Diabetes Clinical Trial
Official title:
PGC-1 and Mitochondrial Dysfunction in Diabetes
The purpose of this study is determine if you have too much fat in your body that it will decrease the conversion of food energy into energy that your body can use.
The investigators' prior research has focused on defining the changes in expression of
nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal
muscle, with the goal of defining the molecular mechanisms underlying the connection between
mitochondrial dysfunction and insulin resistance in skeletal muscle.
The purpose of this study is to determine whether experimental lipid oversupply decreases
mitochondrial respiratory function. We will use mitochondrial respiration studies in vitro
and mass spectrometry and proteomics analysis to test the hypothesis that experimental lipid
oversupply:
1. Decreases mitochondrial respiration in response to lipid fuels.
2. Reduces abundance of mitochondrial proteins.
3. Alters phosphorylation of proteins in the electron transport chain.
Three groups of subjects will be studied: lean, healthy control subjects (n=12), obese
non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total
of 36 subjects. Twenty subjects have completed the study at Arizona State University; the
remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.
Subjects will come to the Mayo Clinic 2 times. On study Day 1 subjects will be screened with
a medical history and physical exam, and a 75 g oral glucose tolerance test, measure body
fat percentage, and an electrocardiogram (EKG). On Study Day 2, subjects will report to the
clinic after an overnight fast. Female subjects will take a urine pregnancy test. A muscle
biopsy will be performed to take a small sample from one thigh. A lipid infusion will be
performed for 5 hours (60 ml/hr), with blood samples taken at 8 intervals during the
infusion. At the end of the 5 hour period, a second muscle biopsy will be taken from the
other thigh. The fat infusion will stop, subjects will be given lunch and allowed to leave
the clinic.
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Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
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