Geffner S Braun B Conrad M Klier, et al. 2006 Improvement in risk factors for metabolic syndrome and insulin resistance in overweight youth who are treated with lifestyle intervention Pediatrics 117 e1111 8 16682491
57. RM Steele S Brage K Corder NJ Wareham U Ekelund 2008 Physical activity, cardiorespiratory fitness, and the metabolic syndrome in youth J Appl Physiol 105 342 51 18369096
58. KD DuBose JC Eisenmann JE Donnelly 2007 Aerobic fitness attenuates the metabolic syndrome score in normal-weight, at-risk-for-overweight, and overweight children Pediatrics 120 e1262 8 17974719
59. AE Mark I Janssen 2008 Relationship between screen time and metabolic syndrome in adolescents J Public Health (Oxf) 30 153 60
60. K Casazza A Dulin-Keita BA Gower JR Fernandez 2009 Differential influence of diet and physical activity on components of metabolic syndrome in a multiethnic sample of children J Am Diet Assoc 109 236 44 19167950
61. SM Grundy JI Cleeman SR Daniels KA Donato RH Eckel BA Franklin, et al. 2006 Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement Curr Opin Cardiol 21 1 6 16355022
62. NJ Stone D Saxon 2005 Approach to treatment of the patient with metabolic syndrome:lifestyle therapy Am J Cardiol 96 15E 21 16098838
63. AK Chen CK Roberts RJ Barnard 2006 Effect of a short-term diet and exercise intervention on metabolic syndrome in overweight children Metab Clin Exp 55 871 8 16784957
64. J Stevens J Cai KR Evenson R Thomas 2002 Fitness and fatness as predictors of mortality from all causes and from cardiovascular disease in men and women in the lipid research clinics study Am J Epidemiol 156 832 41 12397001
65. J Sacheck 2008 Pediatric obesity: an inflammatory condition? JPEN J Parenter Enteral Nutr 32 633 7 18974243
66. NPE Kadoglou F Iliadis N Angelopoulou D Perrea G Ampatzidis CD Liapis, et al. 2007 The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus Eur J Cardiovasc Prev Rehabil 14 837 43 18043308
67. E Goldhammer A Tanchilevitch I Maor Y Beniamini U Rosenschein M Sagiv 2005 Exercise training modulates cytokines activity in coronary heart disease patients Int J Cardiol 100 93 9 15820291
68. AL Carrel RR Clark SE Peterson BA Nemeth J Sullivan DB Allen 2005 Improvement of fitness, body composition, and insulin sensitivity in overweight children in a school-based exercise program: a randomized, controlled study Arch Pediatr Adolesc Med 159 963 8 16203942
69. M Savoye M Shaw J Dziura WV Tamborlane P Rose C Guandalini, et al. 2007 Effects of a weight management program on body composition and metabolic parameters in overweight children: a randomized controlled trial JAMA 297 2697 704 17595270
70. ES Kim J Im KC Kim JH Park S Suh ES Kang, et al. 2007 Improved insulin sensitivity and adiponectin level after exercise training in obese Korean youth Obesity (Silver Spring) 15 3023 30
71. T Reinehr B Stoffel-Wagner CL Roth 2008 Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss J Clin Endocrinol Metab 93 2287 93 18397979
72. O Pinhas-Hamiel L Lerner-Geva N Copperman MS Jacobson 2008 Insulin resistance and parental obesity as predictors to response to therapeutic life style change in obese children and adolescents 10-18 years old J Adolesc Health 43 437 43 18848671
73. TR Rohrer VF Rizzo JJ Cäsar O Muelbredt S Sprengart L Gortner, et al. 2008 Changes in hepatic risk factors, metabolic variables, body composition, and physical fitness in obese children after a one-year weight loss program J Pediatr Endocrinol Metab 21 837 45 18924577
74. GP Nassis K Papantakou K Skenderi M Triandafillopoulou SA Kavouras M Yannakoulia, et al. 2005 Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls Metab Clin Exp 54 1472 9 16253636
75. J Faintuch LM Horie HV Barbeiro DF Barbeiro FG Soriano RK Ishida, et al. 2007 Systemic inflammation in morbidly obese subjects:response to oral supplementation with alpha-linolenic acid Obes Surg 17 341 7 17546842
