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Diabetes mellitus in pregnancy: Screening and diagnosis
Oﬃcial reprint from UpToDate® www.uptodate.com

©2021 UpToDate®

Author: Celeste Durnwald, MD
Section Editors: David M Nathan, MD, Erika F Werner, MD, MS
Deputy Editor: Vanessa A Barss, MD, FACOG
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2021. | This topic last updated: Mar 22, 2021.
What's New
One-step versus two-step diagnosis of gestational diabetes mellitus (March 2021)
A previous meta-analysis of four small trials found that one-step diagnosis of gestational
diabetes (GDM) resulted in better perinatal outcomes than the traditional two-step
diagnosis (table 1) in patients who were subsequently treated according to standard
guidelines. Now, in the largest randomized trial comparing pregnancy outcomes of the
two diagnostic approaches (>23,000 pregnancies), the one-step approach resulted in
more patients diagnosed with GDM (16.5 versus 8.5 percent), but no additional
improvement in pregnancy outcomes (eg, rates of large for gestational age newborn and
preeclampsia were similar for both approaches) [1]. These findings support our
preference for the two-step approach for diagnosis of GDM, with standard treatment of
affected patients. (See "Diabetes mellitus in pregnancy: Screening and diagnosis",
section on 'One-step and two-step approaches'.)
INTRODUCTION
Pregnancy is accompanied by 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 generally most prominent in the last trimester, ensure that the
fetus has an ample supply of nutrients.
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Gestational diabetes mellitus develops during pregnancy in women whose pancreatic function is
insufficient to overcome the insulin resistance associated with the pregnant state. Among the
main consequences are increased risks of preeclampsia, macrosomia, and cesarean delivery,
and their associated morbidities.
The approach to screening for and diagnosis of diabetes in pregnant women will be reviewed
here. Management and prognosis are discussed separately:
● (See "Gestational diabetes mellitus: Glycemic control and maternal prognosis".)
● (See "Gestational diabetes mellitus: Obstetric issues and management".)
TERMINOLOGY
Women with type 1 or 2 diabetes diagnosed prior to pregnancy are classified as having
preexisting diabetes. Historically, the term "gestational diabetes" has been defined as onset or
first recognition of abnormal glucose tolerance during pregnancy [1]. Some organizations have
attempted to distinguish women with probable preexisting diabetes that is first recognized during
early pregnancy from those whose disease is a transient manifestation of pregnancy-related
insulin resistance and diagnosed in the late second or the third trimester. This effort
acknowledges the increasing prevalence of undiagnosed type 2 diabetes in reproductive-age
women related to the ongoing epidemic of obesity [2].
BACKGROUND
Prevalence — The prevalence of gestational diabetes mellitus as traditionally defined is

approximately 6 percent of pregnant women in the United States [3]. The prevalence varies
worldwide (2 to 38 percent [4]) and among racial and ethnic groups, generally in parallel with the
prevalence of type 2 diabetes. In the United States, prevalence rates are higher in African
American, Hispanic American, Native American, Pacific Islander, and South or East Asian
women than in White women [5]. Prevalence also varies because of differences in screening
practices, population characteristics (eg, average age and body mass index [BMI] of pregnant
women), testing method, and diagnostic criteria. Prevalence has been increasing over time,
likely due to increases in mean maternal age and weight, particularly increasing obesity [6-12].
In 2010, the International Association of Diabetes and Pregnancy Study Groups proposed new
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screening and diagnostic criteria for diabetes in pregnancy [13]. Using these criteria, the global
prevalence of hyperglycemia in pregnancy has been estimated at 17 percent, with regional
estimates varying between 10 percent in North America and 25 percent in Southeast Asia [14].
In 2017, the American College of Obstetricians and Gynecologists stated that, although a
diagnosis of gestational diabetes mellitus generally requires that two or more glucose thresholds
must be met or exceeded on a 100 gram three-hour glucose tolerance test (GTT), some
clinicians may choose to make the diagnosis based on one elevated value [15].
Significance — Several adverse outcomes have been associated with gestational diabetes
mellitus [16-19]:
● Preeclampsia, gestational hypertension

● Polyhydramnios
● Macrosomia and large for gestational age infant
● Maternal and infant birth trauma
● Operative delivery (cesarean, instrumental)
● Perinatal mortality
● Fetal/neonatal hypertrophic cardiomyopathy
● Neonatal respiratory problems and metabolic complications (hypoglycemia,
hyperbilirubinemia, hypocalcemia, polycythemia)
Importantly, the risks of these outcomes increase as maternal fasting plasma glucose levels
increase above 75 mg/dL (4.2 mmol/L) and as the one-hour and two-hour oral GTT values
increase from the lowest septile to the highest. This is a continuous effect; there is no clear
threshold that defines patients at increased risk of adverse obstetric outcome [17,20,21].
In addition, if the mother is hyperglycemic during organogenesis, such as women with known or
unknown overt diabetes, the risks of miscarriage and congenital anomalies are increased. (See
"Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and
management".)
Long-term, women with gestational diabetes mellitus are at increased risk of developing type 2
diabetes as well as cardiovascular disease (see "Gestational diabetes mellitus: Glycemic control
and maternal prognosis", section on 'Long-term risk'). Their adolescent and adult offspring
appear to be at risk of long-term sequelae, such as obesity, abnormal glucose tolerance,
hypertension, or metabolic syndrome. In addition, both gestational and pregestational
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(preexisting) diabetes mellitus have been associated with an increased risk of autism and other
adverse neurodevelopmental outcomes in offspring, but it is not clear that these associations are
causal [22-27]. Shared environmental and genetic factors may play a role. (See "Infants of
women with diabetes", section on 'Long-term outcome' and "Autism spectrum disorder:
Terminology, epidemiology, and pathogenesis", section on 'Environmental and perinatal factors'.)
Treatment of gestational diabetes mellitus can reduce the risk of some pregnancy complications
(eg, preeclampsia) and adverse neonatal outcomes (eg, macrosomia). Improvement in long-
term outcomes in offspring is less clear. (See "Gestational diabetes mellitus: Glycemic control
and maternal prognosis", section on 'Rationale for treatment'.)
Risk factors — Pregnant women with any of the following characteristics appear to be at
increased risk of developing gestational diabetes mellitus; the risk is additive when multiple risk
factors are present [15,28-32]:
● Personal history of impaired glucose tolerance, A1C ≥5.7 percent, impaired fasting glucose,
or gestational diabetes mellitus in a previous pregnancy.
● Member of one of the following ethnic groups, which have a high prevalence of type 2
diabetes: Hispanic American, African American, Native American, South or East Asian,
Pacific Islander.
● Family history of diabetes, especially in first-degree relatives [33].
● Prepregnancy weight ≥110 percent of ideal body weight or BMI >30 kg/m2, significant
weight gain in early adulthood and between pregnancies [34], or excessive gestational
weight gain during the first 18 to 24 weeks [35-37].
● Older maternal age (>25 or 30 years of age).
● Previous unexplained perinatal loss or birth of a malformed infant.
● Glycosuria at the first prenatal visit.
● Previous birth of an infant ≥4000 g (approximately 9 pounds).
● High density lipoprotein <35 mg/dL (0.90 mmol/L), triglyceride >250 mg/dL (2.82 mmol/L).
● Medical condition/setting associated with development of diabetes, such as metabolic
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syndrome, polycystic ovary syndrome, current use of glucocorticoids, hypertension or

cardiovascular disease, acanthosis nigricans.
● Multiple gestation.
A low risk of gestational diabetes mellitus is found in younger (<25 years of age) non-Hispanic
White women, with normal BMI (<25 kg/m2 [<23 kg/m2 in Asian women]), no history of previous
glucose intolerance or adverse pregnancy outcomes associated with gestational diabetes
mellitus, and no first-degree relative with diabetes [38]. Only 10 percent of the general obstetric
population in the United States meets all of these criteria for low risk of developing gestational
diabetes mellitus, which is the basis for universal rather than selective screening [39]. (See
'Candidates for screening/testing' below.)
Preventive approaches for risk reduction — In overweight and obese women, weight loss
before pregnancy can reduce the risk of developing gestational diabetes mellitus. During
pregnancy, a program of diet and exercise that prevents excessive gestational weight gain and
is targeted at women at high risk for gestational diabetes also appears to be effective [40]. On
the other hand, in the overall obstetric population, lifestyle interventions (education, diet,
exercise, etc) have not reduced gestational diabetes [41].
● Prepregnancy weight loss – The possible benefit of prepregnancy weight loss is illustrated
by the following two examples of observational studies:
• In a population-based cohort study, obese women who lost at least 10 pounds (4.5 kg)
between pregnancies trended toward decreased risk of gestational diabetes mellitus
relative to women whose weight changed by less than 10 pounds (relative risk [RR]
0.63, 95% CI 0.38-1.02, adjusted for age and weight gain during each pregnancy).
Women who gained 10 pounds (4.5 kg) or more between pregnancies significantly
increased their risk of gestational diabetes mellitus (RR 1.47, 95% CI 1.05-2.04) [42].
• In a study that compared the incidence of gestational diabetes mellitus in 346 women
who delivered before bariatric surgery with the incidence in 354 women who delivered
after bariatric surgery, the incidence of gestational diabetes mellitus was lower after
bariatric surgery (8 versus 27 percent, odds ratio 0.23, 95% CI 0.15-0.36) [43]. Bariatric
surgery also induces hormonal changes that may lower the risk of gestational diabetes
mellitus independent of weight loss.
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● Prepregnancy and early pregnancy exercise – In nonpregnant women, regular moderate
exercise lowers the risk of developing type 2 diabetes compared with being sedentary (see
"Prevention of type 2 diabetes mellitus", section on 'Exercise'). Whether exercise alone or in
combination with diet lowers the risk of developing gestational diabetes mellitus is unclear,
as meta-analyses of randomized trials have reported conflicting findings [44-49]. Overweight
and obese women seem to benefit most [47,50].
The types and durations of the exercise programs in these trials have varied and may
account for the discordancies. In particular, beginning a modest exercise program in the
second trimester appears to be inadequate to impact risk of gestational diabetes mellitus
[44,45,51,52]. Exercise should be started before pregnancy or soon thereafter, performed
three to four times per week for 30- to 60-minute sessions, and continued until delivery (and
ideally thereafter for general health benefits). In one trial in which overweight and obese
pregnant women participated in this type of exercise program, the exercise group had a
significantly lower incidence of gestational diabetes mellitus (22.0 percent versus 40.6
percent with usual care) [53]. (See "Exercise during pregnancy and the postpartum period".)
● Type of diet, smoking – In addition to exercise, a healthy diet and smoking cessation
before pregnancy are healthy behaviors that may be associated with reduced risk of
developing gestational diabetes mellitus [54]. Few studies on the role of dietary factors in
the development of gestational diabetes mellitus have been performed. 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 gestational diabetes mellitus [55,56]. There is low-quality evidence from
randomized trials that advising women about a low-glycemic-index diet does not prevent
development of gestational diabetes mellitus [57].
However, a healthy diet can promote weight loss before pregnancy and reduce excessive
weight gain during pregnancy, which is beneficial for women who are overweight or obese.
Smoking cessation should be encouraged in all patients, and may reduce gestational
diabetes mellitus risk. (See "Prevention of type 2 diabetes mellitus".)
● Supplements – Myo-inositol is a naturally occurring sugar in fruits, beans, grains, and nuts
that can improve insulin resistance. Randomized trials of antenatal myo-inositol
supplementation during pregnancy have reported discordant findings regarding a reduction
in the incidence of gestational diabetes mellitus [58-61]. Before this intervention can be
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recommended, large multicenter, blinded, randomized trials are needed to confirm safety
and demonstrate improvement in clinically important maternal and/or neonatal outcomes.
BENEFITS AND HARMS OF SCREENING
Screening and diagnostic testing for diabetes are performed because identifying pregnant
women with diabetes followed by appropriate therapy can decrease fetal and maternal morbidity,
particularly macrosomia, shoulder dystocia, and preeclampsia. (See "Gestational diabetes
mellitus: Glycemic control and maternal prognosis", section on 'Rationale for treatment'.)
Most of the commonly used screening and diagnostic tests involve drinking a glucose-containing
beverage followed by blood glucose measurement; none of these tests are associated with
serious harmful maternal or fetal effects. However, some women find the hyperosmolar drinks
difficult to tolerate. If gestational diabetes mellitus is diagnosed, management involves changes
in diet, an increased frequency of prenatal visits, blood glucose monitoring, possible
pharmacologic therapy, additional maternal and fetal monitoring, and possibly an increased risk
for induction. As with all screening tests, which are designed to screen positive more individuals
than actually have the disease, there is the possibility of misdiagnosis. Misdiagnosis of
gestational diabetes can lead to heightened maternal anxiety, an increase in pregnancy
interventions, and implementation of treatment without clear benefit to the woman and her
offspring.
The cost implications of screening versus not screening have been modeled, and screening
appears to be cost-effective for prevention of type 2 diabetes in populations with a high
prevalence of gestational diabetes mellitus and type 2 diabetes, provided that lifestyle
interventions are applied subsequent to pregnancy [62].
IDENTIFICATION OF OVERT DIABETES IN EARLY PREGNANCY
As discussed above (see 'Terminology' above), an increasing proportion of women have as yet
unrecognized type 2 diabetes due to the increasing prevalence of obesity and lack of routine
glucose screening/testing in this age group. It has been estimated that approximately 30 percent
of women aged 18 to 44 in the United States have diagnosed or undiagnosed abnormal glucose
metabolism (type 2 diabetes, impaired fasting glucose, and/or impaired glucose tolerance) [63].
Women who are hyperglycemic in early pregnancy are at increased risk of having a child with a
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congenital anomaly, and they may have unrecognized complications (nephropathy, retinopathy)
from diabetes [64-66]. If these women are identified early in pregnancy, they could benefit from
receiving the diagnostic and therapeutic interventions routinely provided to women with
pregestational (preexisting) diabetes mellitus.
The International Association of Diabetes and Pregnancy Study Groups (IADPSG) concluded
that the decision to test for undiagnosed preexisting diabetes at the first prenatal visit should be
based upon the background frequency of abnormal glucose metabolism in the population and on
local circumstances [13]. Both the American Diabetes Association (ADA) [67] and the American
College of Obstetricians and Gynecologists (ACOG) [15] suggest early pregnancy testing for
undiagnosed type 2 diabetes in women who are overweight or obese and/or have one or more
additional risk factors for diabetes. By contrast, a 2014 United States Preventive Services Task
Force (USPSTF) guideline concluded available evidence was insufficient to assess the balance
of benefits and harms of screening asymptomatic pregnant women for glucose intolerance
before 24 weeks of gestation [28].
The ADA and ACOG define women at increased risk of overt diabetes based on:
● Body mass index (BMI) ≥25 kg/m2 (≥23 kg/m2 in Asian Americans) plus one or more of the
following [15,67]:
• Gestational diabetes mellitus in a previous pregnancy.
• Glycated hemoglobin ≥5.7 percent (39 mmol/mol), impaired glucose tolerance, or

impaired fasting glucose on previous testing.
• First-degree relative with diabetes.
• High-risk race/ethnicity (eg, African American, Latino, Native American, Asian

American, Pacific Islander).
• History of cardiovascular disease.
• Hypertension (≥140/90 mmHg) or on therapy for hypertension.
• High-density lipoprotein cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride
level >250 mg/dL (2.82 mmol/L).
• Polycystic ovary syndrome.

