Grant: Project Grant

Gestational diabetes mellitus (GDM) is a form of diabetes that develops during pregnancy and occurs in ~10% of pregnant women. Although this form of diabetes normally resolves post-delivery, women who had GDM are 7 times more likely to develop type 2 diabetes (T2D) than women without a GDM history. In fact, 35%-50% of women who had GDM will progress to T2D within 10 years postpartum. These women not only develop T2D earlier, their children are also far more likely to develop serious medical complications during birth and later in life, including T2D. For these reasons, an accurate means to predict who gets GDM would represent an important avenue for improved awareness and care. Furthermore, understanding the causes of GDM could also help guide the development of new, more effective interventions, both lifestyle and medical. We first aim to facilitate the development more accurate means of identifying one's risk of developing GDM by comprehensively examining the blood of women in the 1st trimester of pregnancy, before the development of GDM. We will also perform this analysis on blood collected from postpartum mothers who had GDM, and their children, now 12-15 years old. In all of these samples, we will identify components that are changed in abundance compared to non-diabetic participants and select specific markers from this panel that can predict future diabetes risk (GDM or T2D). Finally, we aim to identify key master regulators that are implicated in potentially causing these early-stage changes in blood components that are associated with future diabetes and test their causal relationship using cell and animal model-based studies. The studies are poised to improve the precision and efficacy of measures aimed at early prediction and prevention of GDM. This will have significant clinical relevance to young, otherwise heathy women and their offspring, who both face significantly increased risk of T2D and associated complications following a GDM pregnancy.