Table 1

Summary of HbA1c non-glycaemic variables and significance of their effects

Variable	Subcategory	Effect	Comments
Haemoglobinopathies	N/A	Variable, possibly clinically significant	Consult NGSP website at http://www.ngsp.org/interf.asp
Circulatory source	N/A	No significant effect	All circulatory sources of blood acceptable
Anticoagulant	N/A	No significant effect	Consult manufacturer instructions and validate anticoagulant type locally
Storage	Routine analysis	N/A	Store sample at 4°C
	Long-term storage	N/A	Store sample at −80°C
Sample haemolysis	N/A	No effect—analytical methodologies are haemolysis independent	N/A
POCT	N/A	Variable dependent on specific POCT system	If POCT used quality assurance and clinical accreditation must be performed to ensure laboratory equivalence
Time of day	N/A	No significant effect	Sampling time does not need to be considered
Season	N/A	Non-clinically significant increase in HbA1c during winter	Season does not need to be considered
Age	Neonates	Insufficient data	Do not use HbA1c
	Paediatric	Variable, possibly clinically significant effects	Do not use HbA1c for diagnosis
	Adult	HbA1c increases with age	Consider additional/alternative biomarker in those aged>75
Ethnicity	N/A	Variable.	Consult dedicated research literature
Gender	N/A	Variable, but not clinically significant.	Gender does not need to be considered
Asplenism	N/A	May cause both a glycaemic and non-glycaemic mediated increases in HbA1c	Insufficient data to provide recommendation
Iron deficiency	N/A	Statistically but not clinically significant increase in HbA1c	Use HbA1c but caution in supplementation (see below)
Iron	Oral	Reports of clinically significant reduction in HbA1c	Consider use of additional biomarker until red cell indices stable
Iron	Intravenous	Statistically but not clinical significant reduction in HbA1c	Consider use of additional biomarker until red cell indices stable
Vitamin B12	Deficiency	Statistically but not clinically significant increase in HbA1c	Limited data—interpret with caution
Vitamin B12	Supplementation	Statistically significant reduction in HbA1c	Consider use of additional biomarker until red cell indices stable, for example, glucose or OGTT
Folic acid	Deficiency	Statistically but not clinically significant increase in HbA1c	HbA1c use acceptable
Folic acid	Supplementation	Clinically significant reduction in HbA1c	Use additional biomarker until red cell indices stable, for example, glucose or OGTT
Dapsone	N/A	Variable, but potentially clinically significant	Do not use HbA1c
HIV	N/A	Variable	Insufficient data to provide recommendation
Antiretrovirals	N/A	Variable	Insufficient data to provide recommendation
Hydroxyurea	N/A	Potentially clinically significant effect	Consider use of additional biomarker, for example, glucose or OGTT
Acute changes in blood glucose	N/A	HbA1c not-reflective of acute glucose changes, but is reflective of previous mean glucose	Do not use HbA1c for diagnosis (however risk is false negatives, therefore if already raised indicates pre-existing diabetes)
Gestational diabetes mellitus	N/A	HbA1c may indicate pre-existing diabetes Studies suggest potential role in selecting those who may and may not need further testing, for example, OGTT	Insufficient data to suggest use in routine screening for new onset GDM
Hypothyroidism	Subclinical	Statistically significant increase in HbA1c—normalises after treatment	Do not use HbA1c as sole biomarker in hypothyroidism or unstable thyroid states, use glucose or OGTT
Hypothyroidism	Overt
Hyperthyroidism	N/A	No significant effect	HbA1c use acceptable
Liver disease	N/A	Variable, clinically significant effects	Use frequent blood glucose monitoring in advanced liver disease
Chronic kidney disease	Stages 1–3	No clinically significant effect	N/A
	Stages 4–5	Variable, clinically significant effects.	Do not use HbA1c for diagnosis, cautious use for monitoring
	Erythropoietin	Clinically significant reduction	Do not use HbA1c
Acute inflammation	N/A	No clinically significant effect	Ensure follow-up testing if elevated HbA1c detected
Vitamin E	Supplementation in hypovitaminosis E in T2DM	Clinically significant reduction in HbA1 in subgroup analysis	Insufficient evidence at present, further research required

N/A, not available; OGTT, oral glucose tolerance test; POCT, point-of-care testing; T2DM, type 2 diabetes mellitus.