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• Physical inactivity.
• Other clinical condition associated with insulin resistance (eg, severe obesity,
acanthosis nigricans).
• Previous birth of an infant weighing ≥4000 g.
We include older age as a risk factor for early testing and use age 40 years as the threshold.
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 (macrosomia,
primary cesarean delivery, hypertensive disease of pregnancy, shoulder dystocia, neonatal
hyperbilirubinemia, or hypoglycemia) [68]. However, the trial findings were limited by the small
number of women diagnosed with early gestational diabetes mellitus (n = 29) and the timing of
the early screening (between 14 and 20 weeks).
Some organizations (eg, IADPSG) allow for a diagnosis of "overt" diabetes in women who meet
criteria for diabetes at their initial early prenatal visit. ADA criteria for diagnosis of diabetes in
nonpregnant adults may be used to diagnose overt diabetes in early pregnancy (table 1). These
thresholds were chosen because they correlate with development of adverse vascular events in
nonpregnant individuals, such as retinopathy and coronary artery disease over time. If a patient
in early pregnancy (before significant insulin resistance) meets standard ADA criteria for
diabetes, she is assumed to have had the disorder prior to the pregnancy and should be
managed similarly to women with preexisting diabetes mellitus. (See "Clinical presentation,
diagnosis, and initial evaluation of diabetes mellitus in adults" and "Pregestational (preexisting)
diabetes mellitus: Antenatal glycemic control" and "Pregestational (preexisting) diabetes
mellitus: Obstetric issues and management".)
SCREENING AND DIAGNOSTIC TESTING
The purpose of screening is to identify asymptomatic individuals with a high probability of having
or developing a specific disease. Screening can be performed as a two-step process where step
one identifies individuals at increased risk for the disease so that step two, diagnostic testing,
which is definitive but usually more complicated or costly than the screening test, can be limited
to these individuals and avoided in low-risk individuals. Alternatively, a diagnostic test can be
administered to all individuals, which is a one-step process.
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One-step and two-step approaches
● Two-step approach – The two-step approach is the most widely used approach for
identifying pregnant women with gestational diabetes mellitus in the United States. The first
step is a 50 gram one-hour glucose challenge test (GCT) without regard to time of
day/previous meals. Screen-positive patients go on to the second step, a 100 gram, three-
hour oral glucose tolerance test (GTT), which is the diagnostic test for gestational diabetes
mellitus.
● One-step approach – The one-step approach omits the screening test and simplifies
diagnostic testing by performing only a 75 gram, two-hour oral GTT but requires an
overnight fast.
There is no consensus regarding use of the one-step versus the two-step approach among
national and international organizations.
● In a 2018 meta-analysis of four randomized trials (n>2500 women) comparing the one-step
with the two-step approach, the one-step approach resulted in a lower risk of large for
gestational age infant (relative risk [RR] 0.46, 95% CI 0.25-0.83), neonatal intensive care
unit (NICU) admission (RR 0.49, 95% CI 0.29-0.84), and neonatal hypoglycemia (RR 0.52,
95% CI 0.28-0.95), as well as lower mean birth weight (mean difference -112.91 grams,
95% CI -190.48 to -35.33) [69]. It also appeared to reduce the risk of cesarean delivery
(19.6 versus 29.9 percent, RR 0.83, 95% CI 0.66-1.05) and increase the proportion of
women diagnosed with gestational diabetes (8.3 versus 4.4 percent, RR 1.60, 95% CI 0.93-
2.75). However, the total number of women in these trials was relatively small.
● In contrast, a subsequent pragmatic randomized trial comparing short-term outcomes of

one-step versus two-step screening for gestational diabetes in nearly 24,000 pregnant
women reported some different findings [70]. Guidelines for management of gestational
diabetes were the same, regardless of the diagnostic test used. Key findings were:
• Twice as many women in the one-step group were diagnosed with gestational diabetes
(16.5 versus 8.5 percent).
• Primary outcomes were similar for both groups: rates of large for gestational age
newborn, perinatal composite outcome, gestational hypertension or preeclampsia,
primary cesarean birth.
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• Secondary outcomes were also similar for both groups: rates of small-for-gestational-
age newborn, labor induction, and patients needing insulin or oral hypoglycemic
therapy.
• Neonatal hypoglycemia was more common in the one-step group.
• In 39 percent of women assigned to the one-step method, the diagnosis of GDM was
based on an isolated fasting plasma glucose level in the range of 92 to 94 mg/dL (5.1 to
5.2 mmol/L); a glucose level that is within target range of treatment (<95 mg/dL [5.3
mmol/L]).
This is the largest randomized clinical trial evaluating whether there is a difference in
pregnancy outcome in women diagnosed with GDM using the one-step versus the two-step
method. Consistent with the meta-analysis of smaller trials described in the previous bullet,
the one-step approach resulted in a higher frequency of GDM diagnosis than the two-step
approach [69]. However, this trial differed from the meta-analysis in an important way:
Despite the increased frequency of diagnosis, the proportion of treated patients and
perinatal outcomes were similar for both approaches. Based on these findings, it would
appear that using the one-step method increases the number of women 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 [71,72], 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. (See 'Our approach to
screening and diagnosis of diabetes in pregnancy' below.)
Candidates for screening/testing — In the United States, universal screening or testing

appears to be the most practical approach because 90 percent of pregnant women have at least
one risk factor for glucose impairment during pregnancy [39] (see 'Risk factors' above).
Furthermore, as many as 20 percent of women diagnosed with gestational diabetes mellitus
have no risk factors [31,73]. In addition, a meta-analysis of 29 studies (n = >211,000 women)
performed worldwide that evaluated the performance of risk factors to identify women at high
risk of gestational diabetes mellitus also concluded that risk factors were poor predictors of
women who had an abnormal GTT [74].
Timing of screening/testing — While there are no proven benefits to screening/testing for

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diabetes in early pregnancy, testing can be performed as early as the first prenatal visit if there is
a high degree of suspicion that the pregnant woman has undiagnosed type 2 diabetes [15]. In
particular, women with a prior history of gestational diabetes mellitus have a 48 percent risk of
recurrence (95% CI 41-54 percent) [75], and some of these recurrences may represent
unrecognized inter-gestational type 2 diabetes. Although there are no validated criteria for
selecting high risk pregnant women for early screening/testing, the American Diabetes
Association (ADA) and American College of Obstetricians and Gynecologists (ACOG) have
provided risk assessment criteria for estimating diabetes risk. (See 'Identification of overt
diabetes in early pregnancy' above.)
In the absence of early testing or if early testing is negative, universal screening is performed at
24 to 28 weeks of gestation [15,28,67].
A systematic review by the United States Preventive Services Task Force (USPSTF) on the
accuracy of screening tests for gestational diabetes mellitus, the benefits and harms of
screening before and after 24 weeks of gestation, and the benefits and harms of treatment found
good evidence to support universal screening after 24 weeks, but not for universal screening
earlier in pregnancy [28]. A secondary analysis of data from a randomized trial [76] found that
outcomes of pregnancies with early diagnosis and treatment (between 24 and 30+6 weeks of
gestation) of mild gestational diabetes mellitus (fasting value <95 mg/dL and two elevated post-
challenge values) were not significantly different based on when gestational diabetes mellitus
was identified and treatment initiated [77]. Pregnancy outcomes were similar when treatment
was initiated at 24 to 26, 27, 28, or 29 weeks compared with ≥30 weeks of gestation.
Screening methods — Laboratory screening is generally performed with a GCT.
50 gram one-hour glucose screen — A 50 gram oral glucose load is given without regard to
the time elapsed since the last meal and plasma glucose is measured one hour later (sometimes
called a GCT or glucose loading test [GLT]). Glucose concentration should be measured in
venous plasma using an accurate and precise enzymatic method. 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 a positive three-hour oral GTT [78]. Use of a lower threshold
(≥130 mg/dL [7.2 mmol/L] with current methodology) provides greater sensitivity, but results in
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more false positives and would require administering an oral GTT to more patients [79,80]. In a
systematic review of cohort studies of screening tests for gestational diabetes mellitus by the
USPSTF, at the 130 mg/dL (7.2 mmol/L) threshold, sensitivity and specificity were 88 to 99
percent and 66 to 77 percent, respectively [81]. At the 140 mg/dL (7.8 mmol/L) threshold,
sensitivity was lower (70 to 88 percent), but specificity was higher (69 to 89 percent).
Markedly elevated one-hour glucose level — The likelihood of an abnormal GTT is

higher in women who have a high glucose level on their 50 gram one-hour glucose screen. The
positive predictive value (PPV) of this test varies depending on the prevalence of gestational
diabetes mellitus in the population tested and the GTT criteria used for diagnosis of gestational
diabetes mellitus. For example, Carpenter and Coustan found that a 50 gram one-hour plasma
glucose >182 mg/dL (10.1 mmol/L) had >95 percent probability of gestational diabetes mellitus
[79]. At glucose levels ≥200 mg/dL (11.1 mmol/L), others have reported PPVs of 47 to 80
percent for an abnormal GTT [82-84].
For women with 50 gram one-hour glucose results ≥200 mg/dL (11.1 mmol/L), the author makes
a presumptive diagnosis of gestational diabetes mellitus, unless the patient prefers to undergo a
GTT for definitive diagnosis. The GTT can be performed safely, as the 100 gram glucose load
would not lead to diabetic ketoacidosis in women with gestational diabetes mellitus or
unrecognized type 2 diabetes. It has been performed in thousands of patients with no reports of
serious adverse events.
Other tests — In the USPSTF systematic review described above [81]:
● No threshold for glycated hemoglobin (A1C) in the second and third trimesters had both
good sensitivity and specificity as a screening test for gestational diabetes mellitus. In four
studies, A1C thresholds of 5.0, 5.3, 5.5, and 7.5 were evaluated using different diagnostic
criteria for gestational diabetes mellitus [85-88]; there was no clear pattern between A1C
level and probability of gestational diabetes mellitus across the four studies.
● A fasting plasma glucose level less than 85 mg/dL (4.7 mmol/L) by 24 weeks of gestation
performed well for identifying women who did not have gestational diabetes mellitus.
However, a value over 85 mg/dL (4.7 mmol/L) performed less well than the GCT for
identifying women with gestational diabetes mellitus. (See 'Patients unable to tolerate oral
hyperosmolar glucose' below.)
It is worth noting that different populations manifest different proportions of glucose

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elevation at each time point of the GTT. In the Hyperglycemia and Adverse Pregnancy
Outcome (HAPO) study, for example, only approximately 25 percent of women with
gestational diabetes mellitus in Hong Kong and Bangkok had a fasting glucose value on the
GTT that would have exceeded the International Association of Diabetes and Pregnancy
Study Groups' (IADPSG) threshold of ≥92 mg/dL (5.1 mmol/L), whereas in most other
countries, approximately 50 to 75 percent of women with gestational diabetes mellitus would
have exceeded this fasting value [89].
In a simulation study of a Swiss population with a low prevalence of gestational diabetes

mellitus (approximately 11 percent), if the GTT was not performed when the fasting glucose
level was <80 mg/dL (4.4 mmol/L) or ≥92 mg/dL (5.1 mmol/L), 64 percent of women would
avoid the GTT, but 22 percent of gestational diabetes mellitus cases would be missed [90],
which this author considers unreasonable for a resource-rich country. Furthermore, the one-
third of women who would require further testing would have to fast twice if they underwent
a GTT on a separate day.
However, in low-resource settings where universal screening with a GCT or diagnostic

testing with an oral GTT is not feasible, use of fasting plasma glucose at 24 to 28 weeks to
screen women may be a practical approach, a reasonable trade-off between cost-savings
and adverse outcomes in missed cases. In a study from 15 Chinese hospitals, if
performance of the GTT was restricted to women with fasting glucose from 79 mg/dL (4.4
mmol/L) to 90 mg/dL (5.0 mmol/L), then 50 percent of pregnant women could avoid a GTT
since 38 percent of this population had fasting glucose <79 mg/dL (4.4 mmol/L) and 12
percent had fasting glucose >90 mg/dL (5.0 mmol/L), diagnostic of gestational diabetes
mellitus in this system; 12 percent of patients with gestational diabetes mellitus were missed
[91]. These findings may not be generalizable to other low-resource populations since Asian
women have a higher incidence of type 2 diabetes and gestational diabetes mellitus than
White women and fasting hyperglycemia among Asian women with gestational diabetes
mellitus was less prominent in the HAPO subjects [89].
A positive urine dipstick for glycosuria is not very predictive of gestational diabetes mellitus, and
a negative urine dipstick for glycosuria is not very predictive of absence of gestational diabetes
mellitus [92-94]. Glycosuria with a normal blood glucose level is common in pregnant women as
pregnancy is associated with reductions in fractional reabsorption of glucose, which results in
higher rates of urinary excretion.
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Diagnostic testing methods — The diagnosis of gestational diabetes mellitus is based on

results of an oral GTT. However, it should be noted that, although it is also universally used to
diagnose diabetes outside of pregnancy, this is an imprecise test with poor reproducibility [95]. A
study that performed two oral three-hour GTTs one to two weeks apart in 64 pregnant women
whose 50 gram GCT was ≥135 mg/dL found 48 had normal/normal, 11 had normal/abnormal, 3
had abnormal/normal, and 2 had abnormal/abnormal results [96]. Thus, only 50 of 64 (78
percent) had reproducible test results. Nevertheless, it is a practical and widely utilized means of
diagnosing both gestational diabetes mellitus and diabetes in nonpregnant individuals. Proper
handling and processing of blood samples is important for accurate results [97].
The GTT can be performed as a 75 gram two-hour test or a 100 gram three-hour test; there is
no consensus regarding the optimum thresholds for a positive test (table 2). Although the 100
gram three-hour GTT is typically performed as the second step of the two-step approach while
the 75 gram two-hour test is performed as the only test in the one-step approach, this is
arbitrary. In fact, the Canadian Diabetes Association clinical guidelines suggest the 75 gram two-
hour GTT as the second step of the two-step approach [98]. Historically, carbohydrate loading
for three days before the test was recommended but is often no longer recommended and is
probably not necessary if the patient is not on a low-carbohydrate diet [99-102].
Some clinicians obtain a fasting glucose level before administering the GTT. If a 75 gram two-
hour GTT is planned and the fasting glucose level is ≥92 mg/dL (5.1 mmol/L), then the diagnosis
of gestational diabetes mellitus is made and the GTT is cancelled. If a 100 gram three-hour GTT
is planned, no data support a particular fasting cutoff for diagnosing gestational diabetes mellitus
and an abnormal fasting glucose level alone is not diagnostic of gestational diabetes mellitus.
However, a glucose level ≥126 mg/dL (7.0 mmol/L) is a reasonable threshold for cancelling the
GTT as it is diagnostic of diabetes in the general population. This approach requires asking the
patient to have blood drawn for her fasting glucose level and then wait for the results before
proceeding with the GTT later on the same day (and remain fasting) or on another day (and fast
again), which is cumbersome.
As discussed above, it is not necessary to exclude fasting hyperglycemia to safely perform the
test. (See 'Markedly elevated one-hour glucose level' above.)
100 gram three-hour oral glucose tolerance test — The 100 gram three-hour oral GTT is
diagnostic of gestational diabetes mellitus when two glucose values are elevated. The most
commonly used thresholds for defining elevated values have been proposed by Carpenter and
- Page 15 of 34 -
Coustan (table 3) [79], which is a modification of thresholds proposed by O'Sullivan and Mahan
[103], 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 [103]. Treatment of women who meet these diagnostic criteria for
gestational diabetes improves some pregnancy outcomes (eg, pregnancy-induced hypertension,
macrosomia, shoulder dystocia).
However, a 2016 systematic review including 25 studies noted that women with one abnormal
value on the three-hour, 100 gram oral GTT generally had increased risks for the same poor
outcomes as women with two abnormal values (ie, gestational diabetes mellitus) [104]. Citing
this systematic review, the 2017 ACOG practice bulletin on gestational diabetes mellitus stated
that, although a diagnosis of gestational diabetes mellitus generally requires that two or more
glucose thresholds must be met or exceeded, some clinicians may choose to make the
diagnosis based on one elevated value [15]. Whether such patients would benefit from treatment
is unclear.
75 gram two-hour oral glucose tolerance test — The 75 gram two-hour oral GTT is
diagnostic of gestational diabetes mellitus when one glucose value is elevated. The most
commonly used thresholds for defining elevated values have been proposed by the IADPSG (
table 4). The 75 gram two-hour oral GTT is more convenient, better tolerated, and more
sensitive for identifying the pregnancy at risk for adverse outcome (eg, gestational hypertension,
preeclampsia, large for gestational age) than the 100 gram three-hour oral GTT, but requires the
patient to be fasting [105]. Increased sensitivity is primarily related to the fact that only one
elevated glucose value is needed for a positive test [89] although the cutoffs are also slightly
lower.
The IADPSG-defined thresholds for the 75 gram two-hour 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 two-hour oral GTT at 24 to 32
weeks of gestation [13,17]. These thresholds represent the glucose values at which the odds of
infant birth weight, cord C-peptide (surrogate for fetal insulin level), and neonatal 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 women in the HAPO
- Page 16 of 34 -
study with all glucose values below the thresholds, women who exceeded one or more of these
thresholds had a twofold higher frequency of large for gestational age infants and preeclampsia
and >45 percent increase in preterm delivery and primary cesarean delivery. 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 women who were at almost
comparable risk. IADPSG-defined thresholds are also predictive of a more than threefold
increased long-term risk of diabetes and metabolic syndrome [106,107]. In a post hoc analysis of
data from the HAPO Study, 52 percent of women who would meet criteria for gestational
diabetes by IADPSG criteria developed a disorder of glucose metabolism by 10 to 14 years
postpartum compared with 20 percent of mothers without gestational diabetes (OR 3.44, 95% CI
2.85-4.14 [107]). Among women who met criteria for gestational diabetes, 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 women without gestational diabetes. The children of these women were
more likely to be "overweight or obese" (39.5 versus 28.6 percent, OR 1.21, 95% CI 1.00-1.46)
after adjustment for maternal body mass index during pregnancy, and the difference in
prevalence of obesity was statistically significant (19 versus 10 percent, OR 1.58, 95% CI 1.24-
2.01).
No randomized trial data are available on the effect of treating women diagnosed with
gestational diabetes mellitus by IADPSG criteria on pregnancy outcomes, but a randomized trial
has demonstrated that treatment of women who meet similar two-hour glucose criteria for
gestational diabetes mellitus (140 to 198 mg/dL [7.8 to 11.0 mmol/L]) have less preeclampsia
and macrosomia compared with no treatment [108]. No randomized trials have compared
perinatal outcomes in women diagnosed with gestational diabetes mellitus by the one-step
versus two-step approach. For these reasons and the higher prevalence of women identified as
having gestational diabetes with IADPSG criteria (1.03- to 3.78-fold rise [109]), IADPSG criteria
have not been universally accepted and the rationale for using these criteria has been
challenged [110,111].
Patients unable to tolerate oral hyperosmolar glucose — The highly concentrated

