Clin Chem Lab Med 2018; 56(9): e223–e225
Letter to the Editor
Kaustubh Bora*, Bhupen Barman and Abdul Wahid Ayubi
The curious case of postprandial glucose less than
fasting glucose: little things that matter much
https://doi.org/10.1515/cclm-2017-0984
Received October 25, 2017; accepted February 1, 2018; previously
­published online April 7, 2018
Keywords: diabetes mellitus; glucose; patient education;
preanalytical phase; stress test.
To the Editor,
Diabetes mellitus is characterized primarily by hyper­
glycemia, and its detection is based on the laboratory
measurement of plasma glucose and/or glycated hemo­
globin (HbA1c). According to the American Diabetic Asso­
ciation recommendations, the fasting plasma glucose
(FPG), the 2-h postprandial glucose (PPG) after a 75-g
oral glucose tolerance test (oGTT) and the HbA1c criteria
are all appropriate for diagnosis of diabetes. However, it
was reinforced that as compared to the FPG and HbA1c cut
points, the 2-h PPG value diagnoses more people with dia­
betes. As the concordance between these three tests is not
always perfect, they may not necessarily detect diabetes in
the same person [1]. Thus, performing these tests together
improves diabetes detection and maximizes case finding.
Although convenient and straightforward, confusing
and anomalous results may sometimes be obtained during
diabetes testing due to seemingly trivial factors, as the
following report highlights. Two patients, husband and
wife (both long-standing hypertensives on regular losar­
tan medication), aged 55 and 50 years, respectively, were
advised by their physician for diabetes testing as they were
hypertensive, obese, had sedentary lifestyle and had family
*Corresponding author: Dr. Kaustubh Bora, ICMR – Regional Medical
Research Centre, N.E. Region, Dibrugarh 786010, Assam, India,
Phone: +919435572062, E-mail: kaustubhbora1@gmail.com; and
Department of Biochemistry, North Eastern Indira Gandhi Regional
Institute of Health and Medical Sciences, Shillong, Meghalaya, India
Bhupen Barman: Department of Internal Medicine, North Eastern
Indira Gandhi Regional Institute of Health and Medical Sciences,
Shillong, Meghalaya, India
Abdul Wahid Ayubi: Department of Pathology, North Eastern Indira
Gandhi Regional Institute of Health and Medical Sciences, Shillong,
Meghalaya, India
history of diabetes. Their fasting blood samples (collected
by phlebotomist at 9:00 a.m. on outpatient basis) were
received in our lab in sodium fluoride/potassium oxalate
tubes and dipotassium-ethylenediamine­ tetraacetic acid
(K2-EDTA) tubes and processed for FPG and HbA1c estima­
tion, respectively. The FPG values of the two patients (10.3
and 10.9  mmol/L, respectively) were elevated (reference
range <6.1  mmol/L), as were the HbA1c results (63.9 and
67.2  mmol/mol, respectively; reference range <42  mmol/
mol) and thus conformed to the diagnosis of diabetes mel­
litus [1]. After collection of the fasting samples, the patients
had undergone oral glucose load (75 g anhydrous glucose
dissolved in 300 mL water). And as per protocol, the post­
prandial samples collected after 2 h (at 11:15 a.m.) were also
received in our lab in sodium fluoride/potassium oxalate
tubes and processed for PPG testing. However, the PPG
concentrations were lower than the corresponding FPG
values for both the patients (9.2 and 10  mmol/L, respec­
tively). This was counter-intuitive because the PPG values
are ordinarily expected to be higher than the FPG values.
These measurements were performed in VITROS® 4600
autoanalyzer using dry chemistry slides (Vitros Chemistry
Products, Ortho-Clinical Diagnostics Inc., USA). Approxi­
mate time from blood collection until centrifugation and
measurement was 45  min. The samples were non-icteric,
non-lipemic and non-hemolyzed. HbA1c quantification
was done in a Bio-Rad D-10™ cation exchange high-per­
formance liquid chromatography platform (Bio-Rad Labo­
ratories, Hercules, CA, USA). All the measurements were
validated using commercially available control materi­
als. Repeat testing for glucose using the leftover plasma
samples yielded similar results. Analytical errors seemed
unlikely, and therefore, alternate explanations were sought
for the discrepancy between the FPG and PPG values.
Pre-analytical factors like smoking, antidiabetic
medications, caffeinated items and delay in sample pro­
cessing are known to affect glucose testing [2]. However,
these were not applicable in our case. Meal-induced dip
in circulatory glucose in the postprandial phase – an
entity known as postprandial hypoglycemia – is also
known [3]. However, when enquired, both the patients
denied experiencing any glucopenic/hypoglycemic
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e224      Bora et al.: Postprandial glucose less than fasting glucose?
symptoms after the glucose load. Thus, a rare condi­
tion like postprandial hypoglycemia in both the patients
seemed too coincidental and unlikely. Past history of
bariatric surgical procedures, which may mimic post­
prandial hypoglycemia [3], was also absent. On further
enquiry, it was learned that their physician had advised
a cardiology consultation as well, where a treadmill
stress test (TMT) was deemed necessary. On the day
of diabetes screening, the two patients had taken the
appointment for TMT at the cardiology department of
the hospital too. Moreover, approximately 45  min after
having the glucose load, they had undergone TMT and
achieved exercise stages 4 (for the husband) and 2 (for
the wife) as per Bruce’s modified protocol [4].
