Reduced Sublingual Endothelial Glycocalyx in Type 1 Diabetic Patients with Diabetic Nephropathy

Background Glycocalyx is a glycoprotein layer that lines and protects the capillary endothelium. Damage to the glycocalyx may be an early stage in development of microvascular complications in diabetes. Insight into the function and thickness of glycocalyx in vivo, has been limited by the lack of easy and non-invasive quantification tools. With capillaroscopy it is possible to visualize the sublingual capillaries by sidestream dark field imaging and estimates the dimensions of the glycocalyx by measuring the perfused boundary region (PBR). We evaluated the glycocalyx thickness non-invasively in type 1 diabetic patients with different levels of historical and current albuminuria. Methods Cross-sectional study including 77 type 1 diabetic patients stratified by history of normoalbuminuria (<30 mg/g;n=26), microalbuminuria (30-299 mg/g;n=27) and macroalbuminuria (>300 mg/g;n=24). Glycocalyx thickness was assessed by 5 measurements with the GlucoCheck device (GlucoCheck BV, The Netherlands), a non-invasive hand-held microscope generating video recordings of the sublingual capillaries. Endothelial glycocalyx thickness was estimated from the PBR in capillaries with a diameter range of 5-25 μm. Higher PBR indicates smaller glycocalyx width. Urinary albumin-to-creatinine ratio (UACR) was measured in 3 morning samples. Results In normo-, micro-, and macroalbuminuric patients PBR was (mean±SD) 2.30±0.22 μm, 2.32±0.25 μm, and 2.49±0.35 μm, respectively. Differences between normo- and macroalbuminuric patients (p=0.020) and micro- and macroalbuminuric patients (p=0.042) were significant, but the difference between normo- and microalbuminuric patients was not (p=0.74). After adjustment for age, sex, HbA1c, diabetes duration and systolic blood pressure, differences between normo- and macroalbuminuric patients (p=0.018) and micro- and macroalbuminuric patients (p=0.004) remained significant. In pooled (n=77) multivariate linear regression, higher level of current UACR was associated with a higher PBR (p=0.0007). Conclusion In type 1 diabetic patients with a history of macroalbuminuria, measurements with the non-invasive GlucoCheck device revealed significantly higher PBR, suggesting an impaired glycocalyx, compared to patients with normo- or microalbuminuria. Moreover, higher current level of albuminuria was associated with higher PBR