Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition.
OBJECTIVE
To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF.


METHODS
Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated.


RESULTS
No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0--27.9) pg/ml in those without retinopathy, 12.9 (6.0--38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1--33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER.


CONCLUSIONS
Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.
Chaturvedi
N
N
EURODIAB, Department of Epidemiology and Public Health, University College London, London, UK. n.chaturvedi@ic.ac.uk
Fuller
J H
JH
Pokras
F
F
Rottiers
R
R
Papazoglou
N
N
Aiello
L P
LP
D000328:Adult; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000097:blood / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000097:blood*; D005340:Fibrinogen / Q000032:analysis; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D008222:Lymphokines / Q000097:blood*; D008875:Middle Aged; D010919:Placebos; D012907:Smoking; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D016228:Endothelial Growth Factors; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D017706:Lisinopril; D008222:Lymphokines; D010919:Placebos; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor