Endothelial perturbation in children and adolescents with type 1 diabetes: association with markers of the inflammatory reaction.
OBJECTIVE
The progression of diabetic angiopathy is, in most cases, unpredictable. The aim of this study was to investigate early events that could influence the development of diabetic angiopathy.


METHODS
Circulating levels of von Willebrand factor (vWF) and tissue-plasminogen activator (tPA), defining endothelial perturbation, were measured in 40 young patients with type 1 diabetes. Patients were divided into two groups according to the duration of diabetes (group A, <1 year; group B, >1 year) and compared with a control group of age- and sex-matched healthy individuals. Prothrombin fragment 1 and 2 (F(1+2)), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) levels were also determined as markers of a prothrombotic state and inflammatory response. A total of 16 of the 20 children in group A were re-examined after 12 months.


RESULTS
Compared with either normal subjects or patients in group B, children in group A showed increased levels of vWF, tPA, F(1+2), TNF-alpha, and CRP. Significant direct correlations between TNF-alpha or CRP and either vWF, tPA, or F(1+2) were observed. Endothelial perturbation was shown in 70% of group A and 20% of group B. After 1 year, 16 of the 20 patients in group A showed a significant reduction in vWF, tPA, F(1+2), TNF-alpha, and CRP levels, whereas endothelial perturbation was reversed in 5 of these patients.


CONCLUSIONS
Endothelial perturbation represents an early and, in some cases, reversible event in the chronology of type 1 diabetes in children. A correlation might exist between the initial inflammatory reaction and the appearance of endothelial perturbation.
Romano
M
M
Department of Human Pathology, University of Messina, Messina, Italy.
Pomilio
M
M
Vigneri
S
S
Falco
A
A
Chiesa
P L
PL
Chiarelli
F
F
Davì
G
G
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D012016:Reference Values; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D010446:Peptide Fragments; D011498:Protein Precursors; D011516:Prothrombin; D010959:Tissue Plasminogen Activator; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2