Lipid hydroperoxide and markers of renal disease susceptibility in African-Caribbean and Caucasian patients with Type 2 diabetes mellitus.
The reasons for the increased incidence of diabetic nephropathy in African-Caribbean compared with Caucasian subjects are poorly understood. Increased oxidative stress is linked to the development of endothelial dysfunction and histological abnormalities associated with diabetic renal disease. Therefore, it was assessed whether a marker of oxidative stress, lipid hydroperoxide (LOOH) and endothelial damage, von Willebrand factor (vWF) varied according to ethnic origin in the presence or absence of early diabetic nephropathy. Eighty-eight patients with Type 2 diabetes mellitus of African-Caribbean or Caucasian origin without a history of cardiovascular disease or clinical proteinuria were studied. Patients were classified as having microalbuminuria or normal albumin excretion. Fasting plasma vWF and LOOH were measured by an inhouse enzyme-linked immunoassay and ferrous oxidation with xylenol orange (FOX) assay, respectively. The relationship of LOOH to urinary albumin status, the metabolic disturbances of diabetes, blood pressure and ethnic origin were assessed using multivariate analysis. Compared with Caucasian patients those of African-Caribbean origin had higher systolic blood pressure and HDL-cholesterol (157.8 +/- 17.0 vs. 147.8 +/- 24.4, P = 0.041 and 1.6 +/- 0.4 vs. 1.3 +/- 0.5, P = 0.018) but lower total triglycerides (1.3 +/- 0.8 vs. 1.9 +/- 1.1, P = 0.008). LOOH was significantly higher in the African-Caribbean patients compared with Caucasians (5.98 +/- 2.49 vs. 4.49 +/- 2.19, P = 0.006). vWF tended to be higher in microalbuminuric patients but showed no variation with ethnicity. In logistic regression analysis, LOOH was the only independent predictor of a raised albumin excretion rate (P = 0.008). In multiple regression analysis, African-Caribbean ethnicity (P = 0.020) HDL-cholesterol (P = 0.036), total triglycerides (P = 0.002) and a raised albumin excretion rate (P = 0.002) were independent predictors of LOOH. In this group of Type 2 diabetic patients an increase in LOOH is associated with abnormal urinary albumin excretion. African-Caribbean origin was a determinant of LOOH independently of microalbuminuria. It is postulated that increased oxidative stress is of pathophysiological significance in accelerating the development of renal disease in African-Caribbean patients.