Until recently, fasting plasma glucose, and in some situations, oral glucose tolerance testing, have been the investigations of choice for diagnosing people with type II diabetes. Recently, recommendations in New Zealand have changed and HbA1c has become the primary assay for diagnosing type II diabetes, along with its continued role in monitoring glycaemic control. However, there are some clinical scenarios where HbA1c is unreliable, and fasting plasma glucose should be used in preference
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HbA1c is the recommended test for diagnosing type II diabetes in most situations
In September, 2011, the New Zealand Society for the Study of Diabetes (NZSSD) changed its recommendation regarding choice
of test for diagnosing type II diabetes, stating that glycated haemoglobin (HbA1c) was the preferred test over
fasting glucose.1 In addition, it is now recommended that HbA1c is the test of choice for population
screening programmes.2 However, there are some scenarios where measuring HbA1c for diagnostic purposes
may give misleading or inaccurate results (see bullet list and Table 1 below), and therefore a fasting plasma glucose
is recommended.1 Oral glucose tolerance testing (OGTT) is no longer recommended for most people as a test for
type II diabetes.2 N.B. OGTT is still used for diagnosis of women with gestational diabetes.
For further information on the change in guidance and the use of HbA1c,
see: "The new role of HbA1c in diagnosing type 2 diabetes",
BPJ 42 (Feb, 2012), and "Understanding the new HbA1c units for the diagnosis of Type 2 diabetes" Braatvedt
G et al, NZMJ 2012;125(1362).
HbA1c results may be misleading in some people and situations
Fasting plasma glucose should only be used to test for type II diabetes in situations when the use of HbA1c is
inappropriate.1 The two primary situations where HbA1c may be inaccurate are when serum glucose
levels have risen too quickly for glycation rates to provide an accurate picture, or where a condition is present that
will affect the accuracy of HbA1c over the long term. Where serum glucose has risen quickly, HbA1c should
not be used. In clinical situations where HbA1c may be misleading, measuring glycation rates may still be useful,
although consideration should be given to using fasting plasma glucose.
The inter-test variability between HbA1c and fasting glucose
When choosing the most appropriate diagnostic test for people with suspected type II diabetes, it is important that
practitioners understand the limitations of each test.
Multiple studies have shown that HbA1c and fasting plasma glucose tests are frequently discordant when used
to diagnose type II diabetes.3 In some populations, such as Indo-Asian people, HbA1c diagnostic
cut-off levels of 48 mmol/mol (a lower threshold than is used in New Zealand) identify fewer individuals as having type
II diabetes than glucose-based tests.3 However, in the majority of study populations this discordance is minor,
and HbA1c and fasting plasma glucose generally identify similar numbers of people with diabetes.4 In
addition, the convenience of HbA1c testing is thought to significantly increase the absolute number of people
diagnosed with type II diabetes, making it a more effective test for screening populations. HbA1c may not
accurately reflect levels of glycaemic control in some situations or individuals, but in comparison with fasting plasma
glucose, it has greater analytic stability and less daytime variability in any individual patient, as well as far less
stringent patient requirements, particularly the lack of required fasting.
Where serum glucose levels have risen rapidly, do not use HbA1c
A recent UK consensus statement recommended that HbA1c should not be used in the following patients or situations
where blood glucose levels may have risen too fast to affect HbA1c:5.
- All children and young people or anyone with suspected type I diabetes, regardless of age
- People with a short duration of diabetes symptoms
- Women who are pregnant or have been pregnant in the previous two months
- People at high risk of diabetes who are acutely unwell (HbA1c ≥ 50 mmol/mol confirms pre-existing diabetes,
but a value < 50 mmol/mol does not exclude it in an unwell patient and such patients should be retested once the acute
episode has resolved)
- People taking medicines that may cause rapid glucose rise, e.g. corticosteroids or antipsychotics (for two months
or less). HbA1c can be used in people taking such medicines long-term (over two months) who are not clinically
- People with acute pancreatic damage or who have had pancreatic surgery
In these situations, where symptoms have only been present for a short period (less than three months) and glycation
of haemoglobin is unlikely to have occurred, it is more appropriate to request fasting plasma glucose than HbA1c.5 In
addition, in some clinical settings self-monitoring blood glucose (SMBG) measurement, may be indicated to establish glucose
levels to guide an acute intervention, such as hospital admission, in patients with suspected hyperglycaemia.
