medwireNews: People with type 2 diabetes who maintain low glycated haemoglobin (HbA1c) levels have slower progression of frailty over time than those with higher levels, shows an analysis of Look AHEAD participants.
During 8 years of follow-up, the 2181 people who maintained HbA1c below 7.0% (53 mmol/mol) had an average increase of 1.99 points on a 38-item Frailty Index.
By contrast, the average changes were 3.23 points in the 1296 participants with HbA1c of 7.0–7.9% and 4.47 points in the 697 with levels of 8.0% (64 mmol/mol) or higher, with the difference across the three groups being statistically significant.
After accounting for average HbA1c during follow-up, participants had significantly smaller increases in frailty if they were using metformin or did not require any glucose-lowering medications and if they reduced their BMI by at least 5%. Those using insulin, on the other hand, had a larger progression of frailty.
Mark Espeland (Wake Forest School of Medicine, Winston-Salem, North Carolina, USA) and co-investigators say there “is a growing appreciation” of the potential anti-ageing effects of metformin, which “may target multiple pathways” involved in the ageing process.
They note that the benefits of taking metformin did not extent to other oral medications, but stress that glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors were not available at the time of the Look AHEAD trial.
Writing in Diabetes Care, the researchers cite concerns that low HbA1c levels could increase the risk of “functional deficits, falls, and mortality” in people who are frail at baseline.
“This has led to recommendations that HbA1c targets should be adjusted upwards as frailty develops”, they say.
Espeland and team therefore looked specifically at participants in the top tertile of the Frailty Index (>21 points) at baseline, but found that, in common with the cohort overall, lower HbA1c levels were associated with smaller increases in frailty over time.
However, they note a “nonsignificant but troubling” increase in the risk of major cardiovascular events among people with high baseline frailty who were assigned to the trial’s intensive lifestyle intervention group, rather than to receive diabetes support and education.
This was despite the intensive intervention “being equally successful in producing weight losses and fitness gains among participants with both relatively low and high baseline [Frailty Index]”, they add.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group