Does Pioglitazone Increase the Production of Prostacyclin (PGI2) and/or 15-EPI-Lipoxin A4 in Humans With Diabetes Mellitus Type 2?

Type 2 Diabetes Mellitus Clinical Trial

Official title: Does Pioglitazone Increase the Production of Prostacyclin (PGI2) and/or 15-EPI-Lipoxin A4 in Humans With Diabetes Mellitus Type 2?

Status Completed

Clinical Trial 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.

Clinical Trial Description

Type-2 diabetes mellitus is a public health concern. According to the World health organization (WHO), diabetes mellitus affects more than 180 million people worldwide. Type 2 diabetes mellitus accounts for 80-95% of diabetes cases in developed countries and a higher proportion in developing countries (IDF 2006). 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. Several studies have suggested that PIO decreases serum markers of inflammation including C-reactive protein (CRP). 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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

• NCT number: NCT01040819
• Study type: Interventional
• Source: Baylor College of Medicine
• Status: Completed
• Phase: Phase 4
• Start date: February 2010
• Completion date: December 2011