HbA1c has been the gold standard for monitoring long-term glycaemic management since 1976, and it is one method used to diagnose diabetes. Monitoring is usually recommended at three-month intervals (four per year); however, with stable diabetes a six-month interval may be appropriate.
HbA1c measurement and natural test variation
HbA1c can be measured and reported using two different standards:
- as a percentage measure of glycated N‐terminal residue of the β chain of haemoglobin (eg 7%)
- in units of mmol/mol, according to the International Federation of Clinical Chemistry (IFCC) standardised reporting (eg 53 mmol/mol).
The variability of laboratory HbA1c test results in Australia is acceptably low.5 However, there may be some variability,6,7 which needs to be considered when monitoring long-term glucose control. Conditions such as the following that affect HbA1c results also need to be considered.
Conditions that affect HbA1c results
A number of conditions can cause HbA1c discordance, where HbA1c does not accurately reflect mean blood glucose.
Any condition that shortens erythrocyte survival or decreases mean erythrocyte age will falsely lower HbA1c test results, regardless of the assay method used.
The presence of abnormal haemoglobin variants can occur in people of Mediterranean, African or Southeast Asian heritage. Screening for haemoglobinopathies before HbA1c testing should be considered.7 If a haemoglobinopathy is suspected, then a haemoglobin electrophoresis is suggested.
Some important clinical situations may indicate the presence of a haemoglobinopathy, such as when:
- results of self-monitoring of blood glucose (SMBG) have a poor correlation with HbA1c results
- an HbA1c result is discordant with measured alternate laboratory glycaemic values
- an HbA1c result is more than 15% or less than 4%
- a patient’s HbA1c test result is radically different from a previous test result following a change in laboratory HbA1c measurement methods.
Other causes of HbA1c discordance are shown in Box 1.
Alternative forms of diabetes monitoring such as SMBG, continuous glucose monitoring and flash glucose monitoring (refer to the section ‘Use of technology in type 2 diabetes management’) should be considered for these patients.
Note that fructosamine as an alternative longer-term glucose measure may not be suitable in people with iron deficiency anaemia, as this condition raises both HbA1c and fructosamine; conversely, iron infusion spuriously lowers both HbA1c and fructosamine.8–10
Box 1. Other causes of HbA1c discordance
Abnormally low HbA1c can be caused by:
- haemolytic anaemia – congenital (eg spherocytosis, elliptocytosis)
- acquired haemolytic anaemias (eg drug-induced, such as with dapsone, methyldopa)
- recovery from acute blood loss
- blood transfusions, iron infusions
- chronic blood loss
- chronic renal failure (variable).
Abnormally high HbA1c can be caused by:
- iron deficiency anaemia8
HbA1c is an unreliable measure of glycaemic management in the first four weeks of pregnancy.