Table 1: Factors influencing HbA1c results, modified from Gallagher6,7
|Red Cell Survival (erythropoiesis)
Vitamin B12 deficiency
Vitamin B12 or folate supplementation
Chronic liver disease
|Iron deficiency anaemia8-10
|Erythrocyte destruction or removal
Certain medicines, e.g. antiretrovirals, dapsone
Vitamin C or E deficiency
Chronic kidney disease
||Some genotypes, e.g. sickle cell disease
||Recent blood transfusion (previous three months)1
Aspirin (large doses)
Chronic opiate use
In clinical conditions where HbA1c may be misleading, use with caution
Certain clinical conditions may also affect the accuracy of an HbA1c test - the HbA1c may be falsely
low and lead to false-negative results, or falsely elevated and lead to a false-positive result for type II diabetes.
Some conditions have variable effects on HbA1c results and may increase or decrease HbA1c levels.
Table 1 lists the most common conditions and factors that affect HbA1c. HbA1c may still be useful
in these situations, but it should be used with caution, and consideration given to using fasting plasma glucose.
These conditions need to be viewed within the clinical context of the patient. For many, the degree of effect on HbA1c results
is modest. For example, iron deficiency tends to modestly raise HbA1c for unknown reasons.11 However,
if the rate of blood loss is enough to cause anaemia then HbA1c will typically fall due to increased red blood
cell turnover, i.e. HbA1c will be falsely low, rather than high. A similar situation exists with patients who
undergo venesection for haemochromatosis where HbA1c results can be very low. In general, HbA1c will
still be useful, however, results should be viewed with caution and when there is clinical suspicion about the validity
of the HbA1c result, discussion with a clinical biochemist (pathologist) may be appropriate.
Note that there is also a possible age-related effect when using HbA1c, which rises approximately 0.3% each
decade in people with normal glucose tolerance.12 This does not limit the use of HbA1c in older
people, but clinicians should be aware of the possible effect.
Where HbA1c results are borderline or further investigation of the result is necessary, such as in a patient
with two discrepant HbA1c results, a fasting plasma glucose test may be useful if the result would change the
management of the patient. However, waiting six months before retesting HbA1c, with lifestyle interventions
in the interim, would generally be the recommended management strategy.
Fasting plasma glucose as a diagnostic test for type II diabetes
If a fasting plasma glucose test is indicated, rather than HbA1c, this can be undertaken and interpreted
in accordance with previous type II diabetes testing guidance.
Patients are required to fast (i.e. no caloric intake) for at least eight hours, but ideally 12 hours, prior to testing.13 Advise
patients that they may drink water during the fasting period.
In symptomatic people a single fasting plasma glucose result of ≥7.0 mmol/L can be considered diagnostic
of type II diabetes for the majority of people.1 Repeat testing is recommended where the result is borderline
or there is clinical doubt about symptoms.
In asymptomatic people a fasting plasma glucose result of ≥7.0 mmol/L strongly indicates type II diabetes;
however, a second test is required for confirmation.1 The test should be performed on a separate occasion,13 ideally
within two weeks.5 Lifestyle interventions should be encouraged during the waiting period. If the second result
is discordant, repeat testing again in three to six months is recommended, with lifestyle interventions continuing in
The diagnostic criteria for type II diabetes1
|≥50 mmol/ mol, with symptoms
||≥7.0 mmol/L, with symptoms
|≥50 mmol/ mol, no symptoms
||≥7.0 mmol/L, no symptoms
||A second test above the threshold, with either fasting glucose or HbA1c, is required
to confirm diagnosis
|41 - 49 mmol/mol
||6.1 - 6.9 mmol/L
Offer lifestyle advice. Perform CVD risk assessment and follow guidelines for treatment.
Repeat testing every 6 -12 months
Repeat testing at next CVD assessment or when clinically indicated
* Requesting both HbA1c and fasting plasma glucose together in at-risk, asymptomatic people is unnecessary
and discouraged.5 However, if HbA1c and fasting plasma glucose are measured together, and results
are discrepant with regards to a diagnosis of diabetes, the test above the diagnostic cut point should be repeated after
three to six months.1
Who should be screened for type II diabetes?
Current recommendations are for asymptomatic men aged over 45 years and women aged over 55 years to be screened for
type II diabetes as part of a joint diabetes/cardiovascular risk assessment. Screening of asymptomatic Māori, Pacific
and Indo-Asian people should begin at age 35 years for men and age 45 years for women.
Screening should be undertaken every three to five years depending on risk.
