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

• Published in: Diabetologia Vol. 50; no. 12; pp. 2572 - 2579
• Main Authors: WARING, W. S, MCKNIGHT, J. A, WEBB, D. J, MAXWELL, S. R. J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-12-2007; Springer Nature B.V
• Subjects: Acetylcholine - administration & dosage; Adult; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Brachial Artery - drug effects; Brachial Artery - physiology; Cardiology. Vascular system; Cardiovascular disease; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - prevention & control; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium; Endothelium, Vascular - physiology; Female; Humans; Hypertension; Infusions, Intra-Arterial; Male; Medical sciences; Metabolic diseases; Middle Aged; Nitric oxide; Nitroprusside - administration & dosage; omega-N-Methylarginine - administration & dosage; Other metabolic disorders; Placebos; Purines and pyrimidines (gout, hyperuricemia...); Urate Oxidase - administration & dosage; Urate Oxidase - therapeutic use; Uric acid; Uric Acid - blood; United Kingdom > UK; Endocrinopathy; Type 2 diabetes; Urate oxidase; Cardiovascular disease; Endothelial function; Vascular function; Vascular disease; Antioxidants; Hyperuricemia; Blood vessel; Atherosclerosis; Serum; Hyperuricaemia; Human; Enzyme; Metabolic diseases; Uric acid; Antioxidant; Endothelium; Nitric oxide,Type 2 diabetes; Nitric oxide; Cardiovascular risk; Urate oxidase,Uric acid; Purine; Circulatory system; Oxidoreductases
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0817-7

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.
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.
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.
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.