Scandinavian Journal of Clinical & Laboratory Investigation, 2014; 74(Suppl 244): 2733

ORIGINAL ARTICLE

Diagnosis of gestational diabetes

DONALD R. COUSTAN

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Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Providence, RI, USA
Abstract
Previous approaches to diagnosing gestational diabetes mellitus (GDM) have included 50 g, 75 g and 100 g glucose challenges, lasting 13 hours, with 1 or 2 elevations required. Thresholds were validated by their predictive value for subsequent
diabetes, or were the same thresholds used in non-pregnant individuals. None were based on their prediction of adverse
pregnancy outcomes. Diagnostic paradigms vary throughout the world, making comparisons impossible and severely limiting communication among investigators. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study collected
outcome data on 23,000 pregnancies recruited prospectively in nine countries after a blinded 75 g, 2-hour oral glucose
tolerance test (OGTT) at 2428 weeks gestation. Primary outcomes (LGA, PCS, neonatal hypoglycemia, high cord
C-peptide), and most secondary outcomes (e.g. preeclampsia, preterm birth, shoulder dystocia and birth injury), were
significantly, directly and continuously related to each of the three plasma glucose measurements. The International Association of Diabetes in Pregnancy Study Groups (IADPSG) developed recommendations for the use of a 75 g, 2-h OGTT,
1 elevation diagnosing GDM, with thresholds: fasting plasma glucose 5.1 mmol/L (92 mg/dL) , 1 h 10 mmol/L (180
mg/dL) and 2 h 8.5 mmol/L (153 mg/dL). These have generated wide discussion and are currently being considered
throughout the world. They are pregnancy outcome-based; the 75 g glucose load will bring consistency to GTTs; universal adoption will lead to consistency of diagnostic criteria worldwide; studies of treatment at similarly mild levels of glycemia
have demonstrated improvement in outcomes; use of a single abnormal value will obviate the confusion arising when one
elevated value is encountered. The primary argument against the recommendations is that prevalence of GDM will rise to
1618 %, increasing health care costs. Balanced against this is the world-wide epidemic of obesity, prediabetes and diabetes.
Key Words: Oral glucose tolerance test, glucose challenge test, gestational diabetes mellitus, pregnancy, glucose, macrosomia, preeclampsia

Introduction
There is no international agreement regarding
diagnostic paradigms and criteria for gestational
diabetes mellitus (GDM). The most commonly
used paradigm in the United States [1], promulgated by the American College of Obstetricians and
Gynecologists (ACOG), is a two-step process of
screening with a 50 g, 1 h plasma glucose challenge
test (GCT) followed by the diagnostic test, a 100
g, 3 h oral glucose tolerance test (OGTT) for those
gravidas whose GCT meets or exceeds a cutoff,
such as 7.2 mmol/L (130 mg/dL), 7.5 mmol/L (135
mg/dL) or 7.8 mmol/L (140 mg/dL). There are 2
sets of 100-g OGTT thresholds currently in use in
the US. Both are based on the original studies of
OSullivan and Mahan [2] in which 100-g, 3-h
OGTTs were administered to 752 gravidas in the
second and third trimesters and whole blood glucose determinations using the Somogyi-Nelson

method of glucose concentration measurement

were evaluated as predictors of subsequent diabetes
in the mothers. Two or more OGTT values exceeding 2 standard deviations above the mean (Table I)
identified women whose risk of diabetes in the
ensuing 20 years was approximately 50 % [3]. The
requirement for two elevated values was based
upon the desire to avoid misclassification due to
laboratory error or the occasional individual with a
single high glucose peak due to rapid absorption
[2]. In subsequent years most laboratories switched
from venous whole blood glucose measurements
to venous plasma; in 1979 the National Diabetes
Data Group (NDDG) recommended conversion of
the OSullivan thresholds by approximately 15 %
(Table I), to account for the higher levels of measured glucose in plasma than in whole blood [4].
Subsequently Carpenter and Coustan (C&C) further refined the conversion (Table I) to account for

Correspondence: Donald R. Coustan, MD, Attending Maternal-Fetal Medicine Specialist, Women & Infants Hospital of Rhode Island, 101 Dudley Street,
Providence, RI 02905, USA. E-mail: dcoustan@wihri.org
ISSN 0036-5513 print/ISSN 1502-7686 online 2014 Informa Healthcare
DOI: 10.3109/00365513.2014.936677

