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).


CONCLUSIONS
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.
Zitouni
Karima
K
Department of Medicine, Royal Free and University College Medical School, Whittington Hospital, London, United Kingdom.
Harry
Diane D
DD
Nourooz-Zadeh
Jaffar
J
Betteridge
D John
DJ
Earle
Kenneth A
KA
D000368:Aged; D044383:Black People; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D006113:United Kingdom; D014810:Vitamin E / Q000097:blood*; D044465:White People
D001786:Blood Glucose; D008054:Lipid Peroxides; D008055:Lipids; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014810:Vitamin E; D003404:Creatinine