Title:“Hyperglycemic Memory”: Observational Evidence to Experimental Inference
Volume: 21
Issue: 4
Author(s): Mohsen Ahmadi, Soudeh Ghafouri-Fard, Parisa Najari-Hanjani, Firouzeh Morshedzadeh, Tahereh Malakoutian, Mohsen Abbasi, Hounaz Akbari, Mahsa Mohammad Amoli and Negin Saffarzadeh*
Affiliation:
- Department of
Nephrology, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran
- Department of
Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Diabetes, hyperglycemic memory, legacy effect, advanced glycation end products, epigenetics, hyperglycemia.
Abstract:
Several epidemiological studies have appreciated the impact of “duration” and “level”
of hyperglycemia on the initiation and development of chronic complications of diabetes. However,
glycemic profiles could not fully explain the presence/absence and severity of diabetic
complications. Genetic issues and concepts of “hyperglycemic memory” have been introduced as
additional influential factors involved in the pathobiology of late complications of diabetes. In
the extended phase of significant diabetes randomized, controlled clinical trials, including
DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control
at the early time around the diabetes onset could maintain its protective or detrimental impact
throughout the following diabetes course.
There is no reliable indication of the mechanism by which the transient exposure to a given glucose
concentration level could evoke a consistent cellular response at target tissues at the molecular
levels. Some biological phenomena, such as the production and the concentration of advanced
glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C
(PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways,
may be accountable for the development of hyperglycemic memory. This work summarizes evidence
from previous experiments that may substantiate the hyperglycemic memory soundness by
its justification in molecular terms.
