Project Summary/Abstract:
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.