New Zealand Guidelines recommend screening ten years earlier in people with multiple risk factors:1
- A family history of early onset type II diabetes (more than one first-degree relative)*
- A history of gestational diabetes*
- Known ischaemic heart disease, cerebrovascular disease, or peripheral vascular disease*
- Central obesity or increased BMI (BMI > 30 or >27 kg/m2 for Indo-Asian people)*
- Long-term steroid or antipsychotic treatment*
- Intermediate hyperglycaemia on previous assessment, e.g. HbA1c 41 - 49 mmol/mol or fasting plasma glucose
6.1 - 6.9 mmol/L
- An adverse lipid profile, e.g. TC/HDL ratio ≥7.0
- High blood pressure, e.g. ≥160/95 mm Hg
- Polycystic ovary syndrome
- Current smoker (or have quit within the last twelve months)
NZSSD also recommends that children and young adults with BMI >30 (or >27 kg/m2 in Indo-Asian children)
should be screened if:
- There is a family history of early onset type II diabetes or;
- They are of Māori, Pacific or Indo-Asian ethnicity
* Screening should be undertaken from age 25 years in people with multiple high risk factors, as indicated
The disadvantages of fasting plasma glucose as a diagnostic test for type II diabetes
The fasting plasma glucose test has several disadvantages, many of which contributed to the NZSSD and WHO decisions
to recommend that HbA1c be used as the preferred test for the diagnosis of type II diabetes.1,6
The primary disadvantage of fasting plasma glucose is that it requires the patient to fast prior to testing, which can
be difficult in practice.
The diagnostic range of fasting plasma glucose is narrow compared with the biological variation between individuals
when tested with fasting glucose, which is approximately 4.5%.14 This means that if a group of patients have
a fasting plasma glucose level of 7.0 mmol/L, most will have an actual value between 6.7 - 7.3 mmol/L (4.5% biological
variation), but some will have a value outside of this range. Given the narrow diagnostic range for diabetes, with fasting
plasma glucose, this can be significant.
The sample processing of fasting glucose is more complex than for HbA1c, leading to a greater potential for
errors. Variation can be up to 1 mmol/L or more after one to two hours, with an average of approximately 0.4 - 0.5 mmol/L
(even if a fluoride tube is used).15 When added to the biological variation, this difference can have a significant effect
on the diagnostic accuracy of the test.
The reproducibility of fasting plasma glucose is lower than HbA1c. An abnormal or borderline HbA1c result
is far more likely to be abnormal on repeat than a borderline fasting glucose result.16
Fasting plasma glucose has an inferior ability to predict long-term outcomes, particularly beyond 15 years.17
Monitoring patients where the use of HbA1c is misleading
All people with type II diabetes should have regular follow-up in general practice to monitor glycaemic control, risk
level and disease progression. HbA1c is the recommended test for measuring glycaemic control during follow-up.
In the presence of the co-morbidities discussed in Table 1, HbA1c may not accurately reflect the level of glycaemic
control. Alternative methods for assessing control may be more appropriate, such as fasting plasma glucose and a series
of self-monitoring blood glucose measurements for people using insulin. If therapeutic changes are being considered and
there is clinical concern of the validity of the HbA1c test, discussion with a diabetologist is recommended.
Measurement of fructosamine may be an alternative option for some people, however, the availability of this test varies,
so it should be discussed with a clinical pathologist or diabetologist first. Fructosamine is a glycated protein that
indicates glycation levels over the preceding 14 - 21 days.18
How regularly should follow-up occur
Follow-up of people with type II diabetes should occur at least annually. In people with multiple co-morbidities or
where regular medicine adjustments are being made to achieve appropriate control, more frequent consultations and testing
e.g. three to six monthly, should be considered.
A full list of risk factors and the regularity of required follow-up
can be found in the "New Zealand Primary Care Handbook 2012", available from:
Follow-up should include measurement of HbA1c (or an alternative method when HbA1c is not appropriate),
blood pressure and lipid levels, an assessment of diabetes related complications including cardiovascular disease (CVD)
risk assessment, kidney disease assessment and checks for foot and retinal complications.19 In addition, educational
material and advice on diet, exercise and smoking cessation should be discussed and provided at each follow-up visit,
as applicable. N.B. Some factors, e.g. retinopathy will only need to be assessed annually, even in the highest risk groups.
