Effect of long-term and high-dose allopurinol therapy on endothelial function in normotensive diabetic patients.
OBJECTIVE
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).


CONCLUSIONS
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.
Department of Cardiology, Erciyes University, Faculty of Medicine, Kayseri, Turkey.
Ali
A
Dogan
Mikail
M
Yarlioglues
Mehmet Gungor
MG
Kaya
Zakir
Z
Karadag
Serap
S
Dogan
Idris
I
Ardic
Orhan
O
Dogdu
Yusuf
Y
Kilinc
Cemil
C
Zencir
Mahmut
M
Akpek
Ibrahim
I
Ozdogru
Abdurrahman
A
Oguzhan
Nihat
N
Kalay
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D014421:Turkey; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000493:Allopurinol; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D009566:Nitrates; D014527:Uric Acid; D014969:Xanthine Oxidase; C517652:hemoglobin A1c protein, human