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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024. | This topic last updated: Jul 05, 2023.
INTRODUCTION
Pregnancy is generally a state of both enhanced beta-cell function and insulin resistance,
mediated primarily by placental secretion of diabetogenic hormones including growth
hormone, corticotropin-releasing hormone, placental lactogen (chorionic
somatomammotropin), prolactin, and progesterone. These and other metabolic changes,
which are most prominent in the third trimester, ensure that the fetus has an ample supply of
nutrients.
Gestational diabetes mellitus (GDM) develops in pregnant people whose pancreatic beta-cell
function is insufficient to overcome the insulin resistance associated with the pregnant state.
Among the main consequences of GDM are increased risks of preeclampsia, large for
gestational age (LGA) newborns, and cesarean birth, and their associated morbidities.
Patients with GDM are at high risk of developing type 2 diabetes later in life, which is not
surprising since both disorders are characterized by inadequate insulin secretion in the
setting of insulin resistance. In contrast to diabetes that develops pregestationally, GDM is
not generally associated with an increased risk for congenital anomalies since hyperglycemia
develops after organ formation is complete.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
Practitioners tend to follow the guidance of their national medical organizations. Approaches
to screening and diagnosis will be reviewed here. Medical and obstetric management and
prognosis are discussed separately:
● (See "Gestational diabetes mellitus: Glucose management and maternal prognosis".)
● (See "Gestational diabetes mellitus: Obstetric issues and management".)
TERMINOLOGY
BACKGROUND
Prevalence — The prevalence of GDM by the traditional Carpenter and Coustan criteria (
table 3B) [4] was 7.8 percent of births in the United States in 2020 [5] and ranged from 2 to
38 percent of pregnant people in other countries [6]. Worldwide prevalence varies because of
differences in population characteristics (eg, average maternal age and body mass index
[BMI]) and choice of screening and diagnostic criteria. Using the 2010 International
Association of Diabetes and Pregnancy Study Groups (IADPSG) screening and diagnostic
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
criteria for diabetes in pregnancy ( table 3C) [7], the global prevalence of GDM has been
estimated to be 17 percent, with regional estimates of 10 percent in North America and 25
percent in Southeast Asia [8].
Prevalence has been increasing over time, likely due to increases in mean maternal age and
BMI, particularly increasing obesity, and changes in screening practices and methods [9-16].
Significance — GDM has been associated with increased risks of several adverse outcomes.
(See "Gestational diabetes mellitus: Obstetric issues and management", section on
'Consequences of GDM'.)
Although treatment of GDM can reduce the risk of some short-term outcomes (eg,
preeclampsia, macrosomia), a favorable effect on the long-term outcomes described below is
unclear. (See "Gestational diabetes mellitus: Glucose management and maternal prognosis",
section on 'Rationale for treatment'.)
● Short-term – GDM has been associated with increased risks of the following problems,
some of which are interdependent [17-21]:
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
Risk factors
Individuals at increased risk of GDM — Pregnant people with any of the following
characteristics appear to be at increased risk of developing GDM. The risk varies across these
characteristics and is additive when multiple risk factors are present [3,32-39]:
● Personal history of any of the following:
Individuals at low risk of GDM — By comparison, the risk of developing GDM is low in
younger (<25 years of age) non-Hispanic White people, with normal BMI (<25 kg/m2 [<23
kg/m2 in Asian people]), no history of previous glucose intolerance or adverse pregnancy
outcomes associated with GDM, and no first-degree relative with diabetes [41]. Only 10
percent of the general obstetric population in the United States meets all of these criteria for
low risk of developing GDM, which is the basis for universal rather than selective screening
[42]. (See 'Candidates' below.)
Lifestyle interventions for risk reduction — Lifestyle interventions (eg, diet modification,
exercise) are targeted at individuals at increased risk for developing GDM, particularly those
who are overweight or obese and those with a history of GDM in a previous pregnancy. The
primary target of lifestyle interventions is weight loss leading to less insulin resistance and
impaired insulin secretion.
● Diet modification and increased exercise – In a meta-analysis of randomized trials,
lifestyle interventions targeted at individuals with a higher baseline risk of GDM (eg, 20
percent incidence of GDM) reduced the risk of GDM by approximately 20 percent
compared with standard care [43]. The interventions included diet modification,
increased exercise, or both, ideally initiated before pregnancy and continuing across
gestation; exercising at the proper intensity and frequency (eg, moderate intensity for
50 to 60 minutes at least twice a week throughout pregnancy); and managing
gestational weight gain so as to not exceed standard recommendations ( table 1).
