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  • HbA1c variability or changes in HbA1c values per visit is a strong, independent predictor of all‐cause mortality in type 2 diabetes (T2D)
  • HbA1c variability appears to be even more powerful in predicting death compared with HbA1c averages
  • More research is needed to understand the exact involvement of HbA1c variability in this relationship

Glycosylated hemoglobin (HbA1c) variability can better predict all-cause mortality in patients with type 2 diabetes (T2D) compared with taking averages of HbA1c, according to a recent study published in Diabetes, Obesity and Metabolism.

Hemoglobin A1c (HbA1c) levels are an indicator of a sign of diabetes, a chronic condition where the blood sugar levels are high. The test for HbA1c measures the amount of blood sugar or glucose attached to hemoglobin.
Hemoglobin A1c Variability is Associated With All-cause Mortality in Type 2 Diabetes

Hemoglobin is the iron-containing molecule present in red blood cells that carries oxygen from the lungs to the rest of the body.

While a regular glucose monitor measures the blood sugar at a particular point of the day, the HbA1c test shows the average amount of glucose attached to hemoglobin for the past three months. The three-month average coincides with the lifespan of a typical red blood cell.

HbA1c is also known by other names: A1c, glycohemoglobin, glycated hemoglobin, Decoding HbA1c Test for Blood Sugar, glycosylated hemoglobin.

Difference Between Mean HbA1c and HbA1c Variability

In this study, the average of 3 to 5 HbA1c measures was taken over a 2-year period before enrollment from 9 centers that included 8290 patients. This average was used to calculate average HbA1c written as HbA1c - MEAN.

HbA1c variability or variability of HbA1c over time defined as changes in HbA1c values per visit was measured as the standard deviation within the individuals (HbA1c-SD) that was adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV, the ratio of standard deviation to the mean - HbA1c‐SD to HbA1c‐MEAN ratio).

Earlier research had suggested that variability in the levels of blood glucose of T2D patients could be the cause of adverse outcomes in them.


Patient data for the study was collected from an observational, prospective, cohort study, designed initially to determine the effect of estimated glomerular filtration rate on morbidity and mortality in patients with T2D.

There were 19 centers in total, and the patients were monitored from 2006 to 2008.

The average HbA1c and the HbA1c variability were measured using a subset of this group, from 9 participating centers as mentioned before.
  • The results were obtained for 99.5% of the participants (n=8252) and showed that all-cause mortality was only associated with HbA1c-SD, after adjusting for confounders.
  • HbA1c-SD was a more powerful predictor of all-cause death than HbA1c-MEAN.
  • Also, mortality risk increased above the median value and decreased below the median value of HbA1c-SD.
"HbA1c variability is a strong, independent predictor of all-cause death in [T2D] and appears to be even more powerful than average HbA1c in predicting mortality," concluded Emanuela Orsi, M.D., from the University of Milan, and her colleagues. "Further studies are required to understand whether HbA1c variability acts as a mediator or [an] innocent bystander in this relationship."

Reference :
  1. Orsi E, Solini A, Bonora E, et al. "Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes". Diabetes Obes Metab. 2018;1-9.

Source: Medindia

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