"TAKE TIME" Pioglitazone Reverses Defects in Mitochondrial Biogenesis in Patients With T2DM

Inclusion Criteria: * Men and women aged 18-70 with Type 2 diabetes as defined by: * Fasting plasma glucose \> 126 mg/dL at entry * Or a two-hour OGTT glucose \> 200mg/dL * Or current treatment with one or two oral anti-diabetic drugs, except TZD * Or currently using insulin * Fasting plasma glucose \< 200mg/dL at entry * BMI \>27.0 and \<45.0kg/m2 * Adequate contraception for women (including, but not limited to: oral contraception, hysterectomy, tubal ligation, or post-menopausal as defined by \> 6 months without a menstrual cycle and FSH \> 40 mIU/ml). Exclusion Criteria: * Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp \< 140/90 on medications). * Prior use of other thiazolidinediones (rosiglitazone \[AVANDIATM\], pioglitazone \[ACTOSTM\]) * Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc. * Pregnancy * Alcohol or other drug abuse * Unwilling or unable to abstain from caffeine (48h) and tobacco (24h) prior to metabolic rate measurements * Increased liver function tests at baseline (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal) * Metal objects that would interfere with the measurement of body composition /MRS such as implanted rods, surgical clips, etc. * HbA1C of \> 10%. * NYHA class III/IV CHF is an exclusionary cardiac condition.…