An update on gestational diabetes mellitus

July 20, 2016
At first glance, screening pregnant women for gestational diabetes mellitus (GDM) seems like it should be straightforward. After all, the screening tests are designed to identify pregnant woman with high concentrations of blood glucose, and laboratory tests that measure glucose are accurate and precise. So what’s the problem?

Before that question is tackled, consider a few facts about GDM:

  • It is defined as any degree of glucose intolerance with onset or first recognition during pregnancy that isn’t overt diabetes mellitus.
  • Each year in the United States approximately four million women give birth, and 240,000 of these women, or six percent, develop diabetes during their pregnancy.
  • The incidence of GDM is a function of the screening test used to diagnose the disorder (more about this below).
  • Although GDM often resolves after pregnancy, it does place the mother and fetus at risk of serious health issues. For the mother these include preeclampsia and an increased chance for the development of type 2 diabetes after pregnancy. For the fetus these include macrosomia, shoulder dystocia, and increased risk of obesity during childhood.

The question of how best to screen for GDM is one not easily answered because experts don’t agree on how best to screen for the disorder. While all agree that both mother and infant can experience adverse outcomes if GDM goes undetected and untreated, there is lack of consensus on the best way of identifying it.

Some diagnostic dilemmas

To better understand the current debate, consider how GDM screening has been done in the U.S. since 1964. Most practitioners follow a two-step process:

  1. A screening test is done at 24 to 28 weeks of gestation by measuring blood glucose one hour after a non-fasting patient consumes a 50-gram dose of glucose. A result greater than 140 mg/dL is usually used as the cutoff, although a lower cutoff of 130 mg/dL may also be used. Those with a result greater than the cutoff undergo diagnostic testing.
  2. The diagnostic test is the three-hour oral glucose tolerance test (OGTT). This test requires the collection of a fasting blood sample followed by consumption of a 100-gram dose of glucose with additional blood samples obtained every hour for four hours. The test is considered positive, and GDM confirmed, if two or more of the four glucose test results are above designated cutoffs. There are two sets of cutoffs currently used: those of the National Diabetes Data Group or the Carpenter-Coustan cutoffs.

Importantly, these two cutoff sets are modifications of those developed 52 years ago that were selected to identify women who were more likely to have diabetes after pregnancy. Further, the requirement that two or more abnormal results are required to define an abnormal result was arbitrarily selected to avoid misclassifications due to “laboratory errors.” It should also be noted that in much of the rest of the world, a one-step approach is used to diagnose GDM using a two-hour, 75-gram OGTT. GDM is diagnosed when any single glucose result exceeds a diagnostic cutoff recommended by the World Health Organization (WHO).

The lack of a universal protocol for diagnosing GDM has made it impossible to compare different studies of GDM. In addition, because different investigators have used different protocols for identifying women with the disorder, its true prevalence is not known. To further complicate matters, there has been ambiguity regarding the maternal and fetal morbidities associated with varying degrees of maternal hyperglycemia. To address these shortcomings, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study was conducted.

Controversial criteria

HAPO was a multicenter international study that included more than 23,000 women in nine