Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women’s Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses’ Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population.