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Efficacy of Metformin Therapy in Obese Children with Insulin Resistance

Year 2021, , 33 - 41, 06.04.2021
https://doi.org/10.5505/deutfd.2021.42103

Abstract

INTRODUCTION: Obesity and insulin resistance is an important problem of general public health as well as pediatric endocrinology due to the disorders it causes. Metformin, a well-known oral antidiabetic, is increasingly being a common choice in treatment of obese and insulin resistant children. In this study, it was aimed to retrospectively evaluate the subjects who used metformin treatment due to insulin resistance and exogenous obesity in our clinic and to assess the effects of metformin on anthropometric and metabolic variables.
METHODS: The medical records of the 36 patients, who were started metformin therapy due to obesity and insulin resistance and were followed-up in the Pediatric Endocrinology Department of Dokuz Eylül University Medical Faculty between 2005-2015, were retrospectively evaluated. The anthropometric and metabolic variables of these individuals at the sixth month of treatment were compared with basal values.
RESULTS: Statistically significant decrease was detected after six months of metformin treatment in weight SDS (Standard Deviation Score) (mean 2.29 to 1.8), BMI (mean 31.3kg/m2 to 29.8kg/m2), and BMI SDS (mean 2.2 to 1.9) (p<0.001). A mean reduction of 2.41±1.93kg/m2 was present in BMI values of study subjects (p<0.001). Statistically significant reductions were found in post-treatment fasting insulin, fasting glucose/insulin ratio, HOMA-IR and Quick index values (p<0.05).
DISCUSSION AND CONCLUSION: Metformin is one of the treatment options in obese adolescents with insulin resistance. In our study, it was observed that improvement in anthropometric measurements and metabolic parameters was achieved without any serious side effects in patients who received metformin treatment.

