ASSESSING RESPONSES TO SHORT-TERM GLYCEMIC VARIABILITY IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

Abstract

GV has been proposed as the mechanistic link between the development of endothelial dysfunction and the increased risk of cardiovascular disease in individuals with T1D. GV in diabetes has been associated with increased markers of endothelial activation, inflammation and apoptosis. The effects of GV on endothelial cells has been studied using in vitro models where glucose concentration is altered in an oscillating pattern. Glucose oscillation in individuals with T1D typically do not mirror the repeating intervallic changes employed by these in vitro models. The first aim of this study is to utilize an in vitro model using both the intermittent GV models and a physiological glycemic variability-based model to elucidate the effects of a 24-hours GV exposure on varying markers of endothelial function in human umbilical vein endothelial cells (HUVEC). We hypothesized that endothelial dysfunction will be induced in the GV models after 24 hours of exposure. Secondly, the effects of a subsequent 24 hours of gluconormalization on ameliorating the effects of GV on markers of endothelial function was assessed. We hypothesized that 24 hours of gluconormalization would normalize any indicators of endothelial dysfunction that had developed in response to the 24-hour exposure period.

Neither the 24 hours of glycemic variability exposure nor the gluconormalization period was associated with any changes in the indicators of endothelial function, when compared to normoglycemia, regardless of the pattern of GV. The results suggest that 24 hours of GV, was not a sufficient stimulus to induce measurable impacts in markers of endothelial function. Furthermore, as there were no differences in markers of endothelial function between any of the treatment groups longer exposure periods might be necessary to compare the standard intervallic GV and the PGV model employed in this study.