During the whole pathological process, hyperglycemic up-regulation of HIF-1α expression is the intermediate link in the occurrence of DN, which leading to the overexpression of VEGF and causing glomerular capillary dysfunction and leading to proteinuria, as well known, increase of UAER is an important sign of endothelial dysfunction and small vessel disease. The gene discussed is HIF1A; the disease is endothelial dysfunction.