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 published the cohort profile for the study which describes the study, the main findings, and opportunities for collaboration (Zhang BMJ Open 2019). Using data from the two independent populations within the DWH Study, the NHS-II and DNBC, we identified eight novel GDM SNPs (Ding et al. Diabetologia, 2018). These findings offer the potential to improve our understanding of the etiology of GDM, and particularly of biological mechanisms related to beta cell function. This work is being followed with an investigation of the genetic determinants for the progression from GDM to T2D. In ongoing work we are examining the association of a genetic risk score for T2D with the risk of progression from GDM to T2D and how non-genetic risk factors for T2D might modify this association. Using data from the DWH Study, we have demonstrated that GDM may be an early indicator of subsequent subclinical renal dysfunction (Rawal et al. Diabetes Care, 2018). Our findings suggest that in women with a history of GDM, deterioration of renal function may potentially precede the development of overt diabetes, although clinically relevant outcomes such as elevated UACR may manifest only after progression to diabetes. We have also shown that women with GDM during pregnancy were at an increased risk for fatty liver 9-16 years postpartum (Donnelly 2019 Journal of Diabetes). GDM may serve as another risk indicator for early identification and prevention of liver fat accumulation. We also examined for potentially modifiable risk-factors associated with long-term health among women with a history of GDM. In Danish women with a history of GDM, our findings suggest a positive association between a longer duration of lactation and higher levels of thyroid hormone 916 years postpartum, even among women with a single lifetime pregnancy (Panuganti et al. Nutrients, 2018). We identified lactation as a novel potential modifiable factor for thyroid function, and with replication, these findings may add thyroid function to the wide-array of long-term cardiometabolic outcomes associated with increased lactation duration. We also investigated modifiable dietary factors among women with GDM. We found that that among Danish women with a history of GDM, a population at high risk for cardiometabolic diseases, artificially sweetened beverage intake was not associated with either improvements or determents in cardiometabolic complications (Hinkle et al. American Journal of Clinical Nutrition 2019). Although high-risk individuals are recommended to consume artificially sweetened beverage instead of sugar sweetened beverages as a means of reducing sugar intake and risk for cardio-metabolic diseases, we did not observe significant improvements or determents in cardiometabolic health with higher artificially sweetened beverage intake in this population. Current efforts are further investigating lactation and other dietary factors with a range of cardiometabolic and renal outcomes.
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