Incidences of childhood obesity and type 2 diabetes (T2D) are climbing at alarming rates. Evidence points to prenatal exposures to maternal obesity and gestational diabetes mellitus (GDM) as key contributors to these upward trends. Children born to mothers with these conditions face higher risks of obesity and T2D, beyond genetic or shared environmental factors. The underpinnings of this maternal-fetal programming are complex. However, animal studies have shown that such prenatal exposures can lead to changes in brain pathways, particularly in the hypothalamus, leading to obesity and T2D later in life. This article highlights significant findings stemming from research funded by my American Diabetes Association Pathway Accelerator Award and is part of a series of Perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program. This critical support, received more than a decade ago, paved the way for groundbreaking discoveries, translating the neural programming findings from animal models into human studies and exploring new avenues in maternal-fetal programming. Our BrainChild cohort includes >225 children, one-half of whom were exposed in utero to maternal GDM and one-half born to mothers without GDM. Detailed studies in this cohort, including neuroimaging and metabolic profiling, reveal that early fetal exposure to maternal GDM is linked to alterations in brain regions, including the hypothalamus. These neural changes correlate with increased energy intake and predict greater increases in BMI, indicating that early neural changes may underlie and predict later obesity and T2D, as observed in animal models. Ongoing longitudinal studies in this cohort will provide critical insights toward breaking the vicious cycle of maternal-child obesity and T2D.

中文翻译：

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肥胖和 2 型糖尿病的神经发育途径：产前暴露于孕产妇肥胖和妊娠糖尿病的见解：停止糖尿病途径支持的研究报告


儿童肥胖和 2 型糖尿病 （T2D） 的发病率正在以惊人的速度攀升。有证据表明，产前暴露于孕产妇肥胖和妊娠糖尿病 （GDM） 是这些上升趋势的主要因素。除了遗传或共同的环境因素之外，患有这些疾病的母亲所生的孩子面临更高的肥胖和 T2D 风险。这种母胎编程的基础很复杂。然而，动物研究表明，这种产前暴露会导致大脑通路发生变化，尤其是下丘脑，从而导致以后的肥胖和 T2D。本文重点介绍了由我的美国糖尿病协会途径加速器奖资助的研究的重要发现，并且是报告美国糖尿病协会停止糖尿病途径计划资助的研究的一系列观点的一部分。十多年前获得的这一关键支持为突破性发现铺平了道路，将动物模型的神经编程结果转化为人类研究，并探索母胎编程的新途径。我们的 BrainChild 队列包括 >225 名儿童，其中一半在子宫内暴露于母体 GDM，一半由没有 GDM 的母亲所生。该队列的详细研究，包括神经影像学和代谢分析，表明胎儿早期暴露于母体 GDM 与大脑区域（包括下丘脑）的改变有关。这些神经变化与能量摄入的增加相关，并预测 BMI 的更大增加，表明早期神经变化可能是并预测后期肥胖和 T2D 的基础，如在动物模型中观察到的那样。 该队列中正在进行的纵向研究将为打破母婴肥胖和 T2D 的恶性循环提供重要见解。