
Analysis of glycated hemoglobin (HbA1c) in blood provides evidence about an individual’s average blood glucose levels during the previous two to three months, which is the predicted half-life of red blood cells (RBCs). The HbA1c is now recommended as a standard of care (SOC) for testing and monitoring diabetes, specifically the type 2 diabetes. Proteins are frequently glycated during various enzymatic reactions when the conditions are physiologically favorable. However, in the case of hemoglobin, the glycation occurs by the nonenzymatic reaction between the glucose and the N-terminal end of the β-chain, which forms a Schiff base. During the rearrangement, the Schiff base is converted into Amadori products, of which the best known is HbA1c.
The formation of the glycated hemoglobin is a normal part of the physiologic function cycle. However, as the average plasma glucose increases, so does the amount of glycated hemoglobin in the plasma. This specific characteristic of the hemoglobin biomarker is utilized for estimating the average blood glucose levels over the previous two to three months.
The ADA has recently recommended HbA1c with a cut-point ≥6.5% for diagnosing diabetes as an alternative to fasting plasma glucose (FPG ≥7.0 mmol/L)-based criteria. The levels of HbA1c are strongly correlated with FPG. The HbA1c levels differ for different diabetes patients, depending on their history of diabetes and whether they are on tablets or long-term and/or short-term insulin dosage. Type 2 diabetes mellitus (DM) manifests itself in terms of hyperglycemia due to compromised insulin production (no production or nonavailability).
Nondiabetes usually falls within the 4.0%–5.6% HbA1c range. The prediabetes usually has the HbA1c levels as 5.7%–6.4%, while those with 6.4% or higher HbA1c levels have diabetes.
Standardization and comparability of HbA1c results with different methods appear to be an important issue. In 1995, the IFCC established a Working Group (IFCC WG-HbA1c) to achieve international standardization of HbA1c measurement. A reference measurement procedure for HbA1c was developed based on the proteolytic digestion of red cell hemoglobins followed by quantitative peptide mapping by HPLC-mass spectrometry or HPLC-capillary electrophoresis.
Although most laboratories in tertiary care hospitals are well equipped with modern instrumentation including HPLC, many of the primary care centers in low- and middle-income countries do not have access to HPLC, some are still struggling with outdated methods or doubtful point-of-care devices that may not be reliable to monitor diabetes.
The blood glucose data available from HbA1c are used in prescribing and monitoring the medicines for diabetes and prediabetes, along with exercise and diet. The accuracy of this test has continued to evolve over the last several years and is becoming the go-to option for SOC for detecting blood glucose values among patients in clinics. According to the National Glycohemoglobin Standardization Program (NGSP), which developed the A1C tests, the accuracy has continued to evolve and got more precise over time.
As diabetes continues to grow worldwide, HbA1c test may continue to be implemented as part of the diagnostic and prognostic tool, leading to better patient care and successful clinical outcomes.
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