HbA1c analysers & Detection of Haemoglobin variants
HbA1c provides a measure of the amount of glucose attached to haemoglobin. The lab analysers that measure this will sometimes detect the presence of a possible haemoglobin variant. Variants may impact on HbA1c measurement by altering red cell half life, reducing or increasing the rate of glycation and/or interfering with the ability of the lab to accurately quantify the amount of glycated haemoglobin (HbA1c). Therefore whenever the HbA1c analyser indicates that a haemoglobin variant may be present the laboratory will recommend that a heamoglobinopathy screen is arranged to clarify.
If the patient has a haemoglobin variant confirmed on a haemoglobinopathy screen then haematology will indicate whether or not the presence of this variant is likely to be clinically significant. Some variants may not be significant clinically but may still potentially impact on the accuracy of an HbA1c result and the biochemistry lab can provide further advice on this when required.
Some variants may result in the lab not being able to report a HbA1c result, for others the lab will indicate that the absolute value may be inaccurate but the trend in result may still be useful.
If it is indicated that the variant does interfere with HbA1c measurement, then alternative measures of glycaemic status will be recommended. For diabetes screening/diagnosis a fasting glucose and/or OGTT should be arranged. For patients with diabetes Fructosamine should be requested as an alternative method for assessing glycaemic control.
If there are any queries about this please contact loth.biochemadvice@nhs.scot.
Fructosamine information
What is Fructosamine?
Fructosamine is a term used to describe glycated plasma proteins. Glucose binds non-enzymatically to plasma proteins (predominantly albumin) to form Fructosamine. The plasma Fructosamine level is proportional to the mean plasma glucose concentration over the previous 2 to 3 weeks (reflecting the average lifespan of plasma proteins). This gives an intermediate term marker of glycaemic control.
When should it be measured?
It is used to monitor glycaemic control in individuals with a diagnosis of diabetes in whom HbA1c may be misleading (e.g. certain haemoglobin variants, anaemia). Fructosamine should not be used to diagnose diabetes!
How do I order it?
Fructosamine can be ordered via GPOC(ICE). It is measured on a serum (brown capped) tube and does not require any special sample handling.
How do I interpret the result?
Reference range 200-285 µmol/L There are no standardized references ranges for Fructosamine and, in general, trends in value for an individual patient are more important than absolute values. An increase in value indicates a deterioration in glycaemic control. A Fructosamine result within the reference range does not exclude diabetes and Fructosamine should not be used to diagnose diabetes.
Fructosamine values may be misleadingly low in conditions associated with hypoproteinaemia such as nephrotic syndrome, acute severe illness and chronic liver disease.
The below table gives a very rough approximation of Fructosamine values compared to HbA1c. Values are based on the formula:
HbA1c (%) = 0.017 X fructosamine level (µmol/L) + 1.61
| HbA1c (mmol/mol) | HbA1c (%) | Fructosamine (µmol/L) |
| 31 | 5 | 200 |
| 42 | 6 | 258 |
| 53 | 7 | 317 |
| 64 | 8 | 376 |
| 75 | 9 | 435 |
| 86 | 10 | 494 |
| 97 | 11 | 552 |
| 108 | 12 | 611 |
| 119 | 13 | 670 |
References:
https://www.acb.org.uk/our-resources/science-knowledge-hub/analyte-monographs.html
https://labtestsonline.org.uk/tests/fructosamine
Nice guidelines 17 and 28
Robert M. Cohen, Yancey R. Holmes, Thomas C. Chenier, Clinton H. Joiner; Discordance Between HbA1c and Fructosamine: Evidence for a glycosylation gap and its relation to diabetic nephropathy. Diabetes Care 1 January 2003; 26 (1): 163–167. https://doi.org/10.2337/diacare.26.1.163
