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

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. Methods 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. Results Both sublingual dimensions (0.64 [0.57-0.75] mu m vs 0.78 [0.71-0.85] mu m, p<0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88-6.59] mu m vs 8.89 [4.74-11.84] mu m, 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] mu m and to 5.88 [5.33-6.26] mu m, 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. 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.