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Katrin Engelmann, Dieter Appelt, Frank Pistrosch, Dirk Sandner, Elena Henkel, Carsta Koehler, M. Hanefeld; Relationship between vascular endothelial growth factor (VEGFA), biomarkers of inflammation and dysglycemia. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2243.
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Abnormal VEGF plays a pivotal role in the pathogenesis of diabetic maculopathy and retinopathy. Vice versa low systemic VEGF levels seem to be associated with impaired angiogenesis in patients with type 2 diabetes and cardiovascular disease. Recently long lasting decrease in systemic VEGF levels was reported after intraocular anti-VEGF treatment of diabetic macular edema. So far little is known on relationship between VEGF, activation of the inflammation cascade and other cardiovascular risk factors in different categories of glucose intolerance. This proatherogenic cascade may be a link between systemic effects of intraocular anti-VEGF therapy and vascular complications. In addition to previous studies with prediabetes we therefore analysed the relationship between VEGF-A, biomarkers of inflammation (BI), other cardiovascular risk factors (RF) and HbA1c in advanced type 2 diabetes.
251 subjects matched for BMI and age: 50 with normal glucose tolerance (NGT), 50 with pre-diabetes (PRE-DM), 100 with early diabetes (E-DM) and 51 with advanced A-DM were analysed for VEGF-A, BI and HbA1c. Statistics: t-test with CI, Anova, univariate correlation and stepwise regression analysis with VEGF-A as dependent variable.
Patients were well matched for age, BMI and sex. As shown in tab. A-DM shows a significant increase in hsCRP and VEGF-A. In univariate analysis we found a significant correlation of VEGF-A with hsCRP and HbA1c in the overall population. However, VEGF-A was inversely correlated to age. In A-DM age (R=-0,37) and hsCRP (R= 0,36) were significantly correlated to VEGF-A. In multivariate analysis only the parameter hsCRP and adiponectin have an independent association to VEGF-A.
Our analysis reveals a robust correlation between VEGF-A and hsCRP in the overall population and in addition for HbA1c and VEGF-A in patients with poorly controlled diabetes. A DM represents a Bermuda triangle of high HbA1c, elevated VEGF-A and activated inflammation. These data suggest that hsCRP as gold standard of low grade inflammation may be used as risk marker also for follow-up of anti-VEGF-A therapy. Prospective studies are needed to validate cardiovascular risk associated with systemic effects of anti-VEGF-therapy.
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