Institute of Food Research, Colney Lane, Norwich, UK.
Diabet Med. 2010 Nov;27(11):1264-70. doi: 10.1111/j.1464-5491.2010.03099.x.
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.
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).
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.
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.
我们检验了这样一个假说，即妊娠糖尿病导致胎儿胎盘单位和脐血中的染色体 DNA 损伤和端粒磨损，并为后代宫内编程朝向衰老表型提供了证据。
我们从患有孕前 1 型糖尿病（n=26）、2 型糖尿病（n=20）或妊娠期糖尿病（n=71）的孕妇和无糖尿病的对照受试者（分别为 n=45、n=76 和 n=81）中获得了脐血。我们测量了脐血单个核细胞端粒长度、端粒酶活性（一种限制端粒磨损的逆转录酶）以及胰岛素、高敏 C 反应蛋白（hs-CRP）和可溶性细胞间黏附分子-1（sICAM-1）的浓度。
我们未发现任何组间在任何有核细胞类型的脐血端粒长度、hs-CRP 或 sICAM-1 浓度方面存在显著差异，但 1 型（P<0.05）和妊娠期糖尿病妊娠（P<0.05）的脐血中端粒酶活性更高，但 2 型糖尿病妊娠则不然。在任何组中，血糖控制、脐血端粒长度、端粒酶活性或炎症标志物之间均无显著关系。
与对照组相比，我们在糖尿病孕妇的脐血中未发现端粒长度存在差异，但 1 型和妊娠期糖尿病的脐血中端粒酶活性更高。这可能反映了在宫内氧化 DNA 和端粒损伤的情况下，端粒逆转录酶的上调。这些观察结果与妊娠糖尿病导致后代宫内编程朝向衰老的假说有关。