References

  • Must A, Jacques PF, Dallal GE, Bajema CJ, W H Dietz Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 1992;327:1350–5.
  • Pan XR, Li GW, Hu YH, Wang JX, W Y Yang, Z X An, et all. The Da Quing IGT and diabetes study: effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care 1997;20:537–44.
  • Tuomilehto J, Lindström J, Eriksson JG, Valle TT, H Hämäläinen, P Ilanne-Parikka,et all. Prevention of type 2 diabetes by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50.
  • Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.
  • Ratner RE, The Diabetes Prevention Programme Research Group. An update on the diabetes prevention program. Endocr Pract 2006;12: 20–4.
  • Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. American Association of Clinical Endocrinologists and American Collage of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity. Endocr Pract. 2016;22 Suppl 3:1-203.
  • Dumitrescu R, Mehedintu C, Briceag I, Purcărea VL, Hudita D. Metformin-clinical pharmacology in PCOs. J Med Life. 2015;8(2): 187-192
  • Neyzi O, Günöz H, Furman A, Bundak R, Gökçay G, Darendeliler F. Türk çocuklarında vücut ağırlığı, boy uzunluğu, baş çevresi ve vücut kitle indeksi referans değerleri. Çocuk Sağlığı ve Hastalıkları Dergisi. 2008;51:1-14.
  • No authors listed. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics 1996;98:649-58.
  • Sperling MA, Majzoub JA, Menon RK, Stratakis CA. Sperling Pediatric Endocrinology. 5th ed. Philadelphia:PA. Elsevier; 2020; Section III; 565.
  • Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:47-64.
  • Sperling MA, Majzoub JA, Menon RK, Stratakis CA. Sperling Pediatric Endocrinology. 5th ed. Philadelphia:PA. Elsevier, 2020; Section III;590.
  • Kliegman R, Stanton B, St Geme J, Schor N, Behrman R. Nelson Textbook of Pediatrics. 19 th ed. Elsevier Saunders, 2011; Chapter 556: 1886.
  • Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Neyzi O. Body mass index references for Turkish children. Acta Paediatr. 2006;95:194-8.
  • Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, Bas F. Growth references for Turkish children aged 6 to 18 years. Acta Paediatr. 2006;95:1635-41.
  • Phil Zeitler, Junfen Fu, Nikhil Tandon, Kristen Nadeau, Tatsuhiko Urakami, Timothy Barrett et al. International Society for Pediatric and Adolescent Diabetes ISPAD Clinical Practice Consensus Guidelines 2014 Compedium Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2015;16:392.
  • Zimmet, P., Alberti, G., Kaufman, F., Tajima, N., Silink, M., Arslanian, S, et al. The metabolic syndrome in children and adolescents. Lancet. 2007;369: 2059-61.
  • Stephen R. Daniels and Frank R. Greer; Lipid Screening and Cardiovascular Health in Childhood. Pediatrics.2008;122:198.
  • Valerio, G, Licenziati MR, Iannuzzi A, Franzese A, Siani P, Riccardi G, et al. Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy. Nutr Metab Cardiovasc Dis. 2006;16:279-84.
  • Arslanian SA, Bacha F, Saad R, N Gungor. Family History of Type 2 Diabetes Is Associated With Decreased Insulin Sensitivity and an Impaired Balance Between Insulin Sensitivity and Insulin Secretion in White Youth. Diabetes Care. 2005; 28: 115-9.
  • Thejaswini KO, Dayananda G, Chandrakala SP. Association of Family History of type 2 Diabetes Mellitus with Insulin Resistance. IJBMS. 2012;5:155-9
  • Stagi S, Ricci F, Bianconi M, Sammarco MA, Municchi G, Toni S, et al. Retrospective Evaluation of Metformin and/or Metformin Plus a New, Polysaccharide Complex in Treating Severe Hyperinsulinism and Insulin Resistance in Obese Children and Adolescents with Metabolic Syndrome. Nutrients. 2017;9:524.
  • Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89:2526-39.
  • Ice CL, Murphy E, Minor VE. Metabolic syndrome in fifth grade children with acanthosis nigricans: results from the CARDIAC project. World J Pediatr. 2009;5:23-30.
  • Moran A, Jacobs DR, Steinberger J, Hong CP, Prineas R, Luepker R, et al. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999;48:2039-44.
  • Goran MI, Gower BA, Longitudinal Study on Pubertal Insulin Resistance. Diabetes. 2001;50: 2444-50.
  • Rowland AS, Baird DD, Long S, Wegienka G, Harlow SD, Alavanja M, et al. Influence of medical conditions and lifestyle factors on the menstrual cycle. Epidemiology 2002;13:668–74.
  • Sun J, Wang Y, Zhang X, He H. The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98:e14249
  • Freemark M, Bursey D. 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. 2001;107:e55
  • Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab. 2008;21: 339–48.
  • Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG, et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes. 2011;60:477–85.
  • Clarson CL, Mahmud FH, Baker JE, Clark HE, Mckay WM, Schauteet VD, et al. Metformin in combination with structured lifestyle intervention improved body mass index in obese adolesents, but did not improve insulin resistance. Endocrine. 2009;36:141–6.
  • Lustig RH, Mietus-Snyder ML, Bacchetti P, Lazar AA, Velasquez-Mieyer PA, Christensen ML. Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children. J Pediatr. 2006;148:23–29.
  • Lentferink YE, van der Aa MP, van Mill EGAH, Knibbe CAJ, van der Vorst MM. Long term metformin treatment in adolescents with obesity and insülin resistance, results of an open label extension study. Nutr Diabetes 2018;8:47.
  • Quyang J, Isnard S, Lin J, FombuenoB, Peng X, Chen Y and Routy J-P.GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated with Metformin. Front Endocrinol. 2020; 11:581839.
  • Park MH, Kinra S, Ward KJ, White B, Viner RM. Metformin for obesity in children and adolescents: a systematic review. Diabetes Care 2009;32:1743–5.
  • Elmezughi K, Ekpebegh C. Metformin-associated lactic acidosis treated successfully by peritoneal dialysis in a resource limited setting: case report. Pan Afr Med J. 2019;32:112.
  • Seidowsky A, Nseir S, Houdred N, Fourrier F. Metformin–associated lactic acidosis: a prognostic and therapotic study. Crit Care Med. 2009;37: 2191-96.
  • De Fronzo R, Fleming GA, Chen K and Bicsak A. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016; 65:20-9.

