Effect of Prolonged PDE-5 Inhibition on Insulin Signaling in Skeletal Muscle.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) and ≤40kg/m2 Impaired fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (2-hr plasma glucose 140-199 mg/dL) 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 or hormonal 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, 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 on current inhaled corticosteroid therapy.
Clinically significant gastrointestinal impairment that could interfere with drug absorption.
Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase >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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sildenafil citrate	Sildenafil citrate	In the parent study, subjects are randomized to sildenafil 25 mg tid.
placebo oral capsule	Placebo Oral Capsule	In the parent study, subjects are randomized to matching placebo

Primary Outcome Measures

Name	Time	Method
Insulin-stimulated AKT Phosphorylation	3 months	measured using Western blot for pAkt and for total Akt from muscle biopsies obtained at the end of the baseline hyperinsulinemic clamp and the three-month hyperglycemic clamp. The ratio of pAkt to Akt expression was calculated at each time point and the change in ratio from 0 to 3 months is presented.

Secondary Outcome Measures