Insulin may cause deterioration of proliferative diabetic retinopathy

Diabetes mellitus (DM) can cause many systemic complications, including proliferative diabetic retinopathy (PDR). Retinal neovascularization (RNV) is the typical symptom of PDR, representing an important risk factor for severe vision loss in patients with DM. Diabetic hyperglycemia plays a major role in the destruction of retinal capillary walls, resulting in retinal ischemia and up-regulation of vascular endothelial growth factor (VEGF), leading to neovascularization. The transcriptional regulation of VEGF is mediated by transcription factor hypoxia-inducible factor 1 (HIF-1). Insulin is the mainstay of treatment for DM, but some studies have demonstrated that insulin had the ability to stimulate VEGF and HIF-1 expression in retinal pigment epithelial cells, retinal epithelial cells and vascular smooth muscle cells. In addition to the mitogenic effect of insulin makes it as an assistant agent has long been used in vitro cell culture. Other studies confirmed that insulin increased leukostasis in retinal microcirculation. Based on these experimental results, we hypothesize that long-term insulin therapy maybe improves the expression of VEGF and increase the risk of RNV, eventually deteriorates PDR in patients with DM.