28

D. R. Coustan

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the more specific enzymatic methods of glucose

measurements in addition to the use of plasma
samples [5]. The above two conversions of the
OSullivan and Mahan criteria are currently in use
throughout the US.
In much of the rest of the world the diagnostic
test for GDM consists of a 75 g, 2-h OGTT. Until
recently, the World Health Organization (WHO)
promulgated one set of widely used diagnostic criteria which were basically the same as those used to
diagnose diabetes and impaired glucose tolerance
in non-pregnant individuals [6]. Other diagnostic
criteria included those of the Canadian Diabetes
Association [7] and the Australasian Diabetes in
Pregnancy Society [8].

Why the need for new diagnostic criteria?

In 1991 the Third International Workshop-Conference on Gestational Diabetes noted that there was
no international agreement on diagnostic testing for
GDM, with 50, 75 and 100 g glucose loads utilized
in various parts of the world, with various sets of
diagnostic criteria even with a particular glucose
challenge [9]. Furthermore, the OSullivan criteria
were validated by their predictive value for subsequent diabetes in the mother, while the WHO criteria were not developed for pregnant women, but
rather were the same criteria as for non-pregnant
individuals. None of the existing criteria were based
upon pregnancy outcomes, despite the fact that this
was the primary reason for testing pregnant women
for GDM. It was expected that the 75-g, 2-h OGTT
eventually would be universally employed, since this
was already the case for diagnosing diabetes outside
of pregnancy. The report concluded that internationally agreed upon, outcome-based criteria for GDM
using the 75-g 2-h OGTT were highly desirable.
Without agreement on such criteria, it is impossible
to compare the prevalence of GDM across countries,
and to assess the benefits or harms of identification
and treatment. Seven years later the Fourth International Workshop-Conference on Gestational Diabetes [10] noted that little progress had been made, and
stated, there remains a compelling need to develop
diagnostic criteriabased on the specific relationships between hyperglycemia and the risk of adverse
outcome. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was developed in
response to that need.

The HAPO study

The HAPO study [11] was designed to determine
what level of glucose intolerance during pregnancy,
short of diabetes, is associated with increased risk of
adverse outcome. It was a prospective observational
study in which pregnant women in 15 field centers

Table I. Various thresholds for diagnosing gestational diabetes with

100 g, 3-h OGTT. Two or more elevated values are needed for
diagnosis (mmol/L [mg/dL]).
Test
interval
Fasting
1h
2h
3h

OSullivan [2]a
mmol/L
5.0
9.2
8.0
7.0

(90)
(165)
(145)
(125)

National
Diabetes Data
Group [4]b
5.8
10.6
9.2
8.0

(105)
(190)
(165)
(145)

Carpenter &
Coustan [5]c
5.3 (95)
10.0 (180)
8.6 (155)
7.8 (140)

aVenous whole blood, Somogyi-Nelson technique, rounded to

nearest 5 mg/dL.
bCorrected for conversion from whole blood to plasma, based on
rounded OSullivan values.
cCorrected for conversion of whole blood to plasma and SomogyiNelson to enzymatic glucose concentration measurement, and
based on original unrounded OSullivan values.

in nine different countries throughout the world were

recruited between 2000 and 2006, underwent a
blinded 75 g, 2-h OGTT at a mean of 28 weeks
gestation (range 2432 weeks), and delivered at the
field center so that data regarding maternal and neonatal outcomes could be collected. Over 23,000
women completed the study. Primary outcomes
included large babies (birth weight above the 90th
percentile), primary cesarean section, fetal hyperinsulinemia (cord C-peptide above the 90th percentile), and clinically diagnosed neonatal hypoglycemia.
Figure 1 demonstrates that each of the three OGTT
values was significantly and linearly related to each
of the four primary outcomes; there were no evident
inflection points in any of these relationships. The
relationships held even when adjusted for various
confounders such as fetal/neonatal gender, maternal
BMI, field center, ethnicity, and gestational age at
the time of the OGTT. Similar relationships were
present for pre-specified secondary outcomes such
as preeclampsia, birth trauma/shoulder dystocia and
premature delivery. Again, there were no obvious
inflection points, and it was clear that outcome-based
diagnostic criteria for gestational diabetes would of
necessity be arbitrarily selected.

