| Outcome Measures: |
Primary: Insulin Sensitivity, As measured by in intravenous glucose tolerance test (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist., Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline | Secondary: Insulin Secretion (Acute Insulin Response to Glucose, AIRg), As measured by IVGTT as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Please see primary outcome for more detail about timing of measurement., Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline|Disposition Index, Please see primary outcome for more detail about timing of measurement. Disposition index is measured via (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. It reflects the product of outcome measures 1 and 2 (Si x AIRg)., Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline|Low Density Lipoprotein, Please see primary outcome for more detail about timing of measurement., Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline|Insulin-like Growth Factor 1, IGF-1 measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Total Testosterone, Testosterone measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Estradiol, Estradiol measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Sex Hormone Binding Globulin, SHBG measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Dehydroepiandrosterone Sulfate, DHEA-S measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|High Sensitivity C-reactive Protein, hsCRP measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Aspartate Aminotransferase (AST), AST measured in serum at each time point, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Alanine Transaminase (ALT), ALT measured in serum at each time point, Baseline (Tanner 2-3), Tanner 4, Tanner 5|Change in Urinary Luteinizing Hormone, LH measured in an overnight urine sample at time points below, Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline)|Change in Urinary Follicle-stimulating Hormone, FSH measured in overnight urine sample at time points below, Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline|Change in Urinary Estradiol Metabolites, estradiol metabolite (E1c) measured in an overnight urine sample at each time point, Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline|Hemoglobin A1c, HbA1c measured by HPLC at time points below, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Leptin, Leptin measured in serum at time points below, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Percent Body Fat, % body fat measured by DXA at time points below, Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Visceral Adipose, Percent Visceral Fat, Measured in a subset (10 per group) by single slice MRI, Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|Liver Adipose, Liver fat percent. Measured in a subset (10 per group) by fast MRI technique, Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline|High Density Lipoprotein, Please see primary outcome for more detail about timing of measurement., Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline
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