Gestational diabetes mellitus (GDM) is a common complication of pregnancy; its rising incidence is a result of increased maternal obesity and older maternal age together with altered diagnostic criteria identifying a greater proportion of pregnant women with GDM. Its consequences are far-reaching, associated with poorer maternal and neonatal outcomes compared to non-GDM pregnancies, and GDM has implications for metabolic health in both mother and offspring. Objective markers to identify women at high risk for the development of GDM are useful to target therapy and potentially prevent its development. Established clinical risk factors for GDM include overweight/obesity, age, ethnicity, and family history of diabetes, though they lack specificity for its development. The addition of biomarkers to predictive models of GDM may improve the ability to identify women at risk of GDM prior to its development. These biomarkers reflect the pathophysiologic mechanisms of GDM involving insulin resistance, chronic inflammation, and altered placental function. In addition, the role of epigenetic changes in GDM pathogenesis highlights the complex interplay between genetic and environmental factors, potentially offering further refinement of the prediction of GDM risk. In this review, we will discuss the clinical challenges associated with the diagnosis of GDM and its current pathophysiologic basis, giving rise to potential biomarkers that may aid in its identification. While not yet validated for clinical use, we explore the possible clinical role of biomarkers in the future. We also explore novel diagnostic tools, including high throughput methodologies, that may have potential future application in the identification of women with GDM.
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