Glycated haemoglobin (HbA1c) !

HbA1c reflects average glucose over the past 2–3 months, because glucose sticks to haemoglobin over a red cell's life.

Updated 2026-11-01

Key facts

It is haemoglobin A with glucose attached non-enzymatically (glycation) to the N-terminal valine of the β chain.
It reflects mean glucose over about 2–3 months (red cell life about 120 days), weighted towards the last month.
Guidelines (ADA, WHO) accept an HbA1c ≥ 6.5 % by a certified method (NGSP/IFCC) as a diagnostic criterion for diabetes, confirmed on another sample.
It is reported in % (NGSP) or mmol/mol (IFCC).
It fails when red cell lifespan is altered: haemolysis, iron deficiency anaemia, recent transfusion, pregnancy, advanced kidney disease and some haemoglobinopathies.

What it measures: the glycated haemoglobin fraction by liquid chromatography (HPLC), immunoassay or enzymatic methods.
Where it comes from: glucose forms a Schiff base with haemoglobin's free amino group, which rearranges into a stable product (Amadori rearrangement); the higher and longer the glucose, the more HbA1c.
Why it rises: sustained hyperglycaemia (diabetes, prediabetes). It is also falsely raised by iron, B12 or folate deficiency (older red cells), splenectomy and uraemia (carbamylation with some methods).
Why it is falsely low: haemolysis, recent bleeding, transfusion, erythropoietin, pregnancy, advanced liver disease; some variants (HbS, HbC, HbE, high HbF) interfere depending on the method.
When it is unreliable, fasting glucose, the oral glucose tolerance test, fructosamine (reflects 2–3 weeks) or continuous glucose monitoring are used.
Advanced glycation end products formed on long-lived proteins (collagen, lens) explain part of the chronic complications of diabetes.

Each rise in HbA1c is linked to more retinopathy, nephropathy and neuropathy; the target is individualised by age and hypoglycaemia risk.
In populations with frequent sickle cell trait (Afro-descendant communities of Colombia's Pacific and Caribbean coasts) the laboratory's method matters.
An HbA1c that does not match the patient's glucose readings suggests anaemia, a haemoglobinopathy or a method error.

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Why does HbA1c reflect about 3 months of glucose?

Because glucose binds haemoglobin throughout the red cell's life, which lasts about 120 days.

What kind of reaction forms HbA1c?

Non-enzymatic glycation: glucose binds the N-terminal amino group of the β chain and rearranges into a stable product (Amadori).

Why can HbA1c be falsely low after haemolysis?

The young red cells that replace the destroyed ones have been exposed to glucose only briefly.

Which test is used when HbA1c is unreliable?

Fasting glucose, the oral glucose tolerance test, fructosamine or continuous glucose monitoring.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Hemoglobin A1C (HbA1c) Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Blood Glucose Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.