Individuals who are overweight or obese appear to benefit from weight loss before
conception [44,45], whereas beginning a modest unsupervised exercise program in the
second trimester appears to be inadequate to impact the risk of GDM [46-48]. (See
"Exercise during pregnancy and the postpartum period".)
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
● Type of diet – The optimum diet is unclear. There is limited evidence (none from
randomized trials) that a diet favoring fruit, vegetables, whole grains, and fish and low in
red and processed meat, refined grains, and high-fat dairy reduces the risk of
developing GDM [49,50]. The effect of a low glycemic index diet on risk of GDM is
unclear as only a few small randomized trials have been performed. A meta-analysis of
these trials did not demonstrate a clear benefit, but the confidence interval was wide
(risk ratio [RR] 0.91, 95% CI 0.61-1.31; four trials, 912 participants) [51].
● Smoking cessation – Smoking cessation should be encouraged in all patients. The
association between smoking and GDM is uncertain [32,52] and cessation is often
associated with weight gain; cessation has multiple maternal and fetal benefits and may
reduce GDM. (See "Tobacco and nicotine use in pregnancy: Cessation strategies and
treatment options".)
These interventions overlap with those utilized for prevention of type 2 diabetes and are
discussed in detail separately. (See "Prevention of type 2 diabetes mellitus".)
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
● Myoinositol is a naturally occurring sugar in fruits, beans, grains, and nuts that can
improve insulin resistance. A meta-analysis reported a reduction in GDM with
supplementation (RR 0.53, 95% CI 0.31-0.90; 6 trials, 1140 participants), but limitations
include individual small studies, lack of generalizability, and inconsistency, which may be
related to different doses, timing, and combinations of myoinositol supplementation
[60]. Before this intervention can be recommended, a large multicenter, blinded,
randomized trial is needed to confirm safety and demonstrate improvement in clinically
important maternal and/or neonatal outcomes.
● Potential benefits – A 2021 systematic review by the United States Preventive Services
Task Force (USPSTF) found that screening for GDM at 24 weeks of gestation or after was
associated with some favorable maternal and fetal/newborn outcomes (eg, reduction in
cesarean births, birth injuries, neonatal intensive care unit admissions, stillbirth)
compared with historical unscreened controls [61,62]. These findings were largely
derived from two observational studies [63,64]. In addition, randomized trials have
shown that treatment of GDM can reduce some fetal, neonatal, and maternal
morbidities, particularly macrosomia and shoulder dystocia, and possibly preeclampsia
[61,62]. These data are described separately. (See "Gestational diabetes mellitus:
Glucose management and maternal prognosis", section on 'Rationale for treatment'.)
● Potential harms – The commonly used screening and diagnostic tests for diabetes
involve drinking a glucose-containing beverage followed by blood glucose
measurement. None of the screening or diagnostic tests are associated with serious
harmful maternal or fetal effects, but the hyperosmolar drinks are poorly tolerated by
some individuals since they may cause nausea and vomiting.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
dose. Screening and diagnosis of GDM may lead to over- or undertreatment (treatment
without a favorable effect on outcome) and heighten maternal anxiety, but long-term
psychological harm is unlikely.
The cost implications of screening versus not screening are not clear [65-67].
Diabetes diagnosed early in pregnancy has been called overt diabetes and is assumed to be
previously undiagnosed type 2 diabetes.
Our approach to early pregnancy screening (universal screening by A1C) — Given the
increasing frequency of type 2 diabetes and evidence of a reduced risk of large for gestational
age (LGA) newborns with universal early maternal screening and treatment [73], the author of
this topic checks an A1C level to screen for diabetes as part of the routine prenatal laboratory
studies of all patients at the initial prenatal visit.
● A1C ≥6.5 percent (≥48 mmol/mol) – In nonpregnant people, an A1C ≥6.5 percent (≥48
mmol/mol) is one of the criteria used to diagnose diabetes ( table 2). Therefore, an
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
A1C ≥6.5 percent early in pregnancy, when A1C levels are generally slightly lower than in
the nonpregnant state [74], strongly suggests previously undiagnosed type 2 diabetes.
These patients are managed similar to those with preexisting diabetes mellitus. (See
"Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and
management" and "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic
control" and "Pregestational (preexisting) diabetes mellitus: Obstetric issues and
management".)
