The Impact of Glycaemic Variability on Vascular Dysfunction in Diabetes

It is well established that vascular dysfunction is common in people with diabetes mellitus and is associated with increased risk of heart attack, ischaemic stroke and peripheral vascular disease. Although our understanding of the molecular mechanisms responsible is incomplete, persistent hyperglycaemia observed in poorly controlled diabetes has long been thought to be a critical factor. Multiple studies have, therefore, investigated the effects of poor glycaemic control on vascular function in multiple experimental settings, from in vitro and ex vivo models of primary human cells and tissues through to pre-clinical models. This review consolidates our current understanding of how metabolic and cell signalling pathways triggered by poor glycaemic control, impact vascular function in diabetes. We also evaluate how these pathways could be exploited to develop targeted therapeutic approaches to improve cardiovascular outcomes specifically in people with diabetes.