Source of Haemoglobin A1c

{{Infobox concept | name = Haemoglobin A1c | subtitle = Laboratory medicine | Abbreviation = HbA1c | Reflects = Average glucose over ~8–12 weeks | Units = mmol/mol (IFCC); % (DCCT/NGSP) | Confounded by = Anything altering red-cell lifespan }} '''Haemoglobin A1c''' is the fraction of haemoglobin that has been non-enzymatically glycated. Because glycation is irreversible and proceeds at a rate proportional to glucose concentration, the fraction integrates glucose exposure over the lifespan of the circulating red cells — roughly the preceding eight to twelve weeks, weighted towards the more recent.{{r|ada2024}} It is reported in two unit systems: mmol/mol under the IFCC reference method, and percentage under the older DCCT-aligned convention. Both appear in the literature and conversion between them is defined.{{r|nathan2008}} Its principal limitation follows from its mechanism: anything that alters red-cell lifespan alters the result independently of glucose. Haemolysis and blood loss lower it; iron deficiency and reduced turnover raise it.{{r|ada2024}} == What it measures == Glycation is a slow non-enzymatic reaction between glucose and the N-terminal valine of the haemoglobin β-chain. Its extent depends on both glucose concentration and exposure time, and because red cells are replaced continuously the population of cells sampled at any moment carries a weighted history.{{r|nathan2008}} The weighting is not uniform: roughly half the value reflects the preceding month, and the remainder the two months before. A change made three weeks ago is therefore only partly expressed.{{r|ada2024}} Estimated average glucose can be derived from HbA1c by a published regression, and the derivation carries substantial individual variation — two people with identical HbA1c can have appreciably different mean glucose.{{r|nathan2008}} The measure is a laboratory determination with its own method dependence, as any determination is.{{r|usp1503}} == Confounders == | Condition | Direction | |---|---| | Haemolysis, blood loss, transfusion | Lower | | Iron or B12 deficiency | Higher | | Chronic kidney disease | Variable | | Haemoglobin variants | Assay-dependent interference | | Pregnancy | Lower, from increased turnover | Haemoglobin variants interfere with some assay methods and not others, so a discrepancy between HbA1c and other glycaemic measures should prompt a question about the method rather than an assumption about glucose.{{r|ada2024}} Where HbA1c is unreliable, fructosamine or continuous glucose monitoring metrics provide alternatives measuring different windows.{{r|nathan2008}} == Use in this field == HbA1c is the primary glycaemic endpoint in essentially every type 2 diabetes trial discussed on this wiki, including the [[SUSTAIN trial programme|SUSTAIN]] and [[SURPASS trial programme|SURPASS]] programmes. Reductions of 1–2.5 percentage points are the range these agents produce.{{r|drucker2018}} Because the measure integrates over months, a trial cannot demonstrate a glycaemic effect faster than the analyte can move, which is why glycaemic trials run at least six months.{{r|ada2024}} It appears on most of the panels discussed in this field; see [[Baseline laboratory panel]]. Nothing on this wiki is medical advice.{{r|ada2024}} == References == {{reflist}} <ref name="ada2024">American Diabetes Association. "Standards of Care in Diabetes." ''Diabetes Care'' 47(Suppl 1) (2024).</ref> <ref name="nathan2008">Nathan DM, Kuenen J, Borg R, et al. "Translating the A1C assay into estimated average glucose values." ''Diabetes Care'' 31(8):1473–1478 (2008). PMID 18540046.</ref> <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> == See also == * [[Baseline laboratory panel]] * [[Fasting insulin]] * [[C-peptide]] * [[HOMA-IR]] * [[SURPASS trial programme]] {{DEFAULTSORT:Haemoglobin A1c}} [[Category:Metabolic biomarkers]] [[Category:Laboratory medicine]] [[Category:Clinical practice]]