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Gestational diabetes mellitus (GDM), defined as glucose intolerance that starts during pregnancy, represents a major public health challenge because it is a major cause of adverse maternal and fetal outcomes and presents a significant high risk of diabetes, obesity, and cardiovascular disease for both mother and infant. The diagnosis of GDM is currently made through oral glucose tolerance tests (OGTT); other markers of glycemic control have notably failed for GDM diagnosis: Since the treatment of GDM reduces the incidence of adverse pregnancy outcomes, screening for GDM with OGTTs in pregnancy weeks 24-28 is the standard of care in most nations worldwide. However, universal screening is difficult to achieve due in part to the fact that OGTTs are cumbersome and uncomfortable. Thus, the importance of detecting glucose intolerance in pregnant women, the possibility of reducing with treatment the associated risks, the low sensitivity of glycemic markers in pregnancy, and the multiple problems associated with OGTTs highlight the significance of exploring alternative screening/diagnostic methods that are sensitive, accurate, and well tolerated by patients. In this review, we summarize our discovery, development, and clinical validation in six human studies of plasma glycated CD59 (pGCD59), the glucose modified form of the key complement inhibitor CD59, as a biomarker for screening, diagnosis, and monitoring of GDM.