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Title: Insulin action and hypertension : the effect of hyperaldosteronism and its treatment
Author: McMurray, E. M.
ISNI:       0000 0004 2720 9701
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Introduction There has been renewed interest in aldosterone, with evidence that those with primary hyperaldosteronism are at great risk of cardiovascular disease and have higher mortality rates than those with essential hypertension at a similar level. However, screening for primary hyperaldosteronism can be difficult. Aldosterone is also recognised to be a pro-inflammatory hormone, its effects resulting in vascular damage and cardiac fibrosis. Mortality benefits have been demonstrated in patients with heart failure, and post-M I with LV dysfunction following treatment with mineralocorticoid receptor antagonists. There is a link between aldosterone and hypertension and impaired insulin resistance. However evidence is lacking on the effect of eplerenone on insulin action. Methods Three studies are presented. In the first two studies salivary aldosterone is measured using a newly developed assay, initially in normotensive controls and then in a hypertensive cohort. The third study was a randomised, controlled, double-blind, crossover study, investigating the effects of the selective mineralocorticoid receptor antagonist Eplerenone on insulin action in a hypertensive cohort. Results Salivary aldosterone correlated well with serum aldosterone at 1200h in both the normotensive and hypertensive cohorts. Diurnal variation in salivary aldosterone concentration was also demonstrated in both cohorts. Treatment with eplerenone did not affect insulin sensitivity as assessed by a hyperinsulinaemic euglycaemic clamp. Conclusions Salivary aldosterone is a marker for serum aldosterone and varies across the day in both normotensive and hypertensive individuals. Eplerenone has a neutral effect on insulin action in man. Overall, these studies have addressed a number of practical issues concerning screening for primary hyperaldosteronism and shown a neutral effect of MR blockade on insulin action. These issues are highly relevant to current medical practice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available