Abstract 9610: Endothelial Function and Coronary Arterial Imaging in Youth-Onset Type 2 Diabetes: Evidence for Early Vascular Aging Compared to Age-Matched Peers

Abstract

Introduction: Youth-onset type 2 diabetes (Y-T2D) may be associated with accelerated vascular aging, but the tempo and mechanisms are unknown. Non-invasive cardiac MRI coupled with ex-vivo experiments to assess endothelial function are ideal for assessing risk in young adults. Plasma exosomes are pro-inflammatory extra-cellular vesicles that may modulate endothelial dysfunction. Methods: We hypothesized that Y-T2D would have endothelial dysfunction compared to healthy age-matched peers measured by right coronary wall thickness (CWT) and coronary and brachial artery dilation during isometric handgrip exercise using a 3.0 Tesla cardiac MRI. In a subset of 4 Y-T2D, we isolated, characterized, and incubated plasma-derived exosomes in human coronary artery epithelial cells (HCAECs) compared to control cells. Results: Y-T2D (n=14, 40% female, age 19.4±1.3y, BMI 38±9kg/m 2 , mean±SD) compared to peers (n=16, 40% female, age 22.9±2.6 y, BMI 23±3 kg/m 2 ) had higher HbA1c (6.5 ± 1.2 vs 5.0 ± 0.5%), C-reactive protein (6.5±8.3 vs. 3.1±2.0 mg/L), systolic blood pressure (130±14 vs. 114±11 mmHg, all P <0.05) but similar LDL-cholesterol and triglycerides. Y-T2D had greater CWT (1.34±0.13 vs. 1.22±0.13 mm, P =0.02) and impaired arterial dilation (Figure 1A). HCAECs incubated with Y-T2D exosomes induced phenotypic changes of endothelial dysfunction: reduced expression of phosphorylated endothelial nitric oxide synthase (peNOS), increased expression of endothelial membrane ICAM-1 and phosphorylation of pERK(1/2) (Figure 1B). Conclusion: Accelerated vascular aging in Y-T2D was associated with paradoxical exercise-induced coronary artery vasoconstriction and peripheral endothelial dysfunction despite young age and the absence of traditional risk factors such as severe hyperglycemia, frank hypertension, or dyslipidemia. Plasma exosomes should be explored in the pathogenesis of endothelial dysfunction and early vascular aging in Y-T2D.