The Diabetes & Womens Health Study, based on an innovative hybrid design combining new prospective data collection with historical data, aims to understand pathways and determinants underlying the progression from gestational diabetes (GDM) to type 2 diabetes (T2DM) and complications such as cardiovascular diseases. GDM is a common pregnancy complication. Women who develop impaired glucose tolerance and/or GDM in pregnancy are at substantially increased risk for T2DM in the years following pregnancy. Determinants underlying the transition from GDM to T2DM are not well studied and available studies are limited. There is limited information about the genetic and environmental factors that impact this transition in particular. Further, there is limited research aimed at following women with GDM long term through later adulthood for the development of T2DM and co-morbidities. These critical data gaps serve as the impetus for this study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health intervention in relation to the transition of GDM to T2DM. A secondary goal of the study is to evaluate feasibility of investigating the long-term impact of GDM and other intrauterine factors on the health and wellbeing of offspring. Data collection for this study builds upon two large existing cohorts: the Nurses' Health Study II (NHS-II) and the Danish National Birth Cohort (DNBC). The overall design of the study was published in 2014 (Zhang et al. Acta Obstetricia et Gynecologica Scandinavica). The DWH Study data collection was completed in 2016 and initial work focused on long-term comorbidities of GDM and potentially modifiable pathways. We recently found that women who develop GDM in pregnancy were more likely to show increased eGFR levels at 916 years after the index pregnancy postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. Further, these women were at increased risk for CVD, in particular, MI. We have also investigated the impact and underlying mechanisms of how a hyperglycemic intrauterine environment affects short-term and long-term health outcomes in the offspring based on multiple datasets, such as the Nurses' Health Study II and Danish National Birth Cohort. Our findings add to the accumulating evidence suggesting that adverse intrauterine exposures may lead to permanent fetal adaptations in anatomy and physiology, which may be beneficial for short term fetal survival, but result in an altered long-term risk of disease later in life. In particular, exposure to GDM in utero was associated with an increased risk of obesity among male offspring through early adulthood. Furthermore, among high-risk children born to women with gestational diabetes, our findings illustrated positive associations between intrauterine exposure to artificially sweetened beverages and birth size and risk of overweight/obesity at 7 years.
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