Effect of Long-term and High-dose Allopurinol Therapy on Endothelial Function in Normotensive Diabetic Patients

Objectives: Endothelial dysfunction is a well known risk factor for atherosclerosis. Uric acid levels are associated with endothelial dysfunction and atherosclerosis even if in physiological range. Xanthine oxidase inhibition with allopurinol decreases uric acid levels and oxidative stress and improves endothelial function. We have investigated the effect of high-dose and long-term allopurinol therapy on endothelial function in diabetic normotensive patients.

Methods: This study is a randomized, single-blind, placebo-controlled trial. Both treatment and placebo groups consisted of 50 patients. In the treatment group, daily oral 900 mg allopurinol was started after randomization and maintained for 12 weeks. Brachial artery flow-mediated dilatation (FMD) and nitrate-induced dilatation (NID) were measured at baseline and after the allopurinol therapy to evaluate endothelial function.

Results: HbA1c and uric acid levels decreased after allopurinol therapy (6.1 ± 2.1 vs 5.5 ± 1.0%, 5.0 ± 0.8 vs 3.3 ± 0.5 mg/dl, respectively, p = 0.01) but no change was observed in the placebo group (7.7 ± 1.9% vs 7.6 ± 2.0%, 5.3±2.1 vs 5.6 ± 0.8 mg/dl, respectively, p > 0.05). FMD and NID increased significantly in the treatment group (5.6 ± 2.1% vs 8.5 ± 1.2%, 10 ± 7.4% vs 14 ± 4.0%, 10 ± 7.4% vs 14 ± 4.0%, respectively, p = 0.01), whereas no change was observed in the placebo group (5.8 ± 1.8% vs 6.1 ± 0.8%, 12 ± 9.5 vs 10 ± 3.8%, respectively, p > 0.05).

Conclusion: Long-term and high-dose allopurinol therapy significantly improved endothelial function in diabetic normotensive patients. In addition, allopurinol therapy contributes to the lower HbA1c levels.