Historical HbA_1c Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88

Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycemic legacy effects have not been explained. We examined their relationships with prior individual HbA_1c values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy.

Twenty-year ACM and MI hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. Impact of HbA_1c values over time was analyzed by weighting them according to their influence on downstream ACM and MI risks.

Hazard ratios for a one percentage unit higher HbA_1c 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 was 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 HbA_1c 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 sevenfold lower 2.7% (3.1-2.3) risk reduction. Corresponding MI risk reductions were 19.7% (22.4-16.5) when lowering HbA_1c at diagnosis, and threefold lower 6.5% (7.4-5.3%) when imposed 10 years later.

The glycemic legacy effects seen in type 2 diabetes are explained largely by historical HbA_1c 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 maximize reduction of the long-term risk of glycemic complications.