Labile Hemoglobin A_1c (LHbA_1c): From analytical interference to clinically valuable biomarker

Area of Science:

• Biochemistry and Clinical Chemistry
• Diabetes Mellitus Research
• Analytical Chemistry

Background:

• Labile hemoglobin A1c (LHbA1c) is the reversible Schiff base intermediate in hemoglobin glycation.
• Historically considered an analytical interference, LHbA1c's potential clinical value is now being explored.
• Stable HbA1c reflects long-term glycemia (2-3 months), while LHbA1c correlates with shorter glycemic periods (hours to days).

Purpose of the Study:

• To review research on LHbA1c from 2016-2024, covering its biochemistry, measurement, and clinical applications.
• To highlight LHbA1c's emerging role in bridging the information gap for diabetes assessment.
• To evaluate the clinical utility of the LHbA1c/HbA1c ratio.

Main Methods:

• Synthesis of research literature on LHbA1c from 2016 to 2024.
• Analysis of biochemical foundations and measurement methodologies.
• Examination of mathematical modeling for kinetic relationships between glucose, LHbA1c, and stable HbA1c.

Main Results:

• LHbA1c correlates with glycemic levels over hours to days, providing a more immediate glycemic snapshot.
• The LHbA1c/HbA1c ratio can identify approximately 15% of samples where HbA1c may not accurately reflect glycemia.
• LHbA1c aids in detecting acute glycemic excursions, screening for hemoglobin variants, and identifying preanalytical errors.

Conclusions:

• LHbA1c, once dismissed as interference, is a clinically valuable parameter for precision diabetes care.
• The LHbA1c/HbA1c ratio offers a versatile tool for assessing glycemic control.
• Further standardization and prospective outcome studies are needed for widespread clinical adoption of LHbA1c.