hyperosmolar glucose solution used for the GCT and GTT can cause gastric irritation, delayed
emptying, and gastrointestinal osmotic imbalance, leading to nausea and, in a small percentage
of women, vomiting [112-114]. Serving the hyperosmolar glucose drink on ice may reduce
nausea and vomiting.
The following are options for evaluating women who do not tolerate standard testing.
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● Serial glucose monitoring – Obtaining periodic fasting and one- or two-hour postprandial
blood glucose tests is a monitoring option for women at high risk for gestational diabetes
mellitus who are unable to tolerate an oral glucose load. Options for periodic testing include
weekly logs at 24 to 28 weeks (time when GCT would be performed) and at 32 weeks (peak
insulin resistance). Obtaining a periodic fasting glucose and A1C is a similar option. (See
'Other tests' above.)
This approach is also useful for women who have dumping syndrome after a Roux-en-Y
gastric bypass procedure; these women are unlikely to tolerate a hyperosmolar glucose
solution [115]. Monitoring glucose values will only identify those cases of gestational
diabetes mellitus that might require intervention for hyperglycemia and not all cases of
gestational diabetes mellitus. (See "Fertility and pregnancy after bariatric surgery".)
● Other options
• Some women who vomit during the GTT may be willing to come back another day for
repeat testing after premedication with an antiemetic drug.
• Candy, a predefined meal, or commercial soft drinks have been used instead of a
standard glucose monomer or polymer solution [116-121]. These approaches 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.
Repeat testing — In most protocols, a negative GTT at 24 to 28 weeks is not repeated later in
pregnancy. However, several studies have shown that repeating the test after an initially normal
GTT will identify additional cases in 4 to 29 percent of cases, depending on the timing and
indication for repeat testing (routine versus targeted to past history/signs and symptoms) [122-
125].
Repeat GTT can be considered on an individualized basis in women with sonographic findings
suggestive of a diagnosis of gestational diabetes, such as fetal overgrowth or polyhydramnios,
or in those with a past history of gestational diabetes. Women with one abnormal value on GTT
who were not initially diagnosed with gestational diabetes can also be diagnosed with the
disorder if they have these sonographic findings. Regardless, the potential consequences of a
late pregnancy diagnosis versus nondiagnosis of gestational diabetes should be discussed, with
shared decision making by the patient and physician.
- Page 18 of 34 -
OUR APPROACH TO SCREENING AND DIAGNOSIS OF DIABETES IN

PREGNANCY
Initial prenatal visit — The author performs universal screening for overt diabetes at the initial
prenatal visit in all patients by checking A1C; a diagnosis of overt diabetes is made when A1C is
≥6.5 percent (≥48 mmol/mol) (table 1). Given the increasing frequency of type 2 diabetes, she
believes early testing when routine initial prenatal laboratory tests are drawn is both desirable
and convenient and that diagnosis of these patients combined with appropriate management will
improve pregnancy outcome.
The author acknowledges that A1C is not a suitable test to detect mildly impaired glucose
tolerance. In men and nonpregnant women, an A1C ≥6.5 percent (≥48 mmol/mol) is one of the
criteria used to diagnose diabetes (table 1). Therefore, an A1C ≥6.5 percent early in pregnancy,
when A1C levels are generally slightly lower than in the nonpregnant state [126], suggests
previously undiagnosed type 2 diabetes. However, an A1C below 6.5 percent cannot be taken
as strong evidence against the diagnosis of diabetes, especially in pregnant women with A1C
above the upper limit of the normal range.
Early in pregnancy, the author uses American Diabetes Association (ADA) criteria for diagnosis
of overt diabetes (table 1). Neither ACOG criteria (table 5) nor International Association of
Diabetes and Pregnancy Study Groups (IADPSG)/ADA criteria for diagnosis of gestational
diabetes mellitus at 24 to 28 weeks (table 4) have been validated in the first or early second
trimester.
Of note, approximately one-quarter of women with A1C 5.7 to 6.4 percent ([39 to 46 mmol/mol]
suggestive of impaired glucose intolerance) in early pregnancy develop gestational diabetes
mellitus when screened and tested later in pregnancy compared with <10 percent of those with
A1C <5.7 percent (39 mmol/mol) [127].
At 24 to 28 weeks — For women who have not been previously diagnosed with diabetes, we
prefer a two-step testing approach at 24 to 28 weeks of gestation, following the American
College of Obstetrician and Gynecologists (ACOG) guidelines (50 gram oral glucose challenge
test followed by the 100 gram three-hour oral glucose tolerance test [GTT] in screen-positive
women) [15]. Although the one-step 75 gram two-hour oral GTT using the IADPSG thresholds is
more sensitive than the two-step approach for identifying pregnant women with an abnormal
GTT, this has not clearly translated into improved perinatal outcomes. Screening with a glucose
- Page 19 of 34 -
challenge has the practical advantage that it can be performed at any time of day, without dietary
preparation, while the one-step approach requires that all patients undergo an overnight fast
prior to laboratory testing and must be done in the morning. Only a small percentage of women
need to undergo the second test of the two-step approach, which involves an additional
laboratory visit and collection of four additional blood draws [128]. (See 'One-step and two-step
approaches' above.)
For the oral glucose challenge, 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 development of gestational diabetes. 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. We use Carpenter and
Coustan criteria for an abnormal 100 gram, three-hour GTT as the lower, more stringent criteria
for diagnosis identify women with glucose intolerance at the most risk of adverse perinatal
outcomes.
RECOMMENDATIONS OF NATIONAL AND INTERNATIONAL

ORGANIZATIONS
The optimum strategy for diagnosis of gestational diabetes mellitus to improve maternal and
infant health is unclear [129]. Many organizations have published recommendations for
screening and diagnosis of diabetes in pregnancy:
● American College of Obstetricians and Gynecologists (ACOG, two-step approach (table 5

and table 3)) [15]
● International Association of Diabetes and Pregnancy Study Groups (IADPSG, one-step

approach (table 4)) [13]
● American Diabetes Association (ADA, one-step or two-step approach) [67]
● World Health Organization (WHO, one-step approach (table 6)) [130]
● Canadian Diabetes Association (CDA, two-step [preferred] or one-step approach) [98]
● The Endocrine Society (one-step approach) [131]
● Australasian Diabetes in Pregnancy Society (WHO approach) [38]
- Page 20 of 34 -
● National Institute for Health and Care Excellence (NICE, United Kingdom, one-step
approach)
● International Federation of Gynecology and Obstetrics (FIGO, one-step approach) [132]
POSTDELIVERY FOLLOW-UP
Women with gestational diabetes should be screened again postpartum and periodically
thereafter because they are at increased risk for developing type 2 diabetes mellitus.
Postdelivery follow-up is described separately. (See "Gestational diabetes mellitus: Glycemic
control and maternal prognosis", section on 'Follow-up and prevention of type 2 diabetes'.)
SOCIETY GUIDELINE LINKS
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".)
INFORMATION FOR PATIENTS
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 (diabetes that starts during
pregnancy) (The Basics)")
- Page 21 of 34 -
● Beyond the Basics topics (see "Patient education: Gestational diabetes (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● The terminology for diabetes diagnosed in pregnancy is in flux. The terms "overt" and
"gestational diabetes" are based primarily on gestational age at diagnosis. Diagnosis of
diabetes at 24 to 28 weeks of gestation is consistent with gestational diabetes mellitus,
while diagnosis at the first prenatal visit (in early pregnancy) is more consistent with overt
diabetes. (See 'Terminology' above.)
● A reasonable approach to screening for diabetes in pregnant and postpartum patients,

including long-term screening of patients with gestational diabetes, is shown in the algorithm
(algorithm 1). (See 'Identification of overt diabetes in early pregnancy' above and 'Screening
and diagnostic testing' above and 'Postdelivery follow-up' above.)
Overt diabetes — The author obtains an A1C level at the initial prenatal visit in all patients as
part of the initial prenatal bloodwork in order to identify women with overt diabetes; a value ≥6.5
percent (≥48 mmol/mol) is diagnostic. If preexisting diabetes is not present, the author performs
the usual screening/testing for gestational diabetes mellitus at 24 to 28 weeks (see 'Our
approach to screening and diagnosis of diabetes in pregnancy' above). This strategy was
adopted due to the large percentage of women with multiple risk factors for diabetes in the
author's medical center. However, there is no consensus regarding whether or how to test for
diabetes at the first prenatal visit. If clinicians choose to test, any of the standard diagnostic tests
for type 2 diabetes may be performed. (See 'Identification of overt diabetes in early pregnancy'
above.)
Gestational diabetes
● Identifying pregnant women with gestational diabetes mellitus followed by appropriate

therapy can decrease fetal and maternal morbidity, particularly macrosomia, shoulder
dystocia, and preeclampsia. (See 'Significance' above and 'Benefits and harms of
screening' above.)
● We agree with recommendations of major societies to screen/test for gestational diabetes

mellitus (Grade 2B). (See 'Recommendations of national and international organizations'
- Page 22 of 34 -
above.)
● In the United States, universal screening appears to be the most practical approach
because 90 percent of pregnant women have at least one risk factor for glucose impairment
during pregnancy. (See 'Candidates for screening/testing' above.)
● In women who have not been previously diagnosed with diabetes, screening/testing for
gestational diabetes mellitus is performed at 24 to 28 weeks of gestation using a one-step
or two-step approach. (See 'One-step and two-step approaches' above.)
The author suggests using the two-step approach (50 gram glucose challenge screen
followed by a 100 gram three-hour oral glucose tolerance test [GTT]) in screen-positive
patients as endorsed by the American College of Obstetricians and Gynecologists (two-step
approach (table 5 and table 3)). The increased sensitivity of the one-step compared with the
two-step approach does not clearly result in improved perinatal outcomes. (See 'One-step
and two-step approaches' above and 'Our approach to screening and diagnosis of diabetes
in pregnancy' above.)
The International Association of Diabetes and Pregnancy Study Groups (IADPSG) suggests
a one-step testing approach using the 75 gram two-hour oral GTT and IADPSG thresholds.
The American Diabetes Association supports use of either a one-step or two-step approach.
(See 'Recommendations of national and international organizations' above and 'Screening
methods' above and 'Diagnostic testing methods' above.)
ACKNOWLEDGMENTS
The editorial staff at UpToDate would like to acknowledge Lois Jovanovic, MD, Donald R
Coustan, MD, and Michael Greene, MD, who contributed to earlier versions of this topic review.
REFERENCES
1. Proceedings of the 4th International Workshop-Conference on Gestational Diabetes

Mellitus. Chicago, Illinois, USA. 14-16 March 1997. Diabetes Care 1998; 21 Suppl 2:B1.
2. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and high risk for diabetes
using A1C criteria in the U.S. population in 1988-2006. Diabetes Care 2010; 33:562.
3. Deputy NP, Kim SY, Conrey EJ, Bullard KM. Prevalence and Changes in Preexisting
- Page 23 of 34 -
Gestational diabetes mellitus: Glycemic control and maternal prognosis
Oﬃcial reprint from UpToDate® www.uptodate.com

