The purpose of the study is to examine whether a medication called acipimox can improve your body's mitochondria. Mitochondria are the "power house" of the cell and make energy for your body. Obesity is associated with increased risk for developing diabetes. However, the investigators do not know how obesity leads to diabetes. Previous studies have shown levels of fat in the blood (free fatty acids or FFA) are higher in obesity, and elevated FFA can affect how our body uses glucose and responds to insulin. Recent studies have shown that changes in mitochondria may be involved in the development of diabetes and may be affected by FFA. The investigators propose to improve the function of mitochondria in obese people with pre-diabetes by treating with acipimox, a medication which decreases FFA. The investigators will use state of the art techniques to evaluate the mitochondria, including a new magnetic resonance imaging (MRI) technique to measure function of mitochondria in muscle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
39
Massachusetts General Hospital
Boston, Massachusetts, United States
Change From Baseline in Phosphocreatine Recovery (ViPCr) at 6-months
The rate of recovery of phosphocreatine concentration after depletion by exercise is considered a measurement of mitochondrial function. Change in phosphocreatine recovery from baseline to 6 months will therefore give a measurement of change in mitochondrial function. ViPCR is given -- a higher value indicates better mitochondrial function.
Time frame: Change from Baseline to 6-months Visit
Change From Baseline in Insulin Sensitivity at 6-months
Change in insulin resistance assessed by hyperinsulinemic-euglycemic clamp study at Baseline and at 6-months. Change in insulin-stimulated glucose uptake (M) during 40 mU/m2/min insulin clamp is given.
Time frame: Change from Baseline to 6-months visit
Change From Baseline in Mitochondrial Density at 6 Months
Muscle tissue obtained from biopsy will be used to assess mitochondrial number and morphology by microscopes at Baseline and at 6-months. The change in mitochondrial density from 6 months to baseline is given.
Time frame: Change from Baseline to 6-months
Change From Baseline in Intramyocellular Lipid Content at 6-months
Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given.
Time frame: Change from Baseline to 6-months
Change From Baseline in Lipid Profile at 6-months
Change in direct low density lipoprotein (LDL) cholesterol is given
Time frame: Change from Baseline to 6-months
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