Inclusion Criteria:

• Ambulatory subjects, 18 to 70 years of age, inclusive

• For female subjects, the following criteria must be met:

  • Postmenopausal for at least 1 year, or
  • Status-post surgical sterilization, or
  • If of childbearing potential, utilization of barrier contraceptive and willingness to undergo beta-hcg testing prior to drug treatment and on every study day

• Metabolic syndrome as defined by 3 or more of the following:

  • Fasting plasma glucose of at least 100 mg/dL (5.6 mmol/L)
  • Serum triglycerides of at least 150 mg/dL (1.7 mmol/L)
  • Serum HDL less than or equal to 40 mg/dL in men or less than 50 mg/dL in women or on cholesterol-lowering medications
  • Blood pressure of at least 130/85 mmHg or on blood-pressure lowering medications
  • Waist girth of more than 102 cm in med or 88 cm in women
• Statin therapy for hypercholesterolemia must be a steady dose for 6 months prior to study day

Exclusion Criteria:

• Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater or the use of anti-diabetic medication
• History of reported or recorded hypoglycemia (plasma glucose less than 70 mg/dL)
• Use of hormone replacement therapy
• In hypertensive patients, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg
• Pregnancy
• Breast-feeding
• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
• Treatment with anticoagulants
• History of serious neurological disease such as cerebral hemorrhage, stroke, or transient ischemic attack
• History or presence of immunological or hematological disorders
• Diagnosis of current asthma
• History of angioedema associated with use of ACE-I
• Clinically significant gastrointestinal impairment that could interfere with drug absorption
• Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transferase [ALT] > 2.0 x upper limit of normal range)
• Impaired renal function (serum creatinine > 1.5 mg/dl)
• Hematocrit <35%
• Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
• Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
• Treatment with lithium salts
• History of alcohol or drug abuse
• Treatment with any investigational drug in the 1 month preceding the study
• Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
• Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
• Oral contraceptives