İnsülin Direnci olan Obez çocuklarda Metformin Tedavisinin Etkinliği

Year 2021, , 33 - 41, 06.04.2021
https://doi.org/10.5505/deutfd.2021.42103

Abstract

GİRİŞ ve AMAÇ: Obezite ve insülin direnci, yol açtığı bozukluklar nedeniyle pediatrik endokrinolojinin yanı sıra genel toplum sağlığının önemli bir sorunudur. Bilinen eski bir oral antidiyabetik olan Metforminin obez ve insülin direnci olan çocuklarda kullanımı her geçen gün yaygınlaşmaktadır Bu çalışmada kliniğimizde obezite ve insülin direnci için metformin tedavisi alan olguların tedavi öncesi ve sonrası antropometrik ve metabolik parametreleri karşılaştırılarak tedavi etkinliğinin değerlendirilmesi amaçlanmıştır.
YÖNTEM ve GEREÇLER: Dokuz Eylül Üniversitesi Tıp Fakültesi Çocuk Endokrinoloji Bilim Dalında 2005-2015 yılları arasında obezite ve insülin direnci nedeniyle Metformin tedavisi alan 36 olgunun tedavi öncesi ve sonrasındaki antropometrik ve metabolik verileri karşılaştırılarak tedavi etkinliği incelendi.
BULGULAR: Olgularda tedavinin 6. Ayında ağırlık SDS (Standart Deviasyon Skoru) (ort. 2.29’dan 1.8’e), VKİ (vücut kitle indeksi) (ort. 31.3kg/m2 den 29.8kg/m2 ye) ve VKİ SDS (ort 2.2’den 1.9’a) değerlerinde istatistiksel olarak anlamlı düşüş (p<0,001); VKİ değerinde 2.41±1.93kg/m2 düşüş saptandı (p<0,001). Tedavi sonrasında açlık insülin, glukoz/insülin oranı; HOMA-IR ve QUICK indeksinde istatistiksel olarak anlamlı düzelme saptandı (p<0,05).
TARTIŞMA ve SONUÇ: Metformin, obezite ve insülin direnci olan hastalarda 6 aylık tedavide ciddi yan etki olmaksızın ağırlık SDS, VKİ ve VKİ SDS değerlerinde ve bazı metabolik parametrelerde düzelme sağlamıştır.

