Heart Rate Variability in Response to Metformin Challenge

Doctors need to develop tests which inexpensively and reliably evaluates brain metabolism. Current diagnostic tests sample other tissues which often run on different fuels (fats), utilize unproven and often insensitive brain imaging scanners, or sequence thousands to millions of base-pairs of DNA. All of these tests are expensive. None of these tests accurately or completely capture the interactions between the 1000s of proteins involved in brain metabolism.

The investigators suspect that mathematical analysis of the resting heart rate may provide some insight into brain metabolism. The brain controls heart rate in response to changes in blood pressure and blood gases like carbon dioxide and oxygen. Tight control of heart rate is necessary to make sure that the brain has the right mix of fuel and air. Because the brain can't respond instantly to changes in its fuel supply, this system acting as a biological carburetor has a natural oscillatory rhythm that can be monitored just like frequencies on the radio.

The investigators propose to amplify these rhythms by modestly metabolically stressing the brain with metformin, a inhibitor of complex 1 in the mitochondria.

Inclusion criteria

EITHER chronic neurogenic pain meeting American College of Rheumatology criteria for fibromyalgia or previous/current exposure to antipsychotic medications

Exclusion criteria

• recent infection,
• renal failure,
• pre-existing cardiac disease,
• chronic obstructive pulmonary disease
• inability to participate in informed consent,
• lack of transport to return home from study site,
• severe fasting intolerance or hypoglycemia,
• history of stroke-alike episode,
• uncontrolled migraine or cyclic vomiting,
• diabetes on insulin or sulfonylurea,
• non-English speaker,
• medications with strong effects on baseline heart rate variability