Stopping the Intergenerational Risk of Diabetes-From Mechanisms to Interventions: A Report on Research Supported by Pathway to Stop Diabetes.

Embedded in the developmental origins of health and disease (DOHaD) hypothesis, maternal hyperglycemia in utero, from preexisting 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 article, we present the current state of knowledge on the intergenerational transmission of diabetes from epidemiological life course studies. Then, we discuss the potential mechanisms implicated in the intergenerational transmission of diabetes with a focus on epigenetics. We present novel findings stemming from epigenome-wide association 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, with 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. This article is part of a series of perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program.