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

Objectives: Hemoglobin A (HbA) is an established tool in the diagnosis and follow-up of patients with diabetes. However, in some patients the interpretation of HbA results faces challenges due to additional biological variation or non-steady-state conditions. This study aimed to demonstrate the value of the L-HbA/HbA-ratio as a tool to flag HbA 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/HbA-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 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 and glycemia (random glucose and fructosamine) differs significantly between the ratio groups. For the same HbA 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 in patients with high L-HbA/HbA-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/HbA-ratio as an additional check in the interpretation of HbA results in order to detect HbA results not reflecting glycemia as expected.