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The legacy effect in diabetes: are there long-term benefits? – published online 14/08/2021

Folz graphical abstract

Rachel Folz, Neda Laiteerapong

Over the last two decades, a large number of landmark clinical trials and observational and translational research studies have advanced the understanding of how glycaemic control affects diabetes outcomes over time. In this issue, Folz and Laiteerapong ( summarise the evidence on the glycaemic legacy effect. Studies among individuals with early diabetes suggest that there is a long-term effect of early glycaemic control, although long-term follow-up of trials in participants with established diabetes does not corroborate this. In general, the findings of a legacy effect are more conclusive for microvascular than for macrovascular complications. Two main hypotheses exist for the pathophysiological mechanisms of the legacy effect: epigenetic modifications of the endothelium and intracellular production of superoxide anions. This summary suggests that the glycaemic legacy effect largely applies to individuals in the early stages of diabetes, and that those with established diabetes and diabetic complications may no longer benefit from early intensive glycaemic control. The figure from this review is available as a downloadable slide.

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