● A1C <6.5 percent (<48 mmol/mol) – This is a negative test for diabetes in nonpregnant
people. At 24 to 28 weeks of gestation, the author screens these patients for GDM with
the two-step test. Approximately one-quarter of pregnant people with A1C 5.7 to 6.4
percent (39 to 47 mmol/mol) suggestive of impaired glucose intolerance in early
pregnancy are diagnosed with GDM when screened with a two-step test later in
pregnancy compared with <10 percent of those with A1C <5.7 percent (39 mmol/mol)
[75]. (See 'One- and two-step approaches' below.)
The author acknowledges that an A1C <6.5 percent (<48 mmol/mol) is not sufficiently
sensitive to detect mildly impaired glucose tolerance, especially if the A1C is ≥5.7 (which
is above the upper limit of normal in nonpregnant individuals), but the overall value of
detecting and treating mildly impaired glucose tolerance in early pregnancy has not
been established in randomized trials [76].
The ADA and ACOG define patients at increased risk of type 2 diabetes based on [2,3]:
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
● GDM in a previous pregnancy.
● Body mass index (BMI) ≥25 kg/m2 (≥23 kg/m2 in Asian Americans) plus one or more of
the following:
In a randomized trial, early pregnancy diabetes screening because of obesity alone (BMI ≥30
kg/m2) did not demonstrate a reduction in a composite of adverse outcomes (eg,
macrosomia, primary cesarean delivery, hypertensive disease of pregnancy, shoulder
dystocia, neonatal hyperbilirubinemia, or hypoglycemia) [77]. Screening was done using a 50-
gram one-hour GTT followed by a 100-gram, three-hour GTT if the initial screen was ≥135
mg/dL. The trial findings were limited by the small number of participants diagnosed with
early GDM (n = 29) and the timing of the early screening, which was between 14 and 20
weeks.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
Targeting screening to symptomatic patients is not useful because many patients are
asymptomatic or have unrecognized mild symptoms. However, those with random blood
glucose values ≥200 mg/dL (11.1 mmol/L) may have symptoms of hyperglycemia (eg,
increased thirst, polyuria, weight loss, blurry vision). (See "Clinical presentation, diagnosis,
and initial evaluation of diabetes mellitus in adults".)
Choice of screening test — No approach has been validated for diagnosis of diabetes in the
first or early second trimester. Clinical practice varies by institution and clinician preference.
Screening practice varies from a hemoglobin A1C alone, fasting glucose alone, a two-hour 75-
gram oral GTT, or two-step test (one-hour 50-gram GTT followed by a three-hour 100-gram
GTT if the 50-gram GTT is positive). (See 'One- and two-step approaches' below.)
● If a two-step test is used, ACOG criteria for diabetes are shown in the tables (
table 3A-B). These criteria are the same as those used for diagnosis of GDM later in
pregnancy.
● If a one-step test is used:
• ADA criteria for diabetes are shown in the table ( table 2). These thresholds are
the same as those used by the ADA for diagnosis of diabetes in nonpregnant people
and were chosen because they correlate with development of adverse vascular
events, such as retinopathy and coronary artery disease, in these individuals over
time [2].
ADA criteria for "early abnormal glucose metabolism" are fasting glucose 110 to 125
mg/dL (6.1 to 6.9 mmol/L) or A1C 5.9 to 6.4 percent (41 to 47 mmol/mol).
• IADPSG criteria for diabetes are similar to ADA criteria: A1C ≥6.5 percent, fasting
blood glucose ≥126 mg/dL (7.0 mmol/L), or random plasma glucose ≥200 mg/dL
(11.1 mmol/L) confirmed by fasting blood glucose or A1C at these levels.
These criteria for diagnosis of diabetes in early pregnancy are different from those used
by the ADA and IADPSG for diagnosis of GDM later in pregnancy ( table 3C).
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
state, they are assumed to have had the disorder prior to the pregnancy and their
management is similar to those with documented preexisting diabetes mellitus in
pregnancy. (See "Pregestational (preexisting) diabetes: Preconception counseling,
evaluation, and management" and "Pregestational (preexisting) diabetes mellitus:
Antenatal glycemic control" and "Pregestational (preexisting) diabetes mellitus:
Obstetric issues and management".)
