Hemoglobin A1c (HbA1c) variability is a better predictor of mortality in patients with type 2 diabetes (T2D) compared with HbA1c averages, according to a recent study published in Diabetes, Obesity and Metabolism.

Previous research has suggested that variations in glycemic control may be related to the occurrence of adverse outcomes in patients with T2D. HbA1c variability, defined as changes in HbA1c values per visit, is one measure of assessment that requires further investigation.

For this study, investigators collected patient data from the Renal Insufficiency and Cardiovascular Events study (ClinicalTrials.gov identifier: NCT00715481), an observational, prospective, cohort study, originally designed to determine the effect of estimated glomerular filtration rate on morbidity and mortality in patients with T2D. Nineteen centers were included in this initiative, and patients were monitored from 2006 to 2008. 

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Of the sites, 9 participating centers had collected at least 3 HbA1c measures on their patients (n=8290) during the 2-year period before enrollment. Average HbA1c and HbA1c variability, defined as intraindividual standard deviation (HbA1c-SD), were calculated from this subset of patients.

In October 2015, vital statuses were obtained for 99.5% of the participants (n=8252) using the Italian Health Card database for assessment of mortality.

After adjustment for confounders, data analysis revealed associations between all-cause mortality and HbA1c-SD only. An association between all-cause mortality and average HbA1c was not shown. Additionally, mortality risk was decreased in HbA1c-SD values below the median and higher for values above the median.  

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“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,” the authors concluded. “Further studies are required to understand whether HbA1c variability acts as a mediator or [an] innocent bystander in this relationship.”

Disclosures: Funding sources included Eli Lilly, Sigma-Tau, Takeda, Chiesi Farmaceutici, and Boehringer Ingelheim. Several authors declared affiliations with various pharmaceutical companies.


Orsi E, Solini A, Bonora E et al; Renal Insufficiency And Cardiovascular Events (RIACE) Study Group. Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes [published online March 26, 2018]. Diabetes Obes Metab. doi:10.1111/dom.13306