Laboratory Professional FAQs

1 What is HbA_1c?

HbA_1c is formed from a binding process between haemoglobin and glucose. The first step is the binding of glucose by the N-terminal valine of the β-chain of the haemoglobin A molecule. This is followed by an Amadori re-arrangement, the final step of which is irreversible, resulting in the formation ofHbA_1c.

2 What does HbA_1ctell us?

The importance of HbA_1c was not fully recognised until the completion of the US Diabetes Control and Complications Trial (DCCT 1993) for people with type 1 diabetes and the UK Prospective Diabetes Study (UKPDS 1998) for people with type 2 diabetes. Both showed that the risk for development and progression of the complications of diabetes increases as HbA_1c increases. Studies have shown that the complications of diabetes can be delayed or prevented if the HbA_1c level is well controlled. Targets for HbA_1c and blood glucose must be appropriate to the circumstances of the person with diabetes.

3Why measure HbA_1c?

In people with diabetes serial measurements of HbA_1c show how an individual’s glucose control, and thus their risk of developing complications, changes in response to alterations in management. HbA_1c should be measured approximately six-monthly.

4 What are the limitations of HbA_1c measurement?

HbA_1c results (DCCT or IFCC) will be misleading in certain situations for example in haematological conditions where there is abnormal red cell turnover, or an abnormal haemoglobin, or in renal or liver disease. In pregnancy, HbA_1c may be slightly lower. In the presence of abnormal haemoglobin or in conditions with altered red cell survival rates, HbA_1c results may not be reliable. In a patient with a haemoglobinopathy, HbA_1c results are affected by the method of analysis and the particular abnormal haemoglobin. In these situations, HbA_1c results can be used to follow trends in an individual’s glycaemic control rather than for target setting.

5 How has HbA_1c been reported traditionally?

Traditionally HbA_1c was reported as a percentage of total haemoglobin. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established a new reference measurement system for the worldwide standardisation of HbA_1c. The IFCC recommends that HbA_1c concentration be reported in mmol of per mol of haemoglobin (mmol/mol). This will make comparing HbA_1c results from different laboratories and research trials throughout the world much easier. These developments are supported by international diabetes organisations and came about because the HbA_1c assay systems used in both the DCCT and UKPDS trials were nor specific for HbA_1c and were not calibrated in the manner that is now required. The National Glycohaemoglobin Standardisation Program (NGSP) is an organisation set up and based in the United States, responsible for ensuring HbA_1c results are aligned and traceable to the DCCT.

6 What is metrological traceability?

The science of measurement is called metrology and it sets out the requirements for measurement systems including those in laboratory medicine. Amongst these is a requirement for metrological traceability. Metrological traceability is defined as “that property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken sequence of calibrations all having stated uncertainties”. It seeks to relate any measurement, through a chain of calibrations, to the relevant international standard. It is distinct from documentary traceability and material traceability. Metrological traceability underpins the drive to implement standardization of HbA_1c measurement.

VIM 6.10–ref: BIPM, IEC, IFCC, ISO, IUPAC, IUPAP, OIML, International Vocabulary of Basic and Metrological Terms in Metrology, 2nd edition, ISO Geneva, 1993.

The application of metrological traceability to HbA_1c is summarised in the diagram below.

diabetes diagram