In the diabetes emergency section of the outpatient clinic, the HbA1c value is always measured. The result, if too high, is not infrequently a cause for heated discussion within the family. But what exactly does this strange abbreviation stand for? What factors influence this long-term blood sugar value?

Everything goes so fast in the emergency room. Just one finger prick is enough to find out what the current HbA1c value is. This routine often places a lot of stress on the families of diabetic children. But what do these letters really mean?    

Sugar adheres to haemoglobin
Since the 70s, it has been known that the amount of sugar that adheres to the haemoglobin (Hb), i.e., the red blood cells, is dependent upon the amount of sugar in the blood. The fact that sugar sticks to haemoglobin and doesn’t let go means that the HbA1c value provides a true picture of the metabolic state.

Swings do not affect result
But doesn’t the blood sugar value swing a lot? Especially in children? These swings, regardless of high or low, have no effect on the HbA1c value, with the exception of chronic hypoglycaemia. The HbA1c delivers a reliable average blood sugar reading, and that for the preceding six to eight weeks. It is given as a percentage, i.e., the percent of haemoglobin that has bound itself with glucose.

The strong bond between haemoglobin and glucose takes just a few hours to form and remains until the cells themselves die. This occurs after around 100–120 days. Of course, the binding of glucose with haemoglobin and the replacement of old cells with new ones does not happen all at once, but is a constant process. This is why the HbA1c value is valid for a period of six to eight weeks up until the measurement is taken.    

High HbA1c indicates risk
Although we know that the HbA1c value is a good indicator of the general state of the metabolism, it is also an indicator of potential risk. The higher the level of sugar in the blood, the higher it is in the tissues and organs. It has been demonstrated that the protein content of various tissues and organs in the body also reacts to the presence of sugar (known as glycation, or non-enzymatic glycosylation). These sugar-protein bonds are then, in part, the end products which are held responsible for the damage done to the tiny blood vessels (diabetic microangiopathy).

In addition, more and more data are showing that post-prandial glucose spurts also play an important role in the development of diabetic complications.
However, damage to blood vessels is not only caused by high blood sugar. Genetic factors are also involved, so the degree to which vessels are damaged is very different from individual to individual.

Determining HbA1c
The HbA1 molecules make up for around 96 to 98 percent of all the haemoglobin in the body. This is why the HbA1c measurement represents the most important value in obtaining information on the metabolic state.

Many different laboratory techniques can be used to determine how much haemoglobin is glycated, i.e., has bound with glucose. This means that only readings coming from the same laboratory, using the same method, can be compared, due to the fact that discrepancies in results occur from lab to lab, depending on what method they use.

The need for standardization
In 2009, the German Diabetes Association (DDG) joined an international consensus to standardize the procedure for determining HbA1c.

Establishing a reference method
To standardize the values and make them interchangeable, the so-called National Glycohemoglobin Standardization Program (NGSP) was established. The reference method chosen, on which all readings were to be calibrated, and which the American Diabetes Association (ADA) also recommended, was high-performance liquid chromatography (HPLC). This method was used and certified in the DCCT and UKPDS.

In order to be clinically and scientifically recognized, HbA1c measurements had to follow this reference method. According to this method, it was accepted that an HbA1c value of between 4 and 6 percent represented a healthy metabolic state.

Impure HbA1c
New and improved techniques in the analysis of HbA1c values later revealed that the calibration standard of the NGSP was not accurate enough. Until then, it was assumed that the highly pure HbA1c had actually been mixed with other glycated haemoglobin molecules whose presence had little to do with the quality of the metabolic state.

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) now decided to use a more pure form of HbA1c as the gold standard, exclusively indicative of the metabolic state.

As the superfluous particles were now being excluded from the measurement, the so-called norm values had to be altered downwards by around 2.15 percent, and all therapeutical guidelines that had, until then, been recommended, were no longer valid.

The new HbA1c standard
In 2007, an international consensus decided to solve this problem between the ‘old’ and the ‘new’ by giving the ‘new’ HbA1c value in units of mmol HbA1c/mol haemoglobin, i.e., mmol/mol. (The old norm of 4 to 6 percent being equivalent to 20 to 44 mmol/mol.)

This new unit of measurement is already obligatory in laboratories. As of December 2009, the new unit of measurement has to be used. To ease transition, the new unit of measurement will be written alongside the old.
The conversion is as follows:

HbA1c according to IFCC (mmol/mol) = (HbA1c according to NGSP -2,15 %) / 0,0915

In internet there are many sites that help in the conversion. After a certain transition period, only the new units of measurement will be used in Germany.

External influences on the HbA1c value
If a patient has a disease of the blood in which the red blood corpuscles do not live as long, the HbA1c value cannot be used as a routine parameter of the metabolic state. The results will always come out too low. This also applies for individuals with overdoses of vitamin C and E.

If the body produces faulty haemoglobin, inaccurate readings will result, as the measurement technique cannot trace these particles. In alcoholics or drug users, or those with kidney disorders, the HbA1c method is also invalid, and cannot be used as a regular orienteering tool for diabetes therapy.

---

Dr Claudia Nestoris MD
For comments or further enquiries please contact the editorial staff:
e-mail: finkenauer(at)kirchheim-verlag(dot)de