REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
100
VOLUME 7 NUMBER 3 • SEPTEMBER 2010
both time consuming and inconvenient to perform. Because
type 2 diabetes is characterised by slowly rising glucose levels its
diagnosis has traditionally required the measurement of specific
blood glucose values in timed samples to differentiate it from the
naturally variable glucose levels of non-diabetic individuals.
6
Of the tests currently used to evaluate glycaemia and diagnose
diabetes and pre-diabetes, the oral glucose tolerance test (OGTT)
is considered the ‘gold standard’. However, the OGGT has several
drawbacks:
• Performing an OGTT is time consuming and costly
• Patients have to fast for at least eight hours before having the
test
• Consuming the necessary glucose load on an empty stomach
may make patients physically ill (i.e. faint, sweaty, nauseous).
• The need for a confirmatory test on another day is often
inconvenient and some patients may not return for the second
test.
The international expert committee’s recent investigations have
shown that laboratory measurements of blood glucose may not
be as accurate as we would hope, being flawed by the clinical
instruments and methods used to measure it, errors in handling,
length of storage, and even the nature of the molecule itself.
Repeat test reproducibility can also be poor.
6
Why HbA
1c
?
The expert panel based their recommendation on the latest available
evidence. They considered that a measure that captures chronic
glucose exposure is more likely to be informative of the presence
of diabetes than a single measure of glucose. HbA
1c
varies less than
fasting plasma glucose values and the assay for HbA
1c
has technical
advantages compared with the glucose assay. The test is also easier
for patients who would no longer be required to perform a fasting
or oral glucose tolerance test.
Because diabetes is characterised by chronic hyperglycaemia
sufficient to cause diabetes-specific complications, the expert
committee rationalised that laboratory tests that measure long-
term glycaemic exposure should be a better marker of the presence
and severity of the disease than single measures of glucose
concentration.
6
HbA
1c
– which is glucose bound to a haemoglobin
molecule – lasts for the lifespan of a red blood cell, so it reflects the
blood glucose levels over the preceding 2–3 months.
7
The Diabetes Control and Complications Trial (DCCT)
8
and the
UK Prospective Diabetes Study (UKPDS)
9
have shown that in people
with type 1 and type 2 diabetes, the risk of both microvascular and
macrovascular complications increases with rising HbA
1c
levels.
Retinopathy is a common microvascular complication of
diabetes, which may start to develop as early as seven years
before a diagnosis of diabetes is made.
4
Observational studies
examining the link between the measurement of long-term
exposure to glycaemia with HbA
1c
and single or longitudinal
measurement of blood glucose levels have consistently
demonstrated a stronger correlation between retinopathy and
HbA
1c
10–12
than between retinopathy and fasting glucose levels.
13
The expert committee therefore suggests that because
HbA
1c
measures longer-term exposure to raised glucose levels,
it may be both a better biochemical marker of diabetes and
a more accurate predictor of early diabetic complications,
such as retinopathy, than single or episodic measurements of
blood glucose levels.
6
HbA
1c
also offers several other benefits
over OGGT; it can be performed at any time, it involves one
simple blood draw, and it is highly reproducible (see Table 1).
What is prompting the change?
So why haven’t we been using HbA
1c
to diagnose diabetes
and pre-diabetes previously? Well, doubts over a lack of assay
standardisation have, until recently, largely precluded its general
use. However, the expert committee’s recent examination of the
laboratory measurements of both glucose and HbA
1c
indicates that
improvements in instrumentation and standardisation have resulted
in HbA
1c
assays being at least as accurate and precise as glucose
assays. As opposed to glucose levels, HbA
1c
values also appear to
vary less in an individual on a day-to-day basis, and between people
generally. HbA
1c
values are also relatively stable after collection.
6
International Expert Committee recommendations on
the use of HbA
1c
for the diagnosis of diabetes
Based on their research, the expert committee concluded that an
HbA
1c
assay was superior to both fasting plasma glucose (FPG) and
the OGTT for both the diagnosis of diabetes and the identification
of those individuals at high risk of developing diabetes. They went
on to define an HbA
1c
cut-off point of
≥
6.5% for the diagnosis of
diabetes, on the basis of it being at least as sensitive and specific in
identifying the individuals at risk of the early microvascular changes
most characteristic of diabetes.
6
However, the committee points out there is no lower glycaemic
threshold at which risk begins and the cut-off point it has
suggested for diagnosis should not be used as an absolute dividing
line between diabetes and normal glycaemia. Although committee
members don’t define a specific cut-off point for a formal diagnosis
Key points: HbA
1C
in diagnosing diabetes
• An expert committee is recommending that HbA
1c
should
replace fasting glucose and oral glucose tolerance tests in
the diagnosis of diabetes
• HbA
1C
provides a better indicator of overall glycaemic
exposure and risk of complications
• HbA
1C
varies less than fasting plasma glucose and is easier for
patients because they don’t need to fast or consume glucose
• The committee is recommending an HbA
1C
>
6.5% for the
diagnosis of diabetes
Table 1.
Advantages of HbA
1c
over glucose measurement
• Standardised and aligned to DCCT (The Diabetes Control and
Complications Trial)/UKPDS
• Samples don’t need to be fasting or timed
• Substantially less pre-analytic instability
• Substantially less biologic variability
• Relatively unaffected by acute fluctuations in glucose levels (caused by
stress, illness etc.)
• Better indicator of overall glycaemic exposure and predictor of long-term
complications
• Currently used to guide management and therapy.
(Adapted from
The International Expert Committee’s Report
, 2009
6
)
