Glycosylated haemoglobin

Glycated hemoglobin (hemoglobin A1c, HbA1c, A1C, or less commonly HgbA1c, haemoglobin A1c, HbA1c, Hb1c, etc.) is a form of hemoglobin that is covalently bound to glucose. Hemoglobin (abbreviated as Hb since Hg is mercury) carries oxygen in the blood. Hemoglobin is exposed to glucose in the blood, and they are bound together through the glycation process. HbA1c is a measure of the beta-N-1-deoxy fructosyl component of hemoglobin. Glycated hemoglobin (hemoglobin A1c, HbA1c, A1C, or less commonly HgbA1c, haemoglobin A1c, HbA1c, Hb1c, etc.) is a form of hemoglobin that is covalently bound to glucose. Hemoglobin (abbreviated as Hb since Hg is mercury) carries oxygen in the blood. Hemoglobin is exposed to glucose in the blood, and they are bound together through the glycation process. HbA1c is a measure of the beta-N-1-deoxy fructosyl component of hemoglobin. It is measured primarily to determine the three-month average blood sugar level and can be used as a diagnostic test for diabetes mellitus and as an assessment test for glycemic control in people with diabetes. The test is limited to a three-month average because the average lifespan of a red blood cell is four months. Since individual red blood cells have varying lifespans, the test is used as a limited measure of three months. 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. In diabetes, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. 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. The naming of HbA1c 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, and the following fractions were designated HbA1a, HbA1b, and HbA1c, respective of their order of elution. There have subsequently been more sub fractions with improved separation techniques. Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column. It was first characterized as a glycoprotein by Bookchin and Gallop in 1968. Its increase in diabetes was first described in 1969 by Samuel Rahbar et al. The reactions leading to its formation were characterized by Bunn and his coworkers in 1975. 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. Glycated hemoglobin causes an increase of highly reactive free radicals inside blood cells. Radicals alter blood cell membrane properties. This leads to blood cell aggregation and increased blood viscosity, which results in impaired blood flow. 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 monocyte adhesion proteins, which promote macrophage accumulation in blood vessel surfaces, ultimately leading to harmful plaques in these vessels. Highly glycated Hb-AGEs 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 LDLs (i.e. “bad cholesterol”) oxidized form.