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Endothelial Perturbation in Children and Adolescents With Type 1 Diabetes

Association with markers of the inflammatory reaction

¹ Department of Human Pathology, University of Messina, Messina
² Department of Medicine and Aging, Division of Pediatrics, University of Chieti, Chieti
³ Department of Medicine, University of Palermo, Palermo
⁴ Department of Medicine and Aging, Division of Hematology, University of Chieti, Chieti
⁵ the Department of Medicine and Aging, Division of Pediatric Surgery, University of Chieti, Chieti, Italy

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.

RESEARCH DESIGN AND 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 (F₁₊₂), tumor necrosis factor- (TNF-), 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, F₁₊₂, TNF-, and CRP. Significant direct correlations between TNF- or CRP and either vWF, tPA, or F₁₊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, F₁₊₂, TNF-, 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.

Abbreviations: CRP, C-reactive protein • ELISA, enzyme-linked immunosorbent assay • F₁₊₂, prothrombin fragment 1 and 2 • ICA-IgG, anti-islet cell antibodies • IL-1ß, interleukin-1ß • IL-6, interleukin-6 • TNF-, tumor necrosis factor- • tPA, tissue-plasminogen activator • vWF, von Willebrand factor

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