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<0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P<0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p<0.01-0.05) by BQR.
Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect.
M. Ezrokhi: Employee; Self; VeroScience LLC. A. Cincotta: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. N. Cominos: Employee; Self; VeroScience LLC. R.A. DeFronzo: None.