• Prevention & Screening
• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

Ten years of follow-up observations from the United Kingdom Prospective Diabetes Study (UKPDS) demonstrated virtually identical HbA1C levels in subjects who were randomly assigned to 2 different glucose control strategies (intensive or conventional). However, subjects who received intensive glucose control remained at a significantly lower risk of diabetic complications. This continuing benefit of earlier improved glucose control has been termed the type 2 diabetes legacy effect [Chalmers J, Cooper ME. N Engl J Med 2008], an influence that is similar to the metabolic memory that has been described for type 1 diabetes [Stumvoll M et al. N Engl J Med 1995]. Marcus Lind, MD, University of Gothenburg, Gothenburg, Sweden, presented data that examined the degree to which historical HbA1C values contribute to later reductions in the risks of myocardial infarction (MI) and all-cause mortality. An additional aim was to elucidate the time-dependent impact of earlier HbA1C values on a year-by-year basis.

Continuous hazard functions for death and MI from diagnosis of type 2 diabetes in relation to age, sex, HbA1C, and original treatment assignment (intensive/conventional) were estimated in 3849 individuals from UKPDS. These data were then evaluated for different HbA1C levels during a preceding time interval to determine the degree to which they might explain the death and MI legacy effects.

Older age, male sex, and HbA1C, but not treatment group, were all found to be significantly (all p<0.001) related to MI and death. The model was used to estimate the impact of a 1% reduction in HbA1C from each of 2 time periods (at diagnosis and 10 years after diagnosis) on the risk of death and MI. For all-cause mortality, the results indicate the reduction in risk from the legacy effect is almost 3 times stronger when the HbA1C reduction is achieved early (at diagnosis) compared with later (after 10 years), and this effect is mostly because of the lower HbA1C levels at the earlier time points. The pattern is similar, but the effects of early reduction are somewhat less potent for MI.

The model was used to predict the relative reduction in the probability of death for a 50-year-old man with newly diagnosed type 2 diabetes and an HbA1C of 8% in 2 different scenarios: immediate (at diagnosis) reduction of HbA1C by 1% and waiting 10 years for the same HbA1C reduction. Reducing the HbA1C by 1% (to 7%) at diagnosis will result in an 18.6% risk reduction for death compared with only a 6.6% risk reduction if the HbA1C reduction is delayed for 10 years. Similar relationships in risk reduction and timing of the HbA1C reduction were seen when the model was applied to MI and to women.

Statistical modeling of UKPDS data confirmed that earlier HbA1C levels continue to contribute to the risk of diabetic complications, as seen in the Diabetes Control and Complications Trial [The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993]. The long-term impact of achieved HbA1C levels explains to a large extent the sustained reductions in the risk of death and MI that were seen in the UKPDS post-trial monitoring period. Thus, early intensive, optimal, glycemic control is essential to minimize the long-term risk of diabetic complications.

• © 2012 MD Conference Express®