By Carolien Koreneff, CDE-RN, FADEA
HbA1c, also known as glycated haemoglobin (GHb), glycosylated haemoglobin or A1c for short, is a blood test that can be used to diagnose, or monitor people living with, diabetes.
A HbA1c blood test highlights long-term blood glucose levels by looking at how much glucose is attached (glycated) to the haemoglobin (Hb) in the blood stream. Haemoglobin is the protein in the red blood cells that also carries oxygen throughout the body, and as Hb generally lives for around 120 days, the HbA1c gives an average of how much glucose has been in the blood over the past few months.
HbA1c is a weighted average of glucose levels, meaning that glucose levels in the past 30 days contribute substantially more to the level of HbA1c than do glucose levels from 90-120 days earlier.
Most people with diabetes are recommended to have this test every 3-6 months as it is a good indicator to see if someone may be at risk of developing diabetes related complications. The higher the HbA1c, the higher the risk will be.
As the HbA1c is a long-term test no preparation, such as fasting, is required and it can be done at any time of the day.
The Diabetes Control and Complications Trial (DCCT) was a landmark study in diabetes during 1982-1993, the largest study thus far in type 1 diabetes. The DCCT was designed to test the glucose hypothesis and determine whether the complications of type 1 diabetes could be prevented or delayed.
Another landmark diabetes study from around that same period, the United Kingdom Prospective Diabetes Study (UKPDS), similarly established whether the complications of type 2 diabetes could be prevented or delayed.
According to an article published in Clinical Chemistry and Laboratory Medicine, Volume 41, Issue 9, the DCCT and UKPDS “demonstrated conclusively that risks for complications in patients with diabetes are directly related to glycaemic control, as measured by glycated haemoglobin (GHb)”.
In Australia and New Zealand, for the past 30 years or so, HbA1c has been reported as a percent of the total haemoglobin (%) value. This is now referred to as NGSP units, after the National Glycohemoglobin Standardization Program (NGSP).The NGSP was implemented to enable laboratories to report DCCT/UKPDS-traceable GHb/HbA1c results.
Prior to the DCCT and UKPDS, HbA1c values could differ significantly from one method to another or from one laboratory to another, which would have affected the meaningful implementation of specific diabetes care guidelines.
A newer way of reporting HbA1c is known as the International Federation of Clinical Chemistry (IFCC) units, which is reported as a molar proportion (in a mmol/mol measure). The IFCC working group developed reference methods for HbA1c analysis, which standardised the HbA1c reporting internationally.
Currently you will find both the NGSP and IFCC units on pathology reports in Australia. A conversion table between NGSP and IFCC measures can be found here.
Interestingly, there is a simple relationship between the two measures of HbA1c, and also with the predicted Average Blood Glucose (ABG). For each 1% change in the HbA1c (NGSP) percentage, the HbA1c (IFCC) changes by 11 mmol/mol and the ABG changes by 2 mmol/L.
Although this predictable relationship between HbA1c and ABG exists, according to the NGSP “fasting glucose as a surrogate measure of average glucose should be used with caution”. Postprandial glucose levels may better explain variations in mean HbA1c. In short: HbA1c is different from checking a blood glucose level.
Genetic variants of haemoglobin, such as sickle cell trait (HbS) or elevated levels of foetal haemoglobin (HbF), haemoglobinopathies or renal failure can affect the HbA1c results and can give falsely high or low readings. This can lead to over-treatment or under-treatment of diabetes, which can increase the risk of hypoglycaemia and the development of diabetes-related complications.
Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (such as acute blood loss, haemolytic anaemia and blood transfusions), will falsely lower HbA1c results. Iron deficiency anaemia is associated with higher HbA1c results, whereas iron replacement therapy lowers HbA1c in people with diabetes.
It is recommended that alternative measures of glycaemic assessment (e.g., glucose monitoring) is used in the presence of significant iron deficiency anaemia, at least until the iron deficiency has been successfully treated.
In those with renal failure, we should consider the impact of any renal anaemia, potential supplementary erythropoietin (Epoetin or EPO, for example Aranesp) intake, iron replacement therapies, as well as other factors in chronic kidney disease (CKD), on the validity of HbA1c.
It is believed that HbA1c underestimates glycaemic control in people with diabetes who are on dialysis. Jung et al. showed that “the correlation between HbA1c and fasting glucose weakens as renal function worsens”, and, “that this appears particularly to be the case in people with anaemia”. Further studies are needed to fully clarify the role of HbA1c in people with diabetes and CKD.
Fructosamine is a glycated serum protein level that measures glucose in a span of around 1-3 weeks, similar to HbA1c.
HbA1c reflects the average of glycaemic control over 3-4 months, but as the half-life of albumin is much shorter than that of haemoglobin (about 20 days), fructosamine can detect changes in blood glucose control within a few weeks.
The term fructosamine comes from the 5-atom ring that is formed when the serum proteins are glycated. Although it appears similar in structure to fructose, fructosamine is not related to fructose or fructose metabolism at all.
Fructosamine testing is not used all that often in clinical practice, HbA1c and blood glucose monitoring are preferred. However, when a narrow time frame is required or when the HbA1c results are unreliable, it is possible to test the fructosamine level instead.
It is important to note that reductions in serum albumin will lower the serum fructosamine level and fructosamine, similar to how HbA1c is affected, in those with CKD.
Maintaining glucose levels within the target range has been proven to reduce the risk of the development (and the progression) of complications in both people with type 1 and type 2 diabetes. The Australian Diabetes Society recommends a general target HbA1c of ≤7.0% for most patients. HbA1c targets however, need to be individualised to a tighter or lesser degree, with a recommended target HbA1c level of ≤6.0% in some people, or up to ≤8.0% in others.
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