Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:

1. spironolactone
2. hydrochlorothiazide (HCTZ) plus potassium
3. placebo

In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.

Inclusion Criteria:

• age 18-70 years
• type 2 diabetes mellitus
• with or without hypertension

Exclusion Criteria:

• ischemic changes on resting electrocardiogram,

• clinical evidence of heart disease (angina, heart failure, unstable angina),cerebrovascular or peripheral vascular disease,

• significant cardiac arrhythmias,

• aortic stenosis,

• 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia,

• bronchospastic lung disease with active wheezing,

• known hypersensitivity to adenosine,

• hemoglobin A1C (HbA1c) > 8.5%, *

• gout (If not already taking HCTZ),

• the use of Rosiglitazone,**

• estimated glomerular filtration rate (eGFR) < 60 ml/min,

• serum potassium > 5.0 mmol/L,

• use of potassium-sparing diuretics,**

• current smoker,*

• pregnancy,

• renal disease not related to diabetes mellitus,

• uncontrolled hypertension, systolic blood pressure (BP) >160 mm Hg and diastolic BP >100 mm Hg,*

• use of cyclic hormone replacement therapy

• past intolerance of angiotensin-converting enzyme (ACE) inhibitor therapy

• other major medical illnesses. Participants with evidence of a previous myocardial infarction on the first adenosine-stimulated positron emission tomography (PET) study will be withdrawn from the study.

• Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications

  • Participants can enroll in study and proceed with in-patient evaluations if during the run-in period adjustments of medications, diet and habits lead to improved glucose control [equivalent to HbA1c <8.5%, controlled hypertension and cessation of smoking.

    • Participants who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the participant's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.](streamdown:incomplete-link)

All participants who completed the study.

6 months

Adverse events are reported for participants who received study treatment.