Proper counseling and preparation of an individual
is essential to ensure quality laboratory results. Spuri­
ous glucose levels after strenuous exercise is a long
known preanalytical issue [5]. Physical activity pro­
motes glucose uptake in peripheral tissues and may lead
to remarkable decrease in circulating glucose levels in
the postprandial period in type 2 diabetes individuals
via insulin-dependent as well as insulin-independent
mechanisms [6]. Therefore, for accurate documentation
of hyperglycemia, it is recommended to avoid physical
exertion during diabetes screening. Even minor physi­
cal activities like running to the doctor’s chamber or
change in posture during phlebotomy can be a source
of bias during clinical chemistry testing (including
glucose). In fact, recent investigations by Lippi et  al.
[7] highlight the need for standardizing patient posture
during phlebotomy, which may further be preceded by a
minimum period (i.e. 15–20 min) of resting. If for some
reason that is not practicable (e.g. to have patients in an
outpatient clinic rest in one position for 15 min prior to
phlebotomy), then at least the circumstances of physical
activity, if any, may be documented so as to validly inter­
pret the results. In our situation, the spurts of exercise
underwent by the two patients during TMT attenuated
the postabsorptive rise in blood glucose in the postpran­
dial phase. This caused the PPG values to be less than
the FPG values. After 3 days, the tests were repeated (this
time well rested and without physical exertion), and the
PPG values (12.5 and 13.7 mmol/L, respectively) in both
the patients were found to be higher than the FPG values
(10.5 and 11.5 mmol/L, respectively), as expected.
Informed written consent was obtained from both
patients to report these findings. When we enquired if the
two patients had previously received any prior instruction
from the requesting physician or a nurse or phlebotomist
about the requisite precautions like refraining from physi­
cal activity or other sources of preanalytical error (such
as smoking, caffeinated items, dietary habits, etc.) for
glucose testing, it was learned that no such counseling was
provided. They were only informed that two samples will
be drawn for diabetes screening – one sample after over­
night fasting and the other sample 2 h after glucose load
– without any further explanation. Anecdotal evidence
suggests that anomalous test results due to inadequate
patient preparation (e.g. habitual consumption of tea after
waking up or smoking cigarette in the morning, etc. on the
day of glucose testing) may not be an uncommon phenom­
enon. Kackov et al. [8] noted that a substantial proportion
of patients were not familiar with the preparations needed
before undergoing laboratory testing. In their study, they
investigated if patients were adequately prepared for blood
tests needing a fasting state. It was found that more than
50% of the studied subjects had not received any informa­
tion regarding how they needed to prepare themselves for
the testing. Further, a considerable number of patients had
not come adequately prepared for testing even after they
were provided some information about the test require­
ments. The requesting physician is often the preferred
source of information from which patients can familiarize
themselves about the requirements of the requested labo­
ratory tests. According to one study, patients who knew
their general practitioner were more likely to be aware of
the preparations needed for undertaking various blood
tests [9]. On the other hand, R ­ adovanovic and Kocijan­
cic [10] observed that subjects who received information
from the laboratory staff were better informed about the
test procedure (in their case, oral glucose tolerance test)
as compared to those obtaining the information from their
physician. Ensuring error-free and reliable test results is
desirable to all the stakeholders involved in the testing
process, namely, requesting physicians, attending nurses,
laboratory staff and patients [8, 11, 12]. Therefore, it is of
common interest to emphasize upon greater dialogue and
proactive communication between healthcare providers
and patients [8,  9,  11]. The preanalytical phase is a vital
part of the laboratory testing process and also an impor­
tant source of error [11, 12]. In this regard, the laboratory
can play a proactive role by educating the patients about
requirements for the various test parameters and help min­
imize the preanalytical variability [8, 12]. Such information
may be disseminated as succinct and easy-to-understand
instructions towards patient preparation prior to the day
of testing [8], through online databases or through leaflets
(in resource-constrained settings). It would also spare the
patients and staffs of inconveniences and help in reducing
costs due to unnecessary repeat testing. In fact, the labora­
tory can also play a vital role in apprising the clinical and
nursing staff about the importance of preanalytics. Further,
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 Bora et al.: Postprandial glucose less than fasting glucose?      e225
it is desirable that laboratories provide preanalytical, ana­
lytical and postanalytical information on each parameter
they measure. This would enable the clinicians to utilize
the lab resources more efficiently in terms of selection,
preparation and interpretation of tests and help realize the
continuous endeavor of the laboratories to improve their
quality of testing.
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played
no role in the study design; in the collection, analysis and
interpretation of data; in the writing of the report; or in the
decision to submit the report for publication.
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