SAT-651 Ethnic Differences in the Relationship Between Uric Acid Clearance and Insulin Sensitivity

Background: Hyperuricemia is associated with gout, type-2 diabetes, hypertriglyceridemia, and other insulin resistant (IR) states. Impaired clearance of uric acid (UA) has been proposed to play a role in hyperuricemia in IR. In a small study, urinary UA clearance was negatively associated with IR. African-Americans (AA) are more insulin resistant than Caucasians (CA). However, plasma UA levels are lower in AA. Ethnic differences underlying the relationship between UA clearance and insulin sensitivity (Si) remain unknown. Objective: To compare the relationships between UA production, clearance, and Si in AA and CA. Design: In a cross-sectional study, AA (n = 40; age 43 ± 10 years; BMI 41.3 ± 9.7 kg/m2) and CA (n = 88; age 44 ± 13 years; BMI 32.9 ± 8.2 kg/m2) subjects underwent an intravenous glucose tolerance test (IVGTT) to derive Si using the Minimal Model. Plasma UA and creatinine (Cr), were measured in the NIH Department of Laboratory Medicine. Urinary UA and Cr levels in spot urine samples were measured using a colorimetric assay. Fractional Excretion (FE) of UA and urine urate-to-creatinine ratio (UUCR), a measure of uric acid production, were calculated. Results: AA had a significantly higher BMI (p < 0.0001), percent body fat (45.8 ± 8.9 vs. 39.7 ± 11.5 %, p = 0.0007), A1C (5.8 ± 0.4 vs. 5.5 ± 0.3 %, p = 0.0006), diastolic BP (74 ± 9 vs. 71 ± 8 mm of Hg, p = 0.02), and lower Si (2.36 ± 2.7 vs. 4.43 ± 3.4 min−1·μU·ml−1, p = 0.0004) compared to CA. Stepwise multiple regression analysis was performed with independent variables A1c, fasting glucose, fasting insulin, triglycerides, and Si. Among these, Si was a significant predictor of FE of UA in CA (r = 0.33, p=0.001), but not AA (r = - 0.02, p=0.92).There was also a negative association between Si and plasma UA in CA (r = 0.48, p < 0.0001), but not in AA (r = 0.06, p = 0.70). There was no association between Si and UA production in both groups (AA: p = 0.33, CA: p = 0.69). Conclusion: These findings suggest that reduced insulin sensitivity may not play a major role in the pathogenesis of hyperuricemia in AA in insulin-resistant states.