Use of labile HbA1c as a screening tool to minimize clinical misinterpration of HbA1c.

Objectives: Hemoglobin A_1c (HbA_1c) is an established tool in the diagnosis and follow-up of patients with diabetes. However, in some patients the interpretation of HbA_1c results faces challenges due to additional biological variation or non-steady-state conditions. This study aimed to demonstrate the value of the L-HbA_1c/HbA_1c-ratio as a tool to flag HbA_1c results, which do not reflect average glycemia "as expected" in routine clinical practice.

Methods: A total of 450 samples of unique patients were selected based on the L-HbA_1c/HbA_1c-ratio determined on a Tosoh G8 analyzer resulting in a group with a high ratio (≥0.50), a group with a low ratio (≤0.27) and a group with a normal ratio (0.27-0.50). The relationship between HbA_1c and glycemic markers (fructosamine and random glucose) was established for all ratio groups. In a smaller cohort of type 1 diabetes patients, continuous glucose monitoring was used as glycemic marker.

Results: The correlation between HbA_1c and glycemia (random glucose and fructosamine) differs significantly between the ratio groups. For the same HbA_1c level random glucose levels and protein-corrected fructosamine are higher in the high ratio group compared to the normal and low ratio groups, pointing to an underestimation of the glycemic status by HbA_1c in patients with high L-HbA_1c/HbA_1c-ratios. The sensitivity of a high ratio to predict a glycation gap lower than -1.5 NGSP units is 82 % and the specificity is 65 %.

Conclusions: The results of this study reveal the usefulness of the L-HbA_1c/HbA_1c-ratio as an additional check in the interpretation of HbA_1c results in order to detect HbA_1c results not reflecting glycemia as expected.