The benefit of treating a patient whose early pregnancy GTT meets ADA and IADPSG
criteria for GDM ( table 3C) has not been established. A randomized trial including
over 800 pregnant participants with an abnormal two-hour 75-gram oral GTT (defined as
fasting glucose level ≥92 mg/dL [≥5.1 mmol/L], one-hour glucose level ≥180 mg/dL
[≥10.0 mmol/L], or a two-hour glucose level ≥153 mg/dL [≥8.5 mmol per liter]) before 20
weeks of gestation compared immediate treatment versus retesting at 24 to 28 weeks
and starting treatment at that time if results were abnormal [76]. Those discovered to
have overt diabetes at early testing were excluded from randomization (overt diabetes:
fasting glucose level ≥110 mg/dL [≥6.1 mmol/L] or two-hour glucose level ≥200 mg/dL
[11.1 mmol/L]) and treated.
Immediate treatment of patients who meet diagnostic criteria for GDM early in
pregnancy did not result in a clear or substantial reduction in LGA births (16.8 versus
19.6 percent; RR 0.77, 95% CI 0.51-1.17), composite adverse neonatal outcome (24.9
versus 30.5 percent; RR 0.82, 95% CI 0.68-0.98), or pregnancy-related hypertension (10.6
versus 9.9 percent; RR 1.08, 95% CI 0.85-1.38). The modest reduction in adverse neonatal
outcome was largely due to a reduction in neonatal respiratory distress, which was
unexpected. In addition, one-third of participants in the untreated early abnormal test
group had normal results when retested at 24 to 28 weeks. These findings have
prompted stakeholders to review their early pregnancy diabetes screening protocols,
but revised guidelines from major medical organizations have not been published.
● Normal GTT – Patients with normal 75- or 100-gram oral GTT in early pregnancy are
screened for GDM at 24 to 28 weeks of gestation.
• Those who were screened early in pregnancy by the one-step approach are
rescreened using the 75-gram oral GTT.
• Those who were screened early in pregnancy by the two-step approach can omit the
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
first step (50-gram oral glucose solution with glucose testing after one hour) at 24 to
28 weeks as it is likely to be abnormal; these patients can be rescreened using the
three-hour 100-gram oral GTT alone [78,79] .
Candidates — In the United States, universal screening appears to be the most practical
approach because:
● 90 percent of pregnant people have at least one risk factor for glucose impairment
during pregnancy, so limiting testing to those with risk factors would not substantially
reduce testing [42] (see 'Risk factors' above).
● 20 percent of pregnant people with GDM have no risk factors, so limiting testing to
those with risk factors would miss most cases of GDM [80-82].
Two-step test — In the United States, the two-step test is the most widely used approach for
identifying pregnant people with GDM. It is endorsed by American College of Obstetricians
and Gynecologists (ACOG) [3] and the ADA considers it an acceptable option [2]. We prefer the
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
two-step approach because fewer patients are diagnosed and managed as GDM, without
incurring an increase in adverse outcome (see 'Evidence for choosing the two-step versus
one-step approach' below). The first step has the practical advantages that fasting is
unnecessary and only one blood sample is required. A minority of patients need to undergo
the second step (16 percent at the ≥140 mg/dL threshold in a large series [83]).
● The first step is a one-hour 50-gram oral GTT administered without regard to time of
day/previous meals. Screen-positive individuals ( table 3A) are at increased risk for
GDM so all but those with very high (≥200 mg/dL [11.1 mmol/L]) glucose values go on to
have the more cumbersome second step. We use ≥135 mg/dL (7.5 mmol/L) as the cutoff
for a positive test because our patient population is at high risk for developing GDM.
Although there are limited data regarding the clinical benefit of this cutoff, we believe
that it offers the optimum combination of sensitivity and specificity for our population.
Some institutions use a cut-off of ≥130 based on their higher-risk population. A cut-off of
≥140 mg/dL (7.8 mmol/L) is another commonly used cut-off. The procedure and
supporting evidence are described below. (See 'Screening: 50-gram one-hour GTT'
below.)
● The second step is a three-hour 100-gram oral GTT performed after an overnight fast;
the GTT is the diagnostic test for GDM ( table 3B). We use Carpenter and Coustan
criteria for an abnormal GTT as the lower, more stringent criteria for diagnosis identifies
patients with glucose intolerance at the most risk of adverse perinatal outcomes.
Although the three-hour 100-gram oral GTT is typically performed as the second step of
the two-step approach, this is arbitrary and in some countries (eg, Canada) a two-hour
75-gram oral GTT is performed as the second step in the screening/diagnostic process
[84]. The procedure and supporting evidence are described below. (See 'Procedures and
laboratory issues' below and 'Validation of the 100-gram GTT' below.)
