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Historical HbA1c values may explain the type 2 diabetes legacy effect

The UKPDS study demonstrated that a tight glycemic control decreases the risk of micro and macrovascular complications in patients with type 2 diabetes (T2D). However, T2D all-cause mortality and MI glycemic legacy effects have not been explained. The objective of this study was to examine their relationships with prior individual HbA1c values and explored the potential impact on instituting earlier, compared with delayed, glucose-lowering therapy.

In this UKPDS analysis, the included patients were those originally assigned to an intensive glycemic strategy with sulfonylurea or insulin, or to a conventional glycemic strategy with diet.

The results of ten-years posttrial monitoring of surviving UKPDS participants with virtually no glycemic differences at the beginning of the study and before the randomization (to intensive or conventional group), revealed relative risk reductions of 16% for ACM (p=0.007) and 15% of MI (p=0.01) in favor of the intensive group. These findings suggest there is a “legacy” effect conferred by earlier improved glycemic control with increasingly beneficial effects on all-cause mortality and MI risks over time.

It was also estimated that imposing a 1% HbA1c reduction from diagnosis generated an 18.8% reduction in the risk of all-cause mortality and 19.7% for MI 10-15 years later. In addition, the study demonstrates how delaying this 1% HbA1c reduction for 10 years has a direct impact on these two parameters, due to the fact that there was a 2.7% reduction for all-cause mortality and 6.5% for MI versus the 18.8% and 19.7% reductions obtained with an early therapy for glucose control.

The authors conclude that “the glycemic legacy effect seen in type 2 diabetes is explained largely by historical HbA1c values… 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”

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