Glycaemic Variability and Pancreatic ß-cell Dysfunction

摘要

The importance of glycaemic variability (GV) as a factor in the pathophysiology of cellular dysfunction andnlate diabetes complications is currently a matter of debate. However, there is mounting evidence from in vivo and in vitronstudies that GV has adverse effects on the cascade of physiological processes that result in chronic ?cell dysfunctions.nGlucose fluctuations more than sustained chronic hyperglycaemia can induce excessive formation of reactive oxygenn(ROS) and reactive nitrogen species (RNS), ultimately leading to apoptosis related to oxidative stress. The insulinsecretingn?cells are particularly susceptible to damage imposed by oxidative stress. Evidence from experiments, usingnisolated pancreatic islets or ?cell lines, has linked intermittent high glucose, which mimicks GV under diabetic conditions,nto significant impairment of ?cell function. Several clinical studies reported a close association between GV and 遚ellndysfunction, although the deleterious effects are difficult to demonstrate. Notwithstanding, early therapeutic interventionsnin patients with type 1 as well as type 2 diabetes, using different strategies of optimising glycaemic control, havenshown that favourable outcomes on recovery and maintenance of ?cell function correlated with reduction of GV. Thenpurpose of the present review is to discuss the detrimental effects of GV and associations with ?cell function as well asnupcoming therapeutic strategies directed towards minimising glucose excursions, improving ?cell recovery and preventingnprogressive ?cell loss. Measuring GV has importance for management of diabetes, because it is the only one componentnof the dysglycaemia that reflects the degree of dysregulation of glucose homeostasis.