Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status

N/ACompletedNCT01931527

Washington University School of Medicine31 enrolled

Overview

The purpose of this study is to learn more about what is the effect of uric acid on oxidative stress and on the way the body metabolizes sugar in obese people. Understanding this may lead to better diseases such as diabetes.

It has been hypothesized that oxidative stress is involved in the pathogenesis of insulin resistance associated with obesity. Circulating uric acid (UA) is the body's major endogenous plasma antioxidant. Therefore, the investigators evaluated whether alterations in serum UA concentration affect: 1) systemic and skeletal muscle oxidative stress, 2) total antioxidant capacity, and 4) skeletal muscle insulin sensitivity during a hyperinsulinemic-euglycemic clamp.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Obesity Metabolic Syndrome Hyperuricemia

Interventions

RasburicaseDRUG

one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * obese (BMI 30-45 kg/m²); * serum UA concentration either ≥5 mg/dL or ≤4.0 mg/dL (297 µmol/L)\], Exclusion Criteria: * renal dysfunction (serum creatinine \>1.5 mg/dL); * pregnancy or lactating; * take urate-lowering agents, thiazide diuretics, prednisone or medications containing aspirin or other salicylates; * history of xanthinuria, type 2 diabetes or other significant organ system dysfunction; * have G6PD deficiency; * use hormone-replacement or oral-contraceptive therapy; * smoke tobacco; * anemic (Hb \<10 g/dl)

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Percent Increase in Insulin-stimulated Glucose Uptake

Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). A hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope glucose tracer infusion will be used to measure percent increase in insulin-stimulated glucose uptake in obese subjects with high uric acid before and after uric acid reduction.

Time frame: 12 hours after reducing uric acid

Secondary Outcomes

The Effect of Reducing Uric Acid on Oxidative Status

Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). Systemic (urinary isoprostanes) and skeletal muscle (carbonylated protein ratio) oxidative stress and total antioxidant capacity (plasma TRAP and FRAP) will be measured in obese subjects with high uric acid before and after uric acid reduction. Levels of isoprostanes were normalized to urinary creatinine and reported at ng/mg.

Time frame: 12 hours after reducing uric acid

Baseline Carbonylated Protein Ratio

Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle

Time frame: Before reducing uric acid

AFTER Rasburicase Carbonylated Protein Ratio

Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle

Time frame: 12 hours after reducing uric acid

Baseline Plasma TRAP

Total Radical-Trapping Antioxidant Potential

Time frame: Before reducing uric acid

AFTER Rasburicase Plasma TRAP

Total Radical-Trapping Antioxidant Potential

Data from ClinicalTrials.gov

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