High A1c Variability Linked to Increased Mortality in Diabetes, reveals research

A new study published in the journal of Diabetes Research and Clinical Practice showed that greater A1c variability significantly increases the risk of mortality in both type 1 and type 2 diabetes patients, independent of average A1c levels, highlighting the importance of stable glycemic control.

An estimated 828 million persons globally were predicted to have diabetes in 2022, making it one of the top causes of mortality and disability. Therefore, it is critical to comprehend diabetes traits that might influence the burden of morbidity and death. Diabetes management recommendations emphasize the well-established significance of controlling diabetes as shown by average HbA1c.

However, there is mounting evidence that a variety of micro- and macro-vascular outcomes may be influenced by HbA1c fluctuation as well as typical levels. Although they have been less well documented in type 1 diabetes, associations between HbA1c variability and mortality have been discovered in a number of observational studies concentrating on type 2 diabetes.

Since those with the highest mean values also frequently have the largest variability, it can be difficult to distinguish between mean and variability in HbA1c. Thus, after controlling for average HbA1c level, this study examined relationships between HbA1c variability and all-cause mortality in people with diabetes.

For individuals aged 31 to 90 with diabetes (type 1 = 20,347, type 2 = 409,821) who had 4+ HbA1c measures recorded in the Clinical Practice Research Datalink between 2011 and 2014 and who were still living on January 1, 2015, the mean HbA1c and variability score (HVS) was calculated. Using nationwide linked mortality data from 2015–17, Cox models calculated the hazard ratios (HR) for all-cause mortality. Mutual adjustments were made for the HbA1c level and variability as well as other measured confounders.

Younger age, non-white ethnicity (type 1 only), obesity, co-morbidities, and residing in underprivileged regions were all linked to higher HbA1c variability. Almost, 40,723 (9.9%) people with type 2 diabetes and 1,043 (5.1%) people with type 1 diabetes passed away during the follow-up period.

The calculated adjusted HRs for death were 2.78 in type 1 diabetes and 1.91 in type 2 diabetes among individuals with the highest and lowest levels of HbA1c fluctuation, respectively. Overall, this study found that, regardless of average HbA1c, increased variability in HbA1c was linked to eventual mortality in individuals with both type 1 and type 2 diabetes. 

Source:

Bowen, L., Carey, I., Chaudhry, U., DeWilde, S., Audi, S., Limb, E., Cook, D. G., Panahloo, A., Whincup, P., Sattar, N., Harris, T., & Critchley, J. A. (2025). HbA1c variability and all-cause mortality in type 1 and type 2 diabetes: A population-based cohort study using electronic health records. Diabetes Research and Clinical Practice, 112229, 112229. https://doi.org/10.1016/j.diabres.2025.112229