Evidence for choosing the two-step versus one-step approach — The body of evidence
may favor the two-step approach. In a 2022 meta-analysis of randomized trials comparing
outcomes of the one- versus the two-step approach:
● The one-step approach diagnosed twice as many patients with GDM (16.3 versus 8.3
percent; RR 2.13, 95% CI 1.61-2.82) and resulted in twice as many patients receiving
antihyperglycemic pharmacotherapy (7.1 versus 3.8 percent; RR 2.24, 95% CI 1.21-4.15),
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
• Large for gestational age (LGA; 8.8 versus 9.2 percent; RR 0.95, 95% CI 0.88-1.04)
• Hypertensive disorder of pregnancy (13.6 percent versus 13.6 percent; RR 1.00, 95%
CI 0.94-1.07)
• Primary cesarean birth (24.0 versus 24.7 percent; RR 0.98, 95% CI 0.93-1.02)
• Macrosomia (>4000 grams, 11.2 versus 11.3 percent; RR 0.99, 95% CI 0.92-1.07)
• Shoulder dystocia (2.1 versus 2.0 percent; RR 1.06, 95% CI 0.89-1.28)
• Small for gestational age (SGA; 8.6 versus 8.3 percent; RR 1.04, 95% CI 0.95-1.13)
• Stillbirth (0.5 versus 0.6 percent; RR 0.90, 95% CI 0.64-1.28)
● Neonatal hypoglycemia was more common in the one-step group (9.3 versus 7.6
percent; RR 1.23, 95% CI 1.13-1.34)
Results were similar in high-quality observational studies, except for LGA (RR 0.97, 95% CI
0.95-0.98) where the confidence interval was consistent with a modest reduction.
Based on these findings, it appears that using the one-step method increases the number of
patients who receive a diagnosis of GDM and thus has the potential for increased patient and
medical system burden (eg, more prenatal visits, fetal and maternal surveillance, lifestyle
changes, and intervention) with economic, personal, and psychological consequences [85-87],
but without a clear direct benefit over the two-step approach in maternal and newborn
outcomes. Therefore, we believe it is prudent to use the two-step approach to diagnose GDM
followed by treatment of affected patients according to standard guidelines. Nevertheless,
because of limitations of the available trials, the best approach remains controversial [88].
(See 'One- and two-step approaches' above.)
The potential long-term consequences of increasing the number of patients who receive a
diagnosis of GDM is another issue. Increased identification of glucose intolerance in
pregnancy might lead to improved long-term maternal outcomes. Theoretically, if individuals
with GDM are identified and make postpartum lifestyle changes (with or without metformin),
this may prevent or delay development of type 2 diabetes later in life [53]. Data are lacking
due to the low percentage of patients with GDM who complete the recommended
postpartum follow-up. Counseling regarding long-term risk, adherence to a risk-reduction
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
program, and long-term glucose monitoring for diabetes would be essential to assess this
issue.
Screening: 50-gram one-hour GTT — A 50-gram oral glucose solution is given without
regard to the time elapsed since the last meal/beverage and venous plasma glucose is
measured one hour later (sometimes called a glucose challenge test [GCT] or glucose loading
test [GLT]). Glucose concentration should be measured using an accurate and precise
enzymatic method. The majority of patients (70 to 80 percent) screen negative at this step
and thus do not undergo diagnostic testing [4].
The following thresholds have been proposed to define a positive screen: ≥130 mg/dL, ≥135
mg/dL, or ≥140 mg/dL (7.2 mmol/L, 7.5 mmol/L, or 7.8 mmol/L). The original threshold for an
elevated test (equivalent to 143 mg/dL [7.9 mmol/L] with current methodology) was arbitrary,
used whole blood and a nonspecific glucose assay, and was validated by its ability to predict
an abnormal 100-gram oral GTT [89]. Using a lower threshold (≥130 mg/dL [7.2 mmol/L] with
current methodology) increases sensitivity, but results in more false positives and would
require administering a three-hour 100-gram oral GTT to more patients. In a systematic
review of cohort studies of screening tests for GDM by the USPSTF, using Carpenter and
Coustan criteria, sensitivity and specificity at the ≥130 mg/dL threshold was 100 and 25
percent, respectively, in one study; 90 and 81 percent in a second study; and 75 and 86
percent in a third study [90]. The pooled sensitivity and specificity at ≥135 mg/dL was 93 and
79 percent, respectively; at ≥140 mg/dL pooled sensitivity and specificity were both 82
percent.
The precise composition of the glucose solution (other than the 50 grams of glucose) can vary
among manufactures. No studies have compared products.