IADPSG recommendations
In 2008, the International Association of Diabetes
and Pregnancy Study Groups (IADPSG) convened
a meeting of over 220 delegates representing professional groups in 40 different countries to consider
data from the HAPO study as well as other published
data. A consensus panel of approximately 50 delegates met afterwards and organized a writing group
who worked diligently over the following year to draft
recommendations that were then considered at a second meeting in 2009. Thresholds were selected which
identified pregnancies in which the risks of various
adverse outcomes were increased with an odds ratio
of 1.75, compared to mean glucose concentrations.

Diagnosis of gestational diabetes

Birth Weight >90th Percentile

29

Primary C-Section

30

25

30

20

25

Frequency (%)

Frequency (%)

35

15

10

20
15
10
5
0

0
1

Glucose Category

Glucose Category
Clinical Neonatal Hypoglycemia

Cord C-Peptide >90th Percentile

5.0

35

4.5
30

4.0

25

Frequency (%)

3.5

Frequency (%)

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3.0
2.5
2.0
1.5

20
15
10

1.0

0.5
0

0.0
1

Glucose Category

Glucose Category
Fasting

One hour

Two hour

Figure 1. Associations between each of the three OGTT values and each of the four primary outcomes in the HAPO study. From HAPO
Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358:19912002. Copyright 2008
Massachusetts Medical Society. Reprinted with permission.

The resulting recommendations were published in

Diabetes Care in March of 2010 [12]. Salient features
of the recommendations include:

Early pregnancy diagnostic testing of either

all pregnant women, or only those with risk
factors, to detect pre-existing diabetes with a
fasting plasma glucose 7.0 mmol/L (126
mg/dL), HbA1c 6.5 % or random plasma
glucose 11.1 mmol/L (200 mg/dL), with the
latter test requiring confirmation by either of
the first two.
A one-step approach to testing for GDM in
which the diagnostic test, a 75-g, 2-h OGTT,

is administered at 2428 weeks gestation to all

gravidas who have not been previously diagnosed with diabetes. Gestational diabetes is
diagnosed if one or more of the following
thresholds is met or exceeded:

Fasting: 5.1 mmol/L (92 mg/dL)

1 h post 75 g: 10.0 mmol/L (180 mg/dL)
2 h post 75 g: 8.5 mmol/L (153 mg/dL)

These new criteria are the only diagnostic

thresholds based upon pregnancy outcomes rather
than either their prediction of subsequent maternal
diabetes or the values used to diagnose diabetes in

30

D. R. Coustan

Table II. Rates (%) of adverse outcomes in HAPO subjects without and with GDM by IADPSG criteria [12] and untreated and treated
mild GDMs in MFMU network randomized trial [21].
Normal 75 g,
2 h OGTT [12]
LGA (birth weight 90th percentile
Fetal hyperinsulinemia (cord C-peptide 90th percentile)
Neonatal adiposity (percent body fat 90th percentile)
Preeclampsia
Shoulder dystocia/birth injury

8.3
6.7
8.5
4.5
1.3

GDM (IADPSG
proposed criteria)a
16.2
17.5
16.6
9.1
1.8

Untreated mild
GDMs [21]b

Treated mild
GDMs [21]

14.5
22.8
NAc
5.5
4.0

7.1
17.7
NAc
2.5
1.5

differences significant at p 0.01 or better.

differences significant at p 0.02 or better.
cPercent body fat not reported, but neonatal fat mass significantly lower in offspring of treated mothers.
aAll

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bAll

non-pregnant individuals. They utilize the same 75

g 2 h OGTT protocol as is universally accepted for
testing outside of pregnancy. The one-step approach
with a single abnormal value needed for diagnosing
GDM simplifies the process, and also eliminates the
confusing issue of management of patients with a
single elevated 100 g, 3 h OGTT value where two
elevations are necessary. It should be noted that,
when compared to all subjects in the HAPO study
who did not have GDM under the recommended
diagnostic criteria (rather than to those whose glucose values were at the means), GDMs had a doubling or more for most of the adverse outcomes
(Table II).

Why not use the IADPSG recommendations?

