Delayed impact of high glucose levels may explain legacy effect
medwireNews: The so-called legacy effect of a period of good glycemic control in type 2 diabetes may be because the greatest impact of hyperglycemia occurs many years in the future, show data from the UKPDS.
Marcus Lind (University of Gothenburg, Sweden) and co-researchers found that the influence of glycated hemoglobin (HbA1c) level on the risk for mortality and acute myocardial infarction (AMI) was several-fold greater for events 10 or more years in the future than for those within 5 years.
And they stress that type 2 diabetes can go undiagnosed for many years, during which people are exposed to elevated blood glucose levels.
“Our results imply that societies should focus even more on early [type 2 diabetes] detection and glucose optimization,” the team writes.
“Moreover, programs in both children and adults without diabetes could prevent or delay diabetes onset and thereby minimize glycemic exposure at an even earlier time period.”
The findings emerge from data for UKPDS participants, who were an average age of 53.3 years at diagnosis of type 2 diabetes. Of these, 3802 had long-term follow-up for mortality (775 events) and 3219 for AMIs (662 events).
Using these data, the researchers established the expected adverse effect of high HbA1c levels, with each 1 percentage point increase associated with significant increases in the risk for AMI and mortality.
They found that the size of the effect increased over time, from a 13% increased risk for AMI 5 years after diagnosis to a 31% increased risk for an event at 20 years. The corresponding risk increases for mortality were 8% and 36%.
Lind and team say the risk increase at 20 years is greater than the 10–20% reported in other studies, implying that hyperglycemia has a larger effect on cardiovascular and mortality risk than previously believed.
“The difference is due to the increasing effects over time, which likely will increase even more for many patients over a lifetime horizon,” they write in Diabetes Care.
Conversely, the risk for mortality at 20 years fell by 27% with each 1 percentage point reduction in HbA1c if this reduction occurred from the time of diagnosis, but by only 16% if the reduction began from 10 years after diagnosis. There was a similar relationship for AMI risk.
This legacy effect was generally larger for mortality than for AMI, the team notes. For example, the risk reduction for mortality between 10 and 15 years after diagnosis was 18.8% lower with each percentage point HbA1c reduction from the time of diagnosis, but just 2.7% lower for reductions starting at year 10 – almost a sevenfold difference.
But the corresponding reductions for AMI were 19.7% and 6.5% – just over a threefold difference.
The researchers note that, as with the risk associated with elevated blood glucose, the benefits of glucose-lowering medications in cardiovascular outcome trials may also be underestimated, “because the beneficial effects, according to the current results, increase over at least 15–20 years and thus far beyond the duration of most studies, which have generally been 3–5 years.”
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