Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes
Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes
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DOI：
10.1371/journal.pone.0208533
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发表时间：
2018-12-11
期刊：
影响因子：
3.7
通讯作者：
John, Rosalind M.
中科院分区：
文献类型：
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作者：
Garcia-Martin, Isabel;Penketh, Richard J. A.;John, Rosalind M.
与妊娠期糖尿病（GDM）相关的白细胞和胎盘端粒缩短表明，这种暴露引发端粒磨损，导致不良结局。我们应用高分辨率单端粒长度分析（STELA）从GDM妊娠胎盘不同的治疗途径，以确定其有效性，防止端粒磨损。通过协方差分析（ANCOVA）检验对照（N = 69）、GDM生活方式干预（n = 14）和用二甲双胍和/或胰岛素治疗的GDM（n = 17）之间端粒长度的差异，随后使用Fisher最小显著性差异进行组间比较。仅男性胎盘的平均端粒长度（F（2，54）= 4.98，P = 0.01）和小于5 kb的端粒百分比（F（2，54）= 4.65，P = 0.01）存在差异。与对照组（P = 0.02）和药物治疗组（P = 0.003）相比，GDM生活方式干预组的端粒较短。与其他两组相比，GDM生活方式干预组中5 kb以下的端粒更多（P = 0.03和P = 0.004）。虽然进一步的工作是必要的，我们认为，早期采用有针对性的药物治疗的GDM妊娠，胎儿是男性可能是一个有效的策略，以改善不良后果的儿童。
Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher's least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children.