Circulating vitamin E, transforming growth factor beta1, and the association with renal disease susceptibility in two racial groups with type 2 diabetes.

Background: End-stage renal disease caused by diabetes disproportionately affects patients of African origin. The biological mechanism(s) for this observation is unclear. Emerging data from cross-sectional studies suggest that increased oxidative stress and the cytokine, transforming growth factor beta(1), are associated with this phenomenon. Therefore, a pathway involving these factors could alter the vulnerability to renal disease and impact adversely on the rate of loss of renal function.

Methods: We assessed the relationship between renal function, oxidative stress, and transforming growth factor beta(1) in 58 patients with type 2 diabetes of African and Caucasian origin over 174 patient-years of follow-up. Oxidative stress was assessed by measuring plasma lipid hydroperoxide and vitamin E in the postprandial state. Creatinine clearance was calculated from the Cockcroft-Gault equation. Patients received standardized management of hypertension, hyperglycemia, and hypercholesterolemia. Data were adjusted by multiple regression analysis to account for potential confounders.

Results: Lipid hydroperoxide was higher and vitamin E lower, while there was no difference in fasting transforming growth factor beta(1) between the African (N= 22) and Caucasian (N= 36) patients [5.1(1.2) vs. 4.3 (1.8) micromol/L; P= 0.02 and 29.8 (10.8) vs. 41.3(19.7) micromol/L; P= 0.02 and 6.33 (5.5) vs. 6.84 (3.9) ng/mL; P= 0.73], respectively. The mean (95% confidence interval) of the difference in creatinine clearance between the patients of African and Caucasian origin was -12.5 (-23.4 to -1.7) mL/min; P= 0.015 at baseline, the magnitude of which increased to -17.5 (-28.4 to -6.5) mL/min; P= 0.002 after 3 years. The fall in creatinine clearance from baseline among the patients of African origin was greater for lower levels of vitamin E (rho = 0.48; P= 0.03). Final plasma creatinine was significantly higher in the African patients compared with the Caucasian patients [109.0 (25.8) vs. 94.0 (20.0) micromol/L; P= 0.0017]. In regression analysis, vitamin E was a significant and independent predictor of plasma creatinine (t -3.17, P= 0.003).

Conclusion: In these patients with type 2 diabetes, vitamin E is a determinant of renal function, and may explain some of the racial differences in renal disease susceptibility that precedes the divergence in incidence of end-stage renal disease.