Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.
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 glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable 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 microm, 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.
Department of Vascular Medicine, Academic Medical Center University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Max
M
Nieuwdorp
Hans L
HL
Mooij
Jojanneke
J
Kroon
Bektas
B
Atasever
Jos A E
JA
Spaan
Can
C
Ince
Frits
F
Holleman
Michaela
M
Diamant
Robert J
RJ
Heine
Joost B L
JB
Hoekstra
John J P
JJ
Kastelein
Erik S G
ES
Stroes
Hans
H
Vink
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000419:Albuminuria / Q000175:diagnosis*; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D002196:Capillaries / Q000473:pathology; D002463:Cell Membrane Permeability; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D004730:Endothelium, Vascular / Q000473:pathology*; D019276:Glycocalyx / Q000473:pathology*; D006801:Humans; D008875:Middle Aged
D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase