Download Booklet - Diabetes in Asia Study Group

Abstract Title
THE LEGACY OF HYPERGLYCEMIC MEMORY IS ASSOCIATED WITH EPIGENETIC
CHANGES
Assam El-Osta
Vascular complications occur as a result of pathological processes, which are activated by chronic
hyperglycemia. It is know clearly evident that metabolic memory, whereby diabetic complications
continue to develop and progress even in individuals who have returned to improved glycemic
control could have long lasting effects. The Diabetes Control Complications Trial (DCCT) and
The Epidemiology of Diabetes Interventions and Complications Study (EDIC) outcome data
demonstrate that despite similar levels of glycemic control, those individuals in the original
intensive therapy group continue to have reduced rates of complications development despite
having similar levels of glycemic control. Collectively, these observations support the concept
that an earlier period of hyperglycemia can lead to subsequent sustained and long lasting
effects within the vasculature, ultimately resulting in ongoing organ injury and dysfunction. This
recognized phenomenon of hyperglycemic memory is perhaps the most clinically important and
unsolved problem in diabetes research (1). Here we show that ambient or prior hyperglycemia
induces specific epigenetic changes associated with histone methylase and demethylase
enzymes in primary human aortic endothelial cells (2). These results provide a molecular basis
for explaining hyperglycemic memory, and, suggest that the concomitant methylation changes
on histones may play a more general role in regulating transcriptional activity in diabetes. These
studies address a critical gap and add significant new data to advance our understanding of
metabolic memory. The results to these experiments are the first installment in determining
markedly different transcriptional behaviors and epigenetic changes in diabetes using largescale
epigenomic approaches.
56