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

Abstract

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.

Membrane and capillary components of lung diffusion and pro-angiogenic cells in infants

“…In addition, fewer pro-angiogenic circulating progenitor cells in cord blood of infants born very premature is associated with an increased risk of developing BPD, which is characterised by impaired alveolar development and decreased DLCO [17][18][19]. This finding of a relationship between circulating progenitor cells and vascular function in infants would be consistent with our previous report that having fewer CHSPCs was associated with decreased vascular function in adolescents with diabetes [9]. Mobilisation of circulating pro-angiogenic cells may be an effective strategy to induce lung growth, particularly in infants with impaired alveolar development; however, more mechanistic studies are required [4].…”

“…We have previously demonstrated that the normal physiological increase in pro-angiogenic (p) CHSPCs during pregnancy is impaired in females with gestational diabetes mellitus and pCHSPCs were lower in cord blood of mothers with gestational diabetes mellitus [8]. In addition, we have demonstrated that adolescents with diabetes mellitus have impaired endothelium-dependent vasodilation, which correlates with reductions in the ratio of pro-angiogenic to non-angiogenic circulating progenitor cells [9]. Evaluating angiogenic cells in infants has been limited by the previous need for large volumes of blood to identify angiogenic circulating progenitor cells; however, we have previously described a multiparameter flow cytometry technique to identify pCHSPCs in 1-mL blood samples [10,11].…”

Relationship between circulating endothelial progenitor cells and endothelial dysfunction in children with type 1 diabetes: a novel paradigm of early atherosclerosis in high-risk young patients

“…That observation seems sobering because these measures are currently widely used in the clinic for assessment of risk of future microvascular and macrovascular diseases. However, other studies on young T1DM patients also failed to demonstrate these types of relations (23,34). Altogether, these observations suggest that other factors besides 'average' of glycaemic values (such as glucose variability) may affect circulating progenitor cell numbers and vascular reactivity at a given moment in time.…”

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus

“…116 Endothelial dysfunction has been demonstrated in numerous studies in adolescents with T1DM. 96,117 Nonultrasound methods for assessing endothelial function, including peripheral arterial tonometry, 118,119 and laser flow Doppler studies 120 have demonstrated similar case-control differences. Poor endothelial function was associated with higher HbA 1c 121 and poor fitness level 122 but was not related to inflammation.…”