Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects

R. Garg, L. Kneen, G. H. Williams, G. K. Adler

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 45kg/m2] with no other medical problems were randomized to 6weeks of treatment with spironolactone 50mg 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±1.3ng/dl; p<0.02, post-treatment vs. baseline) and urine aldosterone (11.0±7 vs. 4.8±2.4μg/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 6weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.

Original languageEnglish (US)
Pages (from-to)268-272
Number of pages5
JournalDiabetes, Obesity and Metabolism
Volume16
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Endothelial function
  • Insulin resistance
  • Mineralocorticoid receptor
  • Obesity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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