CD36, a protein that facilitates tissue uptake of fat, as a common link between blood fat concentrations and metabolic disease states such as diabetes mellitus. Genetic variants in the CD36 gene are more common in African Americans compared to Whites and it may confer protection against metabolic diseases by altering the amount of fat in the blood. The purpose of this study is to compare the levels of fat in the blood and to assess endothelial dysfunction among carriers versus non-carriers of the coding SNP, rs3211938 of the CD36 gene after a high fat meal challenge

NCT02126735

Conditions

1. Obesity

The purpose of this study is to compare the levels of fat in the blood and to assess endothelial dysfunction among carriers versus non-carriers of the coding SNP, rs3211938 of the CD36 gene after a high fat meal challenge Area Under the Concentration-Time Curve triglycerides levels after high fat meal.

We expect that subjects heterozygous for the minor allele of CD36 rs3211938 (G/T) would have an increase of 250 units in the area under the curve for triglycerides which is ~50% of the observed difference between patients with CD36 deficiency and normal controls.

This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.

NCT03012386

Conditions

1. Insulin Resistance
2. Endothelial Dysfunction

Interventions

1. Drug: Sildenafil Citrate

MeSH:Insulin Resistance

HPO:Insulin resistance

CD36 in Nutrient Delivery and Its Dysfunction This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.

- Cardiovascular disease such as myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy - History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack - History or presence of immunological or hematological disorders - 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) - History of alcohol or drug abuse - Mental conditions rendering a 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, unlikelihood of completing the study, and investigator discretion Insulin Resistance Endothelial Dysfunction Insulin Resistance Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in ~25% of African Americans have endothelial dysfunction.