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| Journal of the New Zealand Medical Association,
05-March-2010, Vol 123 No 1310
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Helen Lunt, Christopher Florkowski, Michael Bignall,
Christopher Budgen
Glucose results derived from hand-held meters are used by
patients and their health care team to make therapeutic decisions such as
insulin dosing. Incorrect glucose values may result in both acute and also
long-term therapeutic consequences. It is therefore essential that results are
as accurate and precise as possible.
Meter technology has shown incremental improvements since
the introduction of the first commercially available hand-held meters in 1970s,
including improvements in ease of use, technical performance and
affordability.1-3 Capillary glucose testing is
an international multi-billion dollar
industry.2 In New Zealand reimbursement of test
strips for the 12 months to June 2009 was $19 million, accounting for 40% of
PHARMAC’s entire diabetes ‘spend’. The number of meters
available has expanded, both in New Zealand as well as
internationally.1,2
Currently in New Zealand, six different meters are available
for use with PHARMAC funded strips (see Table 1). It is
therefore timely to describe current meter technology from a clinical
perspective, highlighting some of the limits of meter performance. This review
focuses on technical issues that impact on clinical interpretation of meter
results in the ambulatory setting. It does not aim to be a comprehensive
technical discussion. Although there are additional meter systems available in
New Zealand with unsubsidised strips such as the Glucocard, which is used in
many hospital inpatient settings, the focus of this review is meters with
subsidised strips.
The clinical impact of recent improvements in hand held blood glucose meter systemsRecent developments in meter technology have improved this
testing system’s ease of use and analytical
robustness.1-3 Test strips now require 8μL
or less of blood (see Table 1).
Using a low blood volume system has the following
advantages: It allows most patients to get a successful sample each time they
undertake lancing. It allows a shallower finger lancing depth, thus patients
should experience less pain.2 In addition, the
need to squeeze fingers for blood letting, a practice that may lead to a change
in the effective composition of the blood test sample and a false glucose value,
is reduced. Strip technology utilises a capillary filling system with a fill
indicator or fill time detector to ensure that the assay does not start until
sufficient blood sample is provided to the strip. This minimises the risk of
obtaining a ‘false low’ result caused by insufficient sample
volume.3
A development that has been appreciated by patients residing
in colder areas of New Zealand, is the wider functional temperature range of
meter and strip systems.3 Historically, low
winter temperatures and cold houses made it difficult for patients to obtain
accurate results. A temperature sensor is now present either in the meter or in
the strips. This allows correction of the glucose value for ambient temperature
across a wide temperature range. Inadvertent patient use of time expired meter
test strips, which often contain ‘spoiled’ analytical reagents, was
a common source of error with older systems. This error has been minimised but
not eliminated in some meter and strip systems. One example of how this is
achieved, is by determining the expiry date of the strip batch from the
calibration chip and pre-setting the meter software to ‘disallow’
strip use after the batch’s expiry date.
One meter system, the Optium Xceed, can be dual calibrated
to measure both glucose and also capillary ketones (beta hydroxybutryrate),
allowing patients to treat mild ketoacidosis at home.
Understanding how the difference between venous and capillary samples impacts on meter performanceFinger stick test results are derived by converting an
electrochemically generated signal to a glucose value by means of an algorithm.
In New Zealand and most other countries, the current expectation from clinicians
is that the algorithm is programmed so that a capillary whole blood glucose
sample (i.e. finger stick result) will read as a laboratory venous plasma sample
(i.e. a venesection result). Thus if a patient went to get a laboratory plasma
venous glucose check and did a simultaneous capillary test with their meter, the
expectation is that the two glucose results should read approximately the same.
The comparison between a capillary finger stick test and a laboratory plasma
venous glucose is not however straightforward, in part because two different
types of samples are being used, which have some shared but also have some
distinct physiological
characteristics.3-5
Whole blood (e.g. a capillary sample) is composed
predominantly of plasma and cells. In the laboratory, glucose is measured on a
plasma sample i.e. a whole blood sample is centrifuged, followed by removal of
the cellular component of blood. Red cells have a lower water and glucose
content than plasma. As a result of this, the glucose concentration of whole
blood is about 11% less than the glucose concentration of
plasma.4 Historically, some meters available in
New Zealand gave capillary results as a whole blood glucose equivalent. When
these meter systems were updated, the algorithm was also updated to display
results as venous plasma equivalent, rather than whole blood equivalent. For
example, a whole blood glucose of 5.0mmol/L from an ‘old’ meter
would equate to a plasma glucose of around 5.6mmol/L, using a ‘new’
meter. This change had the potential to cause confusion.