PHO Performance Indicators for diabetes
There are currently two PHO Performance Programme (PPP) indicators involving diabetes; diabetes detection and diabetes
follow-up after detection. Both of these indicators are still active under the new funding scheme for diabetes: the Diabetes
Care Improvement Package.
The purpose of the diabetes detection PPP indicator is to determine what proportion of the PHO population estimated
to have diabetes has been diagnosed.20
The Indicator comprises 7.5% of a PHO's performance payment, with 2.5% for achieving the target in the total eligible
PHO population and 5% in the high needs population.
The purpose of the diabetes follow-up after detection PPP indicator is to determine what proportion of the PHO population
expected to have diagnosed diabetes has had a diabetes annual review.20
The Indicator comprises 9% of a PHO's performance payment, with 3% for achieving the target in the total eligible PHO
population and 6% in the high needs population.
Thank you to Dr Cam Kyle, Clinical Director of Biochemistry and Immunology, Diagnostic Medlab, Auckland
for expert guidance in developing this article.
- New Zealand Society for the Study of Diabetes. NZSSD position statement on the diagnosis of, and screening for, Type
2 diabetes. NZSSD; 2011. Available from: www.nzssd.org.nz (Accessed
- Braatvedt G, Cundy T, Crooke M, Et al. Understanding the new HbA1c units for the diagnosis of Type 2 diabetes.
NZ Med J 2012;125(1362):In press.
- Malkani S, Mordes J. Implications of using hemoglobin A1c for diagnosing diabetes mellitus. Am J Med 2011;124(5):395-401.
- Carson A, Reynolds K, Fonseca V, Muntner P. Comparison of A1c and fasting glucose criteria to diagnose diabetes among
U.S. adults. Diabetes Care 2010;33(1):195-7.
- John W. Expert position statement: Use of HbA1c in the diagnosis of diabetes mellitus in the UK. The implementation
of World Health Organization guidance 2011. Diabet Med 2012;29:1350-7.
- World Health Organisation (WHO). Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus.
WHO, Geneva; 2011. Available from: www.who.int/diabetes/publications/report-HbA1c_2011.pdf (Accessed
- Gallagher E, Le Roith D, Bloomgarden Z. Review of hemoglobin A1c in the management of diabetes. J Diabetes 2009;1:9-17.
- Arnold J, McGowan J. Delay in diagnosis of diabetes mellitus due to inaccurate use of hemoglobin A1c levels. J Am
Board Fam Med 2007;20(1):93-6.
- Scottish Intercollegiate Guidelines Network (SIGN). Management of diabetes. SIGN; 2010. Available from: www.sign.ac.uk (Accessed
- Clinical Enquiry and Response Service (CLEAR). Does iron deficiency or anaemia affect the HbA1c test in
diabetic patients, particularly those with chronic kidney disease? NHS, Scotland; 2010. Available from: www.knowledge.scot.nhs.uk (Accessed
- Kim C, Bullard K, Beckles G. Association between iron deficiency and A1c levels among adults without diabetes in
the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care 2010;33(4):780-5.
- Pani L, Korenda L, Et al. Effect of aging on A1c levels in individuals without diabetes: evidence from the Framingham
Offspring Study and the National Health and Nutrition Examination Survey 2001-2004. Diabetes Care 2008;31(10):1991-6.
- American Diabetes Association. Executive summary: Standards of medical care in diabetes 2012. Diabetes Care. 2012;35(Supplement
- Westgard QC. Desirable biological variation database specifications. Westgard; 2012. Available from: www.westgard.com/biodatabase1.htm (Accessed
- Bruns D, Knowler W. Stabilization of glucose in blood samples: why it matters. Clin Chem 2009;55(5):850-2.
- Selvin E, Crainiceanu C, Brancati F, Coresh J. Short-term variability in measures of glycemiz and implications for
the classification of diabetes. Arch Intern Med 2007;167(14):1545-51.
- Selvin E, Steffes M, Zhu H, Et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults.
N Eng J Med 2010;362:800-11.
- American Diabetes Association. Fructosamine test. ADA, USA; 2012. Available from: http://professional.diabetes.org/Disease_Backgrounder.aspx?TYP=6&MID=262 (Accessed
- New Zealand Gudelines Group. New Zealand primary care handbook 2012. 3rd ed. Wellington: New Zealand Guidelines Group;
- DHBNZ. PHO Performance Programme. Indicator definitions. Version 5.5. 2012. Available from: www.dhbnz.org.nz/Site/SIG/pho/Operational-Documents.aspx (Accessed