Association Between Visit-To-Visit Hba1c Variability And The Risk Of Cardiovascular Disease In Patients Withtype 2diabetes

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 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 3746 incident cardiovascular disease cases were diagnosed. Multivariate-adjusted hazard ratios 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) (Pfor 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.