©2021 UpToDate®
Gestational diabetes mellitus: Glycemic control and

maternal prognosis
Author: Celeste Durnwald, MD
Section Editors: David M Nathan, MD, Erika F Werner, MD, MS
Deputy Editor: Vanessa A Barss, MD, FACOG
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2021. | This topic last updated: Apr 22, 2021.
INTRODUCTION
Treatment of gestational diabetes can improve pregnancy outcome. Many women can achieve
euglycemia with nutritional therapy alone, but up to 30 percent will require drug therapy [1]. The
general approach to treatment of gestational diabetes mellitus will be reviewed here. Screening,
diagnosis, and obstetric management are discussed separately. (See "Diabetes mellitus in
pregnancy: Screening and diagnosis" and "Pregestational (preexisting) diabetes mellitus:
Obstetric issues and management".)
RATIONALE FOR TREATMENT
Identifying women with gestational diabetes mellitus is important to minimize maternal and
neonatal morbidity. A systematic review and meta-analysis of randomized trials for the United
States Preventive Services Task Force found that appropriate management of gestational
diabetes (nutritional therapy, self-blood glucose monitoring, administration of insulin if target
blood glucose concentrations are not met with diet alone) resulted in reductions in [2]:
● Preeclampsia (relative risk [RR] 0.62, 95% CI 0.43-0.89; 72/1001 [7.2 percent] versus
119/1013 [11.7 percent], three trials).
● Birth weight >4000 g (RR 0.50, 95% CI 0.35-0.71, five trials).
● Shoulder dystocia (RR 0.42, 95% CI 0.23-0.77, three trials).
- Page 1 of 48 -
Two trials showed no difference in maternal weight gain while two large trials showed less
gestational weight gain with treatment; inconsistency across trials and imprecise effect estimates
precluded meta-analysis.
The only potential harm resulting from treatment of gestational diabetes was an increased
number of prenatal visits. No statistically significant changes in rates of cesarean delivery,
induction of labor, small for gestational age neonates, neonatal hypoglycemia, neonatal
hyperbilirubinemia, neonatal respiratory complications, birth trauma, or neonatal intensive care
unit admission were demonstrated compared with no treatment, although the quality of available
evidence was low. The frequency and consequences of maternal hypoglycemia in women
treated with insulin were not reported.
Some authors have suggested that maternal obesity and excessive weight gain during
pregnancy may be more closely related to adverse outcomes than glucose intolerance because
the effects of maternal obesity on fetal growth are overwhelming [3], but data from the
Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study refute this hypothesis. In the
HAPO study, obesity and gestational diabetes (International Association of Diabetes and
Pregnancy Study Groups criteria) were independently predictive of fetal macrosomia,
preeclampsia, primary cesarean delivery, and neonatal adiposity [4]. Macrosomia was more
likely when gestational diabetes was present in the absence of obesity (odds ratio [OR] 2.19,
95% CI 1.93-2.47) than when obesity was present in the absence of gestational diabetes (OR
1.73, 95% CI 1.50-2.00), and the independent effects of gestational diabetes and obesity were
additive.
Prepregnancy weight loss and normalization of body mass index can improve future pregnancy
outcome. As a practical matter, once pregnancy occurs, pharmacologic and surgical
interventions are not used for treating obesity and efforts to limit gestational weight gain have
met with limited success; however, gestational diabetes can be identified and treated, and
treatment can prevent adverse outcomes as well as decrease gestational weight gain [5,6].
Another controversy relates to the timing of treatment in gestational diabetes. A secondary

analysis of data from a randomized trial [6] found that outcomes of pregnancies with early
diagnosis and treatment (all between 24 and 30+6 weeks of gestation) of mild gestational
diabetes (fasting value <95 mg/dL and two elevated post-glucose challenge values) were not
significantly different based on when gestational diabetes was identified and treatment was
initiated [7]. Pregnancy outcomes were similar when treatment was initiated at 24 to 26, 27, 28,
- Page 2 of 48 -
or 29 weeks compared with ≥30 weeks of gestation.
Few studies have evaluated long-term effects of maternal treatment on offspring. In one long-
term study of treated versus untreated pregnancies with mild gestational diabetes mellitus
(defined as fasting plasma glucose <95 mg/dL but two elevated 100-gram, three-hour oral
glucose tolerance test values), treatment during pregnancy did not reduce late adverse
metabolic outcomes (eg, obesity, glucose intolerance) among 5- to 10-year-old offspring [8]. This
may reflect lack of a true treatment effect, inadequate treatment of hyperglycemia during
pregnancy, the mildness of the glucose intolerance, or inadequate power to show modest
differences in outcome because of the low prevalence of these diseases in children at this age
(prior to puberty), and the small numbers of study participants.
MEDICAL NUTRITIONAL THERAPY
Medical nutritional therapy is the process by which the dietary plan is tailored for patients with
diabetes, based on medical, lifestyle, and personal factors. Patients with gestational diabetes
should receive medical nutritional counseling by a registered dietitian (when possible) upon
diagnosis and be placed on an appropriate diet. The goals are to:
● Achieve normoglycemia
● Prevent ketosis
● Provide adequate gestational weight gain based on maternal body mass index (BMI)
● Contribute to fetal well-being
Most women (70 to 85 percent) with gestational diabetes based on Carpenter and Coustan
criteria can achieve normoglycemia with lifestyle modification alone. Lifestyle modification
includes nutritional intervention, physical activity, and weight management. In the two
randomized trials in which diagnosis and treatment of mild gestational diabetes improved
outcomes [5,6], only 20 and 8 percent of women, respectively, required insulin. A detailed review
of medical nutritional treatment of individuals with diabetes can be found separately. (See
"Nutritional considerations in type 1 diabetes mellitus".)
A key intervention is to emphasize the benefits of elimination, or at least reduction, of

consumption of sugar-sweetened beverages (eg, soft drinks, fruit drinks) and drinking water
instead. Noncaloric sweeteners, such as aspartame, sucralose, and others, may be used in
moderation. Saccharine, on the other hand, is known to cross the placenta and is not
- Page 3 of 48 -
recommended in pregnancy.
The American Diabetes Association (ADA) recommends that medical nutritional therapy for
gestational diabetes mellitus provides adequate nutrition to promote fetal and maternal well-
being while achieving normoglycemia with absence of ketosis and providing adequate energy
levels for appropriate weight gain in pregnancy [9]. The food plan should be based on a
nutritional assessment with guidance from the Dietary Reference Intakes for all pregnant women
(minimum of 175 grams of carbohydrate, 71 grams of protein, and 28 grams of fiber) [10]. In
clinical practice, women often require 1800 to 2500 kcal/day.
The specific diet for women with gestational diabetes that achieves optimum maternal and
newborn outcomes is unclear [11]. In a 2018 systematic review of randomized trials comparing a
variety of dietary interventions (eg, low glycemic index, DASH, low carbohydrate, energy
restriction, soy protein, fat modification, ethnic, high fiber) with conventional dietary
recommendations for women with gestational diabetes (18 trials, 1151 women), dietary
intervention overall reduced fasting and postprandial glucose levels (fasting: -4.07 mg/dL, 95%
CI -7.58 to -0.57; postprandial -7.78 mg/dL, 95% CI -12.27 to -3.29), need for medication
(relative risk [RR] 0.65, 95% CI 0.47-0.88), birth weight (-170.62 g, 95% CI -333.64 to -7.60),
and macrosomia (RR 0.49, 95% CI 0.27-0.88) [12]. The lower postprandial glucose level was
only evident postbreakfast. When analyzed by diet-subtype, low glycemic index, DASH, low
carbohydrate, and ethnic diets had beneficial effects on maternal glucose levels; however, all
studies were limited by a small sample size.
Meal plan — A typical meal plan for women with gestational diabetes mellitus includes three
small- to moderate-sized meals and two to four snacks. Adjustment of the meal plan should be
ongoing and based upon results of self-glucose monitoring, appetite, and weight-gain patterns,
as well as consideration for maternal dietary preferences and work, leisure, and exercise
schedules.
Close follow-up is important to ensure nutritional adequacy. Individual assessment and self-
blood glucose monitoring are used to determine and modify specific nutrition/food
recommendations. If insulin therapy is added to nutrition therapy, a primary goal is to maintain
carbohydrate consistency at meals and snacks to facilitate insulin adjustments.
Calories — For women who are of normal BMI (BMI of 18.5 to 24.9 kg/m2) during pregnancy,
a reasonable caloric intake is 30 kcal/kg/day; for women who are overweight (BMI 25.0 to 29.9
kg/m2) and obese (BMI 30.0 to 39.9 kg/m2), a reasonable caloric intake is 22 to 25 kcal/kg/day;
- Page 24 of 48 -
and for obese women with a BMI ≥40.0 kg/m2, a reasonable caloric intake is 12 to 14
kcal/kg/day (present pregnant weight), but it is prudent for obese women to consume a minimum
of 1800 cal/day to prevent ketosis. For women who are underweight (BMI <18.5 kg/m2), a
reasonable caloric intake is 35 to 40 kcal/kg/day to achieve recommended weight gain, blood
glucose goals, and nutrient intake.
When considering caloric intake by trimester, no increase in calories is recommended for the first
trimester, an additional 340 kcal/day above prepregnancy levels is recommended during the
second trimester, and an additional 452 kcal/day above prepregnancy levels is recommended
during the third trimester [13]. There are no strong data to support these standard
recommendations. There are no definitive data for specific optimal caloric intake for women with
gestational diabetes mellitus and no clear data suggesting that their caloric needs are different
from those of pregnant women without gestational diabetes mellitus.
Carbohydrate intake — Once the caloric needs are calculated, carbohydrate intake needs to
be determined as it is the primary nutrient affecting postprandial glucose levels. The total
amount of carbohydrate, the distribution of carbohydrate over meals and snacks, and the type of
carbohydrate can be manipulated to blunt postprandial hyperglycemia. However, reducing
carbohydrates to decrease postprandial glucose levels may lead to higher consumption of fat,
which may have adverse effects on maternal insulin resistance and fetal body composition.
There is sparse evidence from randomized trials as to the ideal carbohydrate intake for
treatment of gestational diabetes. We limit carbohydrate intake to 40 percent of total calories
while ensuring that ketonuria does not ensue [14,15]. A 2014 meta-analysis of randomized trials
of dietary intervention in women with gestational diabetes found low carbohydrate diets did not
change either maternal or newborn outcomes, but the data were insufficient to detect small or
moderate statistical differences in obstetric outcomes between the patient groups [16].
Many women will need individual adjustment (ie, 15 to 30 g of carbohydrate at breakfast or other
meals), depending on postprandial glucose levels, which are directly dependent upon the
carbohydrate content of the meal or snack [17]. The postprandial glucose rise, therefore, can be
blunted if the diet is carbohydrate restricted. In addition, an overall low glycemic index diet in
which carbohydrate sources are mainly comprised of fruits, vegetables, and whole grains, with
low consumption of flour-based products (eg, bread and other baked products) and potatoes had
a favorable effect on postprandial blood glucose concentrations and significantly lowered the
need for insulin therapy in the meta-analysis described above [16]; however, a clear effect on
- Page 5 of 48 -
pregnancy outcome, particularly macrosomia, cesarean delivery, and maternal weight gain, has
not been proven. (See "Dietary carbohydrates", section on 'Glycemic index' and "Nutritional
considerations in type 2 diabetes mellitus", section on 'Glycemic index and glycemic load'.)
Probiotics and high fiber diets do not appear to improve glycemic control [18,19].
Protein and fat intake — The remaining calories come from protein (20 percent of total
calories) and fats (40 percent of total calories; saturated fat intake should be <7 percent of total
calories). Protein intake should be distributed throughout the day and included in all meals and
snacks to promote satiety, slow the absorption of carbohydrates into the bloodstream, and
provide adequate calories. A bedtime high-protein snack may be needed to prevent accelerated
(starvation) ketosis overnight.
Gestational weight gain/loss — After prescribing the diet, it is important to pay attention to
subsequent changes in weight. A retrospective cohort study including 31,074 women with
gestational diabetes mellitus showed that those with appropriate weight gain (per Institute of
Medicine 2000 recommendations [20]) had optimal outcomes, while excessive weight gain was
associated with a significantly increased risk of having a large for gestational age infant, preterm
birth, and cesarean delivery [21]. Suboptimal weight gain increased the likelihood of avoiding
medical therapy of gestational diabetes and decreased the likelihood of having a large for
gestational age neonate; however, there were more small for gestational age neonates in this
group (7.3 versus 5.6 percent). The data in this study were not corrected for potential
confounders, such as smoking. (See "Obesity in pregnancy: Complications and maternal
management" and "Gestational weight gain", section on 'Recommendations for gestational
weight gain'.)
Some women experience a minimal amount (1 to 5 pounds) of weight loss or weight stabilization
for the first few weeks after starting nutritional therapy. This should be evaluated in the overall
context of weight gain in pregnancy and ongoing surveillance of weight gain in the weeks
thereafter.
Weight loss in pregnancy is not generally recommended, although controversy exists regarding
this recommendation for obese women with higher BMIs. Maternal obesity often worsens
impaired glucose tolerance. Furthermore, maternal gestational diabetes and obesity are
independently associated with adverse pregnancy outcomes, such as excessive fetal growth
and preeclampsia, and their combination has a greater impact than either disorder alone [4,22-
24].
2 - Page 6 of 48 -
For obese women (BMI >30 kg/m2), a modest energy restriction to reduce weight gain can be
achieved by restricting caloric intake by approximately 30 percent below the Dietary Reference
Intakes (DRI) for pregnant women. This can be achieved while meeting Institute of Medicine
(IOM) weight gain recommendations and without causing ketosis [25] (see "Gestational weight
gain", section on 'Recommendations for gestational weight gain'). In the 2014 meta-analysis
described above [16], energy restriction did not significantly reduce the cesarean delivery rate,
frequency of macrosomia, or rate of neonatal hypoglycemia, but data were limited to two small
trials and were inconsistent.
Nutritional therapy to decrease the risk of macrosomia — Gestational diabetes mellitus has
major fetal effects on birth weight and body composition: infants of diabetic mothers are at high
risk of being large for gestational age. (See "Infants of women with diabetes".)
Macrosomia may not be prevented by dietary therapy alone. A Cochrane review of four studies
involving 612 women with gestational diabetes treated with primary dietary therapy or no specific
treatment found no differences between groups in birth weight greater than 4000 grams (odds
ratio [OR] 0.78, 95% CI 0.45-1.35) or cesarean deliveries (OR 0.97, 95% CI 0.65-1.44) [26].
However, the variable quality of these studies and wide confidence intervals precluded a
definitive conclusion about the value of dietary intervention. As an example, the investigators did
not consistently assess dietary compliance or postprandial glucose concentration in women in
whom a diet was prescribed.
Some experts have suggested medical nutritional therapy for women who do not meet oral
glucose tolerance test (GTT) criteria for gestational diabetes but have fasting blood glucose
concentrations >90 mg/dL [5 mmol/L] [27], an abnormal glucose challenge test [28,29], or one
abnormal value on the three-hour 100 g oral GTT (see "Diabetes mellitus in pregnancy:
Screening and diagnosis"). The rationale for this approach is that there appears to be a
continuous relationship between glucose concentration and fetal growth/adverse fetal outcome,
even in women who did not meet the former ADA criteria for diagnosis of diabetes [27-33]. This
was best illustrated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study,
which included more than 23,000 pregnant women [32]. After a two-hour 75 g oral GTT, the risk
of macrosomia increased as much as fivefold as fasting plasma glucose concentration increased
above 75 mg/dL (4.2 mmol/L), or one-hour glucose concentration increased above 105 mg/dL
(5.8 mmol/L), or two-hour glucose concentration increased above 90 mg/dL (5.0 mmol/L), and
the risk increased continuously across the spectrum of glucose results. There was also a
positive, but weaker, correlation between increasing glucose concentration and maternal
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complications (eg, preeclampsia) and neonatal metabolic morbidity (eg, hypoglycemia,

hyperbilirubinemia), but not intermediate-term childhood morbidity, such as obesity at age two
years in a small subset of offspring [34], although, as noted above, previous longitudinal studies
have suggested that obesity does not manifest itself in offspring of diabetic mothers until the age
of 6 to 7 years. Of note, women with significant hyperglycemia were excluded from the HAPO
analysis (exclusion criteria: fasting glucose concentration greater than 105 mg/dL [5.8 mmol/L],
two-hour glucose concentration greater than 200 mg/dL [11.1 mmol/L], or a random glucose
concentration later in gestation greater than 160 mg/dL [8.9 mmol/L]).
In a 2012 systematic review of four randomized trials (n = 543 women) of women with one or
more elevated glucose levels on a three-hour 100 g oral GTT who did not meet standard criteria
for gestational diabetes mellitus, glucose monitoring, and medical nutritional therapy (with or
without insulin) resulted in a reduction in delivery of large for gestational age infants compared
with usual care [35]. Similarly, in the Australian Carbohydrate Intolerance in Pregnant Women
trial, medical nutritional therapy (with or without insulin) initiated at two-hour 75 g GTT levels of
140 to 198 mg/dL (7.8 to 11.0 mmol/L; ie, a range between a normal and a diabetic response on
oral GTT) resulted in a lower rate of serious perinatal complications compared with routine care
(1 versus 4 percent, adjusted risk ratio 0.33, 95% CI 0.14-0.75) [5].
Supplements — Myoinositol supplementation during pregnancy has been studied both as a

