Metabolic memory in diabetes: What are the proofs? What are the putative mechanisms?

The long-term follow-up of the patients having participated to glucose trials in diabetes have shown diverging trajectories with regards to diabetes-specific complications, according to the intervention group patients had been randomized to during the intervention phases of the trials. Group-specific risk in the incidence of complication has been observed although blood glucose levels have been largely similar during the long-term follow-up. The long-term persistence of differences has been called metabolic memory. The present manuscript presents the long-term, 30 years, results of the Diabetes control and complications trial (DCCT) and the molecular basis of the metabolic memory, based on several experimental models.