Abstract 3969: Favorable Effects of Pioglitazone on Fasting and Postprandial Levels of Lipid and Hemostatic Variables in Overweight Non-diabetic Patients with Coronary Artery Disease
Objective: Thiazolidinediones improve insulin sensitivity and favorably modify fasting metabolic abnormalities in diabetic patients. However, there is little data in non-diabetics and no information about postprandial effects, even though post-prandial hyperlipemia is a risk factor for cardiovascular disease and is associated with accelerated atherosclerosis. We tested the hypothesis that pioglitazone improves insulin sensitivity and favorably modifies levels of fasting and postprandial lipid and hemostatic and markers associated with thrombotic risk in overweight, nondiabetic subjects with coronary artery disease (CAD).
Methods and Results: 20 adult non-diabetic subjects with CAD and a Body Mass Index between 25 and 36 kg/m2 were randomized to receive either placebo or pioglitazone (45 mg/day) for 12 weeks and then crossed-over to the alternative therapy for an additional 12 weeks. All subjects were on atorvastatin beginning 4 weeks before randomization. Fasting and postprandial lipid and hemostatic variables were measured, and insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Pioglitazone resulted in significant improvement in the insulin sensitivity index (p=0.0002) and caused significant decreases in fasting levels of factor VIIc (p=0.001), factor VIIag (p=0.01) and von Willebrand factor (p=0.01). The primary analysis of the postprandial effects of pioglitazone was based on measurement of the area under the curve from the time of a standarized meal to 12 hours later. While on placebo, there was a postprandial increase in tryglicerides from 96 to 109 mg/dl at 4 hours. Pioglitazone significantly lowered postprandial levels of tryglicerides (-23%, p=0.04), factor VIIag (-7.9%, p=0.0004), factor VIIc (-7.8%, p=0.002), plasminogen activator inhibitor -1 (-34%, p=0.03), von Willebrand factor (-15%, p=0.001), and it resulted in increased high density lipoprotein (+9%, p=0.02). In conclusion, pioglitazone improves insulin sensitivity and favorably modifies fasting and postprandial lipid and hemostatic markers of the metabolic syndrome in overweight, nondiabetic subjects with CAD. These effects may contribute to cardiovascular risk reduction