15-05-2025
High A1c Fluctuations Linked to Mortality Risk in Diabetes
Higher A1c variability, assessed over a 4-year period, was associated with a substantially increased risk for subsequent mortality outcomes in patients with type 1 diabetes (T1D) and those with type 2 diabetes (T2D), regardless of average A1c levels.
METHODOLOGY:
The importance of glycaemic control, as reflected by average A1c levels, is well-established in diabetes management guidelines; however, growing evidence suggests that A1c variability may also be important for various microvascular and macrovascular outcomes.
Researchers in England carried out a population-based cohort study to examine predictors of high A1c variability and evaluate the relationship between high A1c variability and all-cause mortality in patients with diabetes.
They included 20,347 patients with T1D (mean age, 52.9 years; 57.4% men) and 409,821 patients with T2D (mean age, 67.5 years; 55.8% men), all aged 31 years or older, from the Clinical Practice Research Datalink database. All participants had at least four A1c measurements taken at least 30 days apart during 2011-2014 and were followed from 2015 to 2017 for subsequent mortality outcomes.
The A1c variability score was calculated by measuring the frequency of A1c fluctuations of at least 0.5% (or 5.5 mmol/mol) between successive measurements over time, expressed as a percentage; A1c variability score estimates were categorised into four levels: 0 to < 20, 20 to < 50, 50 to < 80, and 80-100.
TAKEAWAY:
Variability measures were generally higher in T2D, with 38% of patients with T2D vs 33% of those with T1D having an A1c variability score ≥ 50.
Predictors of high A1c variability were younger age, obesity, comorbidities, and residence in deprived areas for both T1D and T2D, whereas non-White ethnicity was a predictor of high variability only in T1D.
A higher vs lower A1c variability score (≥ 80 vs < 20) was associated with nearly a threefold increase in mortality risk for patients with T1D and a twofold increased risk for those with T2D (hazard ratio [HR] for T1D, 2.78; 95% CI, 2.15-3.60; HR for T2D, 1.91; 95% CI, 1.83-1.99).
The impact of average A1c levels on mortality was less pronounced than that of A1c variability, as evidenced by higher population attributable fractions for variability (A1c variability score ≥ 20) than for average A1c levels in both T1D and T2D.
IN PRACTICE:
"Regardless of whether variability can be reduced, given its strong effects on mortality risk, it could be incorporated into A1c targets or trigger enhanced monitoring and support," the authors wrote.
SOURCE:
The study was led by Liza Bowen and Iain Carey, School of Health & Medical Sciences, City St George's, University of London, London, England. It was published online on May 6, 2025, in Diabetes Research and Clinical Practice .
LIMITATIONS:
The study included only patients with diabetes who had at least four A1c measurements in primary care between 2011 and 2014. Patients with T1D likely had additional A1c measurements recorded in hospital records that were not included in the primary care dataset.
DISCLOSURES:
The study was funded by the National Institute for Health and Care Research (NIHR) - Research for Patient Benefit Programme and supported by the NIHR Applied Research Collaboration South London at King's College Hospital National Health Service Foundation Trust. One author was supported by an NIHR Clinical Lectureship in General Practice. Another author reported consulting for and/or receiving speaker honoraria and grant support from various healthcare and pharmaceutical companies.
