Oomen P H N, Kant G D, Dullaart R P F, Reitsma W D, Smit A J
Division of General Internal Medicine, University Hospital Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Microvasc Res. 2002 Jan;63(1):1-9. doi: 10.1006/mvre.2001.2347.
Uncomplicated Type 1 (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute hyperglycemia and hyperinsulinemia, both separately and in combination, on skin microvascular flow, capillary permeability, capillary recruitment, and endothelial dysfunction in Type 1 diabetes mellitus. Sixteen Type 1 diabetic patients (all normoalbuminuric, no (pre-)proliferative retinopathy) underwent a euglycemic (glucose target 5.0 mmol/L, insulin infused at 30 mU x kg(-1) x h(-1)), a hyperglycemic (glucose target 12.0 mmol/L, insulin 30 mU x kg(-1) x h(-1)), a hyperinsulinemic (glucose target 5.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)), and a hyperglycemic-hyperinsulinemic (glucose target 12.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)) clamp on separate days, in random order. Skin microvascular flow was measured by laser Doppler flowmetry. Capillary permeability and density were determined by large-window sodium-fluorescein videodensitometry. Increases in serum soluble intercellular adhesion molecule-1 (sICAM-1) and plasma von Willebrand factor antigen (vWF-Ag) were considered to represent abnormal endothelial function. Hyperglycemia (P < 0.01) and hyperinsulinemia (P < 0.05) as well as both interventions combined (P < 0.001) induced an increase in laser Doppler flow, without capillary recruitment. Transcapillary leakage of sodium-fluorescein and sICAM-1 and vWF-Ag levels were unaffected by hyperglycemia or hyperinsulinemia. Microvascular permeability appears to be determined primarily by properties of the capillary wall and not by acute changes in local hemodynamics. The acute hyperglycemia- and hyperinsulinemia-induced vasodilatation is not accompanied by changes in microvascular permeability or endothelial markers.
单纯1型（胰岛素依赖型）糖尿病的特征是全身血管扩张。其可能的相关因素，即微血管通透性增加和内皮功能障碍，与长期并发症有关。目的是研究急性高血糖和高胰岛素血症单独及联合作用对1型糖尿病患者皮肤微血管血流、毛细血管通透性、毛细血管募集和内皮功能障碍的影响。16例1型糖尿病患者（均为正常白蛋白尿，无（预）增殖性视网膜病变）在不同日期随机接受等血糖（血糖目标5.0 mmol/L，胰岛素以30 mU·kg⁻¹·h⁻¹输注）、高血糖（血糖目标12.0 mmol/L，胰岛素30 mU·kg⁻¹·h⁻¹）、高胰岛素血症（血糖目标5.0 mmol/L，胰岛素150 mU·kg⁻¹·h⁻¹）和高血糖-高胰岛素血症（血糖目标12.0 mmol/L，胰岛素150 mU·kg⁻¹·h⁻¹）钳夹试验。通过激光多普勒血流仪测量皮肤微血管血流。通过大窗口荧光素钠视频密度测定法测定毛细血管通透性和密度。血清可溶性细胞间黏附分子-1（sICAM-1）和血浆血管性血友病因子抗原（vWF-Ag）的增加被认为代表异常内皮功能。高血糖（P < 0.01）、高胰岛素血症（P < 0.05）以及两种干预联合（P < 0.001）均导致激光多普勒血流增加，且无毛细血管募集。荧光素钠的跨毛细血管渗漏以及sICAM-1和vWF-Ag水平不受高血糖或高胰岛素血症影响。微血管通透性似乎主要由毛细血管壁的特性决定，而非局部血流动力学的急性变化。急性高血糖和高胰岛素血症诱导的血管扩张并未伴随微血管通透性或内皮标志物的变化。
