HbA1c – Diagnostic threshold and treatment targets

HbA1c (or glycated haemoglobin) refers to a fraction of haemoglobin that has been modified by the presence of glucose over the lifespan of the red blood cell (around 120 days). Higher average blood glucose concentrations are reflected by higher HbA1c.

HbA1c for the diagnosis of diabetes mellitus

An HbA1c ≥ 6.5% or 48 mmol/mol is consistent with a diagnosis of diabetes mellitus.

Medicare will provide a patient rebate for one diagnostic HbA1c per annum.

In patients without typical symptoms of diabetes mellitus, two positive tests are required to confirm the diagnosis (i.e. in addition to an initial HbA1c result ≥ 6.5%, a repeat HbA1c ≥ 6.5%, a fasting blood glucose > 7.0 mmol/L, or a blood glucose > 11.0 mmol/L two hours after a 75 g glucose load). 

HbA1c is not a suitable stand-alone diagnostic test for gestational diabetes or type 1 diabetes mellitus.

HbA1c for monitoring diabetes mellitus

In patients with established diabetes mellitus, treatment targets should be individualised based on a range of factors. A “general” target for most patients is ≤ 7.0% or 53 mmol/mol.  Patient groups in whom less stringent targets may be considered include those at higher risk of hypoglycaemia, older patients or those with comorbidities, and the very young. More stringent targets may be used in patients with type 2 diabetes mellitus of shorter duration. Further information is available in this Position statement of the Australian Diabetes Society

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Medicare will provide a patient rebate for HbA1C when used in monitoring known diabetes four times per annum. Stating whether the patient has diabetes on the request form will help the patient to avoid receiving a bill.

“At target” does not always mean good glycaemic control

As with any laboratory test, meaningful interpretation can only be made in the overall clinical context. For example, whilst an “at target” HbA1c (e.g. 6.0%) in a patient with diabetes mellitus could indicate excellent glycaemic control, poorly controlled diabetes with frequent, alternating hypoglycaemia and hyperglycaemia over a period of weeks or months could also cause this result.

Causes of clinically misleading HbA1c results

While the most important contributor to HbA1c is blood glucose, several factors can cause increases or decreases in HbA1c which may be clinically misleading:

Misleading high HbA1c
Misleading low HbA1c

Iron deficiency anaemia

Haemolytic anaemia

Splenectomy

Recent acute blood loss

Recent steroid therapy, surgery or illness

Recent red blood cell transfusion

Certain haemoglobin variants

Iron, B12 and erythropoietin administration

 

Alcohol excess

 

Chronic kidney disease

 

Certain haemoglobin variants

Measurement issues and identification of haemoglobin variants

The method of measurement for HbA1c at Western Diagnostic Pathology is high-performance liquid chromatography. This method enables us to identify possible haemoglobin variants which may (1) cause misleading HbA1c results; (2) have possible inherent clinical significance; or (3) be of no significance at all. Sometimes we will provide a comment advising that a variant has been detected; haemoglobin electrophoresis may be recommended. If we are concerned about possible analytical interference, we may need to perform additional testing, which may cause a delay in reporting of the result.

References and further reading

D'Emden MC, Shaw JE, Colman PG et al. The role of HbA1c in the diagnosis of diabetes mellitus in Australia. Med J Aust 2012; 197: 220-221. Available from: https://www.mja.com.au/journal/2012/197/4/role-hba1c-diagnosis-diabetes-mellitus-australia

Wah Cheung N, Conn JJ, d’Emden MC et al. Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus. Med J Aust 2009; 191: 339-344. Available from: https://www.mja.com.au/journal/2009/191/6/position-statement-australian-diabetes-society-individualisation-glycated