Endothelial Glycocalyx Damage Coincides With Microalbuminuria in Type 1 Diabetes

Abstract

Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n ‫؍‬ 7), without microalbuminuria (DM1-NA group; n ‫؍‬ 7), and in age-matched control subjects (CON; n ‫؍‬ 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyxpermeable tracer (dextran 40) to that of a glycocalyximpermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 ؎ 0.1, 0.8 ؎ 0.4, and 0.2 ؎ 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 ؎ 0.1 vs. 0.9 ؎ 0.1 m, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.

The endothelial glycocalyx: a review of the vascular barrier

“…Hyperglycaemic damage may be mediated by oxygen radicals or the activation of glycocalyx-degrading enzymes. Further studies are needed to investigate whether endothelial surface layer dysfunction contributes to microvascular complications in diabetes [26].…”

Microcirculatory dysfunction and tissue oxygenation in critical illness

“…The release of inflammatory mediators induces morphological changes of the endothelium and its protective glycocalyx 30, 31. Endothelial exposure to oxidative stress, oxidized lipoproteins,32, 33, 34 and hyperglycemia35 cause further glycocalyx injury which in turn give rise to profound changes in capillary flows and hematocrit 33, 36. The glycocalyx constitutes a fluid barrier, and degradation of the glycocalyx is hence associated with edema and capillary compression 37, 38…”

Effect of anticoagulants on the plasma hyaluronidase activities

“…As physicians/clinicians suggest for evaluating particularly the plasma HAase activity during several pathological conditions, such as diabetes, monoclonal gammapathy, and bladder and prostate tumors (14)(15)(16), prior knowledge of interference by the anticoagulants is very essential. This is in order to avoid misinterpretation of the results obtained.…”

“…In contrast, the enzymes involved in the HA synthesis do not circulate freely (2,13). Moreover, augmented expressions of Hyal-1 mRNA and elevated levels of hHyal-1 are documented in several diseases (14)(15)(16)(17).…”

“…In clinical/pathological conditions, such as diabetes, monoclonal gammapathy, and bladder and prostate tumors, analysis of plasma HAase activity has been widely suggested (14)(15)(16)(17). The preparation of plasma appears to be a critical step as it requires the use of anticoagulants.…”