Electronic Thesis and Dissertation Repository


Master of Science


Physiology and Pharmacology


Fraser, Douglas D.

2nd Supervisor

Cepinskas, Gediminas



Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency resulting in hyperglycemia, ketoacidosis, and inflammation. Children with DKA have an increased risk of microvascular complications (e.g. stroke). The glycocalyx maintains the anti-thrombotic properties of endothelial cells (ECs), however the glycocalyx status is unknown in DKA. We quantified major glycocalyx components: hyaluronic acid (HA), heparan sulfate (HS), chondroitin sulfate (CS), and syndecan-1 in DKA plasma and correlated them with DKA severity. HA/HS were significantly increased in the plasma of DKA patients in comparison to insulin-controlled type-1 diabetics, but only HA correlated to DKA severity. Exogenous addition or removal of HA increased reactive oxygen species generation, while only the latter suppressed basal nitric oxide production in cerebral ECs, implicating a prothrombotic endothelial response to HA shedding. Exogenous supplementation of HA/HS/CS reduced platelet adhesion, suggesting shedding of HA/HS to be a contributor to the prothrombotic state of DKA.