Does Pioglitazone Increase the Production of 15-EPI-Lipoxin A4?

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Treatments: Lipoxin A4; Pioglitazone

Criteria

Inclusion Criteria:

1. Men and women > 21 years old with type 2 diabetes Mellitus and otherwise stable medical conditions

Exclusion Criteria:

1. Serum creatinine >= 1.5 mg/dl and/or renal failure

2. NYHA class III or IV heart failure

3. Known intolerance to TZD

4. Current use of NSAID, COX-2 inhibitors, steroids (oral, topical and inhalation) or immunosuppressive therapy

5. Aspirin > 162 mg/d

6. Recent myocardial infarction, ACS, or stroke <=3 months)

7. Significant comorbid conditions such as: cancer (not cured), end stage renal disease, severe obstructive lung disease, cirrhosis, etc)

8. Recent (<1 month) infection

9. Recent CABG or PCI (<3 months)

10. Use of prostaglandin analogs (i.e., iloprost)

11. Active inflammatory disease

12. Current use of TZD

13. Pregnancy

14. Osteoporosis or high risk for bone fracture. Use of other antihyperglycemic agents is not an exclusion criterion. HbA1c and glucose levels will not restrict enrollment.