Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes

Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes
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DOI:
10.2337/diabetes.55.04.06.db05-1619
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发表时间:
2006-04-01
期刊:
影响因子:
7.7
通讯作者:
Vink, H
Vink, H
中科院分区:
医学1区
文献类型:
--
作者:
Nieuwdorp, M;Mooij, HL;Vink, H

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慢性高血糖是1型糖尿病患者微血管并发症的基础。导致这些血管并发症的机制尚不完全清楚。最近,我们观察到急性高血糖会导致血管内皮细胞糖基化损伤。为了确定糖萼是否与微血管损害有关,我们对有微量白蛋白尿的1型糖尿病患者(DM1-MA组;n=7)、无微量白蛋白尿的1型糖尿病患者(DM1-NA组;n=7)和年龄匹配的对照组(CON;n=7)进行了糖酶微扰体积测量。通过比较可穿透葡聚糖的示踪剂(葡聚糖40)和不透性的示踪剂(标记的红细胞)在血管内的分布体积来确定系统的糖萼体积。用正交偏振光谱显微镜观察舌下毛细血管,以评估微血管的糖萼。根据年龄和BMI将患者和对照组配对。从CON、DM1-NA到DM1-MA受试者,糖萼体积依次减少(分别为1.5+/-0.1、0.8+/-0.4和0.2+/-0.11,P<0.05)。与对照组相比,1型糖尿病组舌下毛细血管内微血管花环减少(0.5±0.1比0.9±0.1微米,P<0.05)。1型糖尿病患者血浆透明质酸和透明质酸酶升高,透明质酸是糖基化的主要成分。总而言之,1型糖尿病患者以内皮细胞糖基化损伤为特征,其严重程度随着微量白蛋白尿的出现而加重。
Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocatyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.11, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9 0.1 mu m, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.