Effects of Pioglitazone on High-density Lipoprotein (HDL) Function in Persons With Diabetes
Status:
Completed
Trial end date:
2010-09-01
Target enrollment:
Participant gender:
Summary
Metabolic defects contributing to the development of type 2 diabetes (T2D) are relative
insulin insufficiency and insulin resistance that are associated with a cluster of
abnormalities that increase the risk for cardiovascular disease including dyslipidemia,
inflammation, hemodynamic changes and endothelial dysfunction. The dyslipidemia associated
with T2D is characterized by elevated triglycerides and decreased high-density
lipoprotein-cholesterol (HDL). The ability of the insulin sensitizing agent pioglitazone
(ACTOS®) , to improve hyperglycemia in subjects with T2D is now well established.
Pioglitazone functions as a PPAR-γ (peroxisome proliferator-activated receptor gamma)
agonists and this class of drugs have demonstrated several other potential benefits, beyond
glucose homeostasis. Specifically pioglitazone can improve diabetic dyslipidemia by
increasing HDL cholesterol and lowing triglycerides. A potential beneficial effect on reverse
cholesterol transport may be mediated by the increased HDL levels. This proposal aims to
examine the effect of PPAR-γ activation by PIO on various aspects of reverse cholesterol
transport by testing the hypothesis that PIO treatment affects key steps in the reverse
cholesterol transport pathway either directly, through induction of protein expression, or
indirectly, by altering HDL structure and composition leading to increase cholesterol flux
through this pathway.