Management of patients with results ≥200 mg/dL — For patients with one-hour 50-
gram glucose concentration ≥200 mg/dL (11.1 mmol/L), the author makes a presumptive
diagnosis of GDM, unless the patient prefers to undergo a three-hour 100-gram oral GTT for
definitive diagnosis. The GTT can be performed safely, as the 100-gram glucose load would
rarely, if ever, lead to a hyperglycemic emergency or other serious adverse events in patients
with GDM or unrecognized type 2 diabetes. It has been performed in thousands of patients
with no reports of serious adverse events.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
The basis for this approach is that patients who have a very high glucose level on their one-
hour 50-gram oral GTT have a high likelihood of an abnormal three-hour 100-gram oral GTT;
the positive predictive value (PPV) varies depending on the prevalence of GDM in the
population tested and the GTT criteria used for diagnosis. For example, Carpenter and
Coustan found that patients whose one-hour 50-gram oral GTT plasma glucose concentration
was >182 mg/dL (10.1 mmol/L) had >95 percent probability of an abnormal three-hour 100-
gram oral GTT [4]. At glucose levels ≥200 mg/dL (11.1 mmol/L), others have reported PPVs of
47 to 80 percent for an abnormal three-hour 100-gram oral GTT [83,91,92].
• If a 75-gram oral GTT is planned and the fasting glucose level is ≥92 mg/dL (5.1
mmol/L), then the diagnosis of GDM is made and the GTT is cancelled.
• If a 100-gram oral GTT is planned, no data support a particular fasting cutoff for
diagnosing GDM and an abnormal fasting glucose level alone is not diagnostic of
GDM. However, a glucose level ≥126 mg/dL (7 mmol/L) is a reasonable threshold for
cancelling the GTT as it is diagnostic of diabetes in the general population.
Diagnostic criteria — The diagnosis of GDM is based on plasma glucose values during
the two-hour GTT using a 75-gram oral glucose load or during the three-hour GTT using a
100-gram oral glucose load. Thresholds for a positive test are shown in the tables (
table 3B-C).
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
Nevertheless, the 100-gram oral GTT is a practical and widely utilized means of diagnosing
GDM, and the 75-gram oral GTT is a widely utilized means of diagnosing diabetes in both
pregnant and nonpregnant individuals. Proper handling and processing of blood samples are
important for accurate results [99].
Options for patients unable to tolerate hyperosmolar oral glucose — The highly
concentrated hyperosmolar glucose solution used for the GTT can cause gastric irritation,
delayed emptying, and gastrointestinal osmotic imbalance, leading to nausea and, in a small
percentage of patients, vomiting [100-102]. Options in these cases include:
● Serving over ice – Serving the hyperosmolar glucose drink on ice may reduce nausea
and vomiting.
● Antiemetic premedication – If the patient vomited during the oral GTT and is willing to
come back another day for repeat testing, premedication with an antiemetic drug may
allow the test to be completed. In one study, 8 percent of patients could not complete
the 100-gram oral GTT because of vomiting [100]. It is possible that fewer patients vomit
with the 75-gram oral GTT.
● Intravenous GTT – The GTT can be performed intravenously instead of orally, although
this is rarely done because it is onerous, expensive, and unvalidated in pregnancy [103].
Considering these limitations, we recommend not using it.
● Structured postprandial glucose assessment – Periodic fasting and one- or two-hour
postprandial blood glucose tests can be obtained in pregnant people at high risk for
GDM. For example, they can be asked to keep a weekly log of self-monitored glucose
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
values from 24 to 28 weeks (the gestational age when screening would be performed)
and at 32 weeks (the gestational age of peak insulin resistance).
This approach is also useful for pregnant people who have dumping syndrome after a
Roux-en-Y gastric bypass procedure; these individuals are unlikely to tolerate a
hyperosmolar glucose solution [104]. Monitoring glucose values will only identify those
cases of GDM that might require intervention for hyperglycemia and not all cases of
GDM. (See "Fertility and pregnancy after bariatric surgery".)
● Other – Other approaches have been tried in patients who do not tolerate or decline to
have an oral GTT, but are not recommended because they have not been validated or
they perform poorly.
• Candy, a predefined meal, or commercial soft drinks with 75 or 100 grams of glucose
have been used instead of a standard glucose monomer or polymer solution [105-
110]. These oral glucose loads are better tolerated but appear to be less sensitive
and have not been validated in large studies. None have been endorsed by the ADA
or ACOG.
