UKPDS 88 Supplement FINAL_cx01.pdf (1.17 MB)
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Historical HbA1c Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88

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posted on 08.07.2021, 13:35 by Marcus Lind, Henrik Imberg, Ruth L. Coleman, Olle Nerman, Rury R. Holman

Objective Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycaemic legacy effects have not been explained. We examined their relationships with prior individual HbA1c values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy.

Research design and methods Twenty-year all-cause mortality (ACM) and myocardial infarction (MI) hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. HbA1c values impact over time were analysed by weighting them according to their influence on downstream ACM and MI risks.

Results Hazard ratios for a 1 percentage unit higher HbA1c for ACM were 1.08 (95% CI 1.07-1.09), 1.18 (1.15–1.21) and 1.36 (1.30–1.42) at 5, 10 and 20 years respectively, and for MI 1.13 (1.11–1.15) at 5 years increasing to 1.31 (1.25–1.36) at 20 years.
Imposing a one percentage unit lower HbA1c from diagnosis generated an 18.8% (95% CI 21.1%–16.0%) ACM risk reduction 10-15 years later, whereas delaying this reduction until 10 years after diagnosis showed a 7-fold lower 2.7% (3.1%-2.3%) risk reduction. Corresponding MI risk reductions were 19.7% (22.4%-16.5%) when lowering HbA1c at diagnosis, and 3-fold lower 6.5% (7.4%-5.3%) when imposed 10 years later.

Conclusions The glycaemic legacy effects seen in type 2 diabetes are explained largely by historical HbA1c values having a greater impact than recent values on clinical outcomes. Early detection of diabetes and intensive glucose control from the time of diagnosis is essential to maximise reduction of the long-term risk of glycaemic complications.


This study was supported by the Swedish State (ALF-grant). RRH is an Emeritus National Institute for Health Research Senior Investigator.