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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

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2021. | This topic last updated: Sep 29, 2020.

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).

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, 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. Individuals who quench their thirst with sugar-sweetened beverages can reduce
glucose levels within a couple of days with this change. 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 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; 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 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].

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 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].
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 [38-40] and, in some women with gestational
diabetes mellitus, the need for insulin may be obviated [41,42]. Circuit resistance training has
a similar effect [43]. (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 [41]. The mean fasting blood glucose concentration fell to 55 to 65 mg/dL
(3.1 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 [44]. 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
[45]. 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 [46].

The value of exercise in women with gestational diabetes requires further exploration to
determine the potential range of benefits [47,48]. 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 [49]. (See "Exercise during pregnancy and the postpartum period".)

GLUCOSE MONITORING

Frequency — The optimal approach to glucose monitoring has not been determined [50].
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) [51,52]. 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 [51,53], many providers decrease the
frequency of glucose monitoring when good glycemic control is accomplished with medical
nutritional therapy. 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 [54]. Thus, it may be reasonable to decrease the frequency of
glucose monitoring in some patients with mild gestational diabetes mellitus to every other
day, saving health care dollars and increasing convenience for patients.

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)
[55]. 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 [56-58]. 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 as well as mean glucose level 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 [59,60]. (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 [61]. One-hour
postprandial monitoring 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 [62]. 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 [63]. 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 [10,52].

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 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 [64].
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 [65].

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 [66-68].

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 [69].

Glycated hemoglobin — A1C may be a helpful ancillary test in assessing glycemic control

during pregnancy [70,71]. 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 [72] 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 [73,74]. 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 [75-77], while
a study of nondiabetic gravidas did not [78].

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 [63]. 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 [63,79-82]. There is a trend toward
more frequent hypoglycemia with use of insulin [82] and some women on oral agents need
supplemental insulin to achieve and maintain euglycemia [83]. 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
[82].

The American College of Obstetricians and Gynecologists (ACOG) [52] 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 [52]. They emphasize that patients should understand the
limitations of available safety data and the 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) [84,85]. FIGO recommends insulin as the first-line treatment in women
in whom diabetes is diagnosed before 20 weeks of gestation, if pharmacologic therapy is
needed >30 weeks, 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) [85].
(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 [86-89]. 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 [90].

It is reasonable for women with fetuses with large abdominal circumferences to receive
insulin to decrease the risk of macrosomia, even if they have no or mild hyperglycemia [53].
Conversely, it is reasonable to relax self-glucose monitoring and initiation of insulin for mild
hyperglycemia in women whose fetuses have a small abdominal circumference (<75th
percentile). Withholding insulin when there is no evidence of increased somatic growth may
limit the risk of iatrogenic growth restriction [87].

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
[91].

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. A four-times-
per-day regimen improved glycemic control and perinatal outcome compared with a twice-
daily regimen in one randomized trial [92], 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, particularly in obese patients with gestational diabetes
mellitus who are unlikely to develop hypoglycemia 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) 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 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 [63]. 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
detemir for the treatment of women with type 1 diabetes reported reassuring safety and
efficacy results [93,94], 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 [95-97]. Either detemir or glargine appears to be
safe for use in pregnancy [98]. 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 [99]. 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 [83]. In a 2020 meta-analysis that evaluated some of these outcomes, metformin
did have some benefits [100]:

● 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.

The frequency of treatment failure (lack of glycemic control) is similar for glyburide and
metformin in most trials directly comparing these two drugs [83,101]. In the 2017 systematic
review, 16 to 17 percent of women taking glyburide or metformin required additional
pharmacotherapy [83], 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) [101].
Although one trial reported that women using metformin were twice as likely to require
supplemental insulin than those using glyburide [102], 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 [83].

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) [103-106].

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 [107].

Of note, in nonpregnant persons, the ADA considers metformin the preferred initial
pharmacologic agent for the treatment of type 2 diabetes [108].

Metformin — Second- and third-trimester metformin treatment of gestational diabetes

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 [81].

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) [100]. 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 [109].

● 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 [105]. 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 [110]. (See "Metformin in the
treatment of adults with type 2 diabetes mellitus".)
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 [111,112], a randomized trial did not [113]. 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 [114,115].