There has been considerable resistance to the universal adoption of the IADPSG recommendations
[13,14]. In 2013 the United States National Institutes of Health convened a Consensus Conference
to consider all aspects of screening and diagnosis of
gestational diabetes [15]. A panel of individuals
from various health professions and fields, assumed
to be unbiased because none had published in the
area of gestational diabetes, was convened. Experts
presented reviews regarding pros and cons of the
new and the existing recommendations, potential
ramifications, and systematic analyses of existing
data by the Agency for Healthcare Research and
Quality (AHRQ). A draft recommendation was
published on the web, and after public comments
were considered, the final document was published
[15]. The panels recommendation was that, while
a standardized, universal approach would be desirable, the two-step approach currently widely used
in the United States (a 50 g, 1 h GCT followed by
a 100 g, 3 h OGTT with 2 or more elevated values
diagnosing gestational diabetes) should be continued because there is not yet sufficient evidence to
adopt the one-step approach recommended by
IADPSG. The rationale for this recommendation
included the following:
(1) Adoption of the one-step approach would
increase the prevalence of GDM to 1520 %.

The care of these additional women will

increase health care costs.
(2) While the additional women who would be
diagnosed with GDM under the one-step process are at increased risk for various adverse outcomes, it is not clear that they would benefit
from identification and treatment.
(3) Identification of these additional women as
having GDM may increase patient anxiety, and
may also increase obstetrical harms such as
induction of labor, intensive maternal/fetal
monitoring, and cesarean section.
(4) Because of the variability in the 2-h OGTT, the
one-step approach is likely to generate more
false positive results than a two-step test.
(5) Having to fast for the diagnostic test, and waiting 2 hours instead of the 1-hour interval for
the screening test, poses an additional burden
for patients.
While each of these is a valid concern, it is worth
considering the counter-arguments.
Increased prevalence of GDM will lead to increased
health care costs
This should be viewed in the context of the current
epidemic of obesity and diabetes throughout the
world. For example, in 20072010, 11.9 % of adult
Americans have diagnosed or undiagnosed diabetes
[16]. An additional 36 % of all adult Americans,
and 26 % of those between the ages of 18 and 44
years, have prediabetes [17]. GDM as defined by
the IADPSG recommendations is somewhat akin
to prediabetes. Thus an 18 % prevalence of GDM
would be considerably lower than the current prevalence of diabetes and prediabetes in our population. Despite the fact that increasing the thresholds
for diagnosing diabetes and prediabetes in nonpregnant individuals would lower the prevalence
and decrease short-term health care costs, no one
advocates that solution. Rather, our various health
care systems work to develop improved methods to
provide efficient and effective care to those afflicted
with diabetes, and to prevent the eventual development of diabetes in those with prediabetes. As the

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Diagnosis of gestational diabetes

prevalence of gestational diabetes increases markedly, as is already the case using the current twostep approach [18], it will be important to develop
novel approaches to counseling and care. It is likely
that patients with milder gestational diabetes may
not require daily self-glucose monitoring, and could
test every other day or even less frequently [19].
Group prenatal visits and counseling may be a reasonable way to lower costs and improve quality of
care. It is an open question whether the risk of
stillbirth with milder GDM is high enough to
require antenatal testing with the same intensity as
for more severe GDM and for pre-existing diabetes.
It is worth noting that diet treatment was successful
in attaining good glucose control in 8092 %
of mild GDMs in randomized trials [20,21] suggesting that expanding the prevalence of GDM will
not lead to large numbers of patients requiring
insulin or oral agents. A recent study compared the
cost-effectiveness of universal diagnostic testing
with the IADPSG one-step approach and screening
with the current ACOG two-step approach [22].
The investigators took into account available data
regarding benefits of treatment in preventing
preeclampsia and other adverse outcomes for mild
gestational diabetes. The compilation of the costs
of treatment of GDM did not assume less intensive
monitoring or intervention for the milder GDMs,
a potential cost-saving opportunity discussed
above. The IADPSG one-step approach was more
expensive than the two-step approach but was more
cost effective in improving maternal and neonatal
outcomes.
Although the IADPSG recommendations were
based on the likelihood of adverse pregnancy outcomes, women who meet these GDM criteria are
presumably also at increased risk for the development of type 2 diabetes. Diagnosing GDM constitutes a teachable moment, an opportunity to
counsel patients about the likelihood of subsequent
diabetes, ways of reducing that risk, and the importance of testing after pregnancy and at intervals
thereafter to detect diabetes in its early stages.
Another recent study [23] compared the cost-effectiveness of the one-step versus two-step approaches
and reported that the IADPSG one-step approach
was cost-effective if post-delivery care reduces the
incidence of subsequent diabetes in the mother.
This finding underscores the importance of caregivers using the occasion of the diagnosis of GDM
to counsel patients about the risk of diabetes in the
future, and arranging follow-up testing and care for
former GDMs. In an analysis of the subgroup of
350 subjects in the Diabetes Prevention Program
who had previous GDM and prediabetes at enrollment, the annual incidence of type 2 diabetes of
15 % was cut in half by either metformin treatment
or intensive lifestyle intervention [24]. The number
needed to treat to prevent one case of diabetes over

