Original Article
Endothelial Abnormalities in Adolescents with Type 1 Diabetes: A Biomarker for Vascular Sequelae?

https://doi.org/10.1016/j.jpeds.2010.04.050Get rights and content

Objective

To evaluate whether counts of circulating colony forming unit-endothelial cells (CFU-ECs), cells co-expressing CD34, CD133, and CD31 (CD34+CD133+CD31+), and CD34+CD45- cells are altered in adolescents with type 1 diabetes and if the changes in counts correlate with endothelial dysfunction.

Study design

Adolescents with diabetes (ages 18 to 22 years) and race- and sex-matched control subjects were studied. We assessed circulating CFU-ECs, using colony assays, and CD34+CD133+CD31+ and CD34+CD45- cells, using poly-chromatic flow cytometry. CFU-ECs and CD34+CD133+CD31+ are hematopoietic-derived progenitors that inversely correlate with cardiovascular risk in adults. CD34+CD45- cells are enriched for endothelial cells with robust vasculogenic potential. Vascular reactivity was tested by laser Doppler iontophoresis.

Results

Subjects with diabetes had lower CD34+CD133+CD31+ cells, a trend toward reduced CFU-ECs, and increased CD34+CD45- cells compared with control subjects. Endothelium-dependent vasodilation was impaired in subjects with diabetes, which correlated with reductions in circulating CD34+CD133+CD31+ cells.

Conclusions

Long-term sequelae of type 1 diabetes include vasculopathies. Endothelial progenitor cells promote vascular health by facilitating endothelial integrity and function. Lower CD34+CD133+CD31+ cells may be a harbinger of future macrovascular disease risk. Higher circulating CD34+CD45- cells may reflect ongoing endothelial damage. These cells are potential biomarkers to guide therapeutic interventions to enhance endothelial function and to prevent progression to overt vascular disease.

Section snippets

Methods

The study was approved by the Indiana University Institutional Review Board. Patients with type 1 diabetes for at least 5 years and healthy sex- and race-matched control subjects ages 18 to 22 years were recruited. Control subjects were recruited both through advertisements and by asking patients to ask a friend without diabetes to participate with them. Subjects were excluded if they had evidence of insulin resistance (acanthosis, extreme obesity), were smokers, or were on medications other

Results

Seventeen adolescents with type 1 diabetes (8 males; 2 black) and 18 control subjects (9 males; 1 black) were enrolled with a mean age of 20.3 ± 1.4 years. Individuals with type 1 diabetes had been diagnosed for a mean of 10.7 ± 3.5 years (range, 4.9 to 17.6) and had no clinical evidence of vascular disease (no microalbuminuria or history of retinopathy). No significant differences were observed between the groups except in A1C and fructosamine (Table). Physical activity scores were not

Discussion

Multiple studies in adults demonstrate that circulating CFU-ECs and CPCs inversely correlate with risk of subsequent cardiovascular disease.14, 15, 16, 17 However, no studies have been conducted in children, and rarely have studies included adolescents with a predisposition to develop vascular morbidities. Interventions to enhance vascular health are likely to be most successful early in disease prior to sustaining irreversible vascular damage, emphasizing the importance of studies in high-risk

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    Supported by UL1RR025761Indiana Clinical and Translational Sciences Institute (L.D. and D.I), P30 CA08709 (D.I. and L.H.), and the Riley Children's Foundation (D.I. and L.H.). The authors declare no conflicts of interest.

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