potential prevention and treatment for gestational diabetes mellitus [36]. A systematic review
found insufficient evidence to support the use of myoinositol for treatment of gestational
diabetes, but available evidence was limited [37]. This continues to be an active area of
investigation [38-40].
EXERCISE
Exercise that increases muscle mass appears to improve glycemic control, primarily from
increased tissue sensitivity to insulin. As a result, both fasting and postprandial blood glucose
concentrations can be reduced [41-43] and, in some women with gestational diabetes mellitus,
the need for insulin may be obviated [44,45]. Circuit resistance training has a similar effect [46].
(See "Effects of exercise in adults with diabetes mellitus".)
In one small randomized trial, six weeks of a cardiovascular fitness program using arm
ergometry three times a week for 20 to 30 minutes per session resulted in normalization of
glucose tolerance [44]. The mean fasting blood glucose concentration fell to 55 to 65 mg/dL (3.1
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to 3.6 mmol/L), and the mean blood glucose concentration was 106 mg/dL (5.9 mmol/L) one
hour after a 50 g oral glucose challenge. In another small randomized trial, use of a recumbent
bicycle was associated with reduction in glucose levels such that exercise-trained subjects and
insulin-treated control subjects had comparable mean glucose values during pregnancy,
comparable infant birth weights, and comparable macrosomia rates [47]. A third randomized trial
confirmed the safety and cardiovascular benefits of exercise programs in women with
gestational diabetes but was unable to demonstrate reduction in glucose levels [48]. An
observational study found that glucose levels fell up to 23 mg/dL (1.3 mmol/L) within 30 minutes
of exercise compared with resting, but the differences were gone by 45 minutes after exercise
[49].
The value of exercise in women with gestational diabetes requires further exploration to
determine the potential range of benefits [50,51]. Nevertheless, based on the data cited above
and that in nonpregnant individuals, the American Diabetes Association encourages a program
of moderate exercise as part of the treatment plan for women with gestational diabetes mellitus
and no medical or obstetric contraindications to this level of physical activity [52]. (See "Exercise
during pregnancy and the postpartum period".)
GLUCOSE MONITORING
Frequency — The optimal approach to glucose monitoring has not been determined [53]. When
initially diagnosed with gestational diabetes mellitus, we ask patients to measure their blood
glucose concentration at least four times daily (fasting and one or two hours after the first bite of
each meal) [54,55]. Multiple daily measurements allow recognition of women who should begin
an antihyperglycemic agent. Results should be recorded in a glucose log, along with dietary
information. This facilitates recognition of glycemic patterns and helps immeasurably in
interpreting results stored in the memory of modern meters.
Results from most available glucose meters and commercial laboratories reflect plasma (not
whole blood) glucose levels. Meters cannot correct for the fact that postprandial glucose
concentrations tend to be higher in capillary samples because of arterial/venous mixing. (See
"Self-monitoring of glucose in management of nonpregnant adults with diabetes mellitus".)
Although there is no strong evidence on the duration of good control sufficient to reduce the
frequency of self-monitoring or the appropriate frequency of testing in gestational diabetes that is
well-controlled with nutritional therapy [54,56], some providers decrease the frequency of
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glucose monitoring when good glycemic control is accomplished with medical nutritional therapy
in individualized cases. In a randomized trial in women with well-controlled gestational diabetes
on nutritional therapy after one week of four times daily blood glucose testing, testing blood
glucose every other day versus four times daily resulted in similar birth weights and frequency of
macrosomia [57]. Thus, it may be reasonable to decrease the frequency of glucose monitoring to
every other day in specific patients with mild gestational diabetes mellitus, proven normal
glucose values, and no signs of fetal overgrowth or polyhydramnios, saving health care dollars
and increasing patient convenience.
Where the new International Association of Diabetes and Pregnancy Study Groups (IADPSG)
recommendations for the diagnosis of gestational diabetes mellitus are in widespread use, as
many as 18 percent of pregnant women are diagnosed with this condition, which increases the
need for more efficient and effective monitoring and treatment strategies (see "Diabetes mellitus
in pregnancy: Screening and diagnosis"). Therefore, studies to test alternative approaches such
as less frequent monitoring are necessary. Fortunately, intervention trials of mild gestational
diabetes mellitus [5,6] demonstrated that only a small proportion of such individuals required
intervention beyond dietary management.
Timing — For women with gestational diabetes mellitus, we suggest measuring blood glucose
on awakening (before eating) and after meals throughout pregnancy because fasting and
preprandial glucose levels alone may not predict the need for insulin therapy (pregnancy is
characterized by postprandial hyperglycemia because of insulin resistance) [58]. Given limited
data, postprandial assessment of blood glucose can be performed either one or two hours after
the beginning of each meal; the optimum time has not been determined [59-61]. We prefer the
one-hour postprandial measurement as it corresponds more closely to the maximum insulin
peak in patients using rapid-acting insulin analogs. The advent of continuous glucose monitoring
has the potential to allow determination of peak postprandial glucose levels, mean glucose level,
episodes of nocturnal hyperglycemia, and percent time in range for a 24-hour period; future
research should determine whether using these data in management of gestational diabetes
mellitus will improve outcomes [62,63]. (See "Self-monitoring of glucose in management of
nonpregnant adults with diabetes mellitus".)
The value of fasting plus postprandial versus preprandial measurement was suggested by a trial
that randomly assigned 66 insulin-treated patients with gestational diabetes mellitus to have their
diabetes managed according to results of fasting plus postprandial monitoring (one hour after
meals) or preprandial-only blood glucose concentrations [64]. One-hour postprandial monitoring
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was associated with the following benefits as compared with preprandial monitoring:
● Better glycemic control (glycated hemoglobin [A1C] value 6.5 versus 8.1 percent)
● A lower incidence of large for gestational age infants (12 versus 42 percent)
● A lower rate of cesarean delivery for cephalopelvic disproportion (12 versus 36 percent)
Continuous glucose monitoring may lead to better outcomes than frequent self-monitoring of
blood glucose (SMBG). In a randomized trial, 340 Chinese women with gestational diabetes
mellitus by the IADPSG criteria were monitored by either continuous glucose monitoring or
seven times daily SMBG [65]. SMBG goals were fasting glucose ≤95 mg/dL (5.3 mmol/L) and
one-hour postprandial values ≤140 mg/dL (7.8 mmol/L); continuous glucose monitoring goals
were the same, with the additional goal that all peak postprandial glucose values >140 mg/dL
(7.8 mmol/L) last ≤10 minutes and any episode of asymptomatic hypoglycemia <60 mg/dL (3.3
mmol/L) lasts <30 minutes. Women randomly assigned to continuous glucose monitoring were
more than twice as likely to require insulin therapy (28 versus 12 percent) and had significantly
less preeclampsia (3.4 versus 10.1 percent), fewer primary cesarean deliveries (35 versus 47
percent), fewer large for gestational age (LGA) infants (14 versus 26 percent), and a lower
likelihood of a composite neonatal outcome (27 versus 50 percent). The rate of small for
gestational age (SGA) infants trended higher in the continuously monitored group (6 versus 3
percent). These results suggest that increasing the intensity of glucose monitoring and insulin
therapy may further improve pregnancy outcomes in gestational diabetes mellitus; however, the
benefits and risks of this approach require more study in other populations, especially given the
resources that would be required to institute it for the large proportion of gravidas with
gestational diabetes.
Glucose target — The glucose level at which the disadvantages of initiating insulin therapy are
clearly outweighed by the benefits has not been definitively determined; there is little consensus
in the literature [66]. The American Diabetes Association (ADA) and the American College of
Obstetricians and Gynecologists (ACOG) recommend the following upper limits for glucose
levels, with insulin therapy initiated if they are exceeded, but acknowledge that these thresholds
have been extrapolated from recommendations proposed for women with preexisting diabetes
[10,55].
Little guidance is available as to what proportion of measurements exceeding these thresholds

should trigger intervention, and some suggest insulin for two or more elevated values in a two-
week interval while others await more consistent elevations, particularly if it is deemed that
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further nutritional counseling may be effective. We initiate insulin (or increase the dose) when
one-third of fasting or postprandial glucose levels exceed the target in a given week.
ADA and ACOG glucose targets are:
● Fasting blood glucose concentration: <95 mg/dL (5.3 mmol/L)

● One-hour postprandial blood glucose concentration: <140 mg/dL (7.8 mmol/L)
● Two-hour postprandial glucose concentration: <120 mg/dL (6.7 mmol/L)
These targets, which represent the upper limit of desirable glucose concentration, are well above
the mean glucose values in nondiabetic pregnant women described in a 2011 literature review of
studies of the normal 24-hour glycemic profile of pregnant women [67]. In this review, which had
a total of 255 nondiabetic women who were mostly nonobese and in the late third trimester, the
pooled weighted mean glucose values (±1 SD) were fasting 71±8 mg/dL (3.9±0.4 mmol/L), one-
hour postprandial 109±13 mg/dL (6.0±0.7 mmol/L), two-hour postprandial 99±10 mg/dL (5.5±0.6
mmol/L), and 24-hour glucose 88±10 mg/dL (4.9±0.6 mmol/L). These levels were derived from
measurements on whole blood, plasma, self-monitored capillary glucose measurements, which
are aligned to plasma levels, or tissue glucose measurements using continuous glucose
monitoring systems. Despite the variations in methodology, there was some consistency in the
results. If two standard deviations are added to the means outlined in the systematic review, the
upper limit of normal fasting glucose would be 87 mg/dL (4.8 mmol/L), the corresponding one-
hour postprandial value would be 135 mg/dL (7.5 mmol/L), and the upper limit of normal two-
hour value would be 119 mg/dL (6.6 mmol/L); while the fasting value is somewhat lower than the
target 95 mg/dL (5.3 mmol/L), the postprandial values are not dissimilar to the targets described
above.
Mean blood glucose values throughout the day appear to be 5 to 10 mg/dL (0.3 to 0.6 mmol/L)
higher in nondiabetic obese pregnant women than in normal weight pregnant women [68].
As described above, the Hyperglycemia and Adverse Pregnancy Outcome study showed a
continuous relationship between maternal glucose and adverse outcomes, with a fasting plasma
glucose level of 100 to 105 mg/dL (5.6 to 5.8 mmol/L) associated with a risk of macrosomia
fivefold greater than that with a fasting glucose level less than 75 mg/dL (4.2 mmol/L; 25 versus
5 percent) [32]. Subsequent studies have consistently reported an association between
increasing fasting maternal glucose levels and increasing neonatal adiposity/size that is large for
gestational age [69-71].
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Whether there would be a benefit to lowering the targets for initiating therapy in gestational
diabetes mellitus in an effort to further lower the increased prevalence of large for gestational
age infants is a hypothesis which could be tested. However, there is evidence that overly tight
metabolic control in gestational diabetes (ie, average blood glucose levels ≤86 mg/dL) can result
in an increase in small for gestational age offspring [72].
Glycated hemoglobin — A1C may be a helpful ancillary test in assessing glycemic control
during pregnancy [73,74]. It is not clear how often it should be monitored in women with
apparently well-controlled gestational diabetes mellitus. If there is a discrepancy between the
A1C and glucose values, potential causes should be investigated. (See "Measurements of
glycemic control in diabetes mellitus", section on 'Racial/ethnic differences' and "Measurements
of glycemic control in diabetes mellitus", section on 'Unexpected or discordant values'.)
Good normative data for A1C during each trimester are not available. A1C values tend to be
lower in pregnant compared with nonpregnant women [75] because the average blood glucose
concentration is approximately 20 percent lower in pregnant women, and in the first half of
pregnancy, there is a rise in red cell mass and a slight increase in red blood cell turnover [76,77].
Other factors that affect A1C levels include race (A1C concentration is higher in African
American, Hispanic, and Asian women than in White women) and iron status (chronic iron
deficiency anemia increases A1C, treatment of iron deficiency anemia with iron lowers A1C).
Sources of variation in A1C levels are discussed in detail separately. (See "Measurements of
glycemic control in diabetes mellitus", section on 'Glycated hemoglobin (A1C)'.)
MONITORING FOR KETONURIA
We do not routinely monitor urinary ketones in women with gestational diabetes mellitus.
Diabetic ketoacidosis is extremely rare in women with gestational diabetes. It is characteristically
associated with type 1 diabetes, but also occurs in type 2 diabetes under conditions of extreme
stress such as serious infection, trauma, or cardiovascular or other emergencies. It is not certain
whether ketonuria is associated with an adverse effect on cognitive development of the fetus.
Early studies primarily consisting of both mothers with gestational diabetes and those with
preexisting diabetes found such an effect [78-80], while a study of nondiabetic gravidas did not
[81].
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PHARMACOLOGIC THERAPY
If normoglycemia cannot be maintained by medical nutritional therapy, then antihyperglycemic

agents should be initiated. As discussed above, the optimum threshold for initiating
pharmacologic therapy has not been established [66]. We initiate therapy when over 30 percent
of the blood glucose values are above the following thresholds:
● Fasting blood glucose concentration >95 mg/dL (5.3 mmol/L)

● One-hour postprandial blood glucose concentration >140 mg/dL (7.8 mmol/L)
● Two-hour postprandial glucose concentration >120 mg/dL (6.7 mmol/L)
Choice of pharmacologic therapy — There are two pharmacologic options in pregnant

