Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis

Inclusion criteria: Age \> 18 years and BMI \> 25 kg/M2 (\> 23 kg/M2 among Asian Americans) Elevated fasting plasma glucose (100-125 mg/dL) IGT (2 hour plasma glucose 140-199 mg/dL) OR metabolic syndrome and/or hemoglobin A1c 5.7-6.4% Exclusion criteria: * Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater, a two hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication. * The use of nitrates or any disease that might require the use of nitrates. * The use of any potent CYP3A4 inhibitor. * subjects who have participated in a weight-reduction program during the last 6 month or whose weight has increased or decreased more than 2 kg over the preceding 6 months. * Pregnancy. Women of child-bearing potential will be required to have undergone tubal ligation or to be using barrier methods of birth control. * 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. * Treatment with metformin. * History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack. * History or presence of immunological or hematological disorders. * Diagnosis of asthma. * Clinically significant gastrointestinal impairment that could interfere with drug absorption. * Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino. transaminase \[ALT\] \>1.5 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