This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to conduct an open-label metformin trial in a small group of adult volunteers who are pre-diabetic (fasting glucose 100-125 mg/dL) and obese (BMI 30-39 kg/m2) to test our primary hypothesis: metformin induces a significant increase in EE at baseline and during physical activities. Our secondary hypothesis is that there are associations between the changes in EE and the activation of AMPK in the skeletal muscle.
Specific Aims : 1. To accurately measure whole-body energy expenditure before and after metformin treatment (4 weeks). 2. To assess the role of muscle AMPK activities in energy expenditure. 3. To assess food intake, body composition, and free-living physical activity. 4. To correlate changes in overall energy balance (EE and diet) with clinical markers such as HbA1c, insulin, glucose, leptin, and catecholamines.
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