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

• Published in: Diabetologia Vol. 53; no. 12; pp. 2646 - 2655
• Main Authors: Broekhuizen, L. N, Lemkes, B. A, Mooij, H. L, Meuwese, M. C, Verberne, H, Holleman, F, Schlingemann, R. O, Nieuwdorp, M, Stroes, E. S. G, Vink, H
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.12.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Albumins - metabolism; Biological and medical sciences; Capillary Permeability - drug effects; Diabetes mellitus type 2; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - etiology; Diabetic Angiopathies - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial glycocalyx; Endothelium - drug effects; Endothelium - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glycocalyx - drug effects; Glycocalyx - metabolism; Glycocalyx - pathology; Glycosaminoglycans - administration & dosage; Glycosaminoglycans - pharmacology; Human Physiology; Humans; Hyaluronan; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mouth Mucosa - blood supply; Mouth Mucosa - drug effects; Mouth Mucosa - metabolism; Sulodexide; Vascular permeability; Endothelial glycocalyx; Hyaluronan; Sulodexide; Vascular permeability; Diabetes mellitus type 2; Endocrinopathy; Type 2 diabetes; Human; Metabolic diseases; Permeability; Endothelium; Blood vessel; Circulatory system
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1910-x

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] 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. 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. Trial registration www.trialregister.nl NTR780/http://isrctn.org ISRCTN82695186 Funding An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037)