patients who require medical therapy aimed at controlling blood glucose: insulin (and some
insulin analogs) and selected oral antihyperglycemic agents (metformin, glyburide). We consider
insulin the treatment of choice, and believe that oral antihyperglycemic agents are a reasonable
alternative for women who fail nutritional therapy and decline to take, or are unable to comply
with, insulin therapy (see 'Insulin' below and 'Oral antihyperglycemic agents' below). Systematic
reviews of studies of pregnancy outcome in women with gestational diabetes mellitus treated
with oral antihyperglycemic agents or insulin have generally found that both approaches can be
effective [66,82-85]. There is a trend toward more frequent hypoglycemia with use of insulin [85]
and some women on oral agents need supplemental insulin to achieve and maintain euglycemia
[86]. However, it is difficult to draw firm conclusions about the optimal approach because of
inconsistencies in criteria for gestational diabetes, glucose targets, patient adherence to
treatment, and clinical outcome measures across studies, as well as lack of data regarding long-
term outcomes in offspring [85].
The American College of Obstetricians and Gynecologists (ACOG) [55] and the American
Diabetes Association (ADA) [10] prefer use of insulin for treatment of diabetes during pregnancy
but have endorsed the use of oral antihyperglycemic agents (metformin or glyburide) in certain
circumstances; in the United States, such therapy has not been specifically approved for
treatment of gestational diabetes mellitus by the US Food and Drug Administration (FDA).
ACOG recommends an oral agent for women who decline insulin therapy or when the health
care provider believes the patient will be unable to afford or safely administer insulin and
recommends metformin over glyburide as the preferred oral antihyperglycemic agent [55]. They
emphasize that patients should understand the limitations of available safety data and the
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possibility that insulin supplementation may be necessary to achieve euglycemia. The ADA also
states that metformin should not be used in women with hypertension, preeclampsia, or at risk
for intrauterine growth restriction due to the potential for growth restriction or acidosis in the
setting of placental insufficiency [10]. (See 'Glyburide' below and 'Metformin' below.)
By contrast, the Society for Maternal-Fetal Medicine concluded that "in women with gestational
diabetes in whom hyperglycemia cannot adequately be controlled with medical nutritional
therapy, metformin is a reasonable and safe first-line pharmacologic alternative to insulin" [1].
However, they also stated that insulin is presumed to be the most effective means to control
hyperglycemia because of the almost limitless ability to increase and titrate doses to control
blood glucose levels.
Some guidelines from other countries (eg, The National Institute for Health and Care Excellence
in the United Kingdom) and international guidelines (eg, International Federation of Gynecology
and Obstetrics [FIGO]) consider oral antihyperglycemic drugs an acceptable first-line approach
in select women (eg, women with low fasting blood glucose levels since oral agents are more
likely to prevent hyperglycemia in these women than in those with high fasting glucose levels)
[87,88]. FIGO recommends insulin as the first-line treatment in women with at least some of the
following factors: diabetes is diagnosed before 20 weeks of gestation, pharmacologic therapy is
needed after 30 weeks of gestation, fasting blood glucose is >110 mg/dL (6.1 mmol/L), one-hour
postprandial glucose is >140 mg/dL (7.8 mmol/L), or pregnancy weight gain is >12 kg (26.5
pounds) [88]. (See 'Society guideline links' below.)
Insulin
When to initiate — For women with gestational diabetes mellitus, common practice is to
initiate insulin therapy when target glucose levels are exceeded despite nutritional therapy. (See
'Glucose target' above.)
Alternatively, data from some randomized trials suggest that prescribing insulin to the subgroup
of women with indirect evidence of fetal hyperinsulinemia (eg, ultrasound showing abdominal
circumference >75th percentile early in the third trimester) allows targeted treatment of those at
highest risk of delivering a macrosomic infant and avoids treatment of those at low risk [89-92]. A
2014 meta-analysis including only two trials concluded that ultrasound-based management of
women with a broad severity-spectrum of gestational diabetes reduced the occurrence of large
for gestational age infants compared with conventional management, but increased ultrasound
examination frequency and the number of women requiring insulin treatment [93].
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It is reasonable for women with fetuses with a large abdominal circumference (>75th percentile)
to receive insulin to decrease the risk of macrosomia, even if they have no or mild
hyperglycemia [56]. Conversely, it is reasonable to relax self-glucose monitoring and initiation of
insulin for mild hyperglycemia in women whose fetuses do not have a large abdominal
circumference. Withholding insulin when there is no evidence of increased somatic growth may
limit the risk of iatrogenic growth restriction [90].
Dose — The dose of insulin varies in different individuals because of varied rates of obesity,
ethnic characteristics, degree of hyperglycemia, and other demographic criteria, but the majority
of studies have reported a total insulin dose ranging from 0.7 to 2 units per kg (present pregnant
weight) to achieve glucose control. The dose and type of insulin used is calculated based upon
the specific abnormality of blood glucose noted during monitoring.
Our approach — Hospitalization is not necessary to initiate insulin therapy. However, if

teaching of insulin technique and dose of multiple insulin injections, self-monitoring blood
glucose, and charting of the blood glucose and insulin is not possible in the outpatient setting,
then the use of an inpatient setting to utilize the expertise of the hospital's nursing staff may
justify the cost of hospitalization. We do not use insulin pumps in women with gestational
diabetes mellitus because there are no data to suggest that they are necessary or more effective
than conventional therapy, and the cost of an insulin pump is not justified over the relatively short
duration of a pregnancy. However, case reports have described successful use in some women.
One principle we have found useful is to start with the simplest regimen and increase the
complexity as needed to address the particular situation. Typically, regardless of body weight,
insulin dosing is based on the glucose levels recorded in the patient's blood glucose log. For
example, if glucose elevations are mostly postprandial, then a starting dose of 10 to 20 units of
intermediate-acting insulin and 6 to 10 units of rapid-acting insulin are prescribed in the morning
before breakfast, based on the degree of elevations. However, if diabetes is diagnosed and
therapy instituted early in pregnancy (prior to third trimester screening), we generally use slightly
lower doses since insulin resistance has not reached its maximum level in the first and second
trimesters. The 2:1 proportion of intermediate to rapid-acting insulin is based on the pattern of
insulin release in normal pregnant women in the third trimester [94].
If the post-dinner glucose level is elevated, then an additional injection of rapid-acting insulin is
given just prior to dinner. If fasting glucose is elevated, then intermediate-acting insulin is
preferably given at bedtime but can be given before dinner instead on an individualized basis.
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Sometimes an additional dose of rapid-acting insulin is necessary to maintain euglycemia after

lunch, so that a total of four injections per day are needed. A four-times-per-day regimen
improved glycemic control and perinatal outcome compared with a twice-daily regimen in one
randomized trial [95], although macrosomia rates were not impacted.
Subsequent adjustments in the various components of the insulin regimen are made based upon
glucose levels recorded from self-blood glucose monitoring.
Because any insulin regimen requires serial dosing adjustments in response to specific fasting
or postprandial glucose levels, the starting dose should be considered just that, a starting point.
Adjustments in insulin dose in response to high glucose values are typically in the range of 10 to
20 percent. The upper end of this range is unlikely to lead to hypoglycemia in patients with both
obesity and gestational diabetes mellitus unless a meal is omitted after insulin is given.
The titration of insulin dose to blood glucose levels is based upon frequent self-monitoring. Four
to six glucose measurements each day are needed to optimize therapy (fasting and one or two
hours postprandial with the possible addition of pre-lunch and pre-dinner as needed) and ensure
a smooth increase of insulin as insulin requirements increase with pregnancy progression. Twin
gestations complicated by gestational diabetes mellitus may require an approximate doubling of
the insulin requirement throughout pregnancy.
Insulin adjustments when specific glucose levels are not well controlled — An
alternative approach to insulin therapy, somewhat more complex and likely most appropriate for
individuals whose glucose levels are not well controlled with simpler paradigms, is described
below:
● If insulin is required because the fasting blood glucose concentration is high, an

intermediate-acting insulin, such as neutral protamine hagedorn (NPH) insulin, is given
before bedtime; an initial dose of 0.2 unit/kg body weight is utilized.
● If postprandial blood glucose concentrations are high, rapid-acting insulin analogs such as
insulin aspart or insulin lispro are given before meals at a dose calculated to be 1.5 units per
10 g carbohydrate in the breakfast meal and 1 unit per 10 g carbohydrate in the lunch and
dinner meals. (See "General principles of insulin therapy in diabetes mellitus".)
● If both preprandial and postprandial blood glucose concentrations are high or if the woman's
postprandial glucose levels can only be blunted if starvation ketosis occurs, then a six
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injection per day regimen is utilized. The total starting dose is 0.7 units/kg up to week 12,
0.8 units/kg for weeks 13 to 26, 0.9 units/kg for weeks 26 to 36, and 1.0 unit/kg for weeks 36
to term. In obese women with higher body mass indexes (BMIs), the initial doses of insulin
may need to be increased to 1.5 to 2.0 units/kg to overcome the combined insulin
resistance of pregnancy and obesity.
The insulin can be divided according to the following schedule: 50 percent as intermediate-
acting insulin, such as NPH (given in two equal doses before breakfast and before bedtime), and
50 percent as three preprandial rapid-acting insulin injections; however, it may be possible to
omit the lunchtime dose in some patients.
Management of hypoglycemia — Hypoglycemia in pregnancy is defined as a blood glucose

<60 mg/dL. Hypoglycemia remote from meal or snack time is rare in women with gestational
diabetes mellitus, especially those on nutritional therapy alone, and is treated by administering
10 to 20 g of a mixed protein and carbohydrate snack immediately. The administration of a pure
simple sugar in a pregnant woman with diabetes may lead to rapid elevation of glucose followed
by rapid decline. The mixed protein and carbohydrate snack tends to dampen the fluctuation.
The ADA suggests skim or low fat milk (8 ounces) to treat hypoglycemia. The sugars in milk
release more slowly into the bloodstream than those in juice or white sugar.
Once patients "feel" better, they may need to give themselves extra insulin to compensate for
overtreatment of the symptoms. They may also choose to check their blood sugar 15 to 30
minutes after treatment. If low glucose values are encountered more than once at the same time
of day, insulin doses are adjusted downward accordingly.
Type of insulin — Use of insulin preparations of low antigenicity may minimize the
transplacental transport of insulin antibodies: Human insulin is the least immunogenic of the
commercially available preparations. The three rapid-acting insulin analogs (lispro, aspart,
glulisine) are comparable in immunogenicity to human regular insulin, but only lispro and aspart
have been investigated in pregnancy and shown to have acceptable safety profiles, minimal
transfer across the placenta, and no evidence of teratogenesis. Neonatal outcomes are similar
to those of women treated with regular insulin [66]. These two insulin analogs both improve
postprandial excursions compared with human regular insulin and are associated with lower risk
of delayed postprandial hypoglycemia.
Long-acting insulin analogs (insulin glargine, insulin detemir) have not been studied as
extensively in pregnancy. In 2012, a multinational trial on the safety and efficacy of insulin
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detemir for the treatment of women with type 1 diabetes reported reassuring safety and efficacy
results [96,97], which led the FDA to reclassify insulin detemir from "C" to "B." In vitro perfusion
studies and a small human study have demonstrated that insulin glargine does not cross the
placenta in measurable levels [98-100]. Either detemir or glargine appears to be safe for use in
pregnancy [101]. Based on available data, we prefer use of human NPH insulin as part of a
multiple injection regimen in pregnant women with gestational diabetes, especially given the
peak at four to six hours after the morning dose, which can help decrease lunch postprandial
blood glucose levels without an additional dose of rapid-acting insulin [102]. There are good data
supporting the safety and effectiveness of NPH in pregnancy, and doses can be adjusted
frequently and quickly in response to changing requirements in pregnant women. In addition,
gestational diabetes is rarely, if ever, so difficult to control to justify the added expense of long-
acting insulin analogs. However, if a longer acting insulin analog is used, we prefer detemir
insulin because it can be dosed twice a day, similar to NPH, with the advantage over NPH of
more consistent absorption and less variability in absorption among patients. Insulin detemir is
preferred over insulin glargine because it has been studied more extensively in pregnancy and
can be dosed twice per day more predictably than glargine, as previously mentioned. (See
"General principles of insulin therapy in diabetes mellitus", section on 'Safety'.)
Oral antihyperglycemic agents
Choice of glyburide versus metformin — Clinically important pregnancy outcomes are

generally similar for glyburide and metformin, with only limited evidence of benefit of one oral
agent over the other. When metformin was compared with glyburide in a 2017 systematic review,
there were no statistical differences in important outcomes, such as perinatal mortality or
neonatal hypoglycemia, but several other outcomes were not evaluated [86]. In a 2020 meta-
analysis that evaluated some of these outcomes, metformin did have some benefits [103]:
● Lower mean birth weight (mean difference -191 g, 95% CI -288 to -95 g; mean birth weight
3103 to 3360 g versus 3329 to 3463 g with glyburide).
● Less macrosomia (odds ratio [OR] 0.32, 95% CI 0.08-1.19) and large for gestational age
infants (OR 0.38, 95% CI 0.18-0.78).
● Less gestational weight gain (mean difference -2.22 kg, 95% CI -3.88 to -0.56 kg).
However, the differences were generally modest, and the confidence intervals were wide.
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The frequency of treatment failure (lack of glycemic control) is similar for glyburide and
metformin in most trials directly comparing these two drugs [86,104]. In the 2017 systematic
review, 16 to 17 percent of women taking glyburide or metformin required additional
pharmacotherapy [86], an observation that was also noted in a subsequent trial not included in
the review (lack of glycemic control: glyburide 23 percent, metformin 28 percent) [104]. Although
one trial reported that women using metformin were twice as likely to require supplemental
insulin than those using glyburide [105], the discordant findings might have been due to an
ethnically differential response to metformin in their study population, which was predominantly
Hispanic women, or to chance [86].
Other evidence suggests that metformin may reduce the frequency of pregnancy-associated
hypertension independent of its effect on glucose, which may be related to differences in the
mechanisms of action of the two drugs (metformin primarily reduces hepatic glucose output and
improves insulin sensitivity, while glyburide stimulates insulin secretion) [106-109].
A disadvantage of glyburide is that the fetal drug level is high (70 percent of maternal level),
which has unknown long-term consequences (see 'Glyburide' below). A disadvantage of
metformin is that fetal drug levels are even higher than with glyburide (200 percent of maternal
level), and there is a theoretical risk that fetal exposure to an insulin-sensitizing agent has long-
term effects on offspring (see 'Metformin' below). Although metformin and glyburide have not
been associated with an increased risk of anatomic birth defects, when either drug is prescribed,
patients should be made aware that information regarding the long-term effects of transplacental
passage is not known, and thus, caution is warranted until more data are available.
As discussed above, the Society for Maternal-Fetal Medicine concluded that "in women with
gestational diabetes in whom hyperglycemia cannot adequately be controlled with medical
nutritional therapy, metformin is a reasonable and safe first-line pharmacologic alternative to
insulin," but went on to say that "although concerns have been raised for more frequent adverse
neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of
benefit of one oral agent over the other remains limited" [1]. However, others believe that it is
premature to consider metformin equivalent to insulin or superior to glyburide and have
expressed concern about potential fetal developmental programming effects [110].
Of note, in nonpregnant persons, the ADA considers metformin the preferred initial
pharmacologic agent for the treatment of type 2 diabetes [111].
Metformin — Second- and third-trimester metformin treatment of gestational diabetes

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mellitus appears to be safe in the short term and is effective in many women, but one-third of
women using metformin will need supplemental insulin to achieve glycemic targets [84]. A typical
metformin dosing regimen is starting 500 mg once daily with the evening meal and if tolerated,
adding a second 500 mg dose with breakfast. The dose can be increased by 500 mg per week
until reaching the usual effective dose of 1500 to 2000 mg per day divided into two doses. (See
"Metformin in the treatment of adults with type 2 diabetes mellitus".)
Metformin therapy has some advantages and disadvantages compared with insulin therapy.
● In a 2020 meta-analysis of randomized trials limited to women with gestational diabetes,

compared with insulin, metformin reduced gestational weight gain (mean difference -1.31
kg, 95% CI -2.34 to -0.27), birth weight (mean difference -74 g, 95% CI -115 to -33 g), and
risk for macrosomia (OR 0.60, 95% CI 0.45-0.79), but the risk for a large for gestational age
infant was similar (OR 0.87, 95% CI 0.66-1.14) [103]. The same authors previously reported
that metformin-exposed children had higher BMI (by 0.8 kg/m2) and evidence of increased
adiposity by mid-childhood compared with insulin-exposed children [112].
● A 2017 meta-analysis of randomized trials and follow-ups of randomized trials comparing

