Genetic Risk Factors and Gene–Lifestyle Interactions in Gestational Diabetes

Abstract

Paralleling the increasing trends of maternal obesity, gestational diabetes (GDM) has become a global health challenge with significant public health repercussions. In addition to short-term adverse outcomes, such as hypertensive pregnancy disorders and fetal macrosomia, in the long term, GDM results in excess cardiometabolic morbidity in both the mother and child. Recent data suggest that women with GDM are characterized by notable phenotypic and genotypic heterogeneity and that frequencies of adverse obstetric and perinatal outcomes are different between physiologic GDM subtypes. However, as of yet, GDM treatment protocols do not differentiate between these subtypes. Mapping the genetic architecture of GDM, as well as accurate phenotypic and genotypic definitions of GDM, could potentially help in the individualization of GDM treatment and assessment of long-term prognoses. In this narrative review, we outline recent studies exploring genetic risk factors of GDM and later type 2 diabetes (T2D) in women with prior GDM. Further, we discuss the current evidence on gene–lifestyle interactions in the development of these diseases. In addition, we point out specific research gaps that still need to be addressed to better understand the complex genetic and metabolic crosstalk within the mother–placenta–fetus triad that contributes to hyperglycemia in pregnancy.