In this issue of the 2 part series about the biomarker HbA1c, the Lab Insights team interviewed Prof Aw Tar Choon, Director of Chemical Pathology at Changi General Hospital, Singapore. He is on the editorial boards of several journals including Proceedings of Singapore Healthcare, The Malaysian Journal of Medical Science and Journal of Hormonal Disorders and Endocrine Research. Prof Aw’s research interests include endocrine disorders (thyroid disease, diabetes), immunoassays, cancer and cardiac biomarkers.

In part 1 of this Q&A, we will understand the importance of HbA1c testing and some lesser-known facts about this biomarker.

In the context of diabetes management, why is HbA1c important?

Diabetes is a chronic state of hyperglycemia. Where many might look to using glucose (which can be variable and fluctuates with diet) as an indicator, testing and its accuracy are varied and subject to interpretation. Glycated haemoglobin (HbA1c), is made every time new haemoglobin is produced by the bone marrow and upon meeting with glucose, irreversibly forms HbA1C.

HbA1c, which is carried on red blood cells (RBCs), is a better reflector of an individual’s glycemic milieu, with its ability to show levels from 8 – 10 weeks prior since RBCs have a survival rate of 120 days.

What are some lesser-known facts about HbA1c that laboratories should note?

We must understand that we now know what glycosylated haemoglobin is exactly. The first five or six amino acids of the N-terminal of the beta chain of the molecule in addition to glucose is what makes glycohaemaglobin. Assays that measure total glycated hemoglobin and/or individual peaks on the chromatography are no longer the first choice.

Secondly, haemoglobinopathies could affect HbA1c measurements, and the different test methods used are also impacted differently, even high-performance liquid chromatography (HPLC) is not immune. Even though haemoglobinopathies could affect HbA1c measurements, they only do so when homozygous. Heterozygous haemoglobinopathies have minor effects on measurements and minimal downstream impacts. To accommodate this in patients, it is good practice to use a patient as their own control. With the use of a continuous glucose monitor, it can tell you whether a patient is in good control [of their glucose levels]. Today, the adoption of continuous glucose monitoring is hindered by its price tag, but I do believe it will get better.

Can you share some key findings from the landmark Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS)?

Both the DCCT and UKPDS were landmark studies completed in the 1990s, and were significant because they showed the importance of intensive blood glucose in controlling blood glucose in diabetes. The trials showed that for both types of diabetes, there was a clear link between poor blood glucose control and common microvascular complications like retinopathy, neuropathy and nephropathy. Subjects with poorer glycemic control fared worse than those with better controls.

The trials paved the way for how diabetes trials are run today, and in the time since, studies have shown a link between diabetes and even more comorbidities, such as the accelerated development of heart failure.

How do you ensure results from different labs are comparable to those reported in the DCCT?

It’s more accurate to say that we now have reference methods, capillary electrophoresis and mass spectrometry, to harmonise results. Capillary electrophoresis separates the A1c fragment, which is followed by using mass ionisation (in the form of mass spectrometry) to measure it. This is the reference method. Capillary electrophoresis is also now considered the gold standard in terms of available reference methods.

Of course, referral labs might also seek to participate in an NGSP programme.

Speaking of the NGSP, can you share more about various quality control assessments for HbA1c?

The best standardisation programme is the one run by the NGSP, and one of the highlights of their programme is that they run 2 types: Monitoring and Certification. For the monitoring programme, it offers 20 samples per challenge, 4 times a year and to perform 10 samples over 2 days. Whilst the certification challenge offers 40 samples once a year and to perform 8 samples over 5 days. But if you do not  participate in the NGSP, the College of American Pathologists (CAP) survey is also sufficient.

In Singapore, the Ministry of Health (MOH) mandates that we have to take part in their own programmes, which comprises of 2 challenges per year with 1 sample per challenge.

Check out Part 2 of the Q&A to get more insights from Prof Aw Tar Choon. To learn more about how your lab could benefit from an HbA1c test and its operational implementations, please reach out to Yingli Huang, Business Manager (Core Lab) at Roche Diagnostics Asia Pacific. ([email protected]).