HbA1C Variability and the Risk of Renal Status Progression in Diabetes Mellitus: A Meta-Analysis

Objective: To explore the association between glycated hemoglobin (A1C) variability and renal disease progression in patients with diabetes mellitus. Methods: A comprehensive search was performed using the PubMed and Embase databases (up to April 26, 2014). The hazard ratio (HR) was pooled per unit increase in the standard deviation of A1C (A1C-SD) to evaluate the dose-response relationship between A1C-SD and the risk of nephropathy. Results: Eight studies with a total of 17,758 subjects provided the HR for A1C-SD and were included in the final meta-analysis. The pooled HR results demonstrated that A1C-SD was significantly associated with the progression of renal status (HR for both T1DM and T2DM 1.43, 95% confidence interval [CI] 1.24-1.64; HR for T1DM 1.70, 95% CI 1.41-2.05; HR for T2DM 1.20, 95% CI 1.12-1.28). A1C-SD was significantly correlated with new-onset microalbuminuria (HR for T1DM 1.63, 95% CI 1.28-2.07; HR for T2DM 1.23, 95% CI 1.08-1.39). These outcomes were also supported in subgroup analyses. Furthermore, sensitivity analyses demonstrated that the results were robust. Conclusions: A1C variability is independently associated with the development of microalbuminuria and the progression of renal status in both type 1 and 2 diabetes patients. A standard method for measuring A1C variability is essential for further and deeper analyses. In addition, future studies should assess the effect of reducing A1C variability on nephropathy complication.