Clinical review 2: The "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications?
BACKGROUND
The concept of a "metabolic memory," that is of diabetic vascular stresses persisting after glucose normalization, has been supported both in the laboratory and in the clinic and in both type 1 and type 2 diabetes.


METHODS
Using PubMed, we searched for publications on diabetic micro- and macrovascular complications using terms such as persistence, prolongation, sustained, and "memory" and focusing on the mechanistic basis behind this metabolic memory.


RESULTS
We found that as early as the mid-1980s this memory phenomenon was described in diabetic animals and isolated cells exposed to high glucose followed by normalized glucose and then, beginning around 2002, in results from large clinical trials such as the Diabetes Complications and Control Trial-Epidemiology of Diabetes Interventions and Complications and the United Kingdom Prospective Diabetes Study. Furthermore, mechanisms for propagating this memory appear focused on the nonenzymatic glycation of cellular proteins and lipids and on an excess of cellular reactive oxygen and nitrogen species, in particular originating at the level of glycated mitochondrial proteins and perhaps acting in concert with one another to maintain stress signaling independent of glucose levels.


CONCLUSIONS
The emergence of this metabolic memory suggests the need for early aggressive treatment aiming to "normalize" metabolic control together perhaps with the addition of agents which reduce cellular reactive species and glycation in order to minimize long-term diabetic complications.
Ceriello
Antonio
A
Warwick Medical School, University of Warwick, Coventry CV2 2DX, United Kingdom. antonio.ceriello@warwick.ac.uk
Ihnat
Michael A
MA
Thorpe
Jessica E
JE
D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology
D001786:Blood Glucose; D017127:Glycation End Products, Advanced