Cortisol and Nutritional Sympathetic Responsiveness
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
This project will examine whether short-term (over a 12-hour period) pharmacological lowering
of the stress hormone 'cortisol' improves the nervous system response to food intake in
overweight or obese individuals who have metabolic syndrome.
The investigators know from our previous research that overweight/obese persons who are
insulin resistant, have a blunted sympathetic nervous response to carbohydrate ingestion.
This means that they are less able to dissipate energy from caloric intake, which would
favour the maintenance of the obese state. Cortisol adversely impacts on insulin action and
transport into the brain and cortisol levels are often elevated in persons with central
(abdominal) obesity.
A randomized, double-blind, placebo controlled, cross-over design will be used to compare the
effects of overnight treatment with metyrapone (15 mg/kg at midnight and 15 mg/kg at 6 am)
versus placebo on sympathetic nervous system activity in response to a standard 75-g oral
sugar (glucose) tolerance test. A 2 week washout will separate treatments.
Metyrapone is a drug that reversibly inhibits the enzyme 11beta-hydroxylase, and therefore
the production of cortisol. It is used clinically to test the activity of the adrenal gland
(the key site of cortisol production) and the pituitary gland. The investigators anticipate
that at the dosage used, it will lower blood cortisol concentration by 44 to 64% during the
experimental morning.
The study protocol comprises two screening visits and two experimental mornings. Key
procedures will include:
- Assessment of insulin action (sensitivity) using the gold standard 'clamp' method.
- Measurement of sympathetic nervous system activity by both biochemical methods (isotope
dilution which provides a measure of the apparent rate of release of 'noradrenaline'-the
key neurotransmitter in the sympathetic nervous system) and direct intra-neuronal nerve
recordings from the peroneal nerve in the lower leg.
- Indirect calorimetry to assess resting metabolic rate and the response to sugar
ingestion.
- DEXA scan to quantify fat and lean mass.
- Assessment of arterial elasticity and calf blood flow by non-invasive methods.
- A standard 75g oral sugar tolerance test.
The results will provide important new information regarding the role of cortisol on nervous
system function in overweight/obese individuals.