HbA 1c testing for diabetes diagnosis: The new standard?

Historically, throughout the world, the oral glucose tolerance test (OGTT) has been used to diagnose diabetes. However, for some years, there has been debate within the diabetes community as to the validity of this test. The OGTT involves fasting for ≥12 hours prior to the test, taking a blood sample, consuming a glucose drink and fasting for a further 2 hours before another blood sample is taken. This procedure is often considered inconvenient and unpleasant for the individual being tested.

During the 2 hours between blood samples being taken the individual should remain at rest. In my experience, however, people have walked home during this “rest” time, which may invalidate the result. In addition, the concentration of Lucozade^© has been changed in recent years, thus if the necessary adjustments are not made to the  protocol, the validity of the test may be affected.

HbA_1c testing measures the average plasma glucose levels over the previous 2–3 months. This test has previously been used only to assess glycaemic control, but is now being considered as an alternative to OGTT for diagnosing diabetes. HbA_1c offers the advantages over OGTT of not involving fasting and also that it is not affected by day-to-day variability in blood glucose levels.

In January 2010, the American Diabetes Association formally advocated the use of HbA_1c testing for diagnosis of diabetes following recommendations by the International Expert Committee (2009).

The World Health Organization (WHO, 2011) has now published a report also recommending that HbA_1c testing be used for diabetes diagnosis where stringent quality assurance tests are in place, assays are standardised in accordance with international reference values and there are no medical conditions present that may cause inaccuracy in the measurement. WHO recommends an HbA_1c cut-off level of 6.5% (48 mmol/mol). A value of <6.5% (<48 mmol/mol) does not exclude diabetes diagnosed using glucose tests. The expert group (WHO, 2011) concluded that there is currently insufficient evidence to make any formal recommendation on the interpretation of HbA_1c levels <6.5% (<48 mmol/mol), although a person without diabetes would have an HbA_1c level of approximately 5% (31 mmol/mol).

In a recent WHO press release (http://bit.ly/edlcND), Dr Ala Alwan, Assistant Director General of WHO’s Noncommunicable Diseases and Mental Health Cluster, stated that this recommendation is a positive development, “but its higher cost in comparison to other diagnostic tools will, for now, make it harder for developing countries to use. It also remains unreliable in medical conditions with rapid red-cell turnover, such as haemolytic or iron deficiency anaemias. So the priority for low-income countries will continue to be ensuring the availability of blood glucose measurement at the primary healthcare level before widely introducing HbA_1c for diagnosing diabetes”.

Research indicates that switching from testing blood glucose levels to HbA_1c levels with a threshold of ≥6.5% (≥48 mmol/mol) could significantly increase GP workload as the number of people diagnosed with diabetes will greatly increase. A study (Khunti et al, 2010), presented at the Diabetes UK 2010 conference, compared the prevalence of type 2 diabetes as diagnosed by either OGTT or HbA_1c testing in 9500 people. OGTT identified 344 individuals (3.6%) with diabetes. Of these, 103 (1.1% of the entire cohort) had an HbA_1c level of <6.5% (<48 mmol/mol) and would not have been classified as having the condition using the new HbA_1c criteria. When using HbA_1c as the diagnostic tool, 591 individuals (6.2%) were detected with type 2 diabetes.

The European Association for the Study of Diabetes is now formally considering the move as with recent technological advances, HbA_1c assays are becoming highly standardised and most are not affected by haemoglobinopathies. 

The debate of the value of introducing HbA_1c as a diagnostic tool continues among clinicians. However, it seems likely that this method of diagnosing diabetes will be adopted in the UK sometime this year – watch this space!