Conditions: Type 2 Diabetes Mellitus
Keywords: insulin resistance insulin signaling endothelium-dependent vasodilation
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 40
Healthy volunteers: yes

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: Acipimox treatment for 7 days arm 2: placebo treatment for 7 days

Interventions: intervention 1: acipimox intervention 2: placebo
Intervention descriptions: intervention 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 intervention 2: matching placebo

Protocol document: