The prevention and successful management of diabetes and its complications are issues of utmost health importance. Over 380 million people are living with diabetes and up to one in three adults will develop diabetes or pre-diabetes in their lifetime. The major costs of diabetes relate to the development of diabetic complications, including blindness, amputations, heart attacks and strokes, kidney failure and premature mortality. However, the burden of complications is unequally shared across individuals with diabetes. A prolonged duration, inadequate metabolic and/or blood pressure control may explain some cases. Yet even with intensive intervention and dedicated compliance, complications still occur. Moreover, the long-term survival of some of Banting and Best’s original patients stand as a testament to the fact that some individuals appear to be ‘protected’ despite many decades of marked hyperglycaemia. It is not simply genetics, as the genetic variability cannot explain why some individuals and some families seem programmed to have an inordinate burden of complications. Studies now indicate that specific epigenetic events contribute to programming for the development and progression of diabetic complications.
Epigenetic modifications are one of the most important means for the temporal and spatial control of gene activity; to store, retain, and recall past experiences in a way to shape present and future behavior in what has become known as cellular memory. Over the last decade studies have shown that key epigenetic changes regulate the expression of genes following exposure to high glucose levels. In addition, this epigenetic programming directly contributes to persistent up-regulation of pro-inflammatory pathways by hyperglycaemia in cells, animal models and in humans, in what has become known as ‘metabolic memory’. These recent discoveries may partly explain the sustained ‘legacy’ of beneficial effects arising from improved glucose control in patients with diabetes, as well as contribute to the irreversible legacy of vascular damage observed in clinical trials of glucose lowering in patients with longstanding diabetes. In this meeting, we explore the legacy of hyperglycaemia and other environmental stimuli implicated in the sustained activation of pathogenic pathways. Not only will this meeting cover current trends and developments, topics will discuss the functional legacy of prior hyperglycaemia of diabetic complications including atherosclerosis and nephropathy and explore where exactly memory resides.