Background: We evaluated whether an abundance of first-trimester plasma mitochondrial DNA (mtDNA) fragments could predict the risk for the development of gestational diabetes mellitus (GDM) by the late second or early third trimester.
Methods: It was a prospective study wherein we enrolled 150 women in their first trimester of gestation. Oral glucose tolerance test (OGTT) was administered both in the first and second trimesters to diagnose GDM.
Results: Among our cohort, 23 women were diagnosed with GDM in the first trimester and excluded from the study. Of the remaining 127, 29 women were diagnosed with GDM in the second trimester, and 98 women who did not develop GDM served as controls. We amplified blood drawn from each participant during the first trimester for three distinct mtDNA gene sequences: COX, ND4, and D-loop. An abundance of each mtDNA sequence, estimated by the ΔCt method between mtDNA and 18S rRNA, correlated with GDM occurrence in the late second or early third trimester. There was a significant difference in ΔCt COX between controls and those with GDM occurrence in the second trimester (p = .006). These levels were not associated with age or fasting plasma glucose levels in the first trimester. ΔCt COX could predict GDM with a sensitivity of 90% and a specificity of 40%. Though ΔCt ND4 was higher in the GDM-positive group, the levels did not reach statistical significance. ΔCt D-loop was similar in GDM-positive cases and controls who did not develop GDM during pregnancy.
Conclusions: These results were in plasma samples collected 3 to 4 months before overt hyperglycemia diagnosis suggestive of GDM. The abundance of plasma mtDNA fragments represents a promising cost-effective, convenient early-stage biomarker for predicting GDM development. Importantly, it can be administered irrespective of the fasting status of the subject. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed for effective clinical utility.
背景:我们评估了孕早期血浆线粒体DNA (mtDNA) 片段的丰度是否可以预测妊娠糖尿病(GDM)的风险 方法:这是一项前瞻性研究，招募了150名处于孕早期的女性。在孕早期和孕中期进行口服葡萄糖耐量试验(OGTT)诊断GDM 结果:在我们的队列中，23名女性在孕早期被诊断为GDM并被排除在本研究之外。其余的127人中，29人在孕中期被诊断为GDM，98名在整个孕期未患GDM的女性作为对照组。我们从每个参与者孕早期抽取的血液中扩增了三个不同的mtDNA基因序列:COX、ND4和D-loop。以ΔCt方法在mtDNA和18S rRNA之间进行估计，发现每个mtDNA序列的丰度与孕中期晚期或孕晚期早期的GDM发生相关。对照组和孕中期GDM发生组之间的ΔCt COX差异有统计学意义(p=.006)。这些水平与孕早期的年龄或空腹血浆葡萄糖无关。ΔCt COX可以预测GDM，敏感度为90%，特异度为40%。虽然ΔCt ND4在GDM阳性组中较高，但差异水平未达到统计学意义。ΔCt D-loop在GDM阳性病例和未在孕期发生GDM的对照组之间相似 结论:这些结果来自在确诊GDM之前3至4个月收集的血浆样本。血浆mtDNA片段的丰度代表了一种有前景的符合成本效益的、方便的早期生物标志物，可用于预测GDM的发展。重要的是，无论受试者是否空腹，都可以使用这一指标。需要在大型、多样化人群中进一步评估这些生物标志物的预测能力，以便有效地应用于临床.
© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.