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

Diabetologia. 2007 Dec;50(12):2572-9. doi: 10.1007/s00125-007-0817-7. Epub 2007 Oct 10.


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 N(G)-monomethyl-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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Adult
  • Brachial Artery / drug effects
  • Brachial Artery / physiology
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Angiopathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Middle Aged
  • Nitroprusside / administration & dosage
  • Placebos
  • Urate Oxidase / administration & dosage
  • Urate Oxidase / therapeutic use*
  • Uric Acid / blood*
  • omega-N-Methylarginine / administration & dosage


  • Placebos
  • Nitroprusside
  • Uric Acid
  • omega-N-Methylarginine
  • Urate Oxidase
  • Acetylcholine