The role of insulin-like growth factor I and hypoxia inducible factor 1α in vascular endothelial growth factor expression in type 2 diabetes.

Background: Vascular endothelial growth factor (VEGF) plays an important role in diabetic vascular complications, and its expression is affected directly or indirectly by hypoxia inducible factor-1 alpha (HIF-1 alpha) and insulin-like growth factor-I (IGF-I) in tumors and certain normal cell lines. However, little is known about the role of HIF-1 alpha/ IGF-I in VEGF expression in patients with diabetic vascular complications. The aim of this study was to elucidate the associations between HIF-1 alpha, IGF-I, and VEGF in type 2 diabetes mellitus (T2DM) patients with or without vascular complications. Methods: Sixty patients with T2DM, with(A), and without vascular disease (B) and 26 controls were enrolled. Clinical parameters, HIF-1 alpha, IGF-I and VEGF were assessed in the study and associations among them were analyzed by Spearman rank correlation. Results: Serum levels of VEGF, HIF-1 alpha and IGF-I were significantly higher in the diabetic patients than in the controls. Positive correlations existed between VEGF and HIF-1 alpha and between HIF-1 alpha and IL-6 in both groups A and B and in the control group. Conclusions: Our data demonstrate that HIF-1 alpha and IL-6 could regulate VEGF expression, and that higher levels of HIF-1 alpha, IL-6, and VEGF may contribute to the pathogenesis of diabetic micro-angiopathy.