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- Title
Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects.
- Authors
Garg, R.; Kneen, L.; Williams, G. H.; Adler, G. K.
- Abstract
Aim Obese individuals have high aldosterone levels that may contribute to insulin resistance ( IR) and endothelial dysfunction leading to obesity-induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo-controlled, double-blind, randomized, parallel-group study ( NCT01406015). Methods Thirty-two non-diabetic, obese subjects [body mass index ( BMI) 30 to 45 kg/m2] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index ( ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation ( FMD) of brachial artery and renal plasma perfusion by clearance of para-aminohippurate ( PAH). Results There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p < 0.02, post-treatment vs. baseline) and urine aldosterone (11.0 ± 7 vs. 4.8 ± 2.4 µg/g creatinine; p < 0.01) and decreases in systolic blood pressure (116 ± 11 vs. 123 ± 10 mmHg; p < 0.001). There were no changes in these variables in the placebo group. Neither spironolactone nor placebo treatment had a significant effect on ISI or other indices of glucose metabolism [insulin resistance by homeostatic model assessment ( HOMA), area under the curve for insulin, area under the curve for glucose], brachial artery reactivity or the renal plasma perfusion values. Changes in these variables were similar in two groups. Conclusions We conclude that 6 weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.
- Subjects
MINERALOCORTICOID receptors; INSULIN resistance; ENDOTHELIAL growth factors; OVERWEIGHT persons; RANDOMIZED controlled trials; VASODILATION
- Publication
Diabetes, Obesity & Metabolism, 2014, Vol 16, Issue 3, p268
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.12224