31

3 years was six for metformin and five for intensive

lifestyle intervention.
Uncertainties regarding benefits of identifying and
treating so many additional GDMs
There are no randomized trials of identification and
treatment of GDM using the new IADPSG diagnostic thresholds. However, there are two published
randomized trials using other criteria for mild gestational diabetes, in which many of the subjects
would have overlapped with the new criteria. The
Eunice Kennedy Shriver NICHD Maternal-Fetal
Medicine Network (MFMU) trial [21] enrolled 958
gravidas whose blinded OGTT (administered after
a 50 g 1 h GCT was 7.511.1 mmol/L [135200
mg/dL]) demonstrated two elevated values (Carpenter & Coustan criteria) but whose fasting plasma
glucose was 5.3 mmol/L (95 mg/dL). Although
the glucose challenge was 100 g rather than 75 g,
the fasting, 1 and 2 h mean values of the subjects
were within one standard deviation of the IADPSG
cutoffs for fasting, 1 h and 2 h time periods. Participants were randomized to identification and
treatment of GDM versus usual care, with caregivers blinded to the OGTT results in the latter group.
Identification and treatment of GDM reduced the
likelihood of large for gestational age ( 90th percentile) and macrosomic ( 4 kg) babies by more
than half. Cesarean section, shoulder dystocia and
preeclampsia were also significantly lower. Rates of
these various adverse outcomes in the untreated
group were similar to the rates in HAPO study participants who would have GDM under the new criteria (Table II), and who also were neither identified
nor treated as GDMs in this observational study.
Identification and treatment of GDM in the MFMU
trial reduced these rates considerably.
The other randomized trial of identification and
treatment of GDM [20] recruited patients whose
elevated 75 g, 2-h OGTT results were based on
thresholds lower than those of the IADPSG recommendations. Gravidas whose 2 h, 75-g OGTT values were 7.811.1 mmol/L (140199 mg/dL) made
up the study cohort, as long as their fasting plasma
glucose was 7.8 mmol/L ( 140 mg/dL). The
mean fasting plasma glucose in subjects was 4.8
mmol/L (86 mg/dL). Recall that the IADPSG recommended 2-h cutoff for GDM was 8.5 mmol/L
(153 mg/dL). Using a similar study design to the
MFMU Network study described above, the investigators found very similar reductions in adverse
outcomes with identification and treatment of GDM.
While neither of the above two RCTs used the identical GDM criteria as IADPSG, and both used a
two-step approach to identifying potential subjects,
the results demonstrate a benefit to identifying and
treating GDM which was mild, with thresholds overlapping those of the IADPSG.

32

D. R. Coustan

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Fasting and waiting 2 hours for the test is an

additional burden
With the 2-step process, for patients whose 50 g, 1-h
GCT is below the threshold for further testing, there
is no question that having the test without regard to
the last meal, and waiting 1 hour for the blood draw,
is preferable to fasting and waiting 2 hours for test
completion when the one-step process is followed.
However, patients whose screening test exceeds the
threshold must come on a subsequent occasion, fasting, for the diagnostic OGTT and wait 3 hours for
completion. Depending upon the threshold chosen
for the screening portion of the two-step process, and
the racial/ethnic characteristics of the population,
between 9 and 30 % require the additional OGTT
[25]. For those patients the burden of two separate
visits, one of which is in the fasting state, and a total
of 4 hours time with five blood draws, compares
quite unfavorably with a single visit (fasting), 2 hours
time, and three blood draws.
The 2-h OGTT is unstable and the 1-step test is likely
to increase false positives
There is no doubt that glucose tolerance tests are
unstable, with less than optimal precision. However,
the one-step test is a diagnostic test, and not a screening test, so false positives are not a consideration. If
the consensus panel used the term false positive to
mean individuals who are diagnosed with GDM who
do not have adverse outcomes, then it is implied that
the diagnosis of GDM is a screening test with the
disease being the adverse perinatal outcomes. In
that case, both the one-step and the two-step process
will have many false positives not to mention false
negatives pregnancies in which adverse outcomes
occur in the absence of GDM. However, identifying
and treating GDM has never been considered as a
way to prevent all big babies, or all cases of preeclampsia. Rather, GDM offers the opportunity to prevent adverse outcomes in a particularly high-risk
group of patients. Finally, it must be pointed out that
instability of the 75 g, 2-h OGTT is not limited to
pregnant women. This test is the world-wide standard for diagnosing diabetes in nonpregnant individuals, despite its instability.