The current international recommendation, aimed to provide
harmonised reporting and reduce confusion, is to report glucose results as
plasma equivalent.4 All meters currently
available in New Zealand do this.
A second major difference between capillary and laboratory
venous results, relates to the fact that the glucose value of a capillary sample
is higher than for a corresponding venous sample, because glucose uptake by
tissues as blood flows from the capillaries to the veins partially depletes the
venous sample of glucose. Tissue uptake of glucose increases after
food.6 The glucose gradient between capillary
and venous samples therefore shows a postprandial increase which may be as high
as 20% total glucose concentration.5,6
In summary, because capillary and plasma glucose samples
have several physiologically distinct characteristics, comparison between these
two samples is not expected to correlate as closely as a comparison that uses
the same type of blood sample, for example comparing the same venous sample
using two different measurement techniques. Clinicians should anticipate a
slight variation in glucose values between capillary and venous samples but at
least 95% of capillary results should show an analytical variance of <20%,
when compared to a laboratory result.7,8
Figures 1a and 1b illustrate this point, using results from
the On Call Advanced meter (methodology is based on a previous
study).8 This meter and test strip system can
measure venous as well as capillary whole blood i.e. a venous sample from the
antecubital fossa can be applied directly to the test strip. Figure 1a compares
a laboratory venous plasma glucose sample with a simultaneously collected
capillary whole blood sample i.e. two distinct samples are used. Figure 1b
compares the same venous sample, obtained from the antecubital fossa, using two
different methods. Not surprisingly, visual inspection of results in Figure 1b
(the same venous sample measured using two different methods) shows a closer
correlation than those of 1a (separate venous and capillary samples, obtained
from different anatomical sites).
Figure 1a. Comparison of venous plasma with
capillary glucose (On Call Advanced)
 Figure 1b. Comparison of venous plasma with
venous whole blood glucose (On Call Advanced)
 Error grid analysisParkes error grid analysis is used to detect clinically
significant errors in glucose measurement, when comparing capillary with
laboratory plasma venous glucose results.9
Using this visual method of analysis, method comparisons are intuitively easy to
understand. The information in Figure 1a has been redrawn in Figure 2 as a
Parkes error grid with a key showing how to interpret the zones contained within
the grid. Error grid analysis of the different meters currently available in New
Zealand is available on www.pharmac.govt.nz/usingmedicine
and shows that all locally available meters perform to a satisfactory standard.
Figure 2. Comparison of simultaneously
collected venous plasma with capillary glucose results
 Clinical implications of limitations in meter accuracy and precision, in other settingsIn other settings, for example in the ICU, factors related
to patient pathology such as hypoxia, hypoperfusion and extremes of haematocrit
may lead to additional sources of error.5 Also,
increased viscosity, which is common in severely dehydrated patients, may impair
capillary strip filling and give an erroneous result with some older
systems.10 It is therefore of passing interest
to note that one reason why very tight glycaemic control in some ICU settings
may result in adverse clinical outcomes,11
relates to the difficulty of safely achieving tight control with intravenous
insulin, when insulin dose is determined using capillary meter glucose
values.12
Another situation where meter inaccuracy and imprecision can
amplify errors in glucose measurement is with CGM (continuous glucose
monitoring) systems,13 as the CGM biosensor
requires ongoing calibration using finger stick readings from a conventional
meter.
Minimising sources of error in the real world settingThe above discussion on meter performance is based
predominantly on tests undertaken under controlled conditions by trained
technicians. In the real world setting,14
end-user (patient or health practitioner) error, including problems with
interpretation of glucose results, may have negative clinical consequences. In
theory, errors can be minimised by reviewing patients’ meter technique on
a regular basis,1 and also by undertaking
quality control checks using commercial control solutions supplied by meter
manufacturers for use with their specific meter. In practice, a combination of
cost of these control solutions and their short shelf life after opening, limits
their use to selected service providers such as hospital based point of care
co-ordinators.
End-user error is minimised by the multiple safety features
embedded into currently available meter systems but many potential sources of
error remain. The clinical cases below describe extreme examples of real world
problems that can occur with current meter systems. We hope that these
illustrations will help improve clinicians’ awareness of potential
problems, as well as help them with troubleshooting. Although major errors in
glucose measurement are rare, minor errors are not uncommon. Further
descriptions of common potential sources of error are given in Table 2.
