Elevated Plasma Vascular Endothelial Cell Growth Factor and Thrombomodulin in Juvenile Diabetic Patients

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Abstract
The major cause of morbidity and mortality in pa tients with type 1 diabetes mellitus is vascular disease and the death rate in this group of patients can be up to six times that of the general population. Elevated levels of blood glucose can cause endothelial cell damage, and markers of endothelial dam age such as von Willebrand factor (vWF) and thrombomodulin (TM) have been reported to increase in adult diabetic patients. Growth factors are strongly linked to smooth muscle cell pro liferation that contributes significantly to the vascular occlusive process and it has been shown that vascular endothelial cell growth factor (VEGF) stimulates release of vWF from endo thelial cells. Vascular endothelial cell growth factor levels have been shown to be increased in vitreous fluid from the eyes of diabetic patients with proliferative retinopathy compared to those without. In this study we have shown that plasma levels of both TM and VEGF were significantly increased in juvenile diabetic patients with no clinical evidence of vascular disease compared to normal age and sex-matched control subjects. Me dian TM levels were 45.5 ng/mL (I.Q.R. 34 to 56 ng/mL) and 61 ng/mL (I.Q.R. 41 to 72 ng/mL) in the control group and in the diabetic patients respectively (p = .0005) and median lev els of VEGF were 19.6 pg/mL (I.Q.R, 15.9 to 28.1 pg/mL) in the control group and 37.1 pg/mL (I.Q.R. 22.1 to 50.3 pg/mL) in the diabetic patients (p = .027 Mann-Whitney U test). This suggests that microvascular disease begins in childhood and can be detected using laboratory tests before any clinical changes are apparent. Key Words: Diabetes mellitus— Thrombomodulin—Vascular endothelial cell growth factor.

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