Journal of diabetes
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The relationships of glycemic control over time with the development of complications have been investigated in several studies, but new areas of debate continue to arise. Does glycemic control have greater benefit when attained earlier than when attained later in the natural history of diabetes? Is it simply the duration of better or worse levels of glycemia that lead a given individual to have fewer or greater levels of complications? Might glycemic control have similar benefit throughout the duration of diabetes until irreversible damage occurs, perhaps varying by organ system (neurologic, renal, retinal, cardiovascular)? Specific benefits or adverse effects of treatment agents may further complicate the interpretation of what has been characterized as "metabolic memory." The notion of metabolic memory was based on findings of the Diabetes Control and Complications Trial (DCCT) of type 1 diabetes (T1D), in which the initial 2% HbA1c separation between the groups of patients randomized to intensive or conventional control was lost during the follow up Epidemiology of Diabetes Interventions and Complications (EDIC) study, when the two groups of participants returned to standard treatment and showed similar HbA1c levels but the initial intensively treated group continued to have lower rates of development of microvascular and, subsequently, macrovascular complications. Similarly, a decade after the conclusion of the UK Prospective Diabetes Study (UKPDS), patients with type 2 diabetes (T2D) in the intensive therapy group, despite showing similar levels of glycemic control to those receiving standard care, continued to have significant reductions in microvascular endpoints and reductions in myocardial infarction and all-cause mortality. ⋯ Perhaps, then, uncontrolled glycemia of long duration may not be offset by subsequent intensive control, but intensive treatment from the time of diagnosis, even with "bad glycemic legacy" (but of short duration), will be effective in decreasing risk of later complications. Does the retrospective study by Pantalone et al. hint at a different aspect of metabolic memory, namely that poor control of glycemia at baseline does not affect the development of complications later if it is effectively managed subsequently? That effects of initial hyperglycemia could be dispelled with excellent glycemic control? Such an interpretation gives cause for optimism and can be used in empowering people developing diabetes to participate in their care. Analysis of more datasets with serial measures of HbA1c may allow us to further understand these relationships, and certainly the underlying molecular mechanisms of metabolic memory deserve further investigation.