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Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects
Author(s) -
Garg R.,
Kneen L.,
Williams G. H.,
Adler G. K.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12224
Subject(s) - mineralocorticoid receptor , endocrinology , insulin resistance , medicine , mineralocorticoid , antagonist , receptor , insulin
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/m 2 ] 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.