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

L. N. Broekhuizen, B. A. Lemkes, H. L. Mooij, M. C. Meuwese, H. Verberne, F. Holleman, R. O. Schlingemann, M. Nieuwdorp, E. S. G. Stroes, and H. Vink
Diabetologia, 2010



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 (nā€‰=ā€‰10) and controls (nā€‰=ā€‰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 [0.57ā€“0.75] Ī¼m vs 0.78 [0.71ā€“0.85] Ī¼m, pā€‰<ā€‰0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88ā€“6.59] Ī¼m vs 8.89 [4.74ā€“11.84] Ī¼m, pā€‰<ā€‰0.05) were reduced in the type 2 diabetes group compared with the controls whereas TERalb was increased (5.6ā€‰Ā±ā€‰2.3% vs 3.7ā€‰Ā±ā€‰1.7% in the controls, pā€‰<ā€‰0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137ā€‰Ā±ā€‰29 vs 81ā€‰Ā±ā€‰8 ng/ml and hyaluronidase 78ā€‰Ā±ā€‰4 vs 67ā€‰Ā±ā€‰2 U/ml, both pā€‰<ā€‰0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83ā€“0.99] Ī¼m and to 5.88 [5.33ā€“6.26] Ī¼m, respectively, pā€‰<ā€‰0.05). In line, a trend towards TERalb normalisation (to 4.0ā€‰Ā±ā€‰2.3%) and decreases in plasma hyaluronidase (to 72ā€‰Ā±ā€‰2 U/ml, pā€‰<ā€‰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.