Embedded in the Developmental Origins of Health and Disease hypothesis, maternal hyperglycemia in utero, from pre-existing diabetes or gestational diabetes mellitus, predisposes the offspring to excess adiposity and heightened risk of prediabetes and type 2 diabetes development. This transmission creates a vicious cycle increasing the presence of diabetes from one generation to another, leading to the question: how can we interrupt this vicious cycle? In this Perspective article, we presented the current state of knowledge on the intergenerational transmission of diabetes from epidemiological life course studies. Then, we discussed the potential mechanisms implicated in the intergenerational transmission of diabetes with a focus on epigenetics. We present novel findings stemming from epigenome-wide associations studies of offspring DNA methylation in blood and placental tissues, which shed light on potential molecular mechanisms implicated in the mother-offspring transmission of diabetes. Lastly, in a perspective on how to break the cycle, we consider interventions to prevent offspring obesity and diabetes development before puberty, as a critical period of the intergenerational cycle.

中文翻译：

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阻止糖尿病的代际风险 – 从机制到干预措施


嵌入健康与疾病的发育起源假说中，母体子宫内高血糖症，由预先存在的糖尿病或妊娠糖尿病引起，使后代容易过度肥胖，并增加患糖尿病前期和 2 型糖尿病的风险。这种传播造成了一个恶性循环，使糖尿病的存在一代又一代增加，从而引发了一个问题：我们如何才能中断这种恶性循环？在这篇 Perspective 文章中，我们介绍了流行病学生命历程研究中糖尿病代际传播的知识现状。然后，我们讨论了糖尿病代际传播所涉及的潜在机制，重点是表观遗传学。我们提出了源自血液和胎盘组织中后代 DNA 甲基化的表观基因组范围关联研究的新发现，这些研究揭示了与糖尿病母后传播有关的潜在分子机制。最后，从如何打破循环的角度来看，我们认为在青春期之前预防后代肥胖和糖尿病发展的干预措施是代际周期的关键时期。