Abstract

Context Oxidative stress is implicated in the development of microvascular disease and is associated with an upregulation of vascular endothelial growth factor (VEGF) which is pathogenetically linked to microvascular complications of diabetes. Patients of African origin have an increased susceptibility to microvascular kidney disease compared with Caucasians, the reasons and the mechanisms that contributes to this vulnerability are unclear. Objectives Primary) Investigate whether there are ethnic differences in Lipopolysaccharide induced monocyte VEGF production in whole blood cell cultures. Secondary) whether stimulated VEGF production is related to prevailing oxidative stress assessed by plasma lipid hydroperoxides (LOOH) and α-Tocopherol. Design and Setting Cross sectional study at a secondary care centre in North London, UK, serving an inner-city community of 154,000 adults. Patients African-Caribbean and Caucasian patients with type 2 diabetes (n=52) Results Lipopolysaccharide induced production of VEGF in whole blood cultures (61.8[31.9] pg/mL to 78.4[36.0] pg/mL; p<0.001) that correlated positively with LOOH levels (r=0.3, P=0.04) and was significantly higher in African-Caribbean than Caucasian type 2 diabetes patients (404 [207.5] vs 268.8 [137.0] pg/mL X109/L monocytes; P=0.018). Plasma α-Tocopherol concentration was higher in Caucasian patients (40.3[18.3] vs 30.0[9.6] µmol/L; p=0.04) compared to African-Caribbeans. Conclusions This study suggests that the redox environment influences VEGF production in response to proinflammatory stimuli in type 2 diabetes. The differential responsiveness by ethnic origin may be of relevance in the variations in susceptibility to the long-term microvascular complications.