None listed
Conditions
Brief summary
Cortisol is a steroid hormone produced by the adrenal gland that is critical for life. Cortisol controls many body functions including appetite, glucose metabolism, blood pressure and immune function. Cortisol secretion varies widely among healthy individuals. Recent studies have shown that higher cortisol secretion, even within the normal range, is associated with an increase in blood glucose and risk of heart disease. How variability in cortisol secretion contributes to increased risk of diabetes and heart disease is unclear. In this study, we will investigate whether variability in cortisol production causes insulin resistance and reduces blood vessel dilation. This could be a mechanism that explains a link between heart disease and diabetes.
Interventions
50 participants aged >40 years living independently in the community will be recruited.
Assessment of insulin sensitivity and secretion and vascular function:
Insulin sensitivity and secretion: Estimates of insulin sensitivity and secretion will be attained from measurements of glucose, insulin and C-peptide before and over two hours after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat) using the Matsuda index and C-peptide deconvolution respectively. Glomerular filtration rat
50 participants aged >40 years living independently in the community will be recruited. Assessment of insulin sensitivity and secretion and vascular function: Insulin sensitivity and secretion: Estimates of insulin sensitivity and secretion will be attained from measurements of glucose, insulin and C-peptide before and over two hours after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat) using the Matsuda index and C-peptide deconvolution respectively. Glomerular filtration rate will be measured at baseline. Arterial stiffness: Arterial stiffness (augmentation index (AI) and pulse wave velocity (PWV)) will be assessed by Pulse-Wave Analysis from the radial, carotid and femoral arteries using a SphygmoCor device (AtCor Medical, West Ryde, NSW, Australia). AI will be assessed before and every 30 minutes post meal for 2 hours and pulse wave velocity will be done twice- before and 90 minutes after meal in a standardized orde Endothelial function: Endothelial function will be estimated using an Endo-PAT 2000 (Itamar Medical, Caesarea, Israel) before and at 2 hours after a mixed-meal. Arginine metabolomics: Plasma concentrations of 7 key compounds (arginine, ADMA, symmetric dimethylarginine, mono-methyl arginine, homoarginine, citrulline and ornithine) will be measured fasting and 2-hours postprandially by ultra-performance liquid-chromatography (UPLC) with detection by quadrupole time-of-flight mass spectrometry. Assessment of cortisol homeostasis and body composition: Twenty-four hour production: In the 24 hours before visit 2 participants will collect urine for quantification of free cortisol excretion (measure of overall cortisol production). Synacthen test: Serum cortisol concentration will be measured before and then 30 and 60 minutes after administration of 1 mcg Synacthen (ACTH1-24, Novartis Pharmaceuticals, NSW, Australia) intravenously (measure of HPA hyperactivity). Salivary cortisol: Participants will be asked to collect salivary samples at 08.00, 08.30, 12.00 and 21.00 for estimation of cortisol (to assess the circadian variation in cortisol secretion) Body composition: Lean body mass, fat mass and central abdominal fat will be measured by DEXA.
Sponsors
Assoc Prof Morton Burt
Eligibility
Sex/Gender
All
Age
41 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Age >40 years and living independently in the community
Exclusion criteria
History of pituitary or adrenal adenoma, taking oral glucocorticoids within the last month, current Atrial fibrillation, Raynaud’s phenomenon, Rheumatoid arthritis, taking oral oestrogen (e.g oral contraceptive or hormone replacement therapy), severe asthma (hospital admission in the last 5 years)
Outcome results
None listed