The legacy effect in diabetes: are there long-term benefits?

In this narrative review, we summarise the evidence for and against the glycaemic legacy effect from the long-term follow-up of major diabetes trials and observational cohort studies. We provide a summary of the pathophysiological basis for the legacy effect and discuss some translational research. Results from trials of early diabetes and observational cohort studies suggest that a long-term effect of early glycaemic control exists; however, long-term follow-up from trials in participants with established diabetes is not supportive. Additionally, findings for the legacy effect are more conclusive for microvascular complications than macrovascular events. Overall, these results suggest that the glycaemic legacy effect is a long-term benefit (or risk) conferred to individuals in the early stages of diabetes and which is muted over time as individuals' vasculature changes and they develop complications from diabetes.