Case studiesCase 1—Meter not coded for current batch of test stripsA patient was diagnosed with Type 1 diabetes 2 years
previously and undertook frequent glucose testing. He had a year-long
discrepancy between his home glucose results, which were consistently
<10mmol/L and his laboratory glucose results which were >10mmol/L. During
the same year his HbA1c increased from 8.5% to 11%. Thus there was a discrepancy
between his finger stick and laboratory values. On reviewing meter technique, he
was found not to have recoded (recalibrated) his meter since the time of
diagnosis. The combination of an old strip batch code and currently available
test strips produced meter glucose results that were much lower than their real
value, leading to significant under-dosing of insulin. The patient was given
structured meter education at the time of diagnosis but does not recall
receiving instructions about calibration and did not recall any update on meter
use at any subsequent appointment.
Comment: This problem is
common.15,16 Another common problem is
inadvertent use of time expired strips,2 which
is less likely to occur in systems that use a strip calibration code which also
signals that the strip batch is past its expiry date . Regular review of meter
technique is recommended, but it may be difficult to achieve in our resource
constrained environment.
Table 2. Commoner potential sources of error in
glucose meter measurement in the ambulatory setting
 Case 2—Dilutional errorAn adolescent on insulin had a history of recurrent diabetic
ketoacidosis. She had a ‘contract’ with her parents to show them her
latest glucose value recorded on her meter. Her parents reported observing
satisfactory glucose results. Computer download of her meter’s memory
demonstrated clusters of tests undertaken over several minutes. A typical series
of glucose results was: 21mmol/L at initial testing followed by 18, 10 and
6mmol/L over the next 5 minutes.
Comment: It is physiologically impossible
to drop glucose levels by this magnitude over 5 minutes. It was assumed she was
manipulating results by undertaking self-dilution of samples, so that the
glucose on the meter display read 6mmol/L, rather than 21mmol/L. Downloading
glucose results from memory meters and comparing this with self recorded glucose
results often highlights discrepancies in self reported
results.17 The concentration of salivary
glucose is much lower than that of blood,18
thus ‘licking fingers clean’ prior to testing may also cause a
dilutional error, as can hand washing followed by incomplete hand drying. These
errors are usually unintentional, but can on occasions be intentional.
Case 3—Change of meter from one calibrated to whole blood glucose, to a system calibrated to plasma glucoseA patient with Type 1 diabetes had tight glucose control
(HbA1c 6.4%), frequent minor hypoglycaemia and hypoglycaemic unawareness. He
updated his meter system but was unaware that his old meter was calibrated to
read as whole blood yet his new meter read as venous plasma equivalent. Glucose
values from the new meter therefore ‘read higher’ than those from
the old meter. The patient concluded that glycaemic control had deteriorated and
increased his insulin. He then had a hypoglycaemic fall and sustained a
fracture.
Comment: All subsidised meters in New
Zealand read glucose as plasma and this calibration related scenario is
therefore now uncommon. However there are some countries that still use meters
calibrated to whole blood,2 thus patients with
diabetes who move to New Zealand may need additional education when changing
meters. This case also highlights the fact that patients become familiar over
time with how their own meter functions and reads and they incorporate meter
performance characteristics into their everyday self care.
Case 4—Interfering substancesA 53-year-old with insulin treated diabetes was commenced on
peritoneal dialysis. He experienced unexplained severe hypoglycaemic symptoms
despite apparently normal or elevated glucose readings using the Accuchek
Perfoma meter. His high mean glucose value from the Performa meter contrasted
with his normal HbA1c value of 5.4%. Paired glucose meter tests were then done
using both the Performa meter (strips use a glucose dehydrogenase system) and
Glucocard meter (strips use a glucose oxidase system).
A Performa glucose reading of around 8.0mmol/L corresponded
to 2.0mmol/L using the Glucocard. T The attending clinical team was advised by
the local laboratory that systemic absorption of 7.5% icodextrin from the
peritoneal dialysis fluid was a source of interference for the glucose
dehydrogenase based strip systems using pyrroloquinoline quinone as a cofactor
(which include Performa, Freestyle Lite, On Call Advanced, but not the Xceed or
CareSens systems). Thus interference from icodextrin resulted in artefactually
high glucose levels.5,13 This was rectified by
changing the patient to a glucose oxidase based meter/strip system.
