Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects
Article first published online: 31 OCT 2013
© 2013 John Wiley & Sons Ltd
Diabetes, Obesity and Metabolism
Volume 16, Issue 3, pages 268–272, March 2014
How to Cite
Garg, R., Kneen, L., Williams, G. H. and Adler, G. K. (2014), Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects. Diabetes, Obesity and Metabolism, 16: 268–272. doi: 10.1111/dom.12224
- Issue published online: 4 FEB 2014
- Article first published online: 31 OCT 2013
- Accepted manuscript online: 11 OCT 2013 12:54PM EST
- Manuscript Accepted: 5 OCT 2013
- Manuscript Revised: 1 AUG 2013
- Manuscript Received: 27 JUN 2013
- NIH. Grant Numbers: K24 HL103845, UL1 RR025758
- endothelial function;
- insulin resistance;
- mineralocorticoid receptor;
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).
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).
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.
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.