Adipokines in Obese Adolescents With Insulin Resistance

Summary

The purpose of this study is to compare serum concentrations of inflammatory cytokines, interleukin 6 (IL-6), High-sensitivity C-reactive protein (hs-CRP), adiponectin, and tumour necrosis factor alpha (TNFα), before and after three months treatment with metformin in obese adolescents with insulin resistance (IR).

Timeline

Start

2007-01

Primary completion

2009-12

Completion

2010-03

Publications

• Background Centers for Disease Control and Prevention (CDC). CDC grand rounds: childhood obesity in the United States. MMWR Morb Mortal Wkly Rep. 2011 Jan 21;60(2):42-6.
• Background Wilfley DE, Tibbs TL, Van Buren DJ, Reach KP, Walker MS, Epstein LH. Lifestyle interventions in the treatment of childhood overweight: a meta-analytic review of randomized controlled trials. Health Psychol. 2007 Sep;26(5):521-32. doi: 10.1037/0278-6133.26.5.521.
• Background Zeller M, Kirk S, Claytor R, Khoury P, Grieme J, Santangelo M, Daniels S. Predictors of attrition from a pediatric weight management program. J Pediatr. 2004 Apr;144(4):466-70. doi: 10.1016/j.jpeds.2003.12.031.
• Background Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004 Jun;89(6):2526-39. doi: 10.1210/jc.2004-0276.
• Background Chiarelli F, Marcovecchio ML. Insulin resistance and obesity in childhood. Eur J Endocrinol. 2008 Dec;159 Suppl 1:S67-74. doi: 10.1530/EJE-08-0245. Epub 2008 Sep 19.
• Background Cruz ML, Weigensberg MJ, Huang TT, Ball G, Shaibi GQ, Goran MI. The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab. 2004 Jan;89(1):108-13. doi: 10.1210/jc.2003-031188.
• Background Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Low-grade systemic inflammation in overweight children. Pediatrics. 2001 Jan;107(1):E13. doi: 10.1542/peds.107.1.e13.
• Background Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH. Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr. 2007 Jan;150(1):12-17.e2. doi: 10.1016/j.jpeds.2006.08.042.
• Background Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM. Determinants of early atherosclerosis in obese children and adolescents. J Clin Endocrinol Metab. 2007 Aug;92(8):3025-32. doi: 10.1210/jc.2007-0619. Epub 2007 May 22.
• Background Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998 Jun 4;338(23):1650-6. doi: 10.1056/NEJM199806043382302.
• Background Type 2 diabetes in children and adolescents. American Diabetes Association. Pediatrics. 2000 Mar;105(3 Pt 1):671-80. doi: 10.1542/peds.105.3.671. No abstract available.
• Background SEARCH for Diabetes in Youth Study Group; Liese AD, D'Agostino RB Jr, Hamman RF, Kilgo PD, Lawrence JM, Liu LL, Loots B, Linder B, Marcovina S, Rodriguez B, Standiford D, Williams DE. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006 Oct;118(4):1510-8. doi: 10.1542/peds.2006-0690.
• Background Kay JP, Alemzadeh R, Langley G, D'Angelo L, Smith P, Holshouser S. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism. 2001 Dec;50(12):1457-61. doi: 10.1053/meta.2001.28078.
• Background Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr. 2008 Jun;152(6):817-22. doi: 10.1016/j.jpeds.2008.01.018. Epub 2008 Mar 19.
• Background Srinivasan S, Ambler GR, Baur LA, Garnett SP, Tepsa M, Yap F, Ward GM, Cowell CT. 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. 2006 Jun;91(6):2074-80. doi: 10.1210/jc.2006-0241. Epub 2006 Apr 4.
• Background Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 2001 Aug;60(3):329-39. doi: 10.1079/pns200194.
• Background Stefan N, Bunt JC, Salbe AD, Funahashi T, Matsuzawa Y, Tataranni PA. Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab. 2002 Oct;87(10):4652-6. doi: 10.1210/jc.2002-020694.
