A/Prof Roy Rasalam
Clinician, Endocrine & Diabetes Department, Alfred Health, Melbourne, Australia
 

HbA1c discrepancies: How can ambulatory glucose profile (AGP) help?

KEY TAKEAWAYS

  • HbA1c and SMBG correlation can be checked by using the average glucose formula (average blood glucose level (mmol/L) = 2 x HbA1c (%) – 6 mmol/L).
  • HbA1c discrepancy with SMBG should be investigated.
  • In the case of HbA1c discordance, a patient’s AGP is a useful tool to measure glucose variability, time in target glucose range and average glucose level.

HbA1c is a key marker used for diagnostic and monitoring purposes in the management of diabetes.1 However, HbA1c has its limitations, including discrepancies with selfmonitoring of blood glucose (SMBG) readings. Associate Professor Roy Rasalam from University of Melbourne, Australia, gave a presentation on HbA1c discordance and how this can be managed in clinical practice.

The significance of HbA1c in diabetes monitoring

HbA1c is formed through the glycosylation of haemoglobin during the 120-day lifespan of a red blood cell.2 HbA1c acts a surrogate marker for blood glucose concentration in the 8-12 weeks prior to measurement. Fifty percent of HbA1c measurement represents glucose exposure in the 30 days prior to measurement, with 40% representing 31-90 days prior, and 10% representing 91-120 days prior.2 Since its discovery in 1966, HbA1c has been shown as a clinical marker of glycaemic control in Type 1 (T1D) and Type 2 Diabetes (T2D), with a cutoff of 7% HbA1c correlating to microvascular (retinopathy) complications.1,3

HbA1c discrepancy

Discrepancies between HbA1c (%) and SMBG (mmol/L) can be a limitation of its use as a biomarker for blood glucose levels. To compare HbA1c and SMBG, HbA1c can be converted to mmol/L using the equation below.

Average blood glucose level (mmol/L) = 2 x HbA1c (%) – 6 mmol/L2

Prof. Rasalam said that to investigate HbA1c discrepancy, an ambulatory glucose profile (AGP) is valuable. An AGP is a summary of a patient’s glucose values over a certain period, as if occurring in a single day. The AGP provides insight into the patient’s glucose variability, time in target glucose range and average glucose level, the latter of which may be compared to the patient’s HbA1c measurement or reported SMBG, to discern where the discordance may have occurred. If the HbA1c is found to not match the patient’s reported SMBG level, there are multiple reasons why this may be the case. Some common reasons for these discrepancies are outlined in Figure 2.

Figure 2_Common causes of HbA1c discrepancies
Figure 2: Common causes of HbA1c discrepancies. Adapted from Wang 2021.2

If suspected, tests can be conducted to elucidate the cause of HbA1c discordance. This may include: a full blood count to assess for anaemia or blood loss, kidney function tests, haemoglobin electrophoresis to check for structural abnormalities and rare haemoglobin types, and tests for iron, folate and vitamin B12 deficiency. In the case of negative tests for these common causes of HbA1c discrepancy, another cause, such as different assay methods, may be investigated.

“It is important to know the causes of HbA1c discordance — they are not niche.”
– A/Prof. Roy Rasalam

Alternatives to HbA1c

“If HbA1c discordance is suspected or HbA1c is unsuitable, there are other options” Prof. Rasalam said. Alternative tests may be used to monitor a patient’s blood glucose. The most prominent of these is the use of flash or continuous glucose monitoring (CGM). Fructosamine testing, or glycated albumin testing, can be used to indicate a patient’s glycaemic control over the previous 21 days. 1.5-anhydroglucitol testing may reflect a patient’s postprandial glycaemia within 2 weeks of testing but is not commonly used in clinical practice.

References
  1. Gebel E. The Start of Something Good: The Discovery of HbA1c and the American Diabetes Association Samuel Rahbar Outstanding Discovery Award. Diabetes Care 2012;35(12):2429-2431. DOI: 10.2337/dc12-1763.
  2. Wang M, Hng T. HbA1c: More than just a number. Australian Journal for General Practitioners 2021;50:628-632. (https://www1.racgp.org.au/ajgp/2021/september/more-than-just-a-number).
  3. Ansari DM, Harahwa T, Abuelgasim E, Harky A. Glycated Haemoglobin Levels and Its Ecect on Outcomes in Cardiac Surgery. Braz J Cardiovasc Surg 2022;37(5):744-753. (In eng). DOI: 10.21470/1678-9741-2020-0188.

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