Endothelial abnormalities in adolescents with type 1 diabetes: a biomarker for vascular sequelae?
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.


METHODS
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.
DiMeglio
Linda A
LA
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202-5225, USA. dimeglio@iupui.edu
Tosh
Aneesh
A
Saha
Chandan
C
Estes
Myka
M
Mund
Julie
J
Mead
Laura E
LE
Lien
Izlin
I
Ingram
David A
DA
Haneline
Laura S
LS
D000293:Adolescent; D015703:Antigens, CD / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
D015703:Antigens, CD; D015415:Biomarkers; D001786:Blood Glucose