1.
Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.
Hamidi, V, Riggs, K, Zhu, L, Bermudez Saint Andre, K, Westby, C, Coverdale, S, Dursteler, A, Wang, H, Miller Iii, C, Taegtmeyer, H, et al
Metabolic syndrome and related disorders. 2020;(5):225-233
-
-
Free full text
-
Abstract
Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.
2.
Regional myocardial function abnormalities are associated with macro- and microcirculation dysfunction in the metabolic syndrome: the RESOLVE study.
Obert, P, Walther, G, Dutheil, F, Lesourd, B, Chapier, R, Courteix, D, Vinet, A
Heart and vessels. 2018;(6):688-694
Abstract
Abnormalities in myocardial and vascular function have been reported in the metabolic syndrome (MetS), but whether these alterations are related remains poorly documented. Our aim was accordingly to investigate interrelationships between macro- and microcirculatory vasoreactivity and left ventricular (LV) myocardial function in MetS patients. Eighty-eight MetS individuals and 44 age- and gender-matched healthy controls were enrolled. LV global longitudinal strain (GLS) was measured using Vector Velocity Imaging. Endothelial-dependent and independent reactivity in macro- and microcirculatory territories was established using flow-mediated dilation and nitrate-mediated dilation of the brachial artery and cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside, respectively. Carotid intima-media thickness (cIMT) was measured according to the Mannheim consensus. Compared to controls, MetS patients presented with reduced GLS (p < 0.001) increased cIMT and impaired (p < 0.001) endothelial and smooth muscle function of the brachial artery and the forearm skin microcirculation. Highly significant relationships (p < 0.01) were noticed between GLS and vascular outcomes. In addition, cIMT (β = 0.21, p = 0.024) and microcirculatory endothelium-dependent reactivity (β = - 0.20, p = 0.035) were identified as independent predictors of GLS. In MetS, abnormalities in myocardial function and endothelial as well as smooth muscle function of small and large arteries co-exist and are closely associated. This study supports a role for microvascular dysfunction in the pathogenesis of LV myocardial dysfunction.