Adipokines in Obese Adolescents With Insulin Resistance
23. april 2012 oppdatert av: Maria Lola Evia-Viscarra, Hospital Regional de Alta Especialidad del Bajio
Inflammatory Mediators in Obese Adolescents With Insulin Resistance Following Metformin Treatment: Controlled Randomized Clinical Trial
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).
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The increased prevalence of obesity in pediatric patients is a public health problem particularly because of the difficulties involved with changing lifestyles. Current studies of obese children and adolescents show increased insulin resistance (IR) and chronic inflammatory states. These conditions increase the risk of disability and/or premature death.
The current treatment schemes for obese children are conservative and are focused on changing their lifestyles (exercise and dietary plans). However, metabolic conditions, such as IR, dyslipidemia, and inflammatory processes, are perpetuated.
Metformin is a biguanide that is used for adolescents with diabetes mellitus and polycystic ovarian syndrome. Several clinical trials with metformin for obese pediatric patients have observed decreases in IR, decreases in weight, and improvements in lipid metabolism.
Adipose tissue is not only an energy repository, but also plays an immunological role by the secretion of cytokines. Both overweight adults and adolescents show decreases in adiponectin levels and increases in tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6). IL-6 can stimulate the production of high-sensitivity C-reactive protein (hs-CRP), which is considered to be a risk marker for the development of cardiovascular disease.
Studietype
Intervensjonell
Registrering (Faktiske)
31
Fase
- Fase 4
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Distrito Federal
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México, Distrito Federal, Mexico, 06720
- Hospital Infantil de Mexico Federico Gomez
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Guanajuato
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León, Guanajuato, Mexico, 37670
- Hospital Regional de Alta Especialidad del Bajio
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
9 år til 18 år (Barn, Voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Obesity defined as Body Mass Index (BMI) ≥ percentile 95
- Tanner stage ≥ 2
- Insulin resistance defined as Basal insulin > 15 µU/mL or Homeostasis Model Assessment index (HOMA) > 4.5
- Patients' parents signed written consents when they and their adolescent children agreed to enroll
Exclusion Criteria:
- Glucose intolerance
- Diabetes mellitus (type 1 or 2)
- Anemia (Hb < 10 g/dL)
- Plasma creatinine > 1.4 mg/dL
- Abnormal hepatic function
- Any associated Disease (Pulmonary, Infection, Autoimmune Disease)
- History of lactic acidosis
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Metformin
Tablet of 500 mg metformin, oral every 12 hours (total metformin dose of 1 g/day) for 3 months.
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Tablet of 500 mg metformin, oral every 12 hours (total metformin dose of 1 g/day) for 3 months.
Andre navn:
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Placebo komparator: Placebo
Tablet of 500 mg oral placebo every 12 hours for 3 months.
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Tablet of 500 mg oral placebo every 12 hours for 3 months.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Adiponectin
Tidsramme: baseline and 3 months
|
Change from baseline in Adiponectin after 3 months of treatment.
|
baseline and 3 months
|
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High-sensitivity C-reactive Protein
Tidsramme: baseline and 3 months
|
Change from baseline in High-sensitivity C-reactive protein after 3 months of treatment.
|
baseline and 3 months
|
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Interleukin 6
Tidsramme: baseline and 3 months
|
Change from baseline in Interleukin 6 after 3 months of treatment.
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baseline and 3 months
|
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Tumour Necrosis Factor Alpha
Tidsramme: baseline and 3 months
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Change from baseline in Tumour necrosis factor alpha after 3 months of treatment.
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baseline and 3 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Fasting Plasma Glucose
Tidsramme: baseline and 3 months
|
Change from baseline in Fasting plasma glucose after 3 months of treatment.
|
baseline and 3 months
|
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Fasting Insulin
Tidsramme: baseline and 3 months
|
Change from baseline in Fasting insulin after 3 months of treatment.
|
baseline and 3 months
|
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Body Mass Index
Tidsramme: baseline and 3 months
|
Change from baseline in Body Mass Index after 3 months of treatment.
|
baseline and 3 months
|
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Waist Circumference
Tidsramme: baseline and 3 months
|
Change from baseline in Waist circumference after 3 months of treatment.
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baseline and 3 months
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Maria L Evia-Viscarra, M.D., Hospital Regional de Alta Especialidad del Bajio
- Studiestol: Edel R Rodea-Montero, Statistician, Hospital Regional de Alta Especialidad del Bajio
- Studiestol: Evelia Apolinar-Jiménez, Nutrition, Hospital Regional de Alta Especialidad del Bajio
- Studiestol: Leticia M García-Morales, M.D., Hospital Infantil de Mexico Federico Gomez
- Studiestol: Constanza Leaños-Pérez, M.D., Hospital Infantil de Mexico Federico Gomez
- Studiestol: Mireya Figueroa-Barrón, Chemestry, Hospital Infantil de Mexico Federico Gomez
- Studiestol: Dolores Sánchez-Fierros, Chemestry, Hospital Infantil de Mexico Federico Gomez
- Studiestol: Nathalie Muñoz-Noriega, Nutrition, Hospital Regional de Alta Especialidad del Bajio
- Studiestol: Juan G Reyes-García, M.D., Escuela Superior de Medicina del IPN
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: MMWR Morb Mortal Wkly Rep. 2011 Feb 11;60(5):142.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. januar 2007
Primær fullføring (Faktiske)
1. desember 2009
Studiet fullført (Faktiske)
1. mars 2010
Datoer for studieregistrering
Først innsendt
4. august 2011
Først innsendt som oppfylte QC-kriteriene
4. august 2011
Først lagt ut (Anslag)
5. august 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
27. april 2012
Siste oppdatering sendt inn som oppfylte QC-kriteriene
23. april 2012
Sist bekreftet
1. april 2012
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 010-08
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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