Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status
- Conditions
- ObesityMetabolic SyndromeHyperuricemia
- Interventions
- Registration Number
- NCT01931527
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- obese (BMI 30-45 kg/m²);
- serum UA concentration either ≥5 mg/dL or ≤4.0 mg/dL (297 µmol/L)],
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Obese subjects with high uric acid Rasburicase Subjects with a body mass index = or \> 30 kg/m² with high uric acid (\>6 mg/dL) Intervention: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min
- Primary Outcome Measures
Name Time Method Percent Increase in Insulin-stimulated Glucose Uptake 12 hours after reducing uric acid 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.
- Secondary Outcome Measures
Name Time Method The Effect of Reducing Uric Acid on Oxidative Status 12 hours after reducing uric acid 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.
Baseline Carbonylated Protein Ratio Before reducing uric acid Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
AFTER Rasburicase Plasma TRAP 12 hours after reducing uric acid Total Radical-Trapping Antioxidant Potential
Baseline Plasma FRAP Before reducing uric acid Ferric-Reducing Antioxidant Potential
AFTER Rasburicase Carbonylated Protein Ratio 12 hours after reducing uric acid Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
Baseline Plasma TRAP Before reducing uric acid Total Radical-Trapping Antioxidant Potential
AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹) 12 hours after reducing uric acid Ferric-Reducing Antioxidant Potential
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States