Hyperglycemia does not inhibit insulin's effects on microvascular perfusion in healthy humans: a randomized crossover study
Hyperglycemia does not inhibit insulin's effects on microvascular perfusion in healthy humans: a randomized crossover study
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DOI：
10.1152/ajpendo.00300.2020
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发表时间：
2020-10-01
影响因子：
5.1
通讯作者：
Barrett, Eugene J.
中科院分区：
文献类型：
--
作者：
Horton, William B.;Jahn, Linda A.;Barrett, Eugene J.
糖尿病通过由高血糖症驱动的多种生化途径加速血管疾病，胰岛素抵抗和/或高胰岛素血症也起作用。与血糖正常的对照组相比，糖尿病患者过早发生大血管和微血管疾病。目前，缺乏临床数据来识别脉管系统对高血糖症的反应有多剧烈以及其他生理因素（例如，血管活性激素）起作用。据我们所知，没有先前的研究已经检查了急性高血糖对胰岛素介导的微血管和大血管功能的动态影响。在这项随机交叉试验中，健康的年轻人接受了两种输注方案，旨在比较正常和高血糖期间胰岛素输注对微血管和大血管功能的影响。正常血糖和高血糖-高胰岛素血症均显著增加骨骼肌（但非心肌）微血管血容量（均P < 0.02）和血流量（均P < 0.04），并且这些增加在不同方案之间没有差异。高血糖-高胰岛素血症倾向于颈动脉-股动脉脉搏波速度增加（表明主动脉僵硬度增加; Bonferroni校正后P = 0.065），而血糖正常-高胰岛素血症则没有。在两种方案中，缺血后血流速度或肱动脉血流介导的扩张均无变化。血浆内皮素-1水平在两种治疗方案中均显著降低（P < 0.02）。在这项研究中，急性高血糖4小时并没有抑制胰岛素增加骨骼肌微血管灌注的能力，但确实引起了主动脉僵硬度的轻微增加。高血压也不会对心肌微血管灌注或内皮功能产生不利影响，也不会阻止胰岛素输注期间内皮素-1的下降。
Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared with normoglycemic controls. Currently, there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiological factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulin-mediated actions on both micro- and macrovascular function in the same subjects. In this randomized crossover trial, healthy young adults underwent two infusion protocols designed to compare the effects of insulin infusion during euglycemia and hyperglycemia on micro- and macrovascular function. Both euglycemic- and hyperglycemic-hyperinsulinemia increased skeletal (but not cardiac) muscle microvascular blood volume (each P < 0.02) and blood flow (each P < 0.04) significantly, and these increases did not differ between protocols. Hyperglycemic-hyperinsulinemia trended toward increased carotid-femoral pulse wave velocity (indicating increased aortic stiffness; P = 0.065 after Bonferroni adjustment), whereas euglycemic-hyperinsulinemia did not. There were no changes in postischemic flow velocity or brachial artery flow-mediated dilation during either protocol. Plasma endothelin-1 levels significantly decreased during both protocols (each P < 0.02). In this study, acute hyperglycemia for 4 h did not inhibit insulin's ability to increase skeletal muscle microvascular perfusion but did provoke a slight increase in aortic stiffness. Hyperglycemia also did not adversely affect myocardial microvascular perfusion or endothelial function or prevent the decline of endothelin-1 during insulin infusion.