Association between visit-to-visit hemoglobin A1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.

AIM To investigate the association between visit-to-visit glycosylated hemoglobin (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 4 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 SD. 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 3,746 incident cardiovascular disease cases were diagnosed. Multivariate-adjusted hazard ratios (HRs) for cardiovascular 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 <0.001), 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 hypoglycemic events. A mediating effect of severe hypoglycemia 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 hypoglycemia may mediate the association between HbA1c variability and incident cardiovascular disease. This article is protected by copyright. All rights reserved.