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)
The Diabetes Control and Complications Trial (DCCT) provided an exhaustive study of type 1 diabetes complexities and put to test “glucose hypothesis” which stated that hyperglycemia is the direct cause for the development of microvascular complications and that achievement of target glycemic levels (i.e., HbA1c 7%) reduced the risk of complications.
The DCCT was followed by the Epidemiology of Diabetes Interventions and Complications (EDIC) observational study of the DCCT cohort. During the EDIC the randomly assigned DCCT treatment groups rapidly converged, yet the favourable effects of prior DCCT intensive versus traditional treatment on diabetes complications lingered and even surged.
This gave rise to the idea of “metabolic memory” in which a prior period of hyperglycemia surges the long-term risk of complications. On the other hand, a time of near-normal glycemia delivers long-term advantageous effects on
complications with such impacts persevering despite the fact that ensuing degrees of glycemia may have risen.
The research titled “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)” was thereby conducted by John M. Lachin and David M. Nathan and the summary of the article has been given below
Objective:
To review the evidence bracing the phenomenon of “metabolic memory” elaborating the role of glycemia over time in the development of micro and macro vascular complications.
To compare the “metabolic memory” with the “legacy effect”.
Method:
A total of 1441 patients with Type 1 diabetes were recruited in the study. 726 of them had no retinopathy whereas 715 of them had mild to moderate retinopathy. The participants were randomly assigned to intensive therapy either with an external insulin pump or by three or more daily injections and directed by periodic monitoring of the blood glucose levels or to traditional therapy with one or two daily insulin injections. This was followed by the EDIC study which enrolled 1375 participants. The methods used in DCCT was also employed in the EDIC study. HbA1c was recorded annually and retinopathy testing was done once in 4 years.
Findings:
Metabolic Memory has two manifestations. One is a biologic effect on the daily hazard of progression which is a manifestation of biologic effects associated with a history of poor glycemic control and another is an epidemiological impact of the cumulative incidence of development that mirrors the population public health impact on the absolute risk of progression presented as the number of subjects with progression over a specified time period.
Hence this suggests that individuals having type 1 diabetes should follow intensive insulin therapy as early as possible.
Identifying the early periods of high blood glucose levels provides the motive behind this approach.
It also highlights that tight glycemic intervention may reduce the adverse outcomes that would otherwise occur with hyperglycemia.
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