Metformin crosses the placenta and, in one study, cord arterial levels were twice as high as
maternal venous levels [116]. 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 [117,118], but metformin-exposed children were larger on some physical
measures at 4 to 9 years [119,120]. 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 [107,121].

Glyburide — Glyburide, a second-generation sulfonylurea, is the other commonly used

oral antihyperglycemic drug treatment for gestational diabetes mellitus [122]. 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) [100].
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) [123].
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) [83]. 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) [123].

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 [124-127]. 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 [127]. 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 [128]. 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 [128]. 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 [129]. 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 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 [130-132].

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 [133]. 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 [101] 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
"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 [134]. 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 [135,136].

Recurrence — One-third to two-thirds of women with gestational diabetes mellitus will have

gestational diabetes in a subsequent pregnancy [137-141]. 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
[140]. 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 [138].
Higher infant birth weight in the index pregnancy and higher maternal prepregnancy weight
have also been associated with recurrent gestational diabetes mellitus [139].

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 [142]. 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
[143-145].

● 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 [141,146-148]. In one study of women with mild
gestational diabetes (ie, normal fasting glucose on glucose tolerance test [GTT]),
approximately one-third developed metabolic syndrome within 5 to 10 years of delivery
[141].

● 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) [149]. 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 [63,150], 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 [151-153].

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) [150]. 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
[63,143,144,151,154-157]. 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) [158]. 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
postpartum, as does the presence of islet-cell autoantibodies [159-161] 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
[161].

● 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 [162-165]. 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 [166]. 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 [167]. 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.

Follow-up and prevention of type 2 diabetes — The American College of Obstetricians and

Gynecologists [52], the American Diabetes Association (ADA) [10] and the Fifth International
Workshop Conference on Gestational Diabetes [53] 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 [168].

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 [145,169]. 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 [169]. 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 [170], 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
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, 95% CI 0.51-0.66) [171]. These interventions
are also beneficial in women with a history of gestational diabetes mellitus, whether
or not they meet criteria for prediabetes [172,173]. 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 [172]. 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 [173]. 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 [174]. 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 [172]. 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.
 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
[167], 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 [175]. (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 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
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.)

● 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.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 6790 Version 126.0
GRAPHICS

American Diabetes Association criteria for the diagnosis of diabetes

1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the
DCCT assay*.
OR

2. FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours*.
OR

3. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by the World
Health Organization, using a glucose load containing the equivalent of 75 gram anhydrous glucose dissolved in water*.
OR

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1
mmol/L).

A1C: glycated hemoglobin; NGSP: National Glycohemoglobin Standardization Program; DCCT: Diabetes Control and Complications
Trial; FPG: fasting plasma glucose; OGTT: oral glucose tolerance test.
* In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two
separate test samples.

Reprinted with permission from: American Diabetes Association. Standards of Medical Care in Diabetes 2011. Diabetes Care 2011; 34:S11.
Copyright © 2011 American Diabetes Association. The content within this table is still current as of the 2020 version of the Standards of
Medical Care in Diabetes.

Graphic 61853 Version 16.0

Categories of increased risk for diabetes (prediabetes)*

FPG 100 to 125 mg/dL (5.6 to 6.9 mmol/L) – IFG

2-hour post-load glucose on the 75 g OGTT 140 to 199 mg/dL (7.8 to 11.0 mmol/L) – IGT

A1C 5.7 to 6.4% (39 to 46 mmol/mol)

FPG: fasting plasma glucose; IFG: impaired fasting glucose; OGTT: oral glucose tolerance test; IGT: impaired glucose tolerance; A1C:
glycated hemoglobin.
* For all 3 tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher
ends of the range.

Reprinted with permission from the American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;
34:S11. Copyright © 2011 American Diabetes Association. Table also published in: American Diabetes Association. Standards of medical care
in diabetes—2013. Diabetes Care 2013; 36 Suppl 1:S11. The content within this table is still current as of the 2020 version of the Standards
of Medical Care in Diabetes.

Graphic 82479 Version 16.0

Contributor Disclosures
Celeste Durnwald, MD Nothing to disclose David M Nathan, MD Nothing to disclose Erika F
Werner, MD, MS Nothing to disclose Vanessa A Barss, MD, FACOG Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
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