NZSSD has recommended that, in most cases, HbA1c should be the first-line test for screening and diagnosis
of type 2 diabetes.4 This recommendation aims to complement and update current guidance from the New Zealand
Guidelines Group and is also broadly in line with many international guidelines.5-7 Until now, the recommended
diagnostic and screening tests for type 2 diabetes have been fasting plasma glucose levels or the two hour post-oral glucose
tolerance test. However HbA1c has several advantages over these tests for the majority of patients.8,9
The advantages of HbA1c for screening and diagnosis of type 2 diabetes
HbA1c testing offers several significant advantages over fasting plasma glucose. Firstly, there is no need
for fasting. Research and anecdotal evidence suggests that many people are not compliant with the requirement for fasting,
thereby reducing the accuracy of fasting plasma and oral glucose tolerance tests.10
HbA1c is less affected by day to day variation in plasma glucose, due to exercise, smoking, medicines and
diet patterns, than fasting plasma glucose testing, because it reflects the average level of glycaemia over six to eight
weeks rather than measuring it at a single moment in time.10
There is also less biological variability associated with HbA1c than with fasting plasma glucose testing.4,10 The
variability between two tests, in the same person, is approximately four times greater with fasting plasma glucose than
with HbA1c.10,11 This means that the likelihood of false negatives and positives, with repeat testing,
is lower with HbA1c than with fasting plasma glucose.
HbA1c measures chronic glycaemic exposure rather than an acute value, therefore providing a more relevant
view of long-term glycaemia and future risk of complications.10 As with fasting plasma glucose, there is a
well established, and accurate relationship between HbA1c and future retinopathy risk.4,5,12-14 For
example, in previously undiagnosed people with HbA1c values above 50 mmol/mol the prevalence of moderate retinopathy
begins to increase exponentially. A value above this level is therefore strongly predictive of a risk of development of
clinically significant retinopathy. There is also overwhelming evidence that HbA1c levels are predictive of
the prevalence of other microvascular complications such as nephropathy and neuropathy.5 HbA1c is
a superior indicator of future cardiovascular (CVD) risk than fasting plasma glucose, although the relationship is not
as well defined as with retinopathy.10,15
HbA1c has simpler sampling and analysis requirements.4 As it is very stable, a blood sample for
HbA1c can be collected either at a laboratory or during a consultation at a general practice clinic, allowing
for more opportunistic testing. While fasting plasma glucose samples can also be taken at the practice, the requirements
are more complex than with HbA1c and values can be misleading if the sample is not processed immediately, due
to pre-analytical instability. This is because glucose consumption continues to occur in blood after sampling, even when
anti-glycolyic fixatives are applied to the tube.16 The pre-analytic variability of fasting plasma glucose
testing is approximately 5 - 10%, with New Zealand laboratories generally accepting approximately 5% variability as inherent.10,17 In
comparison, the pre-analytic variability of HbA1c is negligible.
Concerns about the use of HbA1c for screening and diagnosis
One of the main concerns expressed about the use of HbA1c for screening and diagnosis is that there has previously
been a lack of standardisation with the test. There is now a level of quality standardisation equal to that of fasting
plasma glucose testing.10 This has been driven by:4
- Improvement in the technologies used for processing and analysing samples
- An overall effort and agreement by laboratories towards international standardisation
- The change to international units (mmol/mol)
A further concern has been that the HbA1c test is more expensive than fasting plasma glucose - although still
less expensive than oral glucose tolerance testing.5 However, the long-term cost of diabetes is high, and effective
screening aims to reduce the incidence of diabetes through detection of people with pre-diabetes and reduce the risk of
complications post-diagnosis through early detection.4 The cost in terms of time and inconvenience to the patient
is also less for HbA1c.
HbA1c is not, however, suitable for patients with some haemoglobinopathies and disorders with abnormal red-cell
turnover such as many anaemias, as these falsely alter the value. There is also some evidence of individual and ethnic
variations in HbA1c, although local data on this is very limited.
Table 1 compares the attributes of HbA1c and fasting glucose assays.