PROJECT SUMMARY The pancreas is smaller in individuals with diabetes and individuals at increased risk for developing diabetes, suggesting that small pancreas size may convey risk for developing the disease. However, it is not known whether individuals at risk for developing diabetes are born with a smaller pancreas or whether their pancreas shrinks as part of the pathogenesis of the disease. Establishing the link between pancreas size and development of diabetes is difficult, as the time course of diabetes progression is not well established and time to progression can be long. However, pregnancy is a period of physiological beta cell proliferation that presents a diabetogenic state with known and rapid onset. MRI can safely and noninvasively assay multiple aspects of the maternal and fetal pancreas, including pancreas size as well as other markers of pancreas structure and composition. Image acquisition and analysis will leverage our expertise assessing human pancreas size, shape, fat content, and inflammation using multimodal quantitative MRI. We propose to perform longitudinal MRI of the maternal pancreas over the course of pregnancy and postpartum and correlate imaging metrics with diabetes development and metabolic phenotyping. We will also assess the capability of MRI to measure pancreas growth in the fetus. Study participants will include mothers who not develop diabetes, mothers with pregestational type 2 diabetes, and mothers who develop gestational diabetes during pregnancy. These studies will establish the first model of maternal pancreas growth and multimodal imaging signature and their interactions with diabetes. Our central hypothesis is that maternal pancreas growth will be altered by diabetes and can be used to predict diabetes incidence in the mother. While the focus of this study is on the pancreas, the images generated will encompass the maternal abdomen and entire fetus. Thus, the data generated will be valuable datasets for secondary analysis of the interaction of diabetes with fetal development and maternal liver, fat, and placenta dynamics over the course of pregnancy.

PROJECT NARRATIVE This research examines the influence of pancreas dynamics during pregnancy on the development of diabetes. MRI measurements of pancreas size, shape, and composition will be made over time in both the mother and the fetus to see how the pancreas is affected by maternal diabetes. Pancreas phenotypes will be correlated with metabolic phenotypes as assessed by glucose tolerance testing and continuous glucose monitoring.