Large visit-to-visit hemoglobin A1c (HbA1c) variability is associated with an increased risk for cardiovascular disease in patients with type 2 diabetes, according to a study published in the January issue of Diabetes, Obesity & Metabolism.
Yun Shen, M.D., from the Pennington Biomedical Research Center in Baton Rouge, Louisiana, and colleagues examined the association between visit-to-visit HbA1c variability and the risk for cardiovascular disease in patients with type 2 diabetes. The analysis included 29,260 patients with at least four HbA1c measurements within two years of type 2 diabetes diagnosis.
During a mean follow-up of 4.18 years, the researchers found 3,746 incident cardiovascular disease cases. For the first, second, third, and fourth quartiles of HbA1c values, the adjusted hazard ratios for cardiovascular disease were 1.00, 1.30, 1.40, and 1.59, respectively. Similar associations were seen when examining the HbA1c coefficient of variation and adjusted HbA1c standard deviations as exposures. There was also an association observed between HbA1c variability and risk for first and recurrent severe hypoglycemic events. Severe hypoglycemia mediated the association between HbA1c variability and incident cardiovascular disease.
"We recommend that patients and their doctors implement therapies that can reduce wide swings in blood sugar levels and the associated episodes of severe low blood sugar," a coauthor said in a statement. "Our findings suggest that measuring the swings in blood hemoglobin A1c levels over a specific time -- six months to a year, for example -- could serve as a supplemental blood sugar target."
Aim: To investigate the association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.
Materials and methods: We performed a retrospective cohort study of 29 260 patients with at least four HbA1c measurements obtained within 2 years of their first diagnosis of type 2 diabetes. Different HbA1c variability markers were calculated,
including the standard deviation (SD), coefficient of variation (CV) and adjusted Cox proportional hazards regression models were used to estimate the association of these HbA1c variability markers with incident cardiovascular disease.
Results: During a mean follow-up of 4.18 years, a total of 3746 incident cardiovascular disease cases were diagnosed. Multivariate-adjusted hazard ratios for cardiovas-
cular disease across the first, second, third and fourth quartiles of HbA1c SD values were 1.00, 1.30 (95% confidence interval [CI] 1.18-1.42), 1.40 (95% CI 1.26-1.55) and 1.59 (95% CI 1.41-1.77) (P for trend <.001), respectively. When we utilized HbA1c CV and adjusted HbA1c SD values as exposures, similar positive associations were observed. HbA1c variability was also associated with the risk of first and recurrent severe hypoglycaemic events.
A mediating effect of severe hypoglycaemia was observed between HbA1c variability and incident cardiovascular disease.
Conclusions: Large visit-to-visit HbA1c variability is associated with an increased risk of cardiovascular disease in patients with type 2 diabetes. Severe hypoglycaemia may mediate the association between HbA1c variability and incident cardiovascular disease.