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Oral Glucose Tolerance for Gestational Diabetes

Pregnancy is accompanied by insulin resistance, mediated primarily by placental secretion of diabetogenic hormones including growth hormone, corticotropin-releasing hormone, placental lactogen, and progesterone. These metabolic changes ensure that the fetus has an ample supply of nutrients. The American College of Obstetricians and Gynecologists (ACOG) uses the term "gestational diabetes mellitus (GDM)" to describe diabetes that is first detected during pregnancy. GDM develops during pregnancy in women whose pancreatic function is insufficient to overcome the insulin resistance associated with pregnancy.

Several adverse outcomes have been associated with diabetes during pregnancy. Women with GDM have a higher risk of gestational hypertension, preeclampsia and cesarean delivery with its associated potential morbidities. Up to 50% of women with GDM develop diabetes later in life. Offspring of women with GDM have an increased risk of macrosomia, operative delivery shoulder dystocia, birth trauma and metabolic disturbances such as hypoglycemia and hyperbilirubinemia. The risks of these outcomes increase as maternal fasting plasma glucose levels increase .This is a continuous effect; there is no clear threshold that defines patients at increased risk of adverse outcome.

The prevalence of GDM is not only influenced by diagnostic criteria but also by population characteristics. Depending on the diagnostic criteria used and the population screened, prevalence of GDM in the United States ranges from 1 to 25%. Prevalence is highest among Asian and Hispanic women (8%), intermediate among African-American women (6%), and lower among non-Hispanic white women (5%). Rates of gestational diabetes are rising worldwide with the increase in obesity and sedentary lifestyle.

Historically, the risk of developing GDM relied on a medical history including previous obstetric outcomes, family history of diabetes, obesity and detection of glucose in a routine urinalysis. However, many studies have demonstrated that reliance on these risk factors missed approximately one half of women with GDM.

Today, ACOG recommends universal screening and diagnostic testing of all pregnant women for GDM at 24 to 28 weeks of gestation. Universal screening is recommended because 90% of pregnant women have at least one risk factor for glucose impairment during pregnancy. Over half of the women in the United States' obstetric population are overweight or obese and/or have a first-degree relative with diabetes. Another reason for universal screening is that between 2.7% and 20% of women diagnosed with gestational diabetes have no risk factors.

The purpose of screening for any disease is to identify asymptomatic individuals with a high probability of having or developing a specific disease. Screening is usually performed as a two-step process where step one identifies individuals at increased risk for the disease. Only individuals with an abnormal screening test undergo diagnostic testing, which is definitive but usually more complicated or costly than the screening test.

The first step in screening for GDM is an oral glucose challenge test (OGCT) in which a patient drinks a 50 gram glucose solution and a venous sample is collected one hour later for measurement of plasma glucose. The following glucose thresholds have been proposed to define a positive screen: ≥130 mg/dL, ≥135 mg/dL, or ≥140 mg/dL. Sensitivity and specificity of the lowest and highest thresholds are:

OGCT Threshold Sensitivity Specificity
≥130 mg/dL 99% 77%
≥140 mg/dL 85% 86%

Use of the lower threshold (≥130 mg/dL) provides greater sensitivity, but results in more false positives (lower specificity) and requires administering the diagnostic test to more patients. The lower threshold should be considered in populations with a higher prevalence of gestational diabetes.

The likelihood that a woman will have an abnormal diagnostic test depends on the degree of plasma glucose elevation after the 50-gram one-hour glucose screen, the threshold used for interpretation of the diagnostic test and the prevalence of gestational diabetes in the population being tested. For example, a 50-gram one hour plasma glucose concentration of ≥200 mg/dL has been reported in different studies to have positive predictive values (PPVs) of 50%, 79%, and 75% for an abnormal diagnostic test.

Patients whose screening plasma glucose exceeds the screening threshold undergo a second diagnostic test, which is a 100-gram, three-hour oral glucose tolerance test (OGTT). ACOG's two step approach for screening and diagnosis of gestational diabetes is summarized in the following table.

Step one
1. Give 50-gram oral glucose load without regard to time of day
2. Measure plasma or serum glucose
3. Glucose ≥130 mg/dL, ≥135 mg/dL or ≥140 mg/dL is elevated and requires Step 2
Step two
1. Measure fasting plasma glucose concentration
2. Give 100-gram oral glucose load
3. Measure plasma or serum glucose at one, two, and three hours after glucose load
4. A positive test is defined by elevated glucose concentrations at two or more time points

The 100-gram three-hour OGTT is diagnostic of gestational diabetes when two glucose values are elevated. Two different sets of diagnostic thresholds have been established for interpretation of the 3 hour OGTT.  According to ACOG, either the plasma glucose cutoffs established by Carpentar and Coustan (C&C) or the National Diabetes Data Group (NDDG) can be used for interpretation.

Sample C&C (mg/dL) NDDG (mg/dL)
Fasting 95 105
1 Hour 180 190
2 Hours 155 165
3 Hours 140 145

The C&C criteria use lower thresholds for diagnosis of GDM and result in higher rates of diagnosis. A cross-sectional study that compared the two sets of criteria in more than 26,000 women determined that the use of C&C criteria increased the diagnosis of GDM by 50% compared to the NDDG criteria.

Each institution or physician should consistently use a single set of diagnostic criteria for their patient population. Considerations for selection of one set of criteria over the other include the prevalence of diabetes in their community and the availability of health care resources to appropriately manage GDM. 

Treatment of women who meet either set of criteria for gestational diabetes appears to improve pregnancy outcomes such as pregnancy induced hypertension, macrosomia and shoulder dystocia compared with no treatment.  Treating patients meeting the less stringent Carpenter and Coustan criteria is as effective as treating those meeting the more stringent NDDG criteria.

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