76. LT Bloedon S Balikai J Chittams SC Cunnane JA Berlin DJ Rader, et al. 2008 Flaxseed and cardiovascular risk factors:results from a double blind, randomized, controlled clinical trial J Am Coll Nutr 27 65 74 18460483
77. D Molnár T Decsi B Koletzko 2004 Reduced antioxidant status in obese children with multimetabolic syndrome Int J Obes Relat Metab Disord 28 1197 202 15314634
78. A Lütjens JL Smit 1977 Effect of biguanide treatment in obese children Helv Paediatr Acta 31 473 80 853001
79. K Love-Osborne J Sheeder P Zeitler 2008 Addition of metformin to a lifestyle modification program in adolescents with insulin resistance J Pediatr 152 817 22 18492523
80. S Srinivasan GR Ambler LA Baur SP Garnett M Tepsa F Yap, et al. 2006 Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents:improvement in body composition and fasting insulin J Clin Endocrinol Metab 91 2074 80 16595599
81. TS Burgert EJ Duran R Goldberg-Gell J Dziura CW Yeckel S Katz, et al. 2008 Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance Pediatr Diabetes 9 567 76 18761646
82. ME Atabek O Pirgon 2008 Use of metformin in obese adolescents with hyperinsulinemia:a 6-month, randomized, double-blind, placebo-controlled clinical trial J Pediatr Endocrinol Metab 21 339 48 18556965
83. M Freemark D Bursey 2001 The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes Pediatrics 107 E55 11335776
84. JP Kay R Alemzadeh G Langley L D'Angelo P Smith S Holshouser 2001 Beneficial effects of metformin in normoglycemic morbidly obese adolescents Metab Clin Exp 50 1457 61 11735093
85. WC Knowler E Barrett-Connor SE Fowler RF Hamman JM Lachin EA Walker, et al. 2002 Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin N Engl J Med 346 393 403 11832527
86. P Zeitler L Epstein M Grey K Hirst F Kaufman W Tamborlane, et al. 2007 Treatment options for type 2 diabetes in adolescents and youth:a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes Pediatr Diabetes 8 74 87 17448130
87. N Gungor T Hannon I Libman F Bacha S Arslanian 2005 Type 2 diabetes mellitus in youth:the complete picture to date Pediatr Clin North Am 52 1579 609 16301084
88. S Shalitin M Abrahami P Lilos M Phillip 2005 Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel Int J Obes (Lond) 29 571 8
89. A Fagot-Campagna JB Saaddine KM Flegal GL Beckles 2001 Diabetes, impaired fasting glucose, and elevated HbA1c in U.S. adolescents:the Third National Health and Nutrition Examination Survey Diabetes Care 24 834 7 11347739
90. M Wabitsch H Hauner M Hertrampf R Muche B Hay H Mayer, et al. 2004 Type II diabetes mellitus and impaired glucose regulation in Caucasian children and adolescents with obesity living in Germany Int J Obes Relat Metab Disord 28 307 13 14724655
91. R Sinha G Fisch B Teague WV Tamborlane B Banyas K Allen, et al. 2002 Prevalence of impaired glucose tolerance among children and adolescents with marked obesity N Engl J Med 346 802 10 11893791
92. A Szamosi A Czinner T Szamosi A Sallai M Hatunic Z Berla, et al. 2008 Effect of diet and physical exercise treatment on insulin resistance syndrome of schoolchildren J Am Coll Nutr 27 177 83 18460496
93. IM Libman E Barinas-Mitchell A Bartucci R Robertson S Arslanian 2008 Reproducibility of the oral glucose tolerance test in overweight children J Clin Endocrinol Metab 93 4231 7 18713820
94. MI Goran J Davis L Kelly G Shaibi D Spruijt-Metz SM Soni, et al. 2008 Low prevalence of pediatric type 2 diabetes:where's the epidemic? J Pediatr 152 753 5 18492508
95. AL Rosenbloom JR Joe RS Young WE Winter 1999 Emerging epidemic of type 2 diabetes in youth Diabetes Care 22 345 54 10333956
96. DM Nathan B Balkau E Bonora K Borch-Johnsen JB Buse S Colagiuri 2009 International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes Diabetes Care 32 7 1327 54
