Gestational Diabetes Mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is one of the most common pregnancy complications, with a globally rising incidence. GDM poses serious threats to perinatal outcomes for both mother and child (e.g., macrosomia, cesarean section, pre-eclampsia) and serves as a strong predictor for the future development of type 2 diabetes (T2D), cardiovascular disease, and metabolic syndrome in the mother and her offspring. Despite the widely recognized clinical importance of GDM, several key scientific questions remain unanswered: Firstly, while GDM shares some genetic background with T2D, its unique, pregnancy-specific genetic susceptibility loci are not well defined. Secondly, what is the long-term metabolic trajectory of women with a history of GDM after delivery? Which biomarkers can predict their rapid progression to T2D? Thirdly, beyond metabolic diseases, does a history of GDM independently increase a woman’s future risk of cardiovascular disease, chronic kidney disease, non-alcoholic fatty liver disease, etc.? What are the underlying mechanisms? Last but not the lest, how can we integrate genetic, clinical, and biochemical data to build a predictive model that effectively identifies women at high risk for GDM and its long-term complications? The UK Biobank is a massive prospective cohort resource containing genetic, lifestyle, and health information from 500,000 participants. Its rich phenotypic data, genotyping data, and long-term follow-up data provide a unique opportunity to address these questions systematically. The overall aim of the research is to comprehensively elucidate the genetic and metabolic characteristics of GDM and quantify its association with women’s long-term health outcomes using UK Biobank data.
