Haemoglobin A1c

From Ganfyd

Sugar sticks to proteins damaging them. A convenient protein to measure this in is Haemoglobin

Non-enzymatic glycation of haemoglobin results in the formation of haemoglobin A_1c (HbA_1c). In health, the proportion of HbA_1c in comparison to total HbA should form about <5-6%.^[1] Higher levels are caused hyperglycaemia as caused by diabetes mellitus. As the lifespan of a erythrocyte is generally 120 days, HbA_1c gives an indication of the approximate glycaemic control in the preceding 120 days.

Since the adjustments for standardisation of the assay have been introduced, it has been recommended as diagnostic test for diabetes by the International Diabetes Federation^[2], though this has not been universally accepted given the limitations discussed below.^[3]

Limitations

HbA_1c is known to be affected by several conditions other than diabetes:

Iron Deficiency Anaemia

Results in a HbA_1c about 1% lower than would be expected.^[4][5]

Abnormal Erythrocyte Turnover

In situations of increased red cell turnover, e.g. haemolysis, the lifespan of the red cell is reduced and HbA_1c results should be interpreted with caution (it will be falsely low as haemoglobin molecules will have less average exposure to high sugar levels).

Haemoglobinapathy

Similarly, in patients with hemoglobinopathy such as sickle-cell disease, HbA_1c levels are unreliable.^[6] Glycated albumin or fructosamine are sometimes used as an alternative in these circumstances, although there has been much less research of what reference range is appropriate for these substances.

Age

HbA_1c marginally higher when glycaemic control corrected for.

Renal failure

Variable effect

Ethnicitiy

Higher in Afro-Carribeans.^[7]

Standardisation of Measurements

Guidelines for the standardisation in the reporting and measurement have been published in 2007.^[8] Historical methods used to calculate HbA_1c are considered outdated, but in order to maintain backward comparability, current measurements are produced using newer methods, but with an adjustment to match trials such as the Diabetes Control and Complications Trial (DCCT).

6.5% is about 48mmol/mol

An approximate correlation between old values and new values are available at http://www.diabetes.nhs.uk/reading-room/nhs-diabetes-publications/factsheets/hba1c-leaflets As assay methodology varies between laboratories, an agreed standard will allow universal comparison of values, much in the way INR standardised prothrombin time. Results using the IFCC standard can be expressed as a percentage, but tend to give a lower value than previous methods and if the change in assay it not noted by clinicians, gives a falsely good impression of glycaemic control (and therefore potential undertreatment). To break with the old system, HbA_1c will be expressed in SI units as mmol/mol.

References