Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance.

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). CONCLUSION: 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.

Effects of a weight management program on body composition and metabolic parameters in overweight children: a randomized controlled trial.

CONTEXT: Pediatric obesity has escalated to epidemic proportions, leading to an array of comorbidities, including type 2 diabetes in youth. Since most overweight children become overweight adults, this chronic condition results in serious metabolic complications by early adulthood. To curtail this major health issue, effective pediatric interventions are essential. OBJECTIVE: To compare effects of a weight management program, Bright Bodies, on adiposity and metabolic complications of overweight children with a control group. DESIGN: One-year randomized controlled trial conducted May 2002-September 2005. SETTING: Recruitment and follow-up conducted at Yale Pediatric Obesity Clinic in New Haven, Conn, and intervention at nearby school. PARTICIPANTS: Random sample of 209 overweight children (body mass index [BMI] >95th percentile for age and sex), ages 8 to 16 years of mixed ethnic groups were recruited. A total of 135 participants (60%) completed 6 months of study, 119 (53%) completed 12 months. INTERVENTION: Participants were randomly assigned to either a control or weight management group. The control group (n = 69) received traditional clinical weight management counseling every 6 months, and the weight management group (n = 105) received an intensive family-based program including exercise, nutrition, and behavior modification. Intervention occurred biweekly the first 6 months, bimonthly thereafter. The second randomization within the weight management group assigned participants (n = 35) to a structured meal plan approach (dieting), but this arm of the study was discontinued while enrollment was ongoing due to a high dropout rate. MAIN OUTCOME MEASURES: Change in weight, BMI, body fat, and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 and 12 months. RESULTS: Six-month improvements were sustained at 12 months in weight management vs control, including changes in the following (mean [95% confidence interval]): weight (+0.3 kg [-1.4 to 2.0] vs +7.7 kg [5.3 to 10.0]); BMI (-1.7 [-2.3 to -1.1] vs +1.6 [0.8 to 2.3]); body fat (-3.7 kg [-5.4 to -2.1] vs +5.5 kg [3.2 to 7.8]); and HOMA-IR (-1.52 [-1.93 to -1.01] vs +0.90 [-0.07 to 2.05]). CONCLUSION: The Bright Bodies weight management program had beneficial effects on body composition and insulin resistance in overweight children that were sustained up to 12 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00409422.