Abstract 242: Long-Term Administration of Thiazolidinedione Reverses Vascular Dysfunction of Microvascular Coronary Arteries Irrespective of Improvements in Clinical Insulin Resistant Status
Background and Hypothesis: Effects of insulin sensitizing agents on coronary artery pathophysiology have marked attention, but the long-term effects remain uncertain. We assessed hypothesis that long-term administration of thiazolidinedione, an insulin sensitizer, influences on vasomotion of microvascular coronary arteries that are frequently affected by diabetes mellitus.
Methods: Type-2 diabetic patients (n=22) who underwent coronary angiography and flow-dynamic examinations were randomized where they received troglita-zone (400mg/day) or pioglitazone (30mg/day) (group-T), or they received therapy without thiazolidinedione for more than 1 year (group-C). We measured response of resistance coronary arteries to ATP (50μg) or acetylcholine (50μg) into the study angiographically normal left coronary artery. Reactive changes in coronary blood flow (coronary flow reserve (CFR): maximal hyperemic flow-baseline flow/baseline flow) were quantified by coronary angiography and intracoronary doppler-tipped guidewire. Changes in CFR were compared between the 2 groups.
Results: Group-T (n=11) manifested good compliance to the treatment and improvements in some of insulin resistant variables while group-C showed no improvement. CFR to ATP (FN) significantly increased to normal range in group-T (p=0.027) but not in group-C (p=0.102). CFR to acetylcholine (FE) also increased to normal range in group-T (p=0.006), while decreased in group-C (p=0.028). Changes of CFR did not correlate to those of HbA1c (FN: r=0.19, p=0.66, FE: r=0.13, p=0.89), HOMA-IR (FN: r=0.18,p=0.69, FE: r=0.14, p=0.85), or those of mean blood pressure (FN: r=0.19, p=0.66, FE: r=0.13, p=0.89).
Conclusion: These results from this study suggest that long-term administration of thiazolidinedione improves vasomotion of microvascular coronary arteries independent of clinical insulin resistant status, which may provide novel potential benefits for management of type-2 diabetics.