References

  • Must A, Jacques PF, Dallal GE, Bajema CJ, W H Dietz Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 1992;327:1350–5.
  • Pan XR, Li GW, Hu YH, Wang JX, W Y Yang, Z X An, et all. The Da Quing IGT and diabetes study: effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care 1997;20:537–44.
  • Tuomilehto J, Lindström J, Eriksson JG, Valle TT, H Hämäläinen, P Ilanne-Parikka,et all. Prevention of type 2 diabetes by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50.
  • Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.
  • Ratner RE, The Diabetes Prevention Programme Research Group. An update on the diabetes prevention program. Endocr Pract 2006;12: 20–4.
  • Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. American Association of Clinical Endocrinologists and American Collage of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity. Endocr Pract. 2016;22 Suppl 3:1-203.
  • Dumitrescu R, Mehedintu C, Briceag I, Purcărea VL, Hudita D. Metformin-clinical pharmacology in PCOs. J Med Life. 2015;8(2): 187-192
  • Neyzi O, Günöz H, Furman A, Bundak R, Gökçay G, Darendeliler F. Türk çocuklarında vücut ağırlığı, boy uzunluğu, baş çevresi ve vücut kitle indeksi referans değerleri. Çocuk Sağlığı ve Hastalıkları Dergisi. 2008;51:1-14.
  • No authors listed. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics 1996;98:649-58.
  • Sperling MA, Majzoub JA, Menon RK, Stratakis CA. Sperling Pediatric Endocrinology. 5th ed. Philadelphia:PA. Elsevier; 2020; Section III; 565.
  • Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:47-64.
  • Sperling MA, Majzoub JA, Menon RK, Stratakis CA. Sperling Pediatric Endocrinology. 5th ed. Philadelphia:PA. Elsevier, 2020; Section III;590.
  • Kliegman R, Stanton B, St Geme J, Schor N, Behrman R. Nelson Textbook of Pediatrics. 19 th ed. Elsevier Saunders, 2011; Chapter 556: 1886.
  • Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Neyzi O. Body mass index references for Turkish children. Acta Paediatr. 2006;95:194-8.
  • Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, Bas F. Growth references for Turkish children aged 6 to 18 years. Acta Paediatr. 2006;95:1635-41.
  • Phil Zeitler, Junfen Fu, Nikhil Tandon, Kristen Nadeau, Tatsuhiko Urakami, Timothy Barrett et al. International Society for Pediatric and Adolescent Diabetes ISPAD Clinical Practice Consensus Guidelines 2014 Compedium Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2015;16:392.
  • Zimmet, P., Alberti, G., Kaufman, F., Tajima, N., Silink, M., Arslanian, S, et al. The metabolic syndrome in children and adolescents. Lancet. 2007;369: 2059-61.
  • Stephen R. Daniels and Frank R. Greer; Lipid Screening and Cardiovascular Health in Childhood. Pediatrics.2008;122:198.
  • Valerio, G, Licenziati MR, Iannuzzi A, Franzese A, Siani P, Riccardi G, et al. Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy. Nutr Metab Cardiovasc Dis. 2006;16:279-84.
  • Arslanian SA, Bacha F, Saad R, N Gungor. Family History of Type 2 Diabetes Is Associated With Decreased Insulin Sensitivity and an Impaired Balance Between Insulin Sensitivity and Insulin Secretion in White Youth. Diabetes Care. 2005; 28: 115-9.
  • Thejaswini KO, Dayananda G, Chandrakala SP. Association of Family History of type 2 Diabetes Mellitus with Insulin Resistance. IJBMS. 2012;5:155-9
  • Stagi S, Ricci F, Bianconi M, Sammarco MA, Municchi G, Toni S, et al. Retrospective Evaluation of Metformin and/or Metformin Plus a New, Polysaccharide Complex in Treating Severe Hyperinsulinism and Insulin Resistance in Obese Children and Adolescents with Metabolic Syndrome. Nutrients. 2017;9:524.
  • Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89:2526-39.
  • Ice CL, Murphy E, Minor VE. Metabolic syndrome in fifth grade children with acanthosis nigricans: results from the CARDIAC project. World J Pediatr. 2009;5:23-30.
  • Moran A, Jacobs DR, Steinberger J, Hong CP, Prineas R, Luepker R, et al. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999;48:2039-44.
  • Goran MI, Gower BA, Longitudinal Study on Pubertal Insulin Resistance. Diabetes. 2001;50: 2444-50.
  • Rowland AS, Baird DD, Long S, Wegienka G, Harlow SD, Alavanja M, et al. Influence of medical conditions and lifestyle factors on the menstrual cycle. Epidemiology 2002;13:668–74.
  • Sun J, Wang Y, Zhang X, He H. The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98:e14249
  • Freemark M, Bursey D. 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. 2001;107:e55
  • Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab. 2008;21: 339–48.
  • Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG, et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes. 2011;60:477–85.
  • Clarson CL, Mahmud FH, Baker JE, Clark HE, Mckay WM, Schauteet VD, et al. Metformin in combination with structured lifestyle intervention improved body mass index in obese adolesents, but did not improve insulin resistance. Endocrine. 2009;36:141–6.
  • Lustig RH, Mietus-Snyder ML, Bacchetti P, Lazar AA, Velasquez-Mieyer PA, Christensen ML. Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children. J Pediatr. 2006;148:23–29.
  • Lentferink YE, van der Aa MP, van Mill EGAH, Knibbe CAJ, van der Vorst MM. Long term metformin treatment in adolescents with obesity and insülin resistance, results of an open label extension study. Nutr Diabetes 2018;8:47.
  • Quyang J, Isnard S, Lin J, FombuenoB, Peng X, Chen Y and Routy J-P.GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated with Metformin. Front Endocrinol. 2020; 11:581839.
  • Park MH, Kinra S, Ward KJ, White B, Viner RM. Metformin for obesity in children and adolescents: a systematic review. Diabetes Care 2009;32:1743–5.
  • Elmezughi K, Ekpebegh C. Metformin-associated lactic acidosis treated successfully by peritoneal dialysis in a resource limited setting: case report. Pan Afr Med J. 2019;32:112.
  • Seidowsky A, Nseir S, Houdred N, Fourrier F. Metformin–associated lactic acidosis: a prognostic and therapotic study. Crit Care Med. 2009;37: 2191-96.
  • De Fronzo R, Fleming GA, Chen K and Bicsak A. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016; 65:20-9.
There are 39 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Gizem Atakul This is me 0000-0002-3508-1360

Hale Tuhan 0000-0002-7637-9630

Ayhan Abacı 0000-0002-1812-0321

Ece Böber 0000-0001-8828-0892

Publication Date April 6, 2021
Submission Date October 5, 2020
Published in Issue Year 2021

Cite

Vancouver Atakul G, Tuhan H, Abacı A, Böber E. Efficacy of Metformin Therapy in Obese Children with Insulin Resistance. DEU Tıp Derg. 2021;35(1):33-41.