Lowering serum urate does not improve endothelial function in patients with type 2 diabetes

Aims/hypothesis Endothelial dysfunction contributes to excess cardiovascular risk in patients with type 2 diabetes. There is strong evidence of an association between high serum uric acid concentrations and endothelial dysfunction, and uric acid has been proposed as an independent cardiovascular risk factor in type 2 diabetes. We hypothesised that lowering of uric acid concentrations might allow restoration of endothelial function in this high- risk group. Methods Intravenous urate oxidase (1.5 mg) was administered to ten patients with type 2 diabetes and ten healthy participants in a two- way, randomised, placebo- controlled, crossover study. Forearm blood flow responses to intra-brachial acetylcholine, sodium nitroprusside and NG- mono-methyl-L-arginine (L-NMMA) were measured using venous occlusion plethysmography. The augmentation index (AIx) was determined by pulse wave analysis as a measure of large arterial stiffness. Results Acetylcholine and L- NMMA evoked lesser responses in patients with type 2 diabetes than in healthy participants. Baseline AIx was higher in patients with type 2 diabetes (mean SD: 13.1 +/- 6.9%) than in healthy participants (2.0 +/- 5.1%; p= 0.006). Urate oxidase lowered serum uric acid concentrations by 64 +/- 11% (p< 0.001), but this had no effect on forearm blood flow responses or AIx in either group. Conclusions/interpretation Substantial short- term lowering of uric acid did not have a direct vascular effect, suggesting that, on its own, this might not be an effective strategy for restoring endothelial function in patients with type 2 diabetes.