People who do not have diabetes or cardiovascular disease but have high hemoglobin A1c (HbA1c) variability tend to be at greater risk for major adverse cardiovascular events and all-cause mortality, according to study results published in Diabetes Care.

Researchers conducted a study to determine whether visit-to-visit variability of HbA1c is associated with incident major adverse cardiovascular events, all-cause mortality, and type 2 diabetes in people with no history of diabetes or cardiovascular disease. The study followed 6756 primary care patients living in Denmark (average age, 64.9) for a median duration of 6.3 years, with each patient undergoing 3 HbA1c measurements/year.

Of the total population, 996 patients experienced a major adverse cardiovascular event during the follow-up period. Calculating absolute 5-year risks for combinations of age-, sex-, and disease-specific risk factors and extreme risk profiles, the researchers reported a significant association between increased HbA1c variability and incident major adverse cardiovascular events (hazard ratio per standard deviation increase in variability [HRSD], 1.09; P =.002 per 0.09% increase in variability).

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Of the total cohort, 856 participants died during the follow-up period. As with cardiovascular events, the researchers found a significant association between higher HbA1c variability and all-cause mortality (HRSD, 1.13; P <.001 per 0.09% increase in variability). There were also similarly relevant differences across several age, sex, and comorbidity subgroups.

Although 1267 participants developed type 2 diabetes during follow-up, the researchers concluded that there was not a significant association between increasing HbA1c and risk for type 2 diabetes (HRSD, 1.0; P =.94 per 0.09% increase in variability).

Several limitations were noted for this study, including an inability to control for alternating diets or lifestyle interventions that may have caused fluctuating weight and influenced HbA1c variability.

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The researchers said their results might demonstrate that “patients with large fluctuations in HbA1c levels, although with absolute measurement levels within normal range, may be falsely reassured of their low cardiovascular risk, based on their HbA1c residing within standard guideline limits.”

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Ghouse J, Skov MW, Kanters JK, et al. Visit-to-visit variability of hemoglobin A1c in people without diabetes and risk of major adverse cardiovascular events and all-cause mortality [published online October 23, 2018]. Diabetes Care. doi:10.2337/dc18-1396