Free Fatty Acids and Vascular Function in Subjects With Diabetes
This study will test the hypothesis that reduction in release of free fatty acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Impact of Free Fatty Acid Reduction on Vascular Function and Skeletal Muscle Glucose Utilization in Type 2 Diabetes Mellitus|
- difference in endothelium-dependent vasodilation between test agent and placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- difference in flow-mediated, endothelium-dependent brachial artery vasodilation between test agent and placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- difference in insulin-mediated skeletal muscle glucose utilization between test agent and placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
subjects will receive acipimox 250 mg orally every 6 hours (or matching placebo) for 7 days, including a dose at 6am on the morning of the study testing visit
Other Name: Olbetam
Placebo Comparator: 2
During the past two decades, there has been a steady increase in the incidence of diabetes mellitus, such that nearly 17 million people are now afflicted. The vast majority of these have type 2 diabetes. Over the next 40 years, the type 2 diabetic population in the United States is expected to increase to nearly 30 million.
Diabetes substantially increases the risk of atherosclerosis, and thereby, cardiovascular morbidity and mortality. Indeed, cardiovascular disease causes more than 50% of the mortality in patients with diabetes. People with type 2 diabetes manifest two cardinal signs of dysmetabolism: hyperglycemia and insulin resistance. Insulin resistance is a progressive phenomenon that occurs well before the onset of frank diabetes, and results in alterations in insulin signaling. Experimental studies suggest that insulin signaling is required for vascular homeostasis, and its impairment is associated with endothelial dysfunction. In the clinical setting, insulin resistance is associated with atherosclerosis and predicts cardiovascular events independent of hyperglycemia. Therefore, we will study the importance of insulin signaling in endothelial biology in humans and the effects of free fatty acids on endothelial function in people with type 2 diabetes.
|United States, Massachusetts|
|Brigham & Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Mark Creager, M.D.||Brigham and Women's Hospital|