97. S Benavides J Striet J Germak MC Nahata 2005 Efficacy and safety of hypoglycemic drugs in children with type 2 diabetes mellitus Pharmacotherapy 25 803 9 15927898
98. JPH Shield R Lynn KC Wan L Haines TG Barrett 2009 Management and 1 year outcome for UK children with type 2 diabetes Arch Dis Child 94 206 9 18838418
99. M Gottschalk T Danne A Vlajnic JF Cara 2007 Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes:a randomized, single-blind comparative study Diabetes Care 30 790 4 17392540
100. TS Hannon G Rao SA Arslanian 2005 Childhood obesity and type 2 diabetes mellitus Pediatrics 116 473 80 16061606
101. AL Rosenbloom JH Silverstein S Amemiya P Zeitler GJ Klingensmith 2008 ISPAD Clinical Practice Consensus Guideline 2006-2007. Type 2 diabetes mellitus in the child and adolescent Pediatr Diabetes 9 512 26 18694453
102. E Jacobson-Dickman L Levitsky 2005 Oral agents in managing diabetes mellitus in children and adolescents Pediatr Clin North Am 52 1689 703 16301089
103. KL Jones S Arslanian VA Peterokova J Park MJ Tomlinson 2002 Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial Diabetes Care 25 89 94 11772907
104. BB Yeap 2009 Controversies in type 2 diabetes-An update Aust Fam Physician 38 22 5 19283231
105. CW Chia JM Egan 2008 Incretin-based therapies in type 2 diabetes mellitus J Clin Endocrinol Metab 93 3703 16 18628530
106. A Fleischman SE Shoelson R Bernier AB Goldfine 2008 Salsalate improves glycemia and inflammatory parameters in obese young adults Diabetes Care 31 289 94 17959861
107. M Yuan N Konstantopoulos J Lee L Hansen ZW Li M Karin, et al. 2001 Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta Science 293 1673 7 11533494
108. E Park V Wong X Guan AI Oprescu A Giacca 2007 Salicylate prevents hepatic insulin resistance caused by short-term elevation of free fatty acids in vivo J Endocrinol 195 323 31 17951543
109. RS Hundal KF Petersen AB Mayerson PS Randhawa S Inzucchi SE Shoelson, et al. 2002 Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes J Clin Invest 109 1321 6 12021247
110. J Koska E Ortega JC Bunt A Gasser J Impson RL Hanson, et al. 2009 The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients:results of a randomised double-blind placebo-controlled study Diabetologia 52 385 93 19104769
111. BW McCrindle EM Urbina BA Dennison MS Jacobson J Steinberger AP Rocchini, et al. 2007 Drug therapy of high-risk lipid abnormalities in children and adolescents:a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing Circulation 115 1948 67 17377073
112. GS Berenson SR Srnivasan 2005 Cardiovascular risk factors in youth with implications for aging:the Bogalusa Heart Study Neurobiol Aging 26 303 7 15639307
113. SR Srinivasan MG Frontini J Xu GS Berenson 2006 Utility of childhood non-high-density lipoprotein cholesterol levels in predicting adult dyslipidemia and other cardiovascular risks:the Bogalusa Heart Study Pediatrics 118 201 6 16818566
114. CG Magnussen OT Raitakari R Thomson M Juonala DA Patel JSA Viikari, et al. 2008 Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood:evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study Circulation 117 32 42 18071074
115. J Steinberger A Moran CP Hong DR Jacobs AR Sinaiko 2001 Adiposity in childhood predicts obesity and insulin resistance in young adulthood J Pediatr 138 469 73 11295707
116. SR Daniels FR Greer 2008 Lipid screening and cardiovascular health in childhood Pediatrics 122 198 208 18596007
117. U Korsten-Reck K Kromeyer-Hauschild K Korsten MW Baumstark H Dickhuth A Berg 2008 Frequency of secondary dyslipidemia in obese children Vasc Health Risk Manag 4 1089 94 19183757
118. DS Freedman WH Dietz SR Srinivasan GS Berenson 1999 The relation of overweight to cardiovascular risk factors among children and adolescents:the Bogalusa Heart Study Pediatrics 103 1175 82 10353925
