Glycated hemoglobin (HbA1c, glycohemoglobin, glycosylated hemoglobin, hemoglobin, A1C or A1c) is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymatically) bond with hemoglobin when present in the bloodstream. However, glucose is only 21% as likely to do so as galactose and 13% as likely to do so as fructose, which may explain why glucose is used as the primary metabolic fuel in humans.[1][2]
The formation of the sugar-hemoglobin linkage indicates the presence of excessive sugar in the bloodstream, often indicative of diabetes in high concentration (HbA1c >6.4%).[3] A1C is of particular interest because it is easy to detect. The process by which sugars attach to hemoglobin is called glycation and the reference system is based on HbA1c, defined as beta-N-1-deoxy fructosyl hemoglobin as component.[4]
HbA1c 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.[5] The test is limited to a three-month average because the average lifespan of a red blood cell is four months or 120 days. 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.
^Bunn HF, Higgins PJ (July 1981). "Reaction of monosaccharides with proteins: possible evolutionary significance". Science. 213 (4504): 222–224. Bibcode:1981Sci...213..222B. doi:10.1126/science.12192669. PMID 12192669.
^McPherson JD, Shilton BH, Walton DJ (March 1988). "Role of fructose in glycation and cross-linking of proteins". Biochemistry. 27 (6): 1901–1907. doi:10.1021/bi00406a016. PMID 3132203.
^Pongudom, Saranya (1 November 2019). "Determination of Normal HbA1C Levels in Non-Diabetic Patients with Hemoglobin E". Annals of Clinical & Laboratory Science. 49 (6): 804–809. PMID 31882432. Archived from the original on 24 December 2022. Retrieved 24 December 2022 – via PubMed.
^Miedema K (2005). "Standardization of HbA1c and Optimal Range of Monitoring". Scandinavian Journal of Clinical and Laboratory Investigation. 240: 61–72. doi:10.1080/00365510500236143. PMID 16112961. S2CID 30162967.
^Use of Glycated Haemoglobin (HbA1C) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization. 2011. p. 2, Glycated haemoglobin (HbA1c) for the diagnosis of diabetes. Archived from the original on 12 July 2020. Retrieved 2 December 2018.
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