Gestational diabetes mellitus (gDM) and gestational hypertension (gHTN), including preeclampsia are the most common cardiometabolic complications of gestation, affecting 7-14% and 10% of pregnancies in the U.S, respectively. GDM and gHTN are associated with adverse outcomes for the index pregnancy and indicate increased lifetime risk of cardiometabolic disease for women, including type 2 diabetes, cardiovascular disease, and metabolic syndrome. The risk of progression to overt cardiometabolic disease post-pregnancy is especially high for women who are African American, initiate the pregnancy overweight or obese, and who experience postpartum weight retention. While these risk factors for progression are established at the population level, both the risk for and the timing of progression are highly variable and individual and specific biomarkers of early risk detection do not exist. Notably, traditional cardiovascular risk factors do not adequately predict the progression to overt cardiometabolic disease. Thus, to date, there are no effective means of predicting those for whom cardiometabolic disease will persist or progress after pregnancy, impeding the development and appropriate targeting of effective prevention and mitigation strategies. Omics technologies provide a signature of biological systems' perturbation and offer promise for identifying new risk factors (i.e., perturbation of the gut microbiome) and early biomarkers (i.e., perturbed lipid profiles) of underlying cardiometabolic dysregulation that may signal those at risk for disease progression. The purpose of this proposal is to test the hypothesis that the composition of the gut microbiome, and resulting metabolic endotoxemia, contribute to a unique lipidomic signature, which in turn, is associated with clinical markers of the persistence of pregnancy-associated cardiometabolic dysregulation. The PI, Erin P. Ferranti, PhD, MPH, RN, FAHA, will use omics technologies to interrogate the gut microbiome and circulating lipidome in a cohort of postpartum African American women, with or without previous cardiometabolic complications of pregnancy, in collaboration with a multidisciplinary team of expert mentors (including co-Lead Mentors, Drs. Anne Dunlop and Elizabeth Corwin and Co-Mentors Drs. Eric Ortlund and Vicki Hertzberg). The primary goal of this K01 career development proposal is for Dr. Ferranti to develop expertise in omics technologies, specifically microbiome and lipidomics, for use in clinically oriented risk prevention research, which will highly complement her women's health, cardiometabolic and nutrition training to date. The proposed research, in combination with a structured mentoring and training plan that includes didactic courses and workshops, is designed to facilitate Dr. Ferranti's long-term goal of developing an independently-funded clinical and translational women's health cardiometabolic health promotion and illness prevention research program in underserved women with disparate disease risk, consistent with the mission of the NINR.
Gestational diabetes mellitus (gDM) and gestational hypertension (gHTN) are the most common cardiometabolic complications of pregnancy, with African American women disproportionately affected. The composition of the microbiome and the associated circulating lipidome may be a key mechanism for gDM, gHTN and future disease progression. This project is designed to investigate the gut microbiome and circulating lipidome during postpartum to identify mechanisms and potential biomarkers of cardiometabolic disease.