Department of Vascular Medicine, Academic Medical Centre, Room F4.211, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Diabetologia. 2010 Dec;53(12):2646-55. doi: 10.1007/s00125-010-1910-x. Epub 2010 Sep 25.
AIMS/HYPOTHESIS: Endothelial glycocalyx perturbation contributes to increased vascular permeability. In the present study we set out to evaluate whether: (1) glycocalyx is perturbed in individuals with type 2 diabetes mellitus, and (2) oral glycocalyx precursor treatment improves glycocalyx properties.
Male participants with type 2 diabetes (n = 10) and controls (n = 10) were evaluated before and after 2 months of sulodexide administration (200 mg/day). The glycocalyx dimension was estimated in two different vascular beds using sidestream dark field imaging and combined fluorescein/indocyanine green angiography for sublingual and retinal vessels, respectively. Transcapillary escape rate of albumin (TER(alb)) and hyaluronan catabolism were assessed as measures of vascular permeability.
Both sublingual dimensions (0.64 [0.57-0.75] μm vs 0.78 [0.71-0.85] μm, p < 0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88-6.59] μm vs 8.89 [4.74-11.84] μm, p < 0.05) were reduced in the type 2 diabetes group compared with the controls whereas TER(alb) was increased (5.6 ± 2.3% vs 3.7 ± 1.7% in the controls, p < 0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137 ± 29 vs 81 ± 8 ng/ml and hyaluronidase 78 ± 4 vs 67 ± 2 U/ml, both p < 0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83-0.99] μm and to 5.88 [5.33-6.26] μm, respectively, p < 0.05). In line, a trend towards TER(alb) normalisation (to 4.0 ± 2.3%) and decreases in plasma hyaluronidase (to 72 ± 2 U/ml, p < 0.05) were observed in the diabetes group.
CONCLUSION/INTERPRETATION: Type 2 diabetes is associated with glycocalyx perturbation and increased vascular permeability, which are partially restored following sulodexide administration. Further studies are warranted to determine whether long-term treatment with sulodexide has a beneficial effect on cardiovascular risk.
www.trialregister.nl NTR780/ http://isrctn.org ISRCTN82695186
An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037).
目的/假设：内皮糖萼的破坏会导致血管通透性增加。本研究旨在评估以下两点：（1）2 型糖尿病患者的糖萼是否受到干扰；（2）口服糖萼前体治疗是否能改善糖萼的特性。
评估了 10 名 2 型糖尿病患者（糖尿病组）和 10 名健康对照者（对照组）在 2 个月舒洛地特（200mg/天）治疗前后的情况。使用侧流暗场成像和荧光素/吲哚菁绿血管造影分别评估舌下和视网膜血管的糖萼维度。白蛋白跨毛细血管逃逸率（TER(alb)）和透明质酸代谢产物评估作为血管通透性的指标。
与对照组相比，2 型糖尿病组的舌下糖萼维度（0.64 [0.57-0.75]μm 比 0.78 [0.71-0.85]μm，p<0.05）和视网膜糖萼维度（5.38 [4.88-6.59]μm 比 8.89 [4.74-11.84]μm，p<0.05）均降低，而 TER(alb)则升高（5.6±2.3%比对照组的 3.7±1.7%，p<0.05）。与这些发现一致的是，糖尿病患者的透明质酸代谢产物标志物增加（透明质酸 137±29 比 81±8ng/ml 和透明质酸酶 78±4 比 67±2U/ml，均 p<0.05）。舒洛地特增加了糖尿病患者的舌下和视网膜糖萼维度（分别增加到 0.93 [0.83-0.99]μm 和 5.88 [5.33-6.26]μm，p<0.05）。同样，糖尿病组的 TER(alb)有向正常化的趋势（至 4.0±2.3%），血浆透明质酸酶水平下降（至 72±2U/ml，p<0.05）。
结论/解释：2 型糖尿病与糖萼破坏和血管通透性增加有关，舒洛地特治疗后部分恢复。需要进一步研究以确定长期使用舒洛地特是否对心血管风险有有益的影响。
www.trialregister.nl NTR780/ http://isrctn.org ISRCTN82695186
Novartis 心血管卓越基金会（2006 年）给 M. Nieuwdorp/E. S. G. Stroes 的一项不受限制的赠款，荷兰心脏基金会（2005T037 号）。
