Effects of Pioglitazone on High-density Lipoprotein (HDL) Function in Persons With Diabetes

• Status: Completed
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Miami
• Collaborator: Takeda Pharmaceuticals North America, Inc.
• Treatments: Pioglitazone

Criteria

Inclusion Criteria:

• Type 2 diabetes, men and women, WHO criteria, aged 35-70 years

• HbA1c 7.5-10.0%

• BMI 26-39 Kg/m2

• Either receiving dietary therapy only or monotherapy with either sulfonylurea or metformin

• Already on statin therapy

Exclusion Criteria:

• Cardiovascular disease

• Renal disease

• Other systemic disease

• Abnormal liver function tests (ALT or AST>1.5 X ULN)

• Uncontrolled hypertension (BP >160/110)

• Triglyceride levels >400 mg/dl

• Lipid modifying drugs; fibrates, ezetimibe, niacin, bile sequestrants, but not statins (see below),

• Estrogen treatment or thyroid disease

• Psychiatric condition or substance abuse