• Fasting glucose alone – The USPSTF review also found that a fasting plasma glucose
threshold of 79 mg/dL was required to achieve high (96 percent) sensitivity but
specificity was poor (35 percent) [90]. A fasting plasma glucose threshold of 95.5
mg/dL was required to achieve high specificity (98 percent) but sensitivity was 58
percent at this level.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
(4.4 mmol/L) and 12 percent had fasting glucose >90 mg/dL (5.0 mmol/L), diagnostic
of GDM in this system; 12 percent of patients with GDM were missed [111]. These
findings may not be generalizable to other low-resource populations since Asian
females have a higher incidence of type 2 diabetes and GDM than White females,
and fasting hyperglycemia among Asian females with GDM is less prominent than in
non-Asian populations [112]. In non-Asian populations, 50 to 75 percent of patients
with GDM have fasting glucose levels ≥92 mg/dL (5.1 mmol/L) on an oral GTT [112].
• Testing for glucosuria – A positive urine dipstick for glycosuria is not very predictive
of GDM, and a negative urine dipstick for glycosuria is not very predictive of absence
of GDM, so should not be used for ruling the diagnosis in or out [113-115]. Glycosuria
with a normal blood glucose level is common in pregnant people as pregnancy is
associated with reductions in fractional reabsorption of glucose, which results in
higher rates of urinary excretion.
Validation of the 100-gram GTT — The three-hour 100-gram oral GTT is diagnostic of
GDM when two glucose values are elevated. The most commonly used thresholds for defining
elevated values were proposed by Carpenter and Coustan ( table 3B) [4], which is a
modification of thresholds proposed by O’Sullivan and Mahan [116], originally based on
venous whole blood samples. The Carpenter and Coustan values are based on newer
enzymatic assays performed on plasma samples and reflect current laboratory practices.
The requirement for two abnormal values on the GTT was an arbitrary decision made by
O’Sullivan and Mahan in 1964 [116]. Treatment of patients who meet these diagnostic criteria
for GDM improves some pregnancy outcomes (eg, pregnancy-induced hypertension,
macrosomia, shoulder dystocia) [117]. However, a 2016 systematic review including 25 studies
noted that pregnant people with one abnormal value on the 100-gram oral GTT generally had
increased risks for the same poor outcomes as those with two abnormal values (ie, GDM)
[118]. This subset of patients may warrant closer monitoring for fetal overgrowth and other
adverse outcomes of GDM, as well as closer monitoring for future development of type 2
diabetes [119]. Whether they would benefit from treatment is unknown. The author of this
topic obtains a third-trimester fetal growth scan on these patients. If fetal overgrowth or
polyhydramnios is present, she discusses the option of home glucose monitoring.
Validation of the 75-gram GTT — The two-hour 75-gram oral GTT is diagnostic of GDM
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
when one glucose value is elevated. The most commonly used thresholds for defining
elevated values have been proposed by the IADPSG ( table 3C). The 75-gram oral GTT is
generally more sensitive for identifying the pregnancy at risk for adverse outcome (eg,
gestational hypertension, preeclampsia, LGA) than the 100-gram oral GTT [120]. Increased
sensitivity is primarily related to the need for only one elevated glucose value for a positive
test [112], as well as slightly lower glucose thresholds.
● Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study – The IADPSG-
defined thresholds for the 75-gram oral GTT are primarily based on outcome data
reported in the HAPO study, a prospective observational study of more than 23,000
pregnancies in nine countries evaluated with a 75-gram oral GTT at 24 to 32 weeks of
gestation [7,19]. These thresholds represent the glucose values at which the odds of
neonatal birth weight, cord C-peptide (surrogate for fetal insulin level), and percent body
fat >90th percentile were 1.75 times the estimated odds of these outcomes at mean
glucose levels, based on fully adjusted logistic regression models. Compared with
participants in the HAPO study with all glucose values below the thresholds, those who
exceeded one or more of these thresholds had a twofold higher frequency of LGA
newborns and preeclampsia and >45 percent increase in preterm birth and primary
cesarean birth. Using an odds ratio (OR) of 2 for the thresholds defined a population
with a higher frequency of these outcomes, but the difference was modest and resulted
in failure to identify many pregnant people who were at almost similar risk of these
outcomes but had all glucose values below the thresholds. IADPSG-defined thresholds
are also predictive of a more than threefold increased long-term risk of diabetes and
metabolic syndrome [121,122]. In a post hoc analysis of data from the HAPO Study, 52
percent of pregnant people who would meet IADPSG criteria for GDM developed a
disorder of glucose metabolism by 10 to 14 years postpartum, compared with 20
percent of those without GDM (OR 3.44, 95% CI 2.85-4.14 [122]). Among pregnant
people who met IADPSG criteria for GDM, rates of type 2 diabetes and prediabetes were
10.7 and 41.5 percent, respectively, versus rates of 1.6 and 18.4 percent, respectively, in
those without GDM. The children of these individuals were more likely to be “overweight
or obese” (39.5 versus 28.6 percent in children of mothers without GDM, OR 1.21, 95% CI
1.00-1.46) after adjustment for maternal body mass index (BMI) during pregnancy, and
the difference in prevalence of obesity was statistically significant (19 versus 10 percent
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
• Use of lower glycemic threshold criteria resulted in more patients diagnosed with
GDM (15.3 versus 6.1 percent), but this was not accompanied by a significant
reduction in birth of LGA (8.8 versus 8.9 percent) or macrosomic newborns (11.8
versus 12.3 percent).
