title: Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Garg
authors.forename: L
authors.initials: L
authors.lastname: Kneen
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
authors.forename: G K
authors.initials: GK
authors.lastname: Adler
mesh_terms: D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight; D001916:Brachial Artery; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D013148:Spironolactone / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone
keywords: endothelial function; insulin resistance; mineralocorticoid receptor; obesity