metformin with insulin for treatment of women with gestational diabetes mellitus or pregnant
women with type 2 diabetes provided information on some additional outcomes [108].
Compared with insulin, metformin reduced the risk for neonatal hypoglycemia (risk ratio
[RR] 0.63, 95% CI 0.45-0.87) and pregnancy-induced hypertension (RR 0.56, 95% CI 0.37-
0.85), but other outcomes were similar for both groups: preterm delivery (RR 1.18, 95% CI
0.67-2.07), small for gestational age infants (RR 1.20, 95% CI 0.67-2.14), perinatal mortality
(RR 0.82, 95% CI 0.17-3.92), and cesarean delivery (RR 0.97, 95% CI 0.80-1.19).
The most common side effects of metformin are gastrointestinal, including a metallic taste in the
mouth, mild anorexia, nausea, abdominal discomfort, and soft bowel movements or diarrhea.
These symptoms are usually mild, transient, and reversible after dose reduction or
discontinuation of the drug. Symptoms can be mitigated by starting at a low-dose with slow-dose
escalation as needed. In a clinical trial, only 2 percent of study subjects discontinued metformin
because of the gastrointestinal side effects [113].
Metformin has also been proposed to "prevent" gestational diabetes mellitus since it is an oral
antihyperglycemic agent and would be expected to maintain euglycemia in some women who
would otherwise be diagnosed with gestational diabetes. Although observational studies of
metformin use in women with polycystic ovary syndrome (PCOS) supported this hypothesis
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[114,115], a randomized trial did not [116]. In this trial, 273 pregnancies among 257 women with
PCOS were randomly assigned to receive metformin (2000 mg/day) or placebo from the first
trimester until delivery. There was no significant difference in prevalence of gestational diabetes
mellitus between groups (metformin 17.6 percent versus placebo 16.9 percent). In this trial, and
most other metformin trials, women in the metformin group gained less weight during pregnancy
than those in the placebo group (see "Metformin for treatment of the polycystic ovary syndrome",
section on 'Prevention of pregnancy complications'). In addition, two randomized trials
comparing metformin with placebo in obese pregnant women also showed no significant
reduction in the rate of gestational diabetes [117,118].
Metformin crosses the placenta and, in one study, cord arterial levels were twice as high as
maternal venous levels [119]. It is not known whether fetal exposure to an insulin-sensitizing
agent such as metformin is beneficial or harmful, and thus caution is warranted in its use in
pregnancy. Follow-up studies of the offspring of mothers in trials of metformin in gestational
diabetes or polycystic ovary syndrome reported no difference in neurodevelopmental outcomes
[120,121], but metformin-exposed children were larger on some physical measures at 4 to 9
years [122,123]. Until more studies demonstrate long-term safety, patients who are prescribed
metformin should be informed of the uncertainties about the long-term metabolic and
developmental effects of transplacental passage and possible fetal programming effects
[110,124].
Glyburide — Glyburide, a second-generation sulfonylurea, is the other commonly used oral

antihyperglycemic drug treatment for gestational diabetes mellitus [125]. Use of glyburide has
not resulted in better pregnancy outcomes than use of insulin, and some outcomes may be
worse.
● In a 2020 meta-analysis of randomized trials comparing glyburide therapy with insulin

therapy in women with gestational diabetes mellitus, women assigned to glyburide had a
higher mean birth weight in offspring (mean difference 290 g, 95% CI 68-511 g) and higher
risk for macrosomia (OR 1.38, 95% CI 1.01-1.89); there were also trends toward an
increased risk for a large for gestational age infant (OR 2.49, 95% CI 0.79-7.81) and less
gestational weight gain (mean difference -0.68 kg, 95% CI -1.69 to 0.34 kg) [103]. Neonatal
hypoglycemia was not evaluated, but in the largest trial to date, which included more than
800 women with gestational diabetes, the glyburide group had a higher rate of neonatal
hypoglycemia (11 versus 7 percent) [126].
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Maternal hypoglycemia is the most common side effect of glyburide therapy. The risk was similar
to that in women using metformin in a meta-analysis of three small randomized trials (9/177
versus 8/177) [86]. In a subsequent large randomized trial, the risk was higher than that in
women using insulin (28.8 versus 3.5 percent; difference 25.3 percent, 95% CI 16.6-34.0
percent) [126].
Glyburide is transferred across the placenta; the estimated average ratio of umbilical cord to
maternal blood glyburide concentration at delivery is 0.62 to 0.70 [127-130]. Umbilical cord blood
concentrations of glyburide appear to be related to the time of last maternal ingestion of the
drug, and the risk of neonatal hypoglycemia correlates with the level of umbilical cord
concentrations. Neonatal hypoglycemia related to glyburide may be reduced with last maternal
dosing more than 24 hours prior to delivery [130]. While an increase in congenital anomalies in
offspring exposed to glyburide in utero has not been demonstrated, no studies of long-term
effects in offspring (eg, developmental outcomes, metabolic effects) have been published, and
patients prescribed glyburide should be informed of existing uncertainties.
As with insulin therapy, glyburide must be carefully balanced with meals and snacks to prevent
maternal hypoglycemia. Starting doses of 2.5 to 5 mg once daily are commonly used, and the
dose is increased as needed to a maximum of 20 mg/day. Pharmacokinetic studies suggest that
even higher doses may be utilized [131]. Twice daily dosing is often necessary to maintain
euglycemia. One group that investigated glyburide pharmacokinetics in pregnancy suggested
pregnant women take the drug 30 to 60 minutes before a meal, rather than with the meal, to
improve efficacy [131]. In this study, plasma glyburide concentrations in pregnant women with
gestational diabetes did not increase until 1 hour after drug ingestion, peaked at 2 to 3 hours,
and returned to baseline by 8 to 10 hours. Thus, the drug took longer to reach peak
concentration and was metabolized more rapidly than in nonpregnant women.
There is evidence that glyburide may be less successful in obese patients, and, in a study of 63
glyburide failures, those with: prior gestational diabetes, gestational diabetes diagnosed at ≤26
weeks, one-hour glucose challenge test ≥228 mg/dL, three-hour glucose tolerance test one-hour
value ≥221 mg/dL, multiple postprandial blood sugars >120 mg/dL in the first week of glyburide
therapy, or ≥1 blood sugar >200 mg/dL [132]. More research is needed to determine if glyburide
affects the potential postpartum progression of the woman with gestational diabetes mellitus
towards impaired glucose tolerance/diabetes or on the possibility of gestational diabetes
recurrence and whether glyburide affects the long-term health and development of offspring.
Patients who are contemplating glyburide therapy should be counseled regarding the limited
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information about these important questions.
Other — Tolbutamide or chlorpropamide (older sulfonylureas) therapy is not recommended in

women with gestational diabetes mellitus because these drugs cross the placenta and can
cause fetal hyperinsulinemia, which can lead to macrosomia and prolonged neonatal
hypoglycemia [133-135].
Acarbose, an alpha glucosidase inhibitor, acts in the gastrointestinal tract. Since a small
proportion of this drug may be absorbed systemically, potential transplacental passage and fetal
effects should be studied. Two preliminary studies suggested efficacy in reducing postprandial
glucose excursions in gestational diabetes mellitus, but with the expected high frequency of
abdominal cramping.
Use of thiazolidinediones, meglitinides (repaglinide and nateglinide), DPP-4 inhibitors, amylin

mimetics, and GLP-1 agonists during pregnancy is considered experimental. There are no
controlled data available in pregnancy. One study reported that rosiglitazone (note: use has
been limited by the FDA because of potential cardiovascular side effects) crossed the human
placenta at 10 to 12 weeks of gestation, fetal tissue levels were approximately half of maternal
serum levels [136]. Ex vivo human placental perfusion studies of GLP-1 agonists detected
minimal levels on the fetal side (fetal to maternal ratio 0.017).
Patients who fail to achieve glycemic control with an oral agent — If an oral agent alone
does not control glucose levels, supplemental insulin can be prescribed and may be easier for
the patient to manage than switching to a multidose insulin only regimen. In contrast to
nonpregnant women, dual use of oral agents (eg, metformin plus glyburide) is not recommended
in pregnancy because of minimal safety and efficacy data [104] and concerns about adverse
fetal effects since both drugs cross the placenta.
OBSTETRIC MANAGEMENT
Obstetric management of the pregnancy is discussed separately. (See "Gestational diabetes

mellitus: Obstetric issues and management".)
INTRAPARTUM MANAGEMENT
Intrapartum glucose and insulin management are discussed in detail separately. (See
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"Pregestational (preexisting) and gestational diabetes: Intrapartum and postpartum glycemic

control".)
MATERNAL PROGNOSIS
Most women with gestational diabetes mellitus are normoglycemic after delivery. However, they
are at high risk for recurrent gestational diabetes mellitus, prediabetes (impaired glucose
tolerance or impaired fasting glucose), and overt diabetes over the subsequent five years.
Optimum interpregnancy care to minimize these risks has not been well-studied in randomized
trials [137]. Feasibility trials of a web-based lifestyle intervention and a telephone-based
intervention reported less postpartum weight retention in women with gestational diabetes
assigned to the intervention, suggesting this type of behavioral intervention may have a
favorable impact [138,139].
Recurrence — One-third to two-thirds of women with gestational diabetes mellitus will have
gestational diabetes in a subsequent pregnancy [140-144]. In a study including over 65,000
pregnancies, the risk of gestational diabetes mellitus in the second pregnancy among women
with and without previous gestational diabetes was 41 and 4 percent, respectively [143]. Women
who have a recurrence tend to be older, more parous, and have a greater increase in weight
between their pregnancies than women without a recurrence [141]. Higher infant birth weight in
the index pregnancy and higher maternal prepregnancy weight have also been associated with
recurrent gestational diabetes mellitus [142].
Long-term risk — A history of gestational diabetes mellitus is predictive of an increased risk of

developing type 2 diabetes, type 1 diabetes, metabolic syndrome, and cardiovascular disease.
These risks appear to be particularly high in women with both gestational diabetes and
gestational hypertension [145]. Gestational diabetes has been called a "marker," "stress test," or
"window" for future diabetes and cardiovascular disease; it is not considered causal.
● Impaired glucose tolerance – As many as 30 percent of women with gestational diabetes

mellitus have impaired glucose tolerance during the early postpartum period [146-148].
● Metabolic syndrome – Women with gestational diabetes mellitus in their prior pregnancy
are more likely to have metabolic syndrome, an atherogenic lipid profile, and early vascular
dysfunction at ≥3 months postpartum than women without previous gestational diabetes
mellitus [144,149-151]. In one study of women with mild gestational diabetes (ie, normal
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fasting glucose on glucose tolerance test [GTT]), approximately one-third developed

metabolic syndrome within 5 to 10 years of delivery [144].
● Type 2 diabetes – In a 2020 meta-analysis, women with gestational diabetes mellitus were
at an almost 10-fold higher risk of developing subsequent type 2 diabetes than women with
normoglycemic pregnancies (relative risk [RR] 9.51, 95% CI 7.14-12.67; 20 studies
including nearly 68,000 women with gestational diabetes and over 1.2 million controls)
[152]. The RR was 17 within the first five years after delivery and approximately 10 after
that. Absolute risks for type 2 diabetes at 1 to 5 years, >5 to 10 years, and >10 years
postdelivery follow-up were 9, 12, and 16 percent, respectively, compared with 1 to 2
percent in women without gestational diabetes.
Waist circumference and body mass index (BMI) are the strongest anthropometric
measures associated with development of type 2 diabetes in women with gestational
diabetes [66,153], as they are in women without gestational diabetes mellitus. Type 2
diabetes develops in 50 to 75 percent of obese (BMI ≥30 kg/m2) women with a history of
gestational diabetes mellitus versus fewer than 25 percent of women with gestational
diabetes who achieve normal body weight after delivery [154-156].
Other major risk factors are gestational requirement for insulin and early gestational age at
the time of diagnosis (ie, less than 24 weeks of gestation) [153]. Additional risk factors for
impaired glucose tolerance and overt diabetes later in life include autoantibodies (eg,
glutamic acid decarboxylase, insulinoma antigen-2), high-fasting blood glucose
concentrations during pregnancy and early postpartum, higher-fasting plasma glucose at
diagnosis of gestational diabetes mellitus and high glucose levels in oral GTT), neonatal
hypoglycemia, and gestational diabetes in more than one pregnancy [66,146,147,154,157-
160]. In one study, an additional pregnancy increased the rate ratio of type 2 diabetes
threefold compared with women without an additional pregnancy (RR 3.34, 95% CI 1.80-
6.19) [161]. The authors hypothesized that episodes of insulin resistance contribute to the
decline in beta-cell function that leads to type 2 diabetes in many high-risk individuals.
Parity, large birth weight, and diabetes in a first-degree relative are less correlated with later
diabetes.
● Type 1 diabetes – Gestational diabetes mellitus is also a risk factor for the development of
type 1 diabetes, particularly in populations with a high prevalence of this disorder. Specific
HLA alleles (DR3 or DR4) may predispose to the development of type 1 diabetes
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postpartum, as does the presence of islet-cell autoantibodies [162-164] or antibodies

against glutamic acid decarboxylase or insulinoma antigen-2. Gestational diabetes mellitus
in lean pregnant women, need for insulin treatment of gestational diabetes, diabetic
ketoacidosis during pregnancy, and postpartum hyperglycemia also suggest preexisting
unrecognized type 1 diabetes or high risk of developing type 1 diabetes [164].
● Cardiovascular disease – Women with gestational diabetes mellitus are at higher risk of
developing cardiovascular disease (CVD) and developing it at a younger age than women
with no history of gestational diabetes [165-168]. Even mild glucose impairment defined as
an abnormal glucose challenge test with a normal GTT appears to identify women at
increased risk of future development of CVD, usually heart attack or stroke [169]. Much of
this excess risk is related to development of type 2 diabetes later in life.
In a large epidemiologic study (Nurses' Health Study) that followed women for a median
25.7 years, compared with women with no history of gestational diabetes mellitus or type 2
diabetes, women with a history of gestational diabetes mellitus who progressed to type 2
diabetes were at very high risk of developing CVD (hazard ratio [HR] 3.71, 95% CI 1.79-
7.67), whereas women with a history of gestational diabetes who did not progress to type 2
diabetes had a 30 percent increase in risk (HR 1.30, 95% CI 0.99-1.71), which dropped to
20 percent (HR 1.20, 95% CI 0.91-1.58) after adjusting for lifestyle risk factors for CVD such
as diet, physical activity, smoking status, and weight gain [170]. The absolute excess risk of
CVD was 1.70 per 1000 person-years for women with gestational diabetes who developed
type 2 diabetes versus 0.07 per 1000 person-years for those who did not develop type 2
diabetes. The relatively young age of the study population and correspondingly low rates of
incident CVD, the predominantly White population, and the lack of information about the
number of women not tested for gestational diabetes mellitus are limitations of the study.
In a multicenter, community-based prospective cohort study (CARDIA, Coronary Artery Risk

