Does Pioglitazone Increase the Production of 15-EPI-Lipoxin A4?
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Type-2 diabetes mellitus is a public health concern. Patients with type 2 diabetes mellitus
are at high risk of developing cardiovascular complications. Diabetic patients are two to
four-times more likely to develope cardiovascular disease. The mortality of diabetic patients
with cardiovascular disease is much higher than in non-diabetic matched patients with
cardiovascular disease. Recently, it has become apparent that not all anti-diabetic drugs
have the same effect on the progression of atherosclerosis and on cardiovascular outcomes.
There is a great need to understand the potential protective mechanisms of the various
anti-diabetic drugs in order to decrease their risk for cardiovascular morbidity and
mortality. In addition to increasing insulin sensitivity, Pioglitazone (PIO) has
anti-inflammatory properties. However, the underlying mechanisms of these anti-inflammatory
(and probably anti-atherosclerotic) effects of PIO are unknown. We have shown in the rat that
3-day pretreatment with PIO increases myocardial cyclooxygenase-2 (COX2) activity and levels
of both 6-keto-PGF1a, the stable metabolite of prostacyclin (PGI2) and 15-epi-lipoxin A4, a
lipid mediator with a strong anti-inflammatory properties. Prostacyclin inhibits platelet
aggregation and causes vasodilatation. Increased levels of 6-keto-PGF1a and 15-epi-lipoxin A4
may thus be the explanation for the anti-inflammatory and anti-atherosclerosis effects of
PIO. Several clinical studies have shown that COX2 inhibition is associated with increased
cardiovascular events. Thus, augmenting COX2 activity and the production of prostacyclin and
15-epi-lipoxin A4 may have potential favorable effects. The purpose of the study is to test
whether PIO therapy is associated with an increase in serum and/or urine levels of
6-keto-PGF1a and 15-epi-lipoxin A4 in patients with diabetes mellitus type 2.