119. C Manlhiot P Larsson RC Gurofsky RW Smith C Fillingham NA Clarizia, et al. 2009 Spectrum and management of hypertriglyceridemia among children in clinical practice Pediatrics 123 458 65 19171610
120. J Steinberger C Moorehead V Katch AP Rocchini 1995 Relationship between insulin resistance and abnormal lipid profile in obese adolescents J Pediatr 126 690 5 7751990
121. A Wiegman BA Hutten E de Groot J Rodenburg HD Bakker HR Büller, et al. 2004 Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial JAMA 292 331 7 15265847
122. PO Kwiterovich G Hartmuller L Van Horn KK Christoffel N Gernhoffer S Gidding, et al. 1995 The Writing Group for the DISC Collaborative Research Group. Efficacy and safety of lowering dietary intake of fat and cholesterol in children with elevated low-density lipoprotein cholesterol The Dietary Intervention Study in Children (DISC): JAMA 273 18 1429 35
123. IJAM Jonkers AHM Smelt HMG Princen F Kuipers JA Romijn R Boverhof, et al. 2006 Fish oil increases bile acid synthesis in male patients with hypertriglyceridemia J Nutr 136 987 91 16549462
124. MM Engler MB Engler MJ Malloy SM Paul KR Kulkarni ML Mietus-Snyder 2005 Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study) Am J Cardiol 95 869 71 15781019
125. K Tolfrey AM Jones IG Campbell 2000 The effect of aerobic exercise training on the lipid-lipoprotein profile of children and adolescents Sports Med 29 99 112 10701713
126. BW McCrindle MB O'Neill G Cullen-Dean E Helden 1997 Acceptability and compliance with two forms of cholestyramine in the treatment of hypercholesterolemia in children:a randomized, crossover trial J Pediatr 130 266 73 9042130
127. RM Lauer WR Clarke 1989 Childhood risk factors for high adult blood pressure: the Muscatine Study Pediatrics 84 633 41 2780125
128. E Rademacher D Jacobs A Moran J Steinberger R Prineas A Sinaiko 2009 Relation of blood pressure and body mass index during childhood to cardiovascular risk factor levels in young adults J Hypertens 27 1766 74 19633567
129. JM Sorof D Lai J Turner T Poffenbarger RJ Portman 2004 Overweight, ethnicity, and the prevalence of hypertension in school-aged children Pediatrics 113 475 82 14993537
130. G Paradis M Lambert J O'Loughlin C Lavallée J Aubin E Delvin, et al. 2004 Blood pressure and adiposity in children and adolescents Circulation 110 1832 8 15381642
131. KL McNiece TS Poffenbarger JL Turner KD Franco JM Sorof RJ Portman 2007 Prevalence of hypertension and pre-hypertension among adolescents J Pediatr 150 640 4 17517252 644.e1
132. AR Sinaiko RP Donahue DR Jacobs RJ Prineas 1999 Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults. The Minneapolis Children's Blood Pressure Study Circulation 99 1471 6 10086972
133. SS Gidding W Bao SR Srinivasan GS Berenson 1995 Effects of secular trends in obesity on coronary risk factors in children:the Bogalusa Heart Study J Pediatr 127 868 74 8523181
134. J Sorof S Daniels 2002 Obesity hypertension in children: a problem of epidemic proportions Hypertension 40 441 7 12364344
135. ML Hansen PW Gunn DC Kaelber 2007 Underdiagnosis of hypertension in children and adolescents JAMA 298 874 9 17712071
136. 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):555-76.
137. AP Rocchini V Katch J Anderson J Hinderliter D Becque M Martin, et al. 1988 Blood pressure in obese adolescents:effect of weight loss Pediatrics 82 16 23 3288957
138. T Reinehr G de Sousa AM Toschke W Andler 2006 Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention Am J Clin Nutr 84 490 6 16960161
139. JX Jiang XL Xia T Greiner GL Lian U Rosenqvist 2005 A two year family based behaviour treatment for obese children Arch Dis Child 90 1235 8 16188958
140. BO Yildiz ES Knochenhauer R Azziz 2008 Impact of obesity on the risk for polycystic ovary syndrome J Clin Endocrinol Metab 93 162 8 17925334
141. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.
