Haemoglobin A1c (revision 9)

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.^[1]

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.^[2]

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.^[1]

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.^[2]

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.^[1]

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.^[2] The measure is a laboratory determination with its own method dependence, as any determination is.^[3]

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.^[1]

• Baseline laboratory panel
• Fasting insulin
• C-peptide
• HOMA-IR