Project Summary/Abstract Over 250,000 women develop gestational diabetes mellitus (GDM) each year in the U.S, affecting 6.4% of all pregnancies. Current methods for the diagnosis of GDM are not conducted until the end of the second or early in the third trimester; however, it is possible dysglycemia leading to both adverse maternal and neonatal outcomes are present well before this gold standard screening. With the newest generation of continuous glucose monitors (CGM), the ability to collect accurate data that does not require fingerstick calibration and can be comfortably worn long enough to capture glucose dynamics is now feasible. The present proposal seeks to longitudinally assess glycemia in healthy, non-diabetic pregnant women by using blinded CGM data collection in 4-week intervals beginning between 6-12 weeks’ gestation. These data will allow for determination if a difference in mean sensor glucose levels exists between women who develop GDM vs. those who do not using standard of care oral glucose tolerance test (OGTT) screening. Furthermore, with the frequency of CGM data collection, the optimal time to first detect the difference in mean sensor glucose levels can be explored. Finally, more rigorous OGTTs will be conducted allowing for assessment of the metabolic abnormalities that underlie the diagnosis of GDM including whether the dysglycemia is due to insulin resistance or β-cell dysfunction. With the use of a consortium to conduct the present study, a large cohort is feasible which will allow for assessment of factors that may contribute to risk of dysglycemia and GDM, including race/ethnicity, pre-pregnancy BMI, maternal age, parity and weight gain during pregnancy. The findings of this study may provide a paradigm shift in how we diagnose GDM if blinded CGM can be used in place of an OGTT and understanding of the metabolic alterations that lead to diagnosis of GDM.

Project Narrative To date, diagnosis of gestational diabetes mellitus (GDM) has been relegated to the end of the second trimester or early in the third trimester; yet, it is possible that dysglycemia occurring even earlier in pregnancy may impact both maternal and neonatal outcomes. Furthermore, while it is the gold standard, the oral glucose tolerance test (OGTT) used to diagnose GDM has many limitations: 1- it is not clear that the OGTT represents true physiologic glucose variation with the glucose load provided, 2- debate exists as to what cut-offs should be employed for diagnosis of GDM, 3- it is unclear if earlier performance of OGTT can use the same thresholds for diagnosis and whether earlier diagnosis can be used to improve important maternal and neonatal outcomes. Therefore, the current proposal seeks to assess whether blinded continuous glucose monitors can be employed to diagnose GDM and, potentially, allow for earlier detection of dysglycemia while also conducting rigorous metabolic assessments of women during the course of pregnancy to allow better characterization of the metabolic changes that occur with GDM.