142. S Franks 2006 Controversy in clinical endocrinology:diagnosis of polycystic ovarian syndrome:in defense of the Rotterdam criteria J Clin Endocrinol Metab 91 786 9 16418209
143. CM Boomsma MJC Eijkemans EG Hughes GHA Visser BCJM Fauser NS Macklon 2006 A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome Hum Reprod Update 12 673 83 16891296
144. NI Leibel EE Baumann M Kocherginsky RL Rosenfield 2006 Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome J Clin Endocrinol Metab 91 1275 83 16449341
145. PA Essah EP Wickham JE Nestler 2007 The metabolic syndrome in polycystic ovary syndrome Clin Obstet Gynecol 50 205 25 17304037
146. C Meyer BP McGrath HJ Teede 2005 Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease J Clin Endocrinol Metab 90 5711 6 16046590
147. E Talbott A Clerici SL Berga L Kuller D Guzick K Detre, et al. 1998 Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome:results of a case-control study J Clin Epidemiol 51 415 22 9619969
148. EE Littlejohn RE Weiss D Deplewski DV Edidin R Rosenfield 2007 Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome J Pediatr Endocrinol Metab 20 41 51 17315528
149. F de Zegher L Ibáñez 2006 Prenatal growth restraint followed by catch-up of weight:a hyperinsulinemic pathway to polycystic ovary syndrome Fertil Steril 86 Suppl 1 S4 5 16798286
150. RL Rosenfield 2007 Clinical review:Identifying children at risk for polycystic ovary syndrome J Clin Endocrinol Metab 92 787 96 17179197
151. L Ibáñez N Potau A Carrascosa 1998 Insulin Resistance, Premature Adrenarche, and a Risk of the Polycystic Ovary Syndrome (PCOS) Trends Endocrinol Metab 9 72 7 18406245
152. SA Arslanian V Lewy K Danadian R Saad 2002 Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance:amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance J Clin Endocrinol Metab 87 1555 9 11932281
153. A Dunaif 1997 Insulin resistance and the polycystic ovary syndrome:mechanism and implications for pathogenesis Endocr Rev 18 774 800 9408743
154. VD Lewy K Danadian SF Witchel S Arslanian 2001 Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome J Pediatr 138 38 44 11148510
155. P Sawathiparnich L Weerakulwattana J Santiprabhob S Likitmaskul 2005 Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS J Med Assoc Thai 88 Suppl 8 S33 7 16856423
156. L Ibáñez K Ong A Ferrer R Amin D Dunger F de Zegher 2003 Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adolescents with ovarian hyperandrogenism J Clin Endocrinol Metab 88 2600 6 12788862
157. K Hoeger K Davidson L Kochman T Cherry L Kopin DS Guzick 2008 The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials J Clin Endocrinol Metab 93 4299 306 18728175
158. SA Arslanian VD Lewy K Danadian 2001 Glucose intolerance in obese adolescents with polycystic ovary syndrome:roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease J Clin Endocrinol Metab 86 66 71 11231980
159. B Rossi S Sukalich J Droz A Griffin S Cook A Blumkin, et al. 2008 Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome J Clin Endocrinol Metab 93 4780 6 18812482
160. KA Martin RJ Chang DA Ehrmann L Ibáñez RA Lobo RL Rosenfield, et al. 2008 Evaluation and treatment of hirsutism in premenopausal women:an endocrine society clinical practice guideline J Clin Endocrinol Metab 93 1105 20 18252793
161. RS Legro 2002 Detection of insulin resistance and its treatment in adolescents with polycystic ovary syndrome J Pediatr Endocrinol Metab 15 Suppl 5 1367 78 12510993
162. RL Thomson JD Buckley M Noakes PM Clifton RJ Norman GD Brinkworth 2008 The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome J Clin Endocrinol Metab 93 3373 80 18583464
163. HF Allen C Mazzoni RA Heptulla MA Murray N Miller L Koenigs, et al. 2005 Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome J Pediatr Endocrinol Metab 18 761 8 16200842
164. G Mastorakos I Lambrinoudaki G Creatsas 2006 Polycystic ovary syndrome in adolescents:current and future treatment options Paediatr Drugs 8 311 8 17037948