Development in Young Adults), women at age 18 to 30 years at baseline with a history of
gestational diabetes had a twofold higher risk of developing coronary artery calcium (CAC, a
strong predicator of atherosclerotic CVD) in midlife (24.5 versus 15.0 percent in women
without gestational diabetes) [171]. The increased risk of CAC in midlife was present across
all levels of post-pregnancy glucose tolerance (normal to diabetes). This finding persisted in
multivariable modelling adjusted for age, race, prepregnancy systolic blood pressure,
smoking duration and subsequent hypertension with an adjusted hazard ration of 1.66
(1.13-2.43). These findings provide insight into the risk of CVD in women with a history of
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gestational diabetes regardless of current glucose tolerance status and highlights that
midlife atherosclerotic CVD risk among women with prior GDM is not diminished by
attaining normoglycemia following an affected pregnancy.
Follow-up and prevention of type 2 diabetes — The American College of Obstetricians and
Gynecologists [55], the American Diabetes Association (ADA) [10] and the Fifth International
Workshop Conference on Gestational Diabetes [56] recommend long-term follow-up of women
with gestational diabetes mellitus.
We suggest a GTT 4 to 12 weeks after delivery, using the two-hour 75 g GTT, as recommended
by the ADA [10]. Since many obstetricians see their patients at six weeks postpartum, it makes
sense to order the test prior to this visit, so the results are available for counseling and so the
test can be rescheduled if it has been missed. A fasting plasma glucose test is a reasonable
alternative but does not allow for diagnosis of impaired glucose tolerance; glycated hemoglobin
(A1C) can also be substituted in patients in whom obtaining a fasting specimen is especially
inconvenient but performs less well in postpartum women because of increased peripartum red
cell turnover [172].
Compliance with the 4- to 12-week GTT is poor; however there is increasing evidence that
ordering the test when women are still hospitalized and compliance approaches 100 percent
provides reliable results [148,173]. In an analysis of over 200 patients with gestational diabetes
who completed a postpartum day two 75 gram 2-hour GTT, returned for a GTT at postpartum
week 4 to 12, and had a A1C checked approximately one year after delivery, there were no
significant differences between the day 2 and the 4- to 12-week postpartum GTTs in predicting
impaired glucose metabolism (A1C ≥5.7 and <6.5 percent) or diabetes (A1C ≥6.5 percent) at
one year [173]. At one year postpartum, the A1C was consistent with impaired glucose
metabolism in 35 percent and diabetes in 4 percent of women tested.
Breastfeeding during a GTT appears to have a modest effect on glucose levels. In a prospective
cohort study of nursing women with previous gestational diabetes mellitus who underwent a GTT
6 to 9 weeks postpartum, mean two-hour glucose levels were 5 percent lower in women who
breastfed during the test [174], which could affect interpretation of a borderline test. Patients
should be informed in advance that they might need to repeat the test if this happens so they
can make an informed decision about breastfeeding during the test versus planning the test at a
time/later date when breastfeeding can be avoided.
If a GTT is performed, diabetes is diagnosed if fasting glucose is ≥126 mg/dL (7.0 mmol/L) or
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two-hour glucose is ≥200 mg/dL (11.1 mmol/L); impaired glucose tolerance (IGT) is diagnosed if
fasting glucose is 100 to 125 mg/dL (5.5 to 6.9 mmol/L) or two-hour glucose is 140 to 199 mg/dL
(7.8 to 11.0 mmol/L). If only a fasting glucose level is checked, impaired fasting glucose (IFG) is
a fasting glucose level of 100 to 125 mg/dL (5.6 to 6.9 mmol/L). IGT and IFT are considered
"prediabetes." A hemoglobin A1C of 5.7 to 6.4 percent is also considered prediabetes.
● Women with prediabetes or overt diabetes – Women with an abnormal oral GTT are
classified as having prediabetes or overt diabetes mellitus (table 1 and table 2). (See
"Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults".)
Women with prediabetes should be counseled about their subsequent risk for developing
overt diabetes and referred for discussion of management options (eg, lifestyle modification
such as medical nutritional therapy, use of metformin). They should try to achieve a BMI in
the normal range through diet and exercise, and if possible, they should avoid drugs that
may adversely affect glucose tolerance (eg, glucocorticoids). They should have yearly
assessment of glycemic status. (See "Prevention of type 2 diabetes mellitus".)
Women with prediabetes should also be informed that breastfeeding may decrease their
long-term risk of developing type 2 diabetes. (See "Gestational diabetes mellitus: Obstetric
issues and management", section on 'Breastfeeding'.)
Women with overt diabetes mellitus should receive appropriate education and treatment.
They should also be given advice regarding contraception and the planning of future
pregnancies. (See "Overview of general medical care in nonpregnant adults with diabetes
mellitus".)
In addition, women with prediabetes or overt diabetes should be counseled regarding the
importance of good metabolic control prior to any future pregnancies. (See "Pregestational
(preexisting) diabetes: Preconception counseling, evaluation, and management".)
● Women with normal test results
• Risk of future diabetes – Women with normal glucose tolerance should be counseled
regarding their risk of developing gestational diabetes mellitus in subsequent
pregnancies and their future risk of developing type 2 diabetes. Lifestyle interventions
(diet and exercise) are clearly beneficial for reducing the incidence of type 2 diabetes in
persons at increased risk for the disease (ie, individuals with prediabetes; RR 0.59,
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95% CI 0.51-0.66) [175]. These interventions are also beneficial in women with a
history of gestational diabetes mellitus, whether or not they meet criteria for prediabetes
[176,177]. In a randomized trial comparing use of metformin versus lifestyle intervention
and placebo in 350 women with previous gestational diabetes, the annual incidence of
type 2 diabetes was decreased from 15 to 7.5 percent with either intervention [176].
The number needed to treat to prevent one case of diabetes over three years was 5 to
6. In a subgroup analysis of former women with gestational diabetes enrolled in a 16-
year prospective observational study (Nurses' Health Study II), 14 percent self-reported
the development of type 2 diabetes [177]. Women with a total physical activity level
equivalent to 150 minutes per week of moderate-intensity physical activity or 75
minutes per week of vigorous-intensity physical activity had a 30 to 50 percent lower
risk of developing type 2 diabetes compared with women who did not achieve this level
of activity, which is the minimum recommended for United States adults in national
physical activity guidelines [178]. BMI at baseline was inversely associated with activity
level and adjustment for BMI attenuated the effect of physical activity, although the
benefit of physical activity remained statistically significant.
• Prevention of future diabetes – Drug therapy (eg, metformin, pioglitazone) also may
have a role in preventing future type 2 diabetes. In a multicenter randomized trial, both
intensive lifestyle and metformin therapy reduced the incidence of future diabetes by
approximately 50 percent compared with placebo in women with a history of gestational
diabetes mellitus; metformin was much more effective than lifestyle intervention in
parous women with previous gestational diabetes [176]. This topic is discussed in detail
separately. (See "Prevention of type 2 diabetes mellitus".)
Women with normal results should also be informed that breastfeeding may decrease
their long-term risk of developing type 2 diabetes. (See "Gestational diabetes mellitus:
Obstetric issues and management", section on 'Breastfeeding'.)
• Follow-up laboratory testing – Long-term follow-up is essential. Reassessment of

glycemic status should be undertaken at a minimum of every three years [10]. More
frequent assessment may be important in women who may become pregnant again,
since early detection of diabetes is important to preconception and early prenatal care.
More frequent screening (every one or two years) may also be indicated in women with
other risk factors for diabetes, such as family history of diabetes, obesity, and need for
insulin or oral glucose-lowering medication during pregnancy.
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The best means of follow-up testing has not been defined. The two-hour 75 g oral GTT
is the more sensitive test for diagnosis of diabetes and impaired glucose tolerance in
most populations, but the fasting plasma glucose is more convenient, specific, and
reproducible, and less expensive. A1C is convenient and the preferred test for patients
who have not fasted overnight. (See "Screening for type 2 diabetes mellitus", section
on 'Screening tests'.)
• Prevention of future cardiovascular disease – Given increasing evidence of an

association between gestational diabetes mellitus and future cardiovascular disease
[170], even in the absence of progression to type 2 diabetes, it is reasonable to discuss
healthy lifestyle behaviors (heart-healthy diet, maintenance of a healthy weight, tobacco
avoidance, and physical activity) with all women who have had gestational diabetes
mellitus [179]. (See "Overview of primary prevention of cardiovascular disease".)
Follow-up of women not screened for gestational diabetes mellitus — In women who did
not undergo screening for gestational diabetes mellitus, but diabetes is suspected postpartum
because of infant outcome, postpartum GTT may be considered. However, a normal postpartum
GTT only excludes the presence of type 1 or type 2 diabetes or prediabetes at the time of the
test; it does not exclude the possibility that glucose impairment was present in association with
the metabolic changes occurring during the pregnancy itself. Indications for screening and
screening tests are discussed separately. (See "Screening for type 2 diabetes mellitus".)
SOCIETY GUIDELINE LINKS
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".)
INFORMATION FOR PATIENTS
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
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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 (diabetes that starts during
pregnancy) (The Basics)")
● Beyond the Basics topics (see "Patient education: Gestational diabetes (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Treatment
● We recommend treating women with gestational diabetes mellitus (Grade 1A). Randomized
trials have shown that a program of medical nutritional therapy, self-monitoring of blood
glucose levels, and insulin therapy, when needed, improves perinatal outcome (reduction in
preeclampsia, macrosomia, shoulder dystocia). (See 'Rationale for treatment' above.)
● Medical nutritional therapy is the initial approach. (See 'Medical nutritional therapy' above.)
• Calories are generally divided over three meals and two to four snacks and are
composed of approximately 40 percent carbohydrate, 20 percent protein, and 40
percent fat.
• Self-blood glucose monitoring should be performed to evaluate the effectiveness of

medical nutritional therapy. (See 'Glucose monitoring' above.)
● We suggest a program of moderate exercise as part of the treatment plan for women with
no medical or obstetric contraindications to this level of physical activity (Grade 2C). (See
'Exercise' above.)
● For women who do not achieve adequate glycemic control with nutritional therapy and
exercise alone, we recommend antihyperglycemic treatment (Grade 1A). We suggest
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prescribing insulin rather than oral antihyperglycemic agents during pregnancy (Grade 2B).
Glyburide or metformin is a reasonable alternative for women who decline to take, or are
unable to comply with, insulin therapy. The long-term effects of transplacental passage of
oral antihyperglycemic agents are not known. (See 'Insulin' above and 'Oral
antihyperglycemic agents' above.)
• Common thresholds for initiating insulin are listed below; these values are also
treatment targets. To initiate insulin therapy, the thresholds should be met or exceeded
on at least one-third of glucose measurements within a one-week interval despite
medical nutritional therapy. (See 'Glucose target' above.).
- Fasting blood glucose concentration ≥95 mg/dL (5.3 mmol/L), or

- One-hour postprandial blood glucose concentration ≥130 to 140 mg/dL (7.2 to 7.8
mmol/L), or
- Two-hour glucose >120 mg/dL (6.7 mmol/L)
• For women who require insulin therapy, we suggest monitoring glucose upon
awakening and one or two hours after each meal to guide medical management. (See
'Timing' above.).
● We start with the simplest regimen likely to be effective based on the glucose levels
recorded in the patient's blood glucose log and increase the complexity as needed. If
glucose elevations are mostly postprandial, then a starting dose of 10 to 20 units of
intermediate-acting insulin and 6 to 10 units of rapid-acting insulin are prescribed in the
morning before breakfast, based on the degree of elevations. If the post-dinner glucose
level is elevated, then an additional injection of rapid-acting insulin is given just prior to
dinner. If fasting glucose is elevated, then intermediate-acting insulin is preferably given at
bedtime but can be given before dinner instead on an individualized basis. Sometimes, an
additional dose of rapid-acting insulin is necessary to maintain euglycemia after lunch so
that a total of four injections per day are needed. (See 'Our approach' above.)
Prognosis
● Most women with gestational diabetes mellitus are normoglycemic after delivery, but are at
high risk for developing recurrent gestational diabetes mellitus, prediabetes (impaired
glucose tolerance or impaired fasting glucose), and overt diabetes. (See 'Recurrence' above
and 'Long-term risk' above.)
- Page 33 of 48 -
● We suggest screening for type 2 diabetes mellitus after pregnancy (Grade 2C). We screen
at 4 to 12 weeks postpartum and rescreen at least every three years thereafter. Lifestyle
interventions (eg, achieving a healthy weight, appropriate level of physical activity/exercise)
are beneficial for reducing the incidence of type 2 diabetes, and related comorbidities such
as cardiovascular disease. (See 'Maternal prognosis' above.)
ACKNOWLEDGMENTS
The editorial staff at UpToDate would like to acknowledge Lois Jovanovic, MD, Donald R
Coustan, MD, and Michael Greene, MD, who contributed to earlier versions of this topic review.
REFERENCES
1. Society of Maternal-Fetal Medicine (SMFM) Publications Committee. Electronic address:

pubs@smfm.org. SMFM Statement: Pharmacological treatment of gestational diabetes. Am
J Obstet Gynecol 2018; 218:B2.
2. Hartling L, Dryden DM, Guthrie A, et al. Benefits and harms of treating gestational diabetes
mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task
Force and the National Institutes of Health Office of Medical Applications of Research. Ann
Intern Med 2013; 159:123.
3. Poprzeczny AJ, Louise J, Deussen AR, Dodd JM. The mediating effects of gestational
diabetes on fetal growth and adiposity in women who are overweight and obese: secondary
analysis of the LIMIT randomised trial. BJOG 2018; 125:1558.
4. Catalano PM, McIntyre HD, Cruickshank JK, et al. The hyperglycemia and adverse
pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes.
Diabetes Care 2012; 35:780.
5. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus
on pregnancy outcomes. N Engl J Med 2005; 352:2477.
6. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild
gestational diabetes. N Engl J Med 2009; 361:1339.
7. Palatnik A, Mele L, Landon MB, et al. Timing of treatment initiation for mild gestational
diabetes mellitus and perinatal outcomes. Am J Obstet Gynecol 2015; 213:560.e1.
8. Landon MB, Rice MM, Varner MW, et al. Mild gestational diabetes mellitus and long-term
child health. Diabetes Care 2015; 38:445.
- Page 34 of 48 -

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Diabetes mellitus in pregnancy: Screening and diagnosis

Oﬃcial reprint from UpToDate® www.uptodate.com

Diabetes mellitus in pregnancy: Screening and diagnosis

One-step versus two-step diagnosis of gestational diabetes mellitus (March 2021)

Pregnancy is accompanied by insulin resistance, mediated primarily by placental secretion of

● (See "Gestational diabetes mellitus: Glycemic control and maternal prognosis".)

● (See "Gestational diabetes mellitus: Obstetric issues and management".)

Prevalence — The prevalence of gestational diabetes mellitus as traditionally defined is

● Preeclampsia, gestational hypertension

● Family history of diabetes, especially in first-degree relatives [33].

● Older maternal age (>25 or 30 years of age).

● Previous unexplained perinatal loss or birth of a malformed infant.

● Glycosuria at the first prenatal visit.

● Previous birth of an infant ≥4000 g (approximately 9 pounds).

● Medical condition/setting associated with development of diabetes, such as metabolic

syndrome, polycystic ovary syndrome, current use of glucocorticoids, hypertension or

BENEFITS AND HARMS OF SCREENING

IDENTIFICATION OF OVERT DIABETES IN EARLY PREGNANCY

• Gestational diabetes mellitus in a previous pregnancy.

• Glycated hemoglobin ≥5.7 percent (39 mmol/mol), impaired glucose tolerance, or

• First-degree relative with diabetes.

• High-risk race/ethnicity (eg, African American, Latino, Native American, Asian

• History of cardiovascular disease.

• Hypertension (≥140/90 mmHg) or on therapy for hypertension.

• Polycystic ovary syndrome.

• Previous birth of an infant weighing ≥4000 g.

SCREENING AND DIAGNOSTIC TESTING

One-step and two-step approaches

● In contrast, a subsequent pragmatic randomized trial comparing short-term outcomes of

• Neonatal hypoglycemia was more common in the one-step group.

Candidates for screening/testing — In the United States, universal screening or testing

Timing of screening/testing — While there are no proven benefits to screening/testing for

Screening methods — Laboratory screening is generally performed with a GCT.

Markedly elevated one-hour glucose level — The likelihood of an abnormal GTT is

Other tests — In the USPSTF systematic review described above [81]:

It is worth noting that different populations manifest different proportions of glucose

In a simulation study of a Swiss population with a low prevalence of gestational diabetes

However, in low-resource settings where universal screening with a GCT or diagnostic

Diagnostic testing methods — The diagnosis of gestational diabetes mellitus is based on

Patients unable to tolerate oral hyperosmolar glucose — The highly concentrated

OUR APPROACH TO SCREENING AND DIAGNOSIS OF DIABETES IN

RECOMMENDATIONS OF NATIONAL AND INTERNATIONAL

● American College of Obstetricians and Gynecologists (ACOG, two-step approach (table 5

● International Association of Diabetes and Pregnancy Study Groups (IADPSG, one-step

● American Diabetes Association (ADA, one-step or two-step approach) [67]

● World Health Organization (WHO, one-step approach (table 6)) [130]

● Canadian Diabetes Association (CDA, two-step [preferred] or one-step approach) [98]

● The Endocrine Society (one-step approach) [131]

● Australasian Diabetes in Pregnancy Society (WHO approach) [38]

● International Federation of Gynecology and Obstetrics (FIGO, one-step approach) [132]

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● A reasonable approach to screening for diabetes in pregnant and postpartum patients,

● Identifying pregnant women with gestational diabetes mellitus followed by appropriate

● We agree with recommendations of major societies to screen/test for gestational diabetes

1. Proceedings of the 4th International Workshop-Conference on Gestational Diabetes

Oﬃcial reprint from UpToDate® www.uptodate.com