How much glucose can we actually tolerate without damage?

Details

Supervisors

Lysy, Philippe

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [60] en sciences biomédicales

Abstract

enHyperglycemia impairs endothelial function through oxidative stress and glycation, contributing to type 2 diabetes complications. Before diabetes develops, normal-high postprandial glycemia and repeated glucose spikes gradually alter endothelial function, raising the question of which level of glycemia is best tolerated without damage. This thesis aims to identify glucose tolerance thresholds by analyzing studies that use different hyperglycemia protocols in healthy and diabetic humans, animal models, and cells. In healthy humans, hypoglycemia and acute hyperglycemia of 200 mg/dL were found to increase pro-inflammatory markers and platelet activation, and decrease NO-mediated vasodilation. On the other hand, 136 mg/dL hyperglycemia maintained for 48 hours clearly decreased hepatic insulin sensitivity. In subjects with diabetes, inducing a stepwise increase from 180 to 270 mg/dL increased endothelial dysfunction and oxidative stress in a glucose-concentration-dependent manner. Moreover, oscillating glucose levels altered endothelial function and oxidative stress more than stable hyperglycemia. In the pancreatic β cells of rats, 360 mg/dL hyperglycemia stimulated O-GlcNAc accumulation and protein modification. Endothelial cells cultured in high glucose concentrations were in a more quiescent metabolic state, as reflected by reduced oxygen consumption, and showed a lower endothelial functional activity than those cultured at normal glucose levels. High glucose levels increased lipid peroxidation and attenuated enzyme activity in erythrocytes, whereas the elevated energy supply likely diminished eryptosis, hemolysis, and calcium accumulation. Overall, these findings suggest that both acute and mild sustained hyperglycemia had deleterious effects on the endothelium  of healthy humans. The differences in protocols do not allow a clear determination of a tolerable glucose concentration. Therefore, future research using standardized protocols is necessary to produce more definitive results.