Study of Sildenafil Citrate on Insulin Resistance in African American

Obesity has a greater detrimental impact on the health of African American women than on any other racial or gender group. Nearly 80% of African American women are overweight or obese in the United States. Hypertension and insulin resistance are more prevalent among African American women as compared to men and Caucasians. These conditions put them at increased risk for the development of diabetes mellitus and cardiovascular disease.

Recent studies have reported that a substance named Nitric Oxide (NO)may have some beneficial effect on how the body handles blood sugar and blood pressure. Of interest,some studies have shown that African Americans have decreased function of NO in their blood vessels.

In this study proposal the investigators will test if increasing NO function with a PDE-5 inhibitor (sildenafil citrate) will improve pre-diabetes and the health of the inner layer of the blood vessels in obese African American women.


Eligibility Criteria:
Inclusion Criteria:

* Race will be self-defined, but only subjects who report both parents of the same race will be included.
* Age 18-60 years old.
* The investigators will recruit subjects with wide range of BMI 30-45 kg/m2.
* Subjects who have metabolic syndrome or who have a fasting insulin \>13. The diagnosis include 3 of the following:

Fasting blood glucose of greater than 100 Triglyceride levels of greater than 150 HDL cholesterol of less than 50 in women Blood pressure of at least 130/85, or on blood pressure medicine Waist girth of more than 35 inches in women. Subjects of childbearing potential will be required to have a negative serum/urine pregnancy test. In addition, they will be asked to use a reliable contraceptive method prior to enrollment as determined by the PI (Dr. Cyndya Shibao).

Exclusion Criteria:

* Previous allergic reactions to any of the study medication (sildenafil) or inability to take study medications as prescribed during the course of the study.
* Type 1 or 2 diabetes mellitus as defined by a fasting glucose of 126 mg/dl or greater.
* Use of antidiabetic medication (insulin, metformin, sulfonylurea, troglitazone)
* 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.
* Current smokers.
* Significant weight change \>5% from baseline in the past three months.
* Pregnancy or breast-feeding.
* History of serious neurological disease such as cerebral hemorrhage stroke, transient ischemic attack.
* History or presence of immunological or hematological disorders.
* Clinical significant gastrointestinal impairment that could interfere with drug absorption.
* Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>1.5X upper limit of normal range).
* Impaired renal function (estimated glomerular filtration rate (eGFR) of \<60mL/min).
* 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.
* History of alcohol or drug abuse.
* 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.
* Patients must not be taking nitratest in any form (e.g., nitroglycerin, isosorbide dinitrate, nitroprusside, and others) during this study
* Patients on alpha-blocking drugs (doxazosin, terazosin , or prazosin) will be excluded
* Patients on protease inhibitors (ritonavir and others) will be excluded