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

Authors

  • R. Garg,

    Corresponding author
    1. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
    • Correspondence to: Rajesh Garg, MD, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115, USA.

      E-mail: rgarg@partners.org

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  • L. Kneen,

    1. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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  • G. H. Williams,

    1. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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  • G. K. Adler


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.

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