• Background Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali SE, Shulman G, Caprio S. Low adiponectin levels in adolescent obesity: a marker of increased intramyocellular lipid accumulation. J Clin Endocrinol Metab. 2003 May;88(5):2014-8. doi: 10.1210/jc.2002-021711.
• Background Moon YS, Kim DH, Song DK. Serum tumor necrosis factor-alpha levels and components of the metabolic syndrome in obese adolescents. Metabolism. 2004 Jul;53(7):863-7. doi: 10.1016/j.metabol.2004.02.007.
• Background Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, Bredahl R, Hahnloser E, Martin S. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab. 2007 Dec;92(12):4569-74. doi: 10.1210/jc.2007-0955. Epub 2007 Oct 2.
• Background Cartier A, Lemieux I, Almeras N, Tremblay A, Bergeron J, Despres JP. Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. J Clin Endocrinol Metab. 2008 May;93(5):1931-8. doi: 10.1210/jc.2007-2191. Epub 2008 Mar 4.
• Background Ford ES, Galuska DA, Gillespie C, Will JC, Giles WH, Dietz WH. C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 1988-1994. J Pediatr. 2001 Apr;138(4):486-92. doi: 10.1067/mpd.2001.112898.
• Background Hiura M, Kikuchi T, Nagasaki K, Uchiyama M. Elevation of serum C-reactive protein levels is associated with obesity in boys. Hypertens Res. 2003 Jul;26(7):541-6. doi: 10.1291/hypres.26.541.
• Background Freedman DS, Sherry B. The validity of BMI as an indicator of body fatness and risk among children. Pediatrics. 2009 Sep;124 Suppl 1:S23-34. doi: 10.1542/peds.2008-3586E.
• Background Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000 May 6;320(7244):1240-3. doi: 10.1136/bmj.320.7244.1240.
• Background Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11. 2002 May;(246):1-190.
• Background Reaven GM, Chen YD, Hollenbeck CB, Sheu WH, Ostrega D, Polonsky KS. Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance. J Clin Endocrinol Metab. 1993 Jan;76(1):44-8. doi: 10.1210/jcem.76.1.8421101.
• Background Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883.
• Background Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005 Apr;115(4):e500-3. doi: 10.1542/peds.2004-1921. Epub 2005 Mar 1.
• Background Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001 May;86(5):1930-5. doi: 10.1210/jcem.86.5.7463.
• Background Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2005-10. doi: 10.1073/pnas.98.4.2005. Epub 2001 Feb 6.
• Background Perea-Martinez A, Carbajal R.L, Rodriguez H.R, Zarco R.J, Barrios F.R, Loredo A.A, et al. Association of comorbidity with obesity in mexican children and adolescents. Pediatrics 2008;121(2):S149-S150
• Background Yeh ET. High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. Clin Cardiol. 2005 Sep;28(9):408-12. doi: 10.1002/clc.4960280905.
• Background Balagopal P, George D, Patton N, Yarandi H, Roberts WL, Bayne E, Gidding S. Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents. J Pediatr. 2005 Mar;146(3):342-8. doi: 10.1016/j.jpeds.2004.11.033.
• Background Monzillo LU, Hamdy O, Horton ES, Ledbury S, Mullooly C, Jarema C, Porter S, Ovalle K, Moussa A, Mantzoros CS. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res. 2003 Sep;11(9):1048-54. doi: 10.1038/oby.2003.144.
• Background Huang NL, Chiang SH, Hsueh CH, Liang YJ, Chen YJ, Lai LP. Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation. Int J Cardiol. 2009 May 15;134(2):169-75. doi: 10.1016/j.ijcard.2008.04.010. Epub 2008 Jul 1.
• Background Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505.
• Evia-Viscarra ML, Rodea-Montero ER, Apolinar-Jimenez E, Munoz-Noriega N, Garcia-Morales LM, Leanos-Perez C, Figueroa-Barron M, Sanchez-Fierros D, Reyes-Garcia JG. The effects of metformin on inflammatory mediators in obese adolescents with insulin resistance: controlled randomized clinical trial. J Pediatr Endocrinol Metab. 2012;25(1-2):41-9. doi: 10.1515/jpem-2011-0469.

Drugs

Indications