UKPDS Legacy Effect Background United Kingdom Prospective Diabetes
UKPDS Legacy Effect Background • United Kingdom Prospective Diabetes Study (UKPDS) 10 -year follow-up - Mean Hb. A 1 c levels identical in groups previously randomized to intensive or conventional glucose control - Intensive vs conventional control group remained at significantly lower risk of complications - All-cause mortality: HR=0. 87; p=0. 006 - MI: HR=0. 85; p=0. 014 - This continuing benefit has been termed T 2 DM legacy effect
UKPDS Objectives • Determine the degree to which historic Hb. A 1 c values contribute to later reduced risk of MI and all-cause mortality Determine time-dependent impact of earlier Hb. A 1 c values on year-to-year basis Methods • • • 3849 UKPDS patients examined Analyses restricted to period for which Hb. A 1 c measurements available Continuous hazard functions estimated over 0 -20 years for death and MI in relation to Hb. A 1 c, age, sex, and treatment group
UKPDS Results • Hb. A 1 c, older age, and male sex, but not treatment group, significantly associated with MI and death (p<0. 001 for all) • Reduction in risk of all-cause mortality almost 3 X stronger with early Hb. A 11 c reduction (based on modeled impact of 1% Hb. A 1 c reduction on death) • Early Hb. A 1 c reduction also reduced risk of MI (based on modeled impact of 1% Hb. A 1 c reduction on MI)
UKPDS Conclusions • Despite absence of glycemic difference during 10 -year post-UKPDS observational follow-up, there was continued reduction in risk of complications with emergent risk reductions for MI and death • Statistical modeling confirmed that earlier Hb. A 1 c levels continue to contribute to risk of diabetic complications, as seen in the Diabetes Control and Complications Trial (DCCT) [N Engl J Med 1993] • Waiting years after diagnosis of T 2 DM to minimize glycemia is unlikely to achieve full benefits of immediate intervention • Achieving and maintaining optimal glycemic control is essential to minimize long-term risk of diabetic complications
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