Glycaemic Variability and Pancreatic ß-cell Dysfunction

Klaus-Dieter      Kohnert; Ernst-Joachim      Freyse; Eckhard      Salzsieder

Abstract

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

Keywords: Dysglycaemia, Glycaemic variability, ß-Cell failure, Oxidative stress, Apoptosis, Treatment strategies, Diabetes mellitus, homeostasis, reactive nitrogen species, reactive oxygen