• Use of the lower glycemic threshold criteria resulted in more inductions of labor (33.7
versus 30.2 percent), use of health services, and use of pharmacotherapy (10.9
versus 4.6 percent). The lower glycemic threshold group also had a higher rate of
neonatal hypoglycemia warranting treatment (10.7 versus 8.4 percent), which was
likely related to hospital protocols requiring screening for hypoglycemia in infants of
diabetic mothers.
• Rates of preeclampsia, preterm birth, shoulder dystocia, cesarean birth, and SGA
newborn were similar in the two trial groups.
Interestingly, about half of the patients with glucose test results that fell between the
lower and higher glycemic threshold criteria were considered by their providers to have
a mild degree of GDM and were treated for GDM. These patients had maternal and
infant health benefits, including fewer LGA newborns, compared with those who did not
receive a diagnosis of a mild degree of GDM and therefore not treated.
The results of this trial suggest that the optimum glucose thresholds for diagnosis of
GDM by the 75-gram oral GTT still need to be determined.
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
We recommend not repeating a glucose tolerance test (GTT) later in pregnancy after an
initially normal GTT. Although some studies have reported that repeating the test after an
initially normal GTT (defined as the absence of at least two glucose values above threshold)
will identify additional cases in 4 to 29 percent of cases depending on the timing and
indication for repeat testing [124-127], the value of identifying these individuals versus
nondiagnosis of GDM is unproven. Furthermore, patients with a normal GTT and sonographic
signs of fetal overgrowth or with one abnormal value on the GTT can be given the option of
insulin therapy in an attempt to improve pregnancy outcome.
The optimum strategy for diagnosis of GDM to improve maternal and infant health is unclear
[128]. Many organizations have published recommendations for screening and diagnosis of
diabetes in pregnancy:
● American College of Obstetricians and Gynecologists (ACOG, two-step approach (
table 3A and table 3B)) [3]
● International Association of Diabetes and Pregnancy Study Groups (IADPSG, one-step
approach ( table 3C)) [7]
● American Diabetes Association (ADA, one- or two-step approach) [2]
● World Health Organization (WHO, one-step approach ( table 4)) [129]
● Canadian Diabetes Association (CDA, two-step [preferred] or one-step approach) [84]
● Australasian Diabetes in Pregnancy Society (WHO approach) [41]
● National Institute for Health and Care Excellence (NICE, United Kingdom, one-step
approach)
● International Federation of Gynecology and Obstetrics (FIGO, one-step approach) [130]
POSTDELIVERY FOLLOW-UP
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Gestational diabetes mellitus: Screening, diagnosis, and prevention
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Diabetes mellitus in
pregnancy".)
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Gestational diabetes (The Basics)")
● Beyond the Basics topics (see "Patient education: Gestational diabetes (Beyond the
Basics)")
- Page 24 of 37 -
Gestational diabetes mellitus: Screening, diagnosis, and prevention
GDM has been associated with increased risks of several adverse outcomes ( table 5).
The association between hyperglycemia and adverse pregnancy outcomes is dose-
dependent and continuous. (See 'Significance' above.)
● How to screen
- Page 25 of 37 -
Gestational diabetes mellitus: Screening, diagnosis, and prevention
'Candidates' above and 'Significance' above and 'Benefits and harms of screening'
above and "Gestational diabetes mellitus: Glucose management and maternal
prognosis", section on 'Rationale for treatment'.)
ACKNOWLEDGMENTS
The UpToDate editorial staff acknowledges Lois Jovanovic, MD, Donald R Coustan, MD, and
Michael Greene, MD, who contributed to earlier versions of this topic review.
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