Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus

Abstract

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 (TERalb) 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 TERalb 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 TERalb 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. 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)

DOI: 10.1007/s00125-010-1910-x

Extracted Key Phrases

7 Figures and Tables

0501002011201220132014201520162017
Citations per Year

312 Citations

Semantic Scholar estimates that this publication has 312 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Broekhuizen2010EffectOS, title={Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus}, author={Lysette N. Broekhuizen and B. A. Lemkes and Hans L. Mooij and Marijn C. Meuwese and Hein Jan Verberne and Frits Holleman and Reinier Otto Schlingemann and Max Nieuwdorp and Erik S. G. Stroes and Hans Vink}, booktitle={Diabetologia}, year={2010} }