Cord blood telomere length, telomerase activity and inflammatory markers in pregnancies in women with diabetes or gestational diabetes.
OBJECTIVE
We tested the hypothesis that diabetes during pregnancy leads to chromosomal DNA damage and telomere attrition in the feto placental unit and cord blood, and provides evidence for intrauterine programming towards a senescent phenotype in the offspring.


METHODS
We obtained cord blood from pregnant women with pregestational Type 1 diabetes (n=26), Type 2 diabetes (n=20) or gestational diabetes (n=71), and control subjects without diabetes (n=45, n=76 and n=81, respectively) matched for maternal and gestational age. We measured cord blood mononuclear cell telomere length, telomerase activity (a reverse transcriptase that limits telomere attrition), and concentrations of insulin, high-sensitivity C-reactive protein (hs-CRP) and soluble intercellular adhesion molecule-1 (sICAM-1).


RESULTS
We found no significant differences between groups in cord blood telomere length in any nucleated cell type, or in hs-CRP or sICAM-1 concentrations, but telomerase activity was higher in cord blood from Type 1 (P<0.05) and gestational diabetes pregnancies (P<0.05), but not in Type 2 diabetes pregnancies. There were no significant relationships between glycaemic control, cord blood telomere length, telomerase activity or inflammatory markers in any group.


CONCLUSIONS
We found no difference in cord blood telomere length in pregnancies of women with diabetes compared with control subjects, but higher cord blood telomerase activity in Type 1 and gestational diabetes. This may reflect upregulated telomere reverse transcriptase in response to in utero oxidative DNA and telomere damage. These observations are relevant to the hypothesis that diabetes during pregnancy leads to in utero preprogramming towards senescence in the offspring.
Institute of Food Research, Colney Lane, Norwich, UK.
J A
JA
Cross
R C
RC
Temple
J C
JC
Hughes
N C
NC
Dozio
C
C
Brennan
K
K
Stanley
H R
HR
Murphy
D
D
Fowler
D A
DA
Hughes
M J
MJ
Sampson
D000328:Adult; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics*; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D015415:Biomarkers; D019098:Telomerase