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January 26, 2020
Diabetic Retinopathy

Hemoglobin A1c Variability is Associated With All-cause Mortality in Type 2 Diabetes


  • 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.

‘In patients with type 2 diabetes, variability in the glycosylated hemoglobin scores is an independent and stronger predictor of all-cause mortality, compared to the association between the mean glycosylated hemoglobin scores and all-cause mortality.’
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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.

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.

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.”

References :

  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. https://doi.org/10.1111/dom.13306

Source: Medindia

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