Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition

Diabet Med. 2001 Apr;18(4):288-94. doi: 10.1046/j.1464-5491.2001.00441.x.


Aims: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Glucose / metabolism
  • Blood Pressure
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / physiopathology
  • Endothelial Growth Factors / blood*
  • Fibrinogen / analysis
  • Glycated Hemoglobin A / analysis
  • Humans
  • Lisinopril / therapeutic use*
  • Lymphokines / blood*
  • Middle Aged
  • Placebos
  • Smoking
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor / analysis


  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Endothelial Growth Factors
  • Glycated Hemoglobin A
  • Lymphokines
  • Placebos
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor
  • Fibrinogen
  • Lisinopril