Redox mediating epigenetic changes confer metabolic memories.

It’s not always the case that it’s easy to forgive and forget, particularly when it comes to past memories. The concept of the legacy effect or hyperglycemic memory describes the deferred consequence of antecedent glycemic status on the development of diabetic complications. Anyone researching chronic hyperglycemia appreciates that glucose is still considered the major risk factor implicated in the development and progression of diabetic vascular complications. Now, the same can be concluded for transient hyperglycemia. Large clinical studies have demonstrated that prior glycemic control has a sustained benefit in reducing subsequent diabetic complications.1–4 The Diabetes Control and Complications Trial (DCCT) and the follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC) have determined that episodes of poor glycemic control can lead many years later to the long-term complications of diabetes.5,6 The DCCT study was designed to compare intensive versus conventional approaches to improve glycemic control and determine the effects of these regimens on the development and progression of vascular complications in patients with type-1 diabetes. Because the development of diabetic microvascular complications and cardiovascular disease takes time, the follow-up EDIC study was designed to investigate the long-lasting effects of intensive and conventional therapies. The findings of these extended studies show that early intensive intervention was more effective in slowing the development of diabetic complications and this was clearly evidenced with the benefit of 6.5 years of intensive therapy during the DCCT phase being sustained, the benefits continuing for at least 10 years after return to usual glycemic control. When taken together, these studies in type 1 diabetes as well as the more recent findings from the follow up of the United Kingdom Prospective Diabetes Study emphasize that prior periods of intensive glycemic control significantly reduces the major burden of diabetes, its vascular complications.7