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Jose Halperin, MD

Pronouns:

He/Him/His

Rank:

Associate Professor

Institution:

Brigham and Women's Hospital

Department:

Medicine

Authors:

Michelle Toth-Castillo, Miguel Luque-Fernandez, Jose Halperin*

Principal Investigator:

Jose Halperin

Plasma glycated CD59 (pGCD59) as a novel biomarker for gestational diabetes (GDM)

This work relates to the discovery and clinical validation in human studies of pGCD59, a novel, simple and accurate biomarker for GDM. GDM is a major women’s and public health problem because it is associated with serious adverse maternal and neonatal outcomes, affects 1:6 pregnancies, and heralds a mother-infant pair at risk of future diabetes, obesity and cardiovascular disease.

The presentation will summarize results of prospective and retrospective multicenter human studies supporting the conclusion that pGCD59 is a simple and accurate biomarker for a) GDM diagnosis in first and second trimesters, b) risk assessment of serious adverse pregnancy outcomes associated with GDM, and c) postpartum identification of glucose intolerance in women with GDM.

Overview

GDM represents a major women’s health problem because it is associated with serious adverse maternal and neonatal outcomes, affects 1:6 pregnancies, and heralds a mother-infant pair at risk of future diabetes, obesity and cardiovascular disease. Since treatment reduces the incidence of adverse outcome, screening for GDM with oral glucose load tests (OGTTs) at pregnancy weeks 24-28 is the standard of care in most nations around the world. However, universal screening is difficult to achieve because OGTTs are inconvenient and unreliable; they also impose an arbitrary definition of “normal” and “abnormal” glucose tolerance that fails to recognize the continuous association between maternal hyperglycemia and adverse pregnancy outcomes. These well-known problems of OGTTs, compounded with the failure of HbA1c as a reliable GDM biomarker, underly major efforts to identify alternative screening/diagnostic methods for GDM.

pGCD59, the glycated form of the complement regulatory protein CD59 in blood, is an emerging biomarker for GDM: maternal pGCD59 measured in the first (week <20) or second trimester (week 24-28) classified women with GDM with high sensitivity and specificity, and was positively associated with the prevalence of large for gestational age newborns and other adverse pregnancy outcomes. Remarkably, high levels of pGCD59 also identified women that fall in between currently accepted “normal” and “abnormal” thresholds of glucose tolerance who reportedly also have a high prevalence of adverse pregnancy outcomes. Finally, high levels of pGCD59 6-12 weeks postpartum was associated with conversion to glucose intolerance in women who had GDM in their recent pregnancy.

Our presentation will summarize results of prospective and retrospective multicenter human studies supporting the conclusion that pGCD59 is a simple and accurate biomarker for a) GDM diagnosis in first and second trimesters, b) risk assessment of serious adverse pregnancy outcomes associated with GDM, and c) postpartum identification of glucose intolerance in women with GDM.