Glycated Hemoglobin A1C HbA1C marker

Marker of glucose exposure onto proteins within a blood sample.

«It is important to note that the HbA1c levels are directly proportional to the blood glucose levels.»


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«Glycated hemoglobin (hemoglobin A1c, HbA1c, A1C, or less commonly HgbA1c, haemoglobin A1c, HbA1c, Hb1c, etc.) is a form of hemoglobin that is bound to glucose. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose. It is measured primarily to identify the three-month average plasma glucose concentration and thus can be used as a diagnostic test for diabetes and as assessment test for glycemic control in people with diabetes[1]. The test is limited to a three-month average because the lifespan of a red blood cell is four months (120 days). However, since red blood cell do not all undergo lysis at the same time, HbA1C is taken as a limited measure of three months. HbA1c is a measure of the beta-N-1-deoxy fructosyl component of hemoglobin.[2] The origin of the naming derives from Hemoglobin type A being separated on cation exchange chromatography. The first fraction to separate, probably considered to be pure Hemoglobin A, was designated HbA0, the following fractions were designated HbA1a, HbA1b, and HbA1c, respective of their order of elution. There have subsequently been many more sub fractions as separation techniques have improved.[3] Normal levels of glucose produce a normal amount of glycated hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. This serves as an indicator that blood sugar is increasing and that action should be taken.

In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. A trial on a group of patients with Type 1 diabetes found that monitoring by caregivers of HbA1c led to changes in diabetes treatment and improvement of metabolic control compared to monitoring only of blood or urine glucose.[4] However, a trial designed specifically to determine whether reducing HbA1c below the normal 6%, using primarily insulin and sulfonylureas (both known to easily drive blood sugar too low), would reduce the rate of cardiovascular events in type 2 diabetes found higher mortality—the trial was terminated early.[5] The negative outcomes may well have been a result of the treatment approach, primarily insulin and sulfonylureas, utilized in the "intensive" treatment group instead of LCHF (Low-Carbohydrate High Fat diet), GlP-1 analogues & SGLT-2 inhibitors, none of which have these problems & lower cardiovascular mortality.

Glycated hemoglobin is preferred over glycosylated hemoglobin to reflect the correct (nonenyzmatic) process. Early literature often used glycosylated as it was unclear which process was involved until further research was performed. The terms are still sometimes used interchangeably in English language literature.[6]

Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column.[7] It was first characterized as a glycoprotein by Bookchin and Gallop in 1968.[8] Its increase in diabetes was first described in 1969 by Samuel Rahbaret al.[9] The reactions leading to its formation were characterized by Bunn and his coworkers in 1975.[10]

The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.[11]

Glycated hemoglobin causes an increase of highly reactive free radicals inside blood cell. Radicals alter blood cell membrane properties. This lead to blood cell aggregation and increased blood viscosity which results in impaired blood flow.[12]

Another way glycated Hb causes damage is via inflammation which results in atherosclerotic plaque (atheroma) formation. Free radical build-up promotes the excitation of Fe2+-Hb through Fe3+-Hb into abnormal ferryl Hb (Fe4+-Hb). Fe4+ is unstable and reacts with specific amino acids in Hb to regain its Fe3+oxidation state. Hb molecules clump together via cross-linking reactions and these Hb clumps (multimers) promote cell damage and the release of Fe4+-Hb into the matrix of innermost layers (subendothelium) of arteries and veins. This results in increased permeability of interior surface (endothelium) of blood vessels and production of pro-inflammatory monocyteadhesion proteins, which promote macrophage accumulation in blood vessel surfaces ultimately leading to harmful plaques in these vessels.[12]

Highly glycated Hb-AGE go through vascular smooth muscle layer and inactivate acetylcholine induced endothelium-dependent relaxation possibly through binding to nitric oxide (NO) preventing its normal function. NO is a potent vasodilator and also inhibits formation of plaque promoting LDL (i.e. “bad cholesterol”) oxidized form.[12]

This overall degradation of blood cell also releases heme from them. Loose heme can cause oxidation of endothelial and LDL proteins which results in plaques.[12]

Glycation of proteins is a frequent occurrence, but in the case of hemoglobin, a nonenzymatic condensation reaction occurs between glucose and the N-end of the beta chain. This reaction produces a Schiff base (R-N=CHR', R = beta chain, CHR'= glucose-derived), which is itself converted to 1-deoxyfructose. This second conversion is an example of an Amadori rearrangement.

When blood glucose levels are high, glucose molecules attach to the hemoglobin in red blood cell. The longer hyperglycemia occurs in blood, the more glucose binds to hemoglobin in the red blood cell and the higher the glycated hemoglobin.

Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell, therefore, reflects the average level of glucose to which the cell has been exposed during its life-cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation.» (wikipedia)

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