Hemoglobin A1C

Glycated hemoglobin (glycohemoglobin, HbA1c, hemoglobin A1c, A1c, or less commonly HbA1c, HgbA1c, Hb1c, etc.) are all a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides (glucose, galactose and fructose bond with hemoglobin, when present in the bloodstream of humans. However, glucose is less likely to do so than galactose and fructose (13% that of fructose and 21% that of galactose), which may explain why glucose is used as the primary metabolic fuel in humans.

The formation of the sugar-hemoglobin linkage indicates the presence of excessive sugar in the bloodstream, often indicative of diabetes. A1C is of particular interest because it is easy to detect. The process by which sugars attach to hemoglobin is called glycation.  A1c 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. In diabetes, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, neuropathy, nephropathy, and retinopathy. 

Glycated hemoglobin causes an increase of highly reactive free inside blood cells. Radicals alter cell membrane properties of ther blood vessel. This leads to blood cell aggregation, and increased blood viscosity, which results in impaired blood flow.

Another way glycated hemoglobin causes damage is via inflammation, which results in atherosclerotic plaque formation. Hemoglobin molecules clump together via croos-linking reactions, and these hemoglobin clumps (multimers) promote cell damage and the release of Fe4+-hemoglobin into the matrix of  the innermost layers (subendothelium) of arteries and veins. This results in increased permeability of interior surface of the 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.

This overall degradation of blood cells also releases heme from them. Loose heme can cause oxidation of endothelial and LDL proteins, which results in plaques.