165. G Mastorakos C Koliopoulos E Deligeoroglou E Diamanti-Kandarakis G Creatsas 2006 Effects of two forms of combined oral contraceptives on carbohydrate metabolism in adolescents with polycystic ovary syndrome Fertil Steril 85 420 7 16595221
166. G Mastorakos C Koliopoulos G Creatsas 2002 Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives Fertil Steril 77 919 27 12009344
167. JM Lord IHK Flight RJ Norman 2003 Metformin in polycystic ovary syndrome:systematic review and meta-analysis BMJ 327 951 3 14576245
168. R Mathur CJ Alexander J Yano B Trivax R Azziz 2008 Use of metformin in polycystic ovary syndrome Am J Obstet Gynecol 199 596 609 19084097
169. L Ibáñez C Valls N Potau MV Marcos F de Zegher 2000 Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche J Clin Endocrinol Metab 85 3526 30 11061495
170. CJ Glueck P Wang R Fontaine T Tracy L Sieve-Smith 2001 Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS) J Adolesc Health 29 160 9 11524214
171. VR Aroda TP Ciaraldi P Burke S Mudaliar P Clopton S Phillips, et al. 2009 Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome:a randomized, placebo-controlled clinical trial J Clin Endocrinol Metab 94 469 76 18984667
172. N Brettenthaler C De Geyter PR Huber U Keller 2004 Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome J Clin Endocrinol Metab 89 3835 40 15292314
173. L Narsing Rao JJ Jacob TV Paul S Rajarathinam N Thomas MS Seshadri 2009 Effects of pioglitazone on menstrual frequency, hyperandrogenism and insulin resistance in adoloscents and young adults with polycystic ovary syndrome J Pediatr Adolesc Gynecol 22 91 5 19345914
174. DL Stout SE Fugate 2005 Thiazolidinediones for treatment of polycystic ovary syndrome Pharmacotherapy 25 244 52 15767238
175. P Angulo 2005 Nonalcoholic fatty liver disease Rev Gastroenterol Mex 70 Suppl 3 52 6 17471859
176. AW Marion AJ Baker A Dhawan 2004 Fatty liver disease in children Arch Dis Child 89 648 52 15210498
177. M Manco M Marcellini R Devito D Comparcola MR Sartorelli V Nobili 2008 Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis Int J Obes (Lond) 32 381 7
178. P Vajro C Mandato A Franzese E Ciccimarra S Lucariello M Savoia, et al. 2004 Vitamin E treatment in pediatric obesity-related liver disease:a randomized study J Pediatr Gastroenterol Nutr 38 48 55 14676594
179. V Nobili M Manco R Devito P Ciampalini F Piemonte M Marcellini 2006 Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease Aliment Pharmacol Ther 24 1553 61 17206944
180. V Nobili M Marcellini R Devito P Ciampalini F Piemonte D Comparcola, et al. 2006 NAFLD in children:a prospective clinical-pathological study and effect of lifestyle advice Hepatology 44 458 65 16871574
181. HM Patton JE Lavine ML Van Natta JB Schwimmer D Kleiner J Molleston 2008 Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis Gastroenterology 135 1961 1971.e2 19013463
182. M Manco G Bottazzo R DeVito M Marcellini G Mingrone V Nobili 2008 Nonalcoholic fatty liver disease in children J Am Coll Nutr 27 667 76 19155426
183. TS Burgert SE Taksali J Dziura TR Goodman CW Yeckel X Papademetris, et al. 2006 Alanine aminotransferase levels and fatty liver in childhood obesity:associations with insulin resistance, adiponectin, and visceral fat J Clin Endocrinol Metab 91 4287 94 16912127
184. AL Fracanzani L Valenti E Bugianesi M Andreoletti A Colli E Vanni, et al. 2008 Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels:a role for insulin resistance and diabetes Hepatology 48 792 8 18752331
185. RS Strauss SE Barlow WH Dietz 2000 Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents J Pediatr 136 727 33 10839867
186. A Fraser MP Longnecker DA Lawlor 2007 Prevalence of elevated alanine aminotransferase among US adolescents and associated factors:NHANES 1999-2004 Gastroenterology 133 1814 20 18054554
