1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects

Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events. Aim: To examine the effect of BQR on POS/PI phenotype of blood monocytes in T2DM. Study Design: 15 T2DM subjects treated with a GLP-1 RA received BQR (3.2 mg/day) for 16 weeks. Endothelial function was measured by post-occlusion hyperemia. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment. Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P