Visit-to-visit glycated hemoglobin A1c variability in adults with type 2 diabetes:a systematic review and meta-analysis

Background: Current practice uses the latest measure of glycated hemoglobin (HbA1c) to facilitate clinical decision-making. Studies have demonstrated that HbA1c variability links the risk of death and complications of diabetes. However, the role of HbA1c variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbA1c variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes.Methods: We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbA1c variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbA1c variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbA1c variability score (HVS).Results: In people with type 2 diabetes, the highest quantile of all three HbA1c variability metrics (HbA1c-standard deviation [HbA1c-SD], HbA1c-coefficient of variance [HbA1c-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbA1c-SD on all-cause mortality was 1.89 with 95% confidence interval (95% CI) 1.46-2.45 (HbA1c-CV 1.47, 95% CI 1.26-1.72; HVS 1.67, 95% CI 1.34-2.09).Conclusions: High HbA1c variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbA1c variability need additional attention and care for the potential adverse outcomes.