Glycated haemoglobin

Synonym: glycosylated haemoglobin

What is an HbA1c test?¹

Glycated haemoglobin (HbA1c) laboratory tests are used to diagnose diabetes mellitus and to monitor diabetic control. For further information regarding HbA1c monitoring and targets, see the separate Management of type 1 diabetes and Type 2 diabetes treatment and management articles.

Haemoglobin A1 and haemoglobin A1c

Chromatography of normal adult blood divides into two parts:

• HbA (HbA0) 92-94%.

• HbA1 (6-8%) where the B chain has an additional glucose group. HbA1 itself consists of three different glycations, the HbA1c subgroup being the most useful.

High-performance liquid chromatography, immunoassay-based assessments, and enzymatic assays can all be used to measure HbA1c levels.²

The glycation of haemoglobin occurs at a variable (non-linear) rate during the lifespan of the red blood cell (RBC), which is normally 120 days. The relative proportion of glycated haemoglobin at any one time depends on the mean glucose level over the previous 120 days.³

Normal levels (laboratory normal 'range') will differ depending on the method used.

HbA1c is usually a reliable indicator of diabetic control except in the following circumstances:²

• Situations where the average RBC lifespan is significantly less than 120 days will usually give rise to low HbA1c results because 50% of glycation occurs in days 90-120. Common causes include:³

  • Increased red cell turnover: blood loss, haemolysis, haemoglobinopathies and red cell disorders, myelodysplastic disease.

  • Interference with the test: persistent fetal haemoglobin and haemoglobin variants, carbamylated haemoglobin (uraemic patients).

• In patients who fluctuate between very high and very low levels, HbA1c readings can be misleading (the clinician should compare with extra information obtained from home capillary blood glucose tests).

Normal ranges of HbA1c

HbA1c results in the UK have been standardised to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) allowing global comparison of results, with the normal non-diabetic range of IFCC-HbA1c being 20-42 mmol/mol.

Other important points to consider

• Any HbA1c target for the management of a person with diabetes should be individualised and agreed with the patient (considering comorbidity, life expectancy, hypoglycaemia frequency, etc).

• Do not test more frequently than every three months.

Diagnosing diabetes

• Diabetes is usually diagnosed by an HbA1c of 48 mmol/mol or more. If the use of HbA1c is inappropriate (eg, people with end-stage chronic kidney disease), type 2 diabetes is diagnosed by a fasting plasma glucose level of 7.0 mmol/L or greater.

• In an asymptomatic person, the diagnosis of diabetes should not be based on a single abnormal HbA1c level; at least one additional abnormal HbA1c level is essential. If the second test results are normal, it is prudent to arrange regular repeat HbA1c blood tests.

• In a symptomatic person, diabetes can be diagnosed with more confidence on the basis of a single abnormal HbA1c level (although a second test may be prudent).

• Hyperglycaemia in people with an acute infection, trauma, circulatory or other stress may be transitory and should not be regarded as diagnostic of diabetes.

• HbA1c levels between 43 and 47 are diagnostic of non-diabetic hyperglycaemia or pre-diabetes. Patients with pre-diabetes should have annual HbA1c tests.⁴

Situations where HbA1c is not appropriate for diagnosis of diabetes include:⁵

• Children and young people.

• Pregnancy or women within two months post-partum.

• Patients with symptoms of diabetes for less than two months.

• Patients at high diabetes risk who are acutely ill.

• Patients taking medication that may cause hyperglycaemia - eg, steroids, antipsychotics.

• Patients with acute pancreatic damage, including pancreatic surgery.

• Patients with end-stage renal failure.

HbA1c monitoring for diabetes^{6 7}

For people with type 1 diabetes, the National Institute for Health and Care Excellence (NICE) recommends:

• HbA1c levels every three to six months in adults with type 1 diabetes.

• Consider measuring HbA1c levels more often in adults with type 1 diabetes if their blood glucose control is suspected to be changing rapidly.

For adults with type 2 diabetes, NICE recommends:

• Three-monthly to six-monthly intervals (tailored to individual needs), until the HbA1c is stable on unchanging therapy.

• Six-monthly intervals once the HbA1c level and blood glucose-lowering therapy are stable.

If HbA1c monitoring is invalid because of disturbed erythrocyte turnover or abnormal haemoglobin type, trends in blood glucose control should be estimated using one of the following:⁸

• Fructosamine estimation.

• Quality-controlled blood glucose profiles.

• Total glycated haemoglobin estimation (if abnormal haemoglobins).

Fructosamine