妊娠糖尿病的发生机制和孕早期生物标记

Gestational diabetes mellitus (GDM) is a common pregnancy complication that develops in the 2nd half of pregnancy. The incidence rate of GDM in pregnant women is increasing over the last 3 decades in many countries. The causal mechanisms of GDM remain unclear, and there remains a lack of effective prevention measures. It remains unclear whether there are changes in certain biomarkers in early gestation in patients who are destined to develop GDM in mid/late gestation. Our recent and other studies have demonstrated that circulating levels of certain metabolic hormone (e.g. IGF-1) and adipokines (e.g. adiponectin) are altered in GDM in mid-gestation. In a prospective pregnancy cohort, we plan to further study the roles of oxidative stress, inflammation, metabolic hormone (insulin, IGF-1), adipokines (leptin, adiponectin, resistin, RBP-4, AFABP，SPARC) and fibroblast growth factors (FGF 2, 19, 21) in early pregnancy in relation to the development of GDM, and explore early gestational biomarkers predictive of GDM development in mid/late pregnancy and the optimal prediction models. The findings will shed new light on the causal mechanisms and early gestational biomarkers of GDM, and provide new clues for developing early pregnancy effective intervention measures to reduce the incidence of GDM.

妊娠糖尿病(GDM)是妊娠后半期发生的常见孕期并发症。近30年来， 孕妇GDM的发病率在许多国家呈上升趋势。GDM发生机制尚不清楚，仍缺乏有效的预防措施，亦不清楚在孕早期哪些生物标记的改变与孕中/晚期GDM发病相关。我们和其它的研究表明，GDM孕妇在孕中期血循环中某些代谢激素 （如IGF-1等）和脂肪细胞因子（如脂联素等）的水平有明显改变。我们将进一步在前瞻性妊娠队列中，研究孕早期氧化应激，炎症反应，代谢激素（胰岛素,IGF-1），脂肪细胞因子（瘦素，脂联素，抵抗素，视素结合蛋白4，AFABP，SPARC）和成纤维细胞生长因子(FGF 2, 19, 21)水平在GDM发病中的作用, 探索孕早期可预测孕中/晚期GDM发病风险的生物标记和最佳预测模型。研究结果将增加GDM发病机制和孕早期风险预警生物标记的新知识, 为孕早期有效干预降低GDM的发病率提供新线索。

妊娠糖尿病（GDM）是常见的妊娠并发症。其病因和发病机制仍不清楚，缺乏母婴的健康危险预警生物标志物。我们建立了妊娠/出生队列和生物样本库，分析母体孕期血，脐带血和胎盘中可能与GDM，胎儿过度生长和婴儿糖代谢健康有关的生物标志物。研究结果表明：1）GDM的某些早期妊娠危险因素的影响可能因胎儿性别而异； 2）性激素结合球蛋白（SHBG）可能是妊娠糖尿病发病风险预警的早期妊娠期生物标志物； 3）胎儿过度生长的新生儿（通常与GDM或孕期高血糖症有关）的胰岛素敏感性和β细胞功能下降； 4）脐带血脂联素和生长素释放肽（Ghrelin）可能预测婴儿期糖代谢健康； 5）胎盘11b-HSD2表达水平可预警婴儿期的糖代谢健康（胰岛素抵抗性）； 6）GDM与近200个胎盘基因差异甲基化位点相关。这些发现为GDM的发病机制及与GDM相关的风险预警生物标志物提供了新的线索，为未来开发风险筛查工具和干预措施提供了有价值的新线索。