Shyamasundar Sukanya, Boon Huat Bay, Samuel Sam Wah Tay, S Thameem Dheen, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
World J Diabetes. 2012 Dec 15;3(12):196-200. doi: 10.4239/wjd.v3.i12.196.
Diabetes mellitus rightly regarded as a silent-epidemic is continually on the rise and estimated to have a global prevalence of 6.4 % as of 2010. Diabetes during pregnancy is a well known risk factor for congenital anomalies in various organ systems that contribute to neonatal mortality, including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects are frequently reported. Over the last two to three decades, several groups around the world have focussed on identifying the molecular cues and cellular changes resulting in altered gene expression and the morphological defects and in diabetic pregnancy. In recent years, the focus has gradually shifted to looking at pre-programmed changes and activation of epigenetic mechanisms that cause altered gene expression. While several theories such as oxidative stress, hypoxia, and apoptosis triggered due to hyperglycemic conditions have been proposed and proven for being the cause for these defects, the exact mechanism or the link between how high glucose can alter gene expression/transcriptome and activate epigenetic mechanisms is largely unknown. Although preconceptual control of diabetes, (i.e., managing glucose levels during pregnancy), and in utero therapies has been proposed as an effective solution for managing diabetes during pregnancy, the impact that a fluctuating glycemic index can have on foetal development has not been evaluated in detail. A tight glycemic control started before pregnancy has shown to reduce the incidence of congenital abnormalities in diabetic mothers. On the other hand, a tight glycemic control after organogenesis and embryogenesis have begun may prove insufficient to prevent or reverse the onset of congenital defects. The importance of determining the extent to which glycemic levels in diabetic mothers should be regulated is critical as foetal hypoglycemia has also been shown to be teratogenic. Finally, the major question remaining is if this whole issue is negligible and not worthy of investigation as the efficient management of diabetes during pregnancy is well in place in many countries.
糖尿病被认为是一种无声的流行疾病，发病率持续上升，据估计，截至 2010 年，全球糖尿病发病率为 6.4%。妊娠糖尿病是导致多种器官系统先天畸形的已知危险因素，这些畸形导致新生儿死亡率升高，包括心血管、胃肠道、泌尿生殖和神经系统等，其中神经管缺陷经常被报道。在过去的二三十年里，世界各地的几个研究小组都集中在确定导致基因表达改变和形态缺陷的分子线索和细胞变化上，这些变化与糖尿病妊娠有关。近年来，研究重点逐渐转移到研究预先编程的变化和表观遗传机制的激活，这些变化导致基因表达的改变。虽然已经提出并证明了几种理论，如高血糖引起的氧化应激、缺氧和细胞凋亡，是导致这些缺陷的原因，但确切的机制或高血糖如何改变基因表达/转录组并激活表观遗传机制的联系在很大程度上尚不清楚。虽然已经提出了孕前控制糖尿病（即在怀孕期间控制血糖水平）和宫内治疗作为管理妊娠糖尿病的有效方法，但血糖指数的波动对胎儿发育的影响尚未详细评估。在怀孕前开始严格的血糖控制已被证明可以降低糖尿病母亲所生孩子的先天畸形发生率。另一方面，在器官发生和胚胎发生开始后进行严格的血糖控制可能不足以预防或逆转先天缺陷的发生。确定糖尿病母亲的血糖水平应在何种程度上进行调节是至关重要的，因为胎儿低血糖也被证明具有致畸性。最后，一个主要的问题仍然是，如果这个问题是微不足道的，不值得研究，因为在许多国家，妊娠糖尿病的有效管理已经到位。
