Understanding Metabolic Memory: The Prolonged Influence of Glycemia During the Diabetes Control and Complications Trial (DCCT) on Future Risks of Complications During the Study of the Epidemiology of Diabetes Interventions and Complications (EDIC)

levels during DCCT. These observations give rise to the concept of metabolic memory. Subsequent similar findings from the UKPDS gave rise to a similar concept, which they called the legacy effect. In this report, we present the evidence to support metabolic memory as both a biological and epidemiological phenomenon and discuss potential underlying mechanisms. We also compare metabolic memory and the legacy effect and conclude that the two are likely biologically similar, with comparable effects on long-term outcomes. The long-term influence of metabolic memory on the risk of micro- and macrovascular complications supports the implementation of intensive therapy, with the goal of maintaining near-normal levels of glycemia, as early and as long as safely possible in order to limit the risk of complications.