Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease.
BACKGROUND
Endothelial cell dysfunction is an early feature of vascular disease and oxidative stress may be involved in its pathogenesis.


METHODS
Fifty-one children, adolescents and young people with Type 1 diabetes with no clinical diabetic angiopathy, mean age+/-SD of 16+/-4 years, diabetes duration of 8+/-5 years, and HbA(1c) of 8.5+/-1.6%, and 29 age, sex matched normal controls had blood samples assayed for E-selectin, intercellular cell adhesion molecule-1, von Willebrand Factor, red cell superoxide dismutase, plasma thiol and red cell glutathione.


RESULTS
E-selectin and ICAM-1 levels were significantly higher in the diabetic patients at 72+/-24 ng/ml and 287+/-57 ng/ml, respectively vs 43+/-16 ng/ml and 248+/-71 ng/ml in the normal controls (p<0.0002 and p<0.013). Von Willebrand Factor levels were not different between the two groups. Superoxide dismutase activity was significantly higher in the diabetic group at 220+/-58 micro/ml vs 175+/-24 micro/ml in the normal controls p<0.001, and those of plasma thiol and red cell glutathione were significantly lower in the diabetic group, at 1267+/-202 micromol/l and 458+/-38 micromol/l, respectively vs 1403+/-278 micromol/l and 487+/-70 micromol/l in the controls p<0.02 and p<0.03. Levels of superoxide dismutase correlated negatively with plasma thiol, age and diabetes duration r=-0.318, p<0.02; r=-0. 328, p<0.02; and r=-0.286, p<0.05, respectively.


CONCLUSIONS
These results confirm evidence of endothelial perturbation in young people with diabetes mellitus, and they also suggest that free radical generation may contribute to this dysfunction. This supports the hypothesis that vascular disease starts early in the course of childhood diabetes, akin to the situation in adults with diabetes.
Elhadd
T A
TA
Department of Endocrinology, North Staffordshire Hospitals, Stoke-on-Trent, UK.
Kennedy
G
G
Hill
A
A
McLaren
M
M
Newton
R W
RW
Greene
S A
SA
Belch
J J
JJ
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D018826:CD13 Antigens / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000473:pathology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000097:blood; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000097:blood; D013482:Superoxide Dismutase / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D019040:E-Selectin; D005609:Free Radicals; D013438:Sulfhydryl Compounds; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase; D018826:CD13 Antigens; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005978:Glutathione