Abstract

Background: Diabetes and cardiovascular disease (CVD) disproportionally affect African American (AA) women. Prior studies suggest extracellular vesicles (EV) are involved in atherogenesis, but little is known about relationships between PA and EVs in AA women. Thus, we examined associations between diabetes risk markers, EV, and PA in a community-based cohort of AA women at risk for CVD from resource-limited Washington, D.C. neighborhoods. Methods: Participants were enrolled in pilot testing of Step It Up, a place-tailored mobile app designed to increase PA. Baseline daily step counts for PA were measured by Fitbit® (Charge 2) and fasting baseline blood samples were cryopreserved. NMR (Nuclear magnetic resonance) spectroscopy was used to measure Lipoprotein Insulin Resistance Index (LP-IR), a diabetes risk marker. EV were isolated from heparinized plasma using size exclusion chromatography with size and numbers determined by nanoparticle tracking analysis. Associations between LP-IR, EVs, and daily step count were analyzed using multivariable regressions adjusted for BMI and ASCVD 10-year risk score. Results: The study cohort was a convenience sample of AA women with overweight/obesity (N=24, Age: 57±12, BMI: 35±6, ASCVD: 9±5). Smaller EV size associated with higher LP-IR (β=-0.45, p=0.04) with EV concentration trending to a positive association with LP-IR (β=0.38, p=0.08). Higher daily step count associated with larger EV particle size (β=0.48, p=0.02) but not with EV concentration. Additionally, higher daily step count associated with lower LP-IR (β=-0.42, p=0.04). Conclusions: Our data show that reduced EV size and increased EV concentration associate with higher LP-IR, a diabetes index among a community-based cohort of AA women. Additionally, our findings suggest that PA might help mitigate these associations. More research is needed to understand the potential impact of PA on EV, diabetes risk and subsequent CVD. Future PA interventions in at-risk patients may reduce existing diabetes and CVD-related health disparities and EVs may emerge as a mechanistic link.

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