Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.
Level 2 - randomized trial
Randomized crossover experimental trial in humans
PubMed 16443784 · doi:10.2337/diabetes.55.02.06.db05-1103
What was done
Ten healthy male subjects underwent five experimental conditions in random order: two control measurements, two normoinsulinemic hyperglycemia sessions (with or without N-acetylcysteine [NAC] infusion), and one mannitol infusion as an osmotic control. Systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx-permeable tracer (dextran 40) with a glycocalyx-impermeable tracer (labeled erythrocytes). Plasma hyaluronan and coagulation markers were also quantified.
What was found
Glycocalyx measurements were reproducible across control conditions (1.7 +/- 0.2 vs. 1.7 +/- 0.3 l). Hyperglycemia significantly reduced glycocalyx volume to 0.8 +/- 0.2 l (P < 0.05), which was prevented by NAC infusion (1.4 +/- 0.2 l); mannitol had no significant effect (1.6 +/- 0.1 l). Hyperglycemia increased plasma hyaluronan from 70 +/- 6 to 112 +/- 16 ng/ml (P < 0.05), prothrombin activation fragment 1 + 2 from 0.4 +/- 0.1 to 1.1 +/- 0.2 nmol/l (P < 0.05), and d-dimer from 0.27 +/- 0.1 to 0.55 +/- 0.2 g/l (P < 0.05), coinciding with endothelial dysfunction.
Why it matters
This study provides direct in vivo human evidence that acute glucose spikes rapidly degrade the protective endothelial glycocalyx and activate coagulation via oxidative pathways.
Limits
The sample size is very small (n = 10) and exclusively comprised healthy young males, limiting generalizability to females and individuals with chronic diabetes or vascular disease. Glycocalyx volume was estimated indirectly via tracer dilution rather than direct vessel visualization, and only short-term acute hyperglycemia was evaluated.
Cited by
- supports Repeated glucose and insulin spikes wear down and damage the endothelial glycocalyx lining of artery walls, initiating plaque formation.