Effect of Pioglitazone on TIMP-3 and TACE in Type 2 Diabetes
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Background: Pioglitazone has been shown to have potent anti-inflammatory as well
anti-atherosclerotic effects. However, the mechanisms by which pioglitazone exerts these
effects are not clear. The investigators propose that Tissue Inhibitor of MetalloProteinase-3
(TIMP-3) and TNF-alfa converting enzyme (TACE) play a major role in pioglitazone mediated
improvement in insulin sensitivity and endothelial function. In animal models, low dose
pioglitazone inhibits lesion progression and matrix metalloproteinase expression in advanced
atherosclerotic plaques. The investigators believe that a lower dose of Pioglitazone will
also have anti-inflammatory effects.
Aim: To examine the effect of low dose Pioglitazone (15mg/day) on TIMP and TACE in
Pioglitazone mediated improvements in insulin sensitivity.
Methods: Thirty subjects with T2DM will participate in following studies: (i) oral glucose
tolerance test (OGTT); (ii) Dual energy absorptiometry(DXA) for body fat content, (iv)
skeletal muscle biopsy. Subjects will be randomized to receive either placebo or pioglitazone
for 24 weeks. The investigators will study the effect of Pioglitazone on (1) TIMP and TACE
substrate activity in skeletal muscle, adipose tissue, mononuclear cells, and their
relationship to insulin sensitivity and vascular reactivity, other adipocytokines- resistin,
TNF-α and Visfatin; (2) markers of inflammation and atherosclerosis- C-reactive protein,
VCAM-1 (vascular cell adhesion molecule 1), ICAM-1 (Intercellular Adhesion Molecule 1),
endothelin 1, E-selectin, P-selectin, TNFrecI (Tumor Necrosis Factor Receptor I), TNFrecII
(Tumor Necrosis Factor Receptor II), IL-6 (Interleukin 6) receptor.
Phase:
Phase 4
Details
Lead Sponsor:
The University of Texas Health Science Center at San Antonio
Treatments:
Matrix Metalloproteinase Inhibitors Pioglitazone TIMP1 protein, human TIMP3 protein, human Tissue Inhibitor of Metalloproteinase-1 Tissue Inhibitor of Metalloproteinase-3 Tissue Inhibitor of Metalloproteinases