187. JB Schwimmer R Deutsch T Kahen JE Lavine C Stanley C Behling 2006 Prevalence of fatty liver in children and adolescents Pediatrics 118 1388 93 17015527
188. R Sagi S Reif G Neuman M Webb M Phillip S Shalitin 2007 Nonalcoholic fatty liver disease in overweight children and adolescents Acta Paediatr 96 1209 13 17655622
189. I Jankowska P Socha J Pawlowska M Teisseyre D Gliwicz P Czubkowski, et al. 2007 Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy Pediatr Transplant 11 796 8 17910660
190. JB Schwimmer MS Middleton R Deutsch JE Lavine 2005 A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis Aliment Pharmacol Ther 21 871 9 15801922
191. NJ Barshop CB Sirlin JB Schwimmer JE Lavine 2008 Review article:epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease Aliment Pharmacol Ther 28 13 24 18397387
192. C Wang L Liang J Fu C Zou F Hong J Xue, et al. 2008 Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children World J Gastroenterol 14 1598 602 18330955
193. T Reinehr C Schmidt AM Toschke W Andler 2009 Lifestyle intervention in obese children with non-alcoholic fatty liver disease:2-year follow-up study Arch Dis Child 94 437 42 19224892
194. V Nobili M Manco R Devito V Di Ciommo D Comparcola MR Sartorelli, et al. 2008 Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease:a randomized, controlled trial Hepatology 48 119 28 18537181
195. SE Nissen K Wolski 2007 Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes N Engl J Med 356 2457 71 17517853
196. S Singh YK Loke CD Furberg 2007 Long-term risk of cardiovascular events with rosiglitazone:a meta-analysis JAMA 298 1189 95 17848653
197. V Nobili M Manco P Ciampalini A Alisi R Devito E Bugianesi, et al. 2008 Metformin use in children with nonalcoholic fatty liver disease:an open-label, 24-month, observational pilot study Clin Ther 30 1168 76 18640473
198. JE Lavine JB Schwimmer 2006 Clinical Research Network launches TONIC trial for treatment of nonalcoholic fatty liver disease in children J Pediatr Gastroenterol Nutr 42 129 30 16456401
199. P Vajro A Franzese G Valerio MP Iannucci N Aragione 2000 Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children J Pediatr 136 739 43 10839869
200. KD Lindor KV Kowdley EJ Heathcote ME Harrison R Jorgensen P Angulo, et al. 2004 Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial Hepatology 39 770 8 14999696
201. N Méndez-Sánchez V González N Chávez-Tapia MH Ramos M Uribe 2004 Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial Ann Hepatol 3 108 12 15505596
202. SK Satapathy P Sakhuja V Malhotra BC Sharma SK Sarin 2007 Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis J Gastroenterol Hepatol 22 634 8 17444848
203. T Andersen C Gluud MB Franzmann P Christoffersen 1991 Hepatic effects of dietary weight loss in morbidly obese subjects J Hepatol 12 224 9 2051001
204. S de Ferranti D Mozaffarian 2008 The perfect storm:obesity, adipocyte dysfunction, and metabolic consequences Clin Chem 54 945 55 18436717
205. K Rabe M Lehrke KG Parhofer UC Broedl 2008 Adipokines and insulin resistance Mol Med 14 741 51 19009016
206. AH Berg PE Scherer 2005 Adipose Tissue, Inflammation, and Cardiovascular Disease Circ Res 96 939 49 15890981
207. TJ Guzik D Mangalat R Korbut 2006 Adipocytokines - novel link between inflammation and vascular function? J Physiol Pharmacol 57 505 28 17229978
208. SD de Ferranti K Gauvreau DS Ludwig EJ Neufeld JW Newburger N Rifai 2004 Prevalence of the metabolic syndrome in American adolescents:findings from the Third National Health and Nutrition Examination Survey Circulation 110 2494 7 15477412
209. Alberti G, Zimmet P, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The IDF consensus definition of the metabolic syndrome in children and adolescents. In: International Diabetes Federation. 2007. http://www.idf.org/ met-syndromechildren Accessed 5 Aug 2009.
210. American Diabetes Association 2009 Standards of Medical Care in Diabetes-2009 Diabetes Care 32 S13 61