PROJECT SUMMARY/ABSTRACT: Gestational diabetes (GDM) rates are on the rise in the US, particularly among racial and ethnic minorities. GDM is associated with higher rates of large for gestational age (LGA) infants, C-section, and serious perinatal complications, and increased long-term risks of Type 2 diabetes and morbidity in both mothers and infants. Women who get treatment for GDM are less likely to experience perinatal complications and give birth to LGA infants than those who do not; therefore, rapid detection of GDM may be critical to reducing perinatal complications and disparities in birth outcomes. GDM is normally diagnosed by oral glucose tolerance testing (OGTT) at 24-28 weeks gestation, but clinically important insulin resistance and metabolic dysfunction may be missed by not testing earlier. A metabolically unhealthy uterine environment in early pregnancy may lead to long-term negative impacts on mother and child, but how and when to test for insulin resistance and associated metabolic dysfunction in pregnancy is poorly defined. More data are needed on how glucose levels and other metabolic measures change across pregnancy to better evaluate women's metabolic risks and how those risks relate to perinatal and long-term outcomes. Using continuous glucose monitoring (CGM) and metabolic biomarker assays, we will describe detailed metabolic phenotype profiles over the course of pregnancy and examine how they are associated with perinatal and postpartum outcomes. We propose to recruit a diverse sample of 400 women in their first trimester from Kaiser Permanente Northwest and Kaiser Permanente Hawaii and to perform CGM, OGTT, and obtain biomarkers at 12 weeks, 20 weeks, and 28 weeks of gestation to examine how these measures relate to each other and to perinatal outcomes. Aim 1 and Aim 3 will assess the effects of CGM variables (Aim 1) and OGTT and other biomarkers (Aim 3) at each time point on the risk of LGA, other perinatal outcomes, and postpartum diabetes. Aim 2 will assess the relationship between CGM variables and diagnosis of GDM by OGTT, as well as the relationship between CGM variables and other metabolic biomarkers. We hypothesize that dysglycemia is just one marker of a much larger metabolic dysregulation that can be characterized through the work of this consortium. Characterizing a broader spectrum of metabolic dysregulation and its association with adverse perinatal outcomes will lead to improved screening regimens and treatments for pregnant women and better outcomes for both mothers and babies.