Non-enzymatic glycation of haemoglobin results in the formation of haemoglobin A1c (HbA1c). In health, the proportion of HbA1c in comparison to total HbA should form about <5-6%. Higher levels are caused hyperglycaemia as caused by diabetes mellitus. As the lifespan of a erythrocyte is generally 120 days, HbA1c 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, though this has not been universally accepted given the limitations discussed below.
HbA1c is known to be affected by several conditions other than diabetes:
- Abnormal Erythrocyte Turnover
- In situations of increased red cell turnover, e.g. haemolysis, the lifespan of the red cell is reduced and HbA1c results should be interpreted with caution (it will be falsely low as haemoglobin molecules will have less average exposure to high sugar levels).
- Similarly, in patients with hemoglobinopathy such as sickle-cell disease, HbA1c levels are unreliable. 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.
- HbA1c marginally higher when glycaemic control corrected for.
- Renal failure
- Variable effect
- Higher in Afro-Carribeans.
Standardisation of Measurements
Guidelines for the standardisation in the reporting and measurement have been published in 2007. Historical methods used to calculate HbA1c are considered outdated, but in order to maintain backward comparability, current measurements are produced using newer methods, but with an adjustment to match trials such as the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).
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, HbA1c will be expressed in SI units as mmol/mol.
- ↑ The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. The New England journal of medicine. 1993 Sep 30; 329(14):977-86.
- ↑ International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes care. 2009 Jul; 32(7):1327-34.(Link to article – subscription may be required.)
- ↑ Kilpatrick ES, Bloomgarden ZT, Zimmet PZ. Is haemoglobin A1c a step forward for diagnosing diabetes? BMJ (Clinical research ed.). 2009; 339:b4432.(Epub)
- ↑ El-Agouza I, Abu Shahla A, Sirdah M. The effect of iron deficiency anaemia on the levels of haemoglobin subtypes: possible consequences for clinical diagnosis. Clinical and laboratory haematology. 2002 Oct; 24(5):285-9.
- ↑ Coban E, Ozdogan M, Timuragaoglu A. Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta haematologica. 2004; 112(3):126-8.(Link to article – subscription may be required.)
- ↑ Reynolds TM, Smellie WS, Twomey PJ. Glycated haemoglobin (HbA1c) monitoring. BMJ (Clinical research ed.) 2006;333(7568):586-8. (Direct link – subscription may be required.)
- ↑ Herman WH, Ma Y, Uwaifo G, Haffner S, Kahn SE, Horton ES, Lachin JM, Montez MG, Brenneman T, Barrett-Connor E. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes care. 2007 Oct; 30(10):2453-7.(Link to article – subscription may be required.)
- ↑ Consensus statement on the worldwide standardisation of the HbA(1c) measurement : The American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. Diabetologia. 2007 Oct; 50(10):2042-3.(Link to article – subscription may be required.)