What is HbA1c?
Glucose in the blood binds irreversibly to a specific part of haemoglobin in red blood cells, forming HbA1c. The higher the glucose, the higher the HbA1c. HbA1c circulates for the lifespan of the red blood cell, so reflects the prevailing blood glucose levels over the preceding 2-3 months
What does it tell us?
The Diabetes Control and Complications Trial (DCCT) in Type 1 diabetes and the UK Prospective Diabetes Study (UKPDS) in Type 2 diabetes both showed that the risk of microvascular and macrovascular complications of diabetes increases as HbA1c increases. HbA1c thus gives a measure of an individual’s risk of the long-term complications of diabetes.
Why measure it?
HbA1c measured 3-6 monthly shows how an individual’s glucose control, and thus risk of complications, changes in response to alterations in management. Target HbA1c levels can be set for individual patients and therapy adjusted to reach them.
Current HbA1c Numbers
Current HbA1c assays are aligned to the assay used in the DCCT, so that an individual’s risk of complications can be inferred from the result. The non-diabetic reference range is HbA1c-DCCT 4.0- 6.0 %
Current Targets
The general target currently is HbA1c-DCCT < 7.0%. However, this should be individualised, considering the person's risk of severe hypoglycaemia, cardiovascular status and co-morbidities.
Why Change?
The new International Federation of Clinical Chemistry (IFCC) reference method is more specific for HbA1c than the assay used for standardisation in the DCCT and UKPDS. Comparing results from different labs throughout the world and interpreting clinical trial results will now be easier. In future, HbA1c-IFCC results will be reported in mmol/mol after standardisation using the IFCC reference method
New Units and Numbers
The non-diabetic reference range for HbA1c-IFCC using the IFCC reference method will be 20- 42 mmol/mol, rather than the HbA1c-DCCT-aligned range of 4.0 – 6.0 %.
How Old and New Relate
A guide to the new values expressed as mmol/mol is:
HbA1c-DCCT HbA1c-IFCC
(%) (mmol/mol)
4.0 20
5.0 31
6.0 42
7.0 53
8.0 64
9.0 75
10.0 86
Targets in New Units
The equivalent of the current HbA1c-DCCT target of < 7.0% is HbA1c-IFCC < 53 mmol/mol in the new units.
Reporting of Results
The new units for HbA1c are obviously very different to those currently in use. To give everyone time to become familiar with the new units, and how they relate to the current DCCT figures and thus to risk of complications, from 1 June 2009, all HbA1c reports in the UK will give the result in current HbA1c-DCCT units (%) and in new HbA1c-IFCC units (mmol/mol). This dual reporting will continue until 30 November 2011.
Changeover to New Units
From 1 June 2009. results will be given as HbA1c-DCCT units (%) and HbA1c-IFCC units (mmol/mol)/
From 1 December 2011, results will be given only as HbA1c-IFCC mmol/mol.
Limitations of HbA1c Measurement
HbA1c results (DCCT or IFCC) will be misleading in certain situations eg a variety of haematological conditions where there is abnormal red cell turnover, where there is an abnormal haemoglobin, pregnancy and in some patients with renal or liver disease. The effect of these (and other) conditions can also vary depending on the HbA1c method used by a particular laboratory. Some methods for HbA1c can give more reliable results in some haemoglobinopathies, but if this or any other condition leads to a change in red cell survival, then HbA1c measurement by any means can, at best, be used to track changing trends in glycaemia. Other measures of glycaemia may then be required, such as more reliance on self monitored blood glucose values or the use of a serum fructosamine assay, if available.
Why not report eAG?
Conceptually, converting the HbA1c result to an equivalent “average glucose” level might help our understanding and interpretation of HbA1c. A recent large study reported calculating an estimated average glucose (eAG) from an HbA1c result. However, the study was carried out in a restricted population; issues have been raised about the study design; and an eAG will have limited applicability to the majority of patients who do not measure their own blood glucose levels. In some patients, the estimate may also prove inaccurate enough to be misleading. It has been agreed that in the UK, eAG results will not be reported the moment. Further research into the applicability and utility of eAG to the wide range of people with diabetes is warmly welcomed.