OBJECTIVE -Lipid hydroperoxide, a marker of oxidative stress, is linked to the development of nephropathy and is reportedly higher in patients of African origin compared with Caucasians. This may be relevant to race-specific differences in susceptibility to nephropathy. We investigated whether alterations in antioxidant enzyme activity could account for this biochemical phenotype and examined the relationship with conventional markers of renal disease.RESEARCH DESIGN AND METHODS -Two hundred seventeen individuals were studied. Patients with type 2 diabetes (n ϭ 75) of African and Caucasian origin were matched by sex and racial origin with healthy control subjects (n ϭ 142). Plasma total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were spectrophotometrically measured, and total cholesterol and triglycerides were measured by enzymatic methods.RESULTS -SOD activity was higher and GPx activity lower in patients with diabetes than in healthy control subjects (573 Ϯ 515 vs. 267 Ϯ 70 units/l, P Ͻ 0.001 and 150 Ϯ 93 vs. 178 Ϯ 90 units/l, P ϭ 0.019, respectively). Patients of African origin with diabetes had lower GPx and higher SOD activity compared with Caucasian patients (126 Ϯ 82 vs. 172 Ϯ 97 units/l, P ϭ 0.03 and 722 Ϯ 590 vs. 445 Ϯ 408 units/l, P ϭ 0.002, respectively). Patients of African origin with normal urinary albumin excretion had significantly higher plasma creatinine concentrations (100.7 Ϯ 14.2 vs. 88.1 Ϯ 14.9 mol/l, P ϭ 0.007) and lower GPx activity (99.0 Ϯ 72.4 vs. 173.7 Ϯ 107.4 units/l, P ϭ 0.02) compared with those of Caucasian origin. African origin was an independent predictor of elevated SOD (P ϭ 0.007) and reduced GPx activity (P ϭ 0.02) in regression analysis.CONCLUSIONS -SOD and GPx enzyme activities vary according to race and could account for differences in lipid hydroperoxide. In patients of African origin, susceptibility to renal disease may be associated with lowered GPx activity.
Diabetes Care 28:1698 -1703, 2005P eople of African origin have an increased susceptibility to renal disease compared with Caucasians. In the U.K. and U.S., there is a four-to sixfold difference in the incidence of endstage renal disease due to diabetic nephropathy (1-3). The higher prevalence of end-stage renal disease in patients of African origin exceeds that which is explained by the prevalences of hypertension and diabetes.Plasma measures of oxidative stress are increased in patients with diabetes compared with control subjects (4). A nonspecific lipid peroxidation product, malonyldialdehyde, which is indicative of oxidant stress and advanced glycation end products, localizes in the nodular glomerular lesions characteristic of diabetic nephropathy (5-7). Free radicals are also implicated in endothelial and basement membrane damage and, as such, are pathophysiologically related to increased urinary albumin excretion, the most powerful marker of the onset and progression of diabetic nephropathy (8 -10).The major reactive oxygen species produced in the course of oxidative metabolism is s...