Long-term follow-up of non-diabetic obese children and adolescents treated with metformin

Abstract

Aim: Childhood obesity is an important public health problem with increasing prevalence.Type 2 diabetes mellitus(T2DM) is strongly associated with obesity and metabolic syndrome. Adressing obesity and insulin resistance by drug treatment represents a rational strategy for the prevention of T2DM. The aim of our study was to evaluate the one year metformin treatment’slong-term effectiveness in children and adolescent.

Material and Methods: Patients who were diagnosed with obesity (VKİ>+2 SDS)and found to have insulin resistance (total insulin at OGTT >300 mIU/ml and homa-IR >3.4)and other obesity co-morbidities, agedbetween 10-18 years, treated with metformin in addition to lifestyle change for a year and with regular follow-up for a minimum of 2 years after metformin treatmentin our clinicwere included inthe study.

Results: A total of 12 cases including 8 girls with a mean age of 13.2±2.1 years and mean follow-up duration of 3.9±1 years were included in the study. While the body mass index (BMI) of the cases at presentation was 31.2±5.6 kg/m² and BMI-SDS was 2.7±0.7, the BMI-SDS value after one year of metformin treatment was found to have regressed to 1.9±1 (p:0.04), and the BMI-SDS value two years after the interruption of metformin treatment had increased to 2.1±1.04 but was not as high as the period before metformin treatment (p:0.033).

Conclusion: One-year metformin treatment improved the BMI SDS and homa-IR values of the obese children and this improvement decreased but continued in the second year after the discontinuation of the treatment.

Keywords

• Obesity,insulin resistance,childhood

Metformin ile tedavi edilen non-diyabetik obez çocuk ve adolesanların uzun sureli izlemi

Abstract

Amaç: Çocukluk döneminde obezite artan sıklıkla izlenen önemli bir halk sağlığı problemidir.  Tip 2 Diyabetes mellitus (T2DM) obezite ve metabolik sendrom ile güçlü ilişki içindedir. Tip 2 DM ‘nin önlenmesi için obezite ve insulin direncini hedef alan ilaç tedavileri rasyonel bir strateji olarak görülmektedir.Çalışmamızın amacı bir yıl süre ile metformin tedavisi alan çocuk ve adolesanlarda bu tedavinin uzun dönem etkinliğini değerlendirmektir.

Gereç ve Yöntemler: Kliniğimizde obezite (VKI>+ 2SDS ) tanısı alan ve insulin direnci olan (OGTT’de total insulin düzeyi >300 mIU/ml ve homa IR >3,4 ) ve diğer obezite ilişkili komorbiditeleri bulunan, yaşları 10-18 arası değişen, yaşam tarzı değişikliği ile birlikte bir yıl süre ile metformin tedavisi alan ve ardından en az iki yıl süre ile takip edilen hastalar dahil edildi.

Bulgular: Çalışmaya 8’ i kız , ortalama yaşı 13,2±2,1 yıl olan  ve ortalama izlem süresi 3,9±1 yıl olan toplam 12 dahil edildi. Başlangıçta  olguların vücut kitle indeksi (VKİ) 31,2±5,6 kg/m²ve VKİ-SDS’i 2,7±0,7 iken bir yıllık metformin tedavisi ile VKİ-SDS’inin 1,9±1 (p:0,04) ‘ e gerilediği, iki yıl süre ile metformin tedavisi kesilen olguların  VKİ-SDS’ inin 2,1±1,04 (p:0,033)’ e yükseldiği ancak metformin tedavisi öncesi kadar yüksek olmadığı görüldü.

Sonuç: Bir yıllık metformin tedavisinin obez çocuk ve adolesanlarda VKİ-SDS ve  Homa-IR değerlerinde düzelme sağladığı, bu düzelmenin tedavi kesiminden sonraki ikinci yılda da azalmakla birlikte devam ettiği saptandı. 

Keywords

• Obezite,insülin direnci, Çocukluk dönemi

References

1. 1. McDonagh MS, Selph S, Ozpınar A, Foley C. Systematic reviewof the benefits and risks ofmetforminin treating obesity in children aged 18 years and younger. JAMA Pediatr 2014; 168: 178-84
2. 2. Ho M, Garnet SP, Baur LA. Childhood Obesity and Insulin Resistance: How should It be Managed?.Curr Treat Cardio Med 2014; 16: 351
3. 3. WangY, Lobstein T. Worldwide trends in childhood overweight and obesity. IntJ PediatrObes, 2006; 1: 11-25
4. 4. van der Aa MP, Elst MA, van Mil EG, Knibbe CA, van der Vorst MM. METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents - study protocol of a randomized controlled study. Trials 2014; 15: 207
5. 5. BrufaniC, Crino A, Fintini D, Patera IP, Cappa M, Manco M. Systematic Review of Metformin Use in Obese Nondiabetic Children and Adolescents. Horm Res Paediatr 2013; 80: 78-80
6. 6. Park MH, Kinra S, Ward KI,White B, VinerRM. Metformin for obesity in children and adolescents: a systematicreview. Diabetes Care 2009; 32: 1743-45 7. 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: 55
7. 8. 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 ClinEndocrinolMetab 2006; 91: 2074–80
8. 9. 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

9. 10. Clarson CL, Mahmud FH, Baker JE, Clark HE, McKay WM, Schauteet VD, Hill DJ. Metformin in combination with structured lifestyle intervention improved body mass index in obese adolescents, but did not improve insulin resistance. Endocrine 2009; 36: 141–46
10. 11. Wiegand S, l’Allemand D, Hübel H, Krude H, Bürmann M, Martus P, Grüters A, Holl RW. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin resistant adolescents: a prospective, placebo-controlled, randomized study. Eur J Endocrinol 2010; 163: 585–92
11. 12. Wilson D.M, Abrams SH, Aye T, Lee PDK, Lenders C, Lusting RH, OsganianSV, Feldman HA. Metformin extended release treatment of adolescent obesity. Arch PediatrAdolescMed 2010; 164: 116-23
12. 13. Rynders C, Weltman A, Delgiorno C, Balagopal P, Damaso L, Killen K, Mauras N. Lifestyle intervention improves fitness independent of metformin in obese adolescents. Med Sci Sports Exerc 2012; 44: 786–92
13. 14. Mauras N, DelGiorno C, Hossain J, Bird K, Killen K, Merinbaum D, Weltman A, Damaso L, Balagopal P. Metformin use in children with obesity and normal glucose toleranceeffects on cardiovascular markers and intrahepatic fat. J PediatrEndocrinolMetab 2012; 25: 33–40
14. 15. Weiss R, Kaufman FR. Metabolic complications of childhood obesity: identifying and mitigating the risk. DiabetesCare 2008; 31: 310-16
15. 16. MatthaeiS, Stumvoll M, Kellerer M, Haring HU. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 2000; 21: 585-618
16. 17. Cali AM, Man CD, Cobelli C, Dziura J, Seyal A, Shaw M, Allen K, Chen S, Caprio S. Primary defects in ß-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents. Diabetes Care 2009; 32: 456-61