title: Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance.
abstract: OBJECTIVE
  Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT).
  
  
  METHODS
  We therefore conducted a 4-month double-blind clinical trial in 28 obese [mean body mass index (BMI): 40.3 +/- 5.7 kg/m(2)], insulin-resistant [homeostasis model assessment - insulin resistance: 7.6 +/- 2.8 and whole body insulin sensitivity index (WBISI): 1.5 +/- 0.7] adolescents (age 15.0 +/- 1.3 yr) randomized to MET (n = 15, dose 1500 mg daily) or placebo (n = 13).
  
  
  RESULTS
  The treatment with MET was well tolerated. MET treatment was associated with a decreased BMI (p = 0.02) as well as with a reduction in subcutaneous fat (p = 0.03), particularly the deep subcutaneous fat (p = 0.04) as assessed by magnetic resonance imaging. Postintervention, the MET group had a 35% improvement in insulin sensitivity (WBISI) compared with the placebo group (p = 0.008). However, significance was lost with adjustments for differences in baseline insulin sensitivity (p = 0.09). While there was no change in inflammatory cytokines or lipid parameters, cardiovascular function as assessed by heart rate recovery after exercise improved with MET and worsened in placebo (p = 0.03).
  
  
  CONCLUSIONS
  Short-term use of MET is well tolerated by obese children with NGT and has a beneficial effect on BMI and autonomic control of the heart as well as a trend toward improved insulin sensitivity. Thus, long-term treatment with MET may provide a means to ameliorate the cardio-metabolic consequences of adolescent obesity.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA. tania.burgert@yale.edu
authors.forename: Tania S
authors.initials: TS
authors.lastname: Burgert
authors.forename: Elvira J
authors.initials: EJ
authors.lastname: Duran
authors.forename: Rachel
authors.initials: R
authors.lastname: Goldberg-Gell
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Yeckel
authors.forename: Stuart
authors.initials: S
authors.lastname: Katz
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio