Effects of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes

Abstract

Endothelial dysfunction is thought to be a critical event in the pathogenesis of vasculopathy in type 2 diabetes and oxidant stress is a major etiological factor. Gliclazide, a second generation sulfonylurea, contains an azabicyclo-octyl ring, which has been described to have antioxidant properties. However, the effect of gliclazide on endothelial function is unknown. Therefore, in this study, we examined the effect of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes (diabetic group; n=33). A control group of non-diabetic subjects was also enrolled (n=25). All of the diabetic patients were treated with gliclazide for 12 weeks. Endothelial function was evaluated by flow-mediated vasodilation (FMD) before and after treatment. We also determined the number of circulating endothelial progenitor cells (EPCs), which were defined by CD45(low)/CD34(+)/VEGFR2(+) and quantified by flow cytometry, because these cells may offer a new biomarker for circulatory diseases. Oxidative stress was evaluated in terms of the serum levels of malondialdehyde, superoxide dismutase and nitric oxide. FMD, circulating EPC count and superoxide dismutase activity were significantly lower in the diabetic group than in the control group at baseline (P<0.05), and improved significantly following gliclazide treatment (P<0.05). Malondialdehyde and nitric oxide levels were higher in the diabetic group than in the control group at baseline (P<0.05), and decreased following gliclazide treatment. These results suggest that gliclazide could improve endothelial function in diabetes, which may be related to its antioxidant properties.