Comparative analysis of hemoglobin a1c measurement methods: inter-device agreement and clinical impact

Glycated hemoglobin (HbA1c) is widely recommended for the diagnosis and monitoring of diabetes mellitus (DM). Minimal changes in HbA1c concentration can influence clinical decisions, making accurate and interference-free measurement essential. To compare the analytical performance and inter-method agreement of three HbA1c measurement techniques-Capillary Electrophoresis, High-Performance Liquid Chromatography (HPLC), and Turbidimetric Immunoinhibition-used in routine clinical practice. Fifty EDTA-anticoagulated patient samples were consecutively analyzed using HPLC (Tosoh G8), Capillary Electrophoresis (Sebia Capillarys 3 Tera), and an autoanalyzer (Beckman DXC 700 AU). Results were stratified into four HbA1c ranges (4-6%, 6-8%, 8-10%, 10-12%) and analyzed using Pearson correlation, Bland-Altman, and Passing-Bablok regression. Capillary Electrophoresis and HPLC showed a high degree of agreement (r = 0.998, bias = 0.07). Capillary Electrophoresis vs. autoanalyzer also demonstrated high correlation (r = 0.997) but a larger bias (0.52) that increased at higher concentrations. HPLC vs. autoanalyzer yielded r = 0.997 and bias = 0.45, with proportional bias at high HbA1c levels. Passing-Bablok analysis confirmed concentration-dependent deviations for the autoanalyzer. Capillary Electrophoresis and HPLC provide highly consistent HbA1c results, while the autoanalyzer may introduce clinically relevant bias, particularly at higher HbA1c levels, which may influence clinical interpretation near commonly used decision thresholds. However, given the limited sample size, these findings should be interpreted with caution.