Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaernic control, endothelial damage/dysfunction and atherosclerosis

Background: microvascular complications in diabetes identify those at risk of cardiovascular disease (CVD), suggesting a link between abnormal neovascularisation and CVD. This may be related to high plasma vascular endothelial growth factor (VEGF). We hypothesised increased angiopoietins (Ang)-1 and -2 in patients with diabetes that are related to VEGF, medium-term glycaemic control, endothelial damage/dysfunction and atherosclerosis. Methods and patients: we measured plasma Ang-1 and Ang-2 alongside VEGF (all by ELISA) in 96 patients with type-2 diabetes mellitus (41 with and 56 without overt CVD) who were compared to 35 age- and sex-comparable healthy controls. Common carotid intima-media thickness (CC-IMT) was used to assess carotid atherosclerosis, plasma von Willebrand factor (vWf) and urine albumin:creatinine ratio (UACr) to quantify and endothelial damage/dysfunction, and HbA1c to mark medium-term hypergylcaemia. Results: Ang-2 (but not Ang-1) was higher inpatients with diabetes compared to controls (p < 0.01), with no significant difference between patients with and without CVD. As expected, CC-IMT, UACr, HbA1c, vWf, and VEGF were also abnormal in the patients. Within the patient group alone, and in the entire cohort, VEGF and Ang-2 correlated strongly (both p < 0.001) and with several other markers. However, in multivariate analysis, the only significant relationship that remained after adjustments was between VEGF and HbA1c (P < 0.001). Conclusions: Angiogenic growth factor Ang-2, like VEGF, is raised in diabetes regardless of vascular disease. Both growth factors correlated with HbA1c and with each other, not with endothelial injury or atherosclerosis, but after multiple adjustment, only that between HbA1c and VEGF significant remained. VEGF is likely to have a more prominent role in diabetes than Ang-2. (c) 2004 Elsevier Ireland Ltd. All rights reserved.