medwireNews: Accounting for the age of red blood cells (RBCs) strengthens the association between glycated haemoglobin (HbA1c) and glucose levels, improving estimates of glycaemic control in patients with diabetes, a study shows.
An average glucose level “of 150 mg/dl may be associated with HbA1c anywhere between 5.5 and 8.0%, and an HbA1c of 6.5% may reflect [average glucose] anywhere between 125 and 175 mg/dl”, say John Higgins (Massachusetts General Hospital, Boston, USA) and co-researchers.
But the team’s modelling showed that variation in average RBC age accounted for all the variability in HbA1c levels that was not explained by blood glucose levels. They explain that haemoglobin in older RBCs “has had more time to become glycated, and older RBCs therefore have higher glycated fractions.”
By measuring RBC age, Higgins et al were able to calculate a patient-specific corrected relationship between HbA1c and blood glucose, based on the weighted average level measured by continuous glucose monitoring. In four sets of patients (ranging from 30 to 234 patients), the coefficient of variation for this corrected relationship was as high as 10.8% – but could always be explained entirely by inter-patient differences in RBC age.
For standard HbA1c measurements (16 from nine patients), the median absolute error in estimated average glucose level was 15 mg/dL.
The researchers say that the difference in average glucose level between someone without diabetes and a diabetic patient with poor glycaemic control can be around 15 mg/dL, so errors of this magnitude “could mislead clinicians and patients and compromise patient care and optimal management of long-term risk of complications.”
And the error in estimated average glucose level was more than 15 mg/dL for 31.4% of patients, they report in Science Translational Medicine.
But applying the patient-specific corrected model reduced the median absolute error by two-thirds, to 5 mg/dL, and the team confirmed this superior performance in measurements from over 300 more patients, finding the patient-specific model improved the median absolute error by at least 50%.
Furthermore, the proportion of patients whose estimated average glucose level was inaccurate by more than 15 mg/dL fell to just 9.6%.
The researchers point out that the model is only as accurate as the inputted data, being dependent on variability in HbA1c measurement methods and the duration of glucose monitoring, the optimum length of which remains to be determined.
They also note that some individual patients had relatively high glucose estimation errors, even with the patient-specific model, “and the source of those errors warrants further investigation”.
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