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Chemical Pathology

Notes

  • Haemoglobin is glycated by circulating blood glucose and HbA1c is the most quantitatively prevalent glycated haemoglobin complex.
  • The amount of HbA1c formed is directly related to the average level of blood glucose over the lifespan of the red blood cell; it therefore reflects the prevailing blood glucose levels over the preceding 2–4 months.
  • HbA1c measurement is used in the monitoring of diabetes and can also be used for diagnosis, although this is not appropriate in all patients.
  • In diagnosed diabetes, effective control of glycaemia delays the onset and slows the progression of diabetic retinopathy, nephropathy and neuropathy.
  • Changes in red cell turnover will affect HbA1c production meaning in some cases it is not a suitable test for diagnosis and/or monitoring.
  • The methodology used locally is Ion Exchange Chromatography (Tosoh Diagnostics, introduced in July 2025).

Diagnosis of diabetes

HbA1c can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement (WHO guidance 2011).

HbA1c ≥48 mmol/mol can be used to diagnose diabetes in most situations

  • In patients without symptoms but with an HbA1c ≥48 mmol/mol, repeat venous HbA1c in the same lab within 2 weeks (to confirm result and exclude any sampling/analytical error).
  • If the second sample is <48 mmol/mol treat as high risk of diabetes and repeat the test in 6 months or sooner if diabetes symptoms develop.
  • In symptomatic adults with relatively slow onset of symptoms a single result ≥48 mmol/mol is considered diagnostic.

Situations where HbA1c must not be used as the sole test to diagnose diabetes:

  • Symptomatic children and young people (<16 years of age).
  • Symptoms suggesting Type 1 diabetes (any age).
  • Short duration diabetes symptoms (<2 months).
  • Patients at high risk of diabetes who are acutely unwell.
  • Taking medication that may cause rapid glucose rise e.g. steroids, antipsychotics.
  • Acute pancreatic damage/pancreatic surgery.
  • In pregnancy.
  • Patients with CKD 4 or 5.
  • Patients with HIV infection and or those taking anti-retroviral medication(s).
  • Presence of other genetic, haematologic and illness-related factors that influence HbA1c and its measurement (for common examples see table below).

HbA1c <48 mmol/mol

  • A value of less than 48 mmol/mol does not exclude diabetes diagnosed using glucose tests.
  • Glucose tests are recommended where patients have symptoms of diabetes or are clinically at very high risk of diabetes.
  • HbA1c 42 – 47 mmol/mol: Provide intensive lifestyle advice. Warn patients to report symptoms of diabetes. Monitor HbA1c at least annually.
  • HbA1c <42 mmol/mol: Generally low risk but those at high risk of developing diabetes should be monitored annually.

Monitoring diabetes

In type 2 Diabetes, HbA1c should be measured at 3–6 monthly intervals initially until stable on unchanging antidiabetic treatment, and then every 6 months to ensure adequate blood glucose control. Treatment targets should be individualised based on treatment regime and clinical picture.

What interferes with HbA1c reporting?

Anything that affects red blood cell turnover will potentially affect the HbA1c result, for examples see the table below:

Table of factors that can affect the HbA1c results
Raised HbA1c Lower HbA1c Variable HbA1c
Red cell life span Increased red cell survival:
Previous splenectomy
Iron deficiency anaemia
Erythropoietin
B12 treatment
Iron treatment
Erythropoiesis reduction
Red cell destruction:
Splenomegaly
Rheumatoid arthritis
Haemolysis
Drugs e.g. ribavirin or antiretrovirals
Haemoglobinopathies
HbF
MetHb
Glycation Alcoholism
Chronic renal failure
Aspirin
Vitamin C and E
Haemoglobinopathies
Genetic heterogeneity
Analytical interference Hyperbilirubinaemia
High dose aspirin
Opiates
Carbamylated Hb
Hypertriglyceridaemia Haemoglobinopathies

The ion exchange method detects haemoglobin variants that would not have been detected previously. In response to such a finding, an interpretative comment will be added to the report. For any concerns on the impact of the analytical method in revealing new haemoglobin variants, or other factors that may affect HbA1c results, please contact the Duty Biochemist to discuss.

Sample requirements

For adults, blood taken into an 4mL EDTA Tube

EDTA with cap


For children, blood taken into a 2mL EDTA tube

2ml EDTA tube


Storage/transport

Send at ambient temperature to the laboratory. If unavoidable, samples can be stored refrigerated overnight.

Required information

Relevant clinical details including whether monitoring known diabetes or whether for diagnosis.

Turnaround times

The assays are run on a daily basis Monday to Friday. The in-lab turnaround time is normally less than 72 hours.

Reference ranges

Target HbA1c values vary according to clinical circumstances as described above.

Further information

To learn more about HbA1c visit the HbA1c Test page on Lab Tests Online or view the diabetes page on G-Care

References

  1. World Health Organisation report on Use of HbA1c in diagnosis of diabetes 2011
  2. O’Doherty, M. and Day, A. (2016). ‘Glycated haemoglobin and diagnosis of diabetes mellitus: now well established but beware the pitfalls’, Annuals of Clinical Biochemistry, Vol. 53(3) p.309–311


Page last updated: 01/07/2025