Glycated Hemoglobin (HbA1c)

TGlycated hemoglobin (HemoglobinA1c; HbA1c) is a stable compound in human blood in which glucose is covalently bonded to valine residues at the N-terminal end of the hemoglobin β-chain, the full name of which is: hemoglobin β-chain (blood)-N-(1- deoxyfructose-1-yl) hemoglobin β-chain. Hemoglobin A1c accounts for 80% of HbA1 and has the chemical structure of a hemoglobin molecule with a specific hexapeptide structure. The major sites of hemoglobin glycosylation are β-Val-1, β-Lys-66, and α-Lys-61. Glycosylated hemoglobin formation is a normal part of the cycle of physiological function. However, as mean plasma glucose increases, the amount of glycated hemoglobin in plasma also increases. This specific feature of hemoglobin biomarkers is used to predict average blood glucose levels over the past 2-3 months.

KMD Bioscience, as a supplier of in vitro diagnostic raw materials, provides high-quality diagnostic antigen and antibody raw materials for the IVD industry for over several years, which are suitable for a variety of assay platforms, such as flow, colloidal gold, CLIA-Chemiluminescence Immunoassay, Turbidimetric inhibition immunoassay, etc. KMD Bioscience's antibody and antigen diagnostic raw materials are strictly monitored during the R&D and production stages to ensure that the IVD raw materials are characterized by low inter/intra-batch variation, high specificity, wide linear range, good stability and high sensitivity.

he inventory of reagents associated with Glycosylated hemoglobin (HemoglobinA1c; HbA1c)  that KMD Bioscience can offer:

Composition of HbA1c

Hemoglobin is composed of one bead protein and four heme proteins; heme is composed of porphyrins and iron. Pearl proteins have two pairs of peptide chains, one alpha chain and one non-alpha chain (β, γ, δ,). Due to the different peptide chains hemoglobin is divided into HBA (α2β2), HBA2 (α2δ2), and HBF (α2γ2). In adults, hemoglobin (Hb) usually consists of HbA (97%), HbA2 (2.5%), and HbF (0.5%).HbA can be further divided into non-glycosylated hemoglobin, i.e., the natural hemoglobin HbA0 (94%), and glycosylated hemoglobin HbA1 (6%). Depending on the glycation sites and reaction participants, HbA1 can be further divided into subfractions such as HbA1a, HbA1b and HbA1c.

Figure 2 Molecular structure of HbA1c

Pathway of HbA1c formation

Glucose can attach to a wide range of proteins through non-enzymatic reactions, resulting in proteins often being glycosylated under various enzymatic conditions in a total of two stages of reaction: (1) production of aldimines (or Schiff bases) (a reversible reaction) (2) ketoamines formed through Amadori rearrangement (irreversible). Glycation of hemoglobin occurs through a non-enzymatic reaction between glucose and the N-terminus of the β-chain to form Shiff bases. During rearrangement, Shiff bases equilibrate proportionally to blood glucose concentrations within a few hours and then undergo Amadori rearrangement to form early stable glycation products of which HbA1c is a product. In the primary step of glycated hemoglobin formation, hemoglobin and blood glucose interact in a reversible reaction to form aldimines, which are gradually converted to the stable ketamine form in an irreversible second step. As mentioned above, the open-chain form of glucose binds to the N-terminus to form aldimine before undergoing the Amadori rearrangement to form the more stable ketoamine. This is a nonenzymatic process that occurs continuously in vivo.

Relationship between HbA1c and blood glucose

The binding process of glucose and hemoglobin is slow, and once the two of them are joined, they cannot be separated. The amount of glycated hemoglobin is related to the amount of glucose in the blood, and when the blood glucose concentration reaches a certain high level, the amount of glycated hemoglobin also increases. Therefore, by measuring the amount of glycated hemoglobin in the blood, it can be used to assess the overall glycemic control of a diabetic patient. HbA1c can consistently reflect the average glycemic control of a diabetic patient over the past 2-3 months and is not easily affected by factors such as food intake and the time of blood sampling. However, it is more lagging. Whereas ordinary blood glucose monitoring has immediacy and can reflect the fluctuation of blood glucose, which can be used as the most direct evidence for the adjustment of glucose-lowering medication. Therefore, glycated hemoglobin cannot replace blood glucose monitoring. That is to say, blood glucose test reflects the immediate blood glucose level, i.e. the blood glucose level at a specific time, which is easily affected by diet and glucose metabolism and other related factors. Glycated hemoglobin, on the other hand, reflects blood glucose control over the past 8-12 weeks and is not significantly affected by factors such as the time of blood sampling, fasting or not, and the use of insulin or not.