Comment: Many other substances, including
high dose ascorbic acid and aspirin,5,13 may
also interfere with glucose measurement (see Table 2) but, in contrast to
icodextrin, they usually produce only a small change in measured glucose value.
Case 5—Meter reading glucose values as mg/dLA teenager with Type 1 diabetes switched meters and
inadvertently set his new meter to the mg/dL setting (i.e. to the glucose units
used in the USA and several other countries) rather than to mmol/L. The
conversion factor between the two units is 18:1. The patient was unclear how to
interpret results, but worked on the assumption that 100mg/L equated to
10mmol/L.
He therefore titrated his insulin dose to achieve results
between 40mg/L and 100mg/L (i.e. 2.2 to 5.6mmol/L), assuming erroneously that
this was equivalent to 4 to 10mmol/L. Over the next four months, the
patient’s HbA1c dropped from 8.7% to 5.9%. He experienced frequent
hypoglycaemia and excessive weight gain and developed hypoglycaemic unawareness.
Fortunately all these negative clinical developments reversed when the error was
identified and corrected.
Comment: Whilst this patient’s
persistent misinterpretation of results was unusual, we have witnessed patients
making similar errors for short periods of time. The Care Sens meters are able
to be set to read glucose units as either mg/dL or mmol/L. This may be
advantageous for occasional patients who move between countries and health
systems that utilise different units.
ConclusionsMeter analytical performance and ease of use has improved
markedly over recent years. Safety features in the meter and strip systems may
result in potentially erroneous values being ‘disallowed’, for
example by giving an error message. Also, there are now far fewer potential
sources of errors in measurement, but errors in measurement and in
interpretation of results can nevertheless occur. An understanding of glucose
physiology and meter performance should help minimise meter related errors and
help with trouble shooting.
Most published data about meter performance is based on
assessments undertaken in controlled environments. The error contribution made
by end users (i.e. patients and health care practitioners), in real world
settings is acknowledged to be large. There are however few systematic studies
of the reasons for and magnitude of this source of error. Patients and their
health practitioners therefore need to remain vigilant about the possibility of
meter error. Undertaking occasional comparisons between simultaneous laboratory
and finger prick samples measured on the patient’s own meter system and
undertaking regular reviews of meter technique remain important tools for
minimising errors.
Clinicians want their meter derived glucose results to show
close agreement with a plasma laboratory value. There are however challenges in
achieving this, which relate in part to intrinsic physiological differences
between these two specimens. Although current meter systems are accurate, they
lack precision and only 95% of results might fall within 20% of the reference
plasma laboratory value. Clinicians need to be aware of this fact, especially in
situations such as diabetes in pregnancy and insulin pump therapy, where the
patients and their health care team are aiming for tight glucose control. In
practice, patients who use the same, familiar meter system over a prolonged
period seem to be the least troubled by issues related to meter accuracy and
imprecision. This may in part be because regular use of the same meter system
yields consistent readings in similar situations. From the health
practitioner’s perspective, an understanding of the differences between
currently available funded meter systems should enable practitioners to select
meters that best fulfil their patients’ and their practice’s needs.
Encouraging staff and patients within your practice to become very familiar with
one or two meter systems allows for an in depth understanding of the behaviour
of that particular meter system and its related software for downloading of
meter results, in the real world setting.
Author information: Helen Lunt, Physician
and Clinical Senior Lecturer, Christchurch Diabetes Centre and Department of
Medicine, University of Otago, Christchurch; Christopher Florkowski, Associate
Professor of Clinical Biochemistry, Canterbury Health Laboratories; Michael
Bignall, Therapeutic Group Manager, PHARMAC; Christopher Budgen, Point of Care
co-ordinator, Canterbury Health Laboratories.
Acknowledgements: We thank Christchurch
Diabetes Centre staff for providing the Case Studies and acknowledge the
contribution of patients in our local studies of glucose meter performance.
Deborah Kendall, research nurse, was responsible for the co-ordination of the
clinical studies on which much of the authors’ experience of the
performance of newer meters is based. We also thank the New Zealand distributors
of glucose meters for their help in providing details of their meter’s
technical performance.
Correspondence: Dr Helen Lunt, Diabetes
Centre, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand.
Fax: +64 (0)3 3640171. Email: helen.lunt@cdhb.govt.nz
References:
This article was corrected on 9 April 2010 to
reflect the Erratum published at http://www.nzma.org.nz/journal/123-1312/4069
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