Stopping the intergenerational risk of diabetes – from mechanisms to interventions

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.