HbA1c Variability as an Independent Risk Factor for Microvascular Complications in Type 1 Diabetes

Background: There are few studies on the role of long-term glycemic variability in complications of type 1 diabetes (T1D). This study was aimed to investigate the associations of HbA1c variability represented by the coefficient of variation of HbA1c with incident microvascular complications in T1D by analyzing the data set from the DCCT/EDIC study. Methods: Patients (n = 1240) were divided into four groups by HbA1c variability quartiles. Incident microvascular complications were assessed for a duration of an average of 20.5 years. Multivariable models were performed to examine the associations between HbA1c variability and incident microvascular complications. Results: All incident microvascular complications were higher in the fourth quartile of the HbA1c variability group. After adjusting for clinical risk factors, HbA1c variability was positively associated with a higher risk of all diabetic microvascular complications ( P < .05). Specifically, it had 1.125 (1.082-1.170), 1.114 (1.074-1.154), 1.061 (1.024-1.099), or 1.088 (1.052-1.125) times higher odds (95% confidence interval [CI]) of having retinopathy, nephropathy, clinical neuropathy, or autonomic neuropathy, independent of mean HbA1c values ( P < .05). Furthermore, there were higher incident microvascular complications with higher HbA1c variability when HbA1c value was above the group median of 7.9%, while only higher incident autonomic neuropathy with higher HbA1c variability when HbA1c was below the group median. Conclusions: Our results showed a significant independent association between HbA1c variability and the risk of microvascular complications in T1D. HbA1c variability might be a supplemental risk stratification tool to mean HbA1c for microvascular complications in T1D.