Current status
The IADPSG recommendations were published in
2010. In 2011 the American Diabetes Association
(ADA) adopted these recommendations with a few
minor changes [26], although in 2014 ADA altered
its recommendations [27], such that either the onestep or the two-step protocol was acceptable, based
on the NIH Consensus Panels 2013 recommendations. ACOG continues to support the two-step
approach [1]. In 2013 the World Health Organization

adopted the recommendation for the one-step

IADPSG approach [28]. At the time of this writing
professional organizations throughout the world are
considering whether to adopt some variation of the
IADPSG one-step approach, or to continue with the
various other approaches currently in use. As more
research is carried out with the IADPSG approach,
the situation is likely to be clarified, although this will
probably take considerable time. It is to be hoped
that eventually there will be a single, uniform
approach to identifying GDM in use throughout the
world.
Questions and answers
Q (Young): Which recommendations are being used
in the USA?
A (Coustan): In the USA we are waiting for the
ACOG recommendations for gestational diabetes.
Q (OShea): Regarding screening for gestational
diabetes, you have spoken of the disparity between
the USA and Europe, but we have disparity in
approach in Ireland. There are several issues:
(1) One problem is economic because, to have
fasting, 1-hour and 2-hour specimens collected, the patients have to stay for a long
period in the clinic which can be difficult for
them. Could we do just the 1-hour specimen,
since the 2-hour value picks up only an additional 2 % of cases?
(2) Could we do fasting glucose and HBA1c picking up at least 20 % of cases then screen the
others fully?
(3) Should there be universal screening or targeting of those at high risk?
A (Coustan): A single, fasting measurement is
ideal for convenience but also a 1 hour, or fasting
and 1-hour or 2-hour post glucose load, all contribute independently to adverse outcomes and for this
reason, all three are recommended. However, in different centers there are different attitudes.
Regarding HbA1c, it is very useful in early pregnancy in pre-existing diabetes. Its not very sensitive
for gestational diabetes. Economic problems are a big
issue in every country but the solution is not to
ignore the problem and strive for cheaper solutions.
Q (Kallner): When we make these recommendations we work with population means and medians
but when we move to the real world we have to judge
results from an individual patient: When you say 5.1
mmol/L as cut off for fasting glucose, that translates
into an individual result with an uncertainty. If you
look at the German recommendation they allow an
uncertainty of 11 % (95 % level) for glucose measurements. This means 1 mmol/L, i.e. an uncertainty interval of 4.16.1 (k 2) mmol/L. In a recent
study we found an uncertainty of 3 % or 4.95.3
mmol/L (k 2). The cut-off is not as distinct as you

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Diagnosis of gestational diabetes

assume and decisions need to take the uncertainty
into account.
A (Coustan): In the laboratory this is a problem
not only for glucose. What is the alternative to cutoff? It depends on a good quality control in the laboratory. There is concern in the real world on the real
value of the quality control. Whether the CV is 1 %
or 5 %, there has to be a cut off somewhere.
Q (Kallner): As an alternative we may incorporate
the uncertainty depending on what you want, to
increase sensitivity or specificity.
A (Coustan): That is true for screening but not
for diagnosis.
Q (Kallner): It could be applied also to diagnosis.
Do we know if the cut-off has been set to optimize
rule-in or rule-out?
Comment (Young): The test is defining the disease
so it is difficult to speak about the sensitivity and
specificity of the test.
Comment (Lazzarotto): A screening test needs
very high sensitivity, and consequently the specificity
could be lower.
Comment (Coustan): I do not agree because I
would like 100 % for both sensitivity and specificity.
Declaration of interest: The author reports no
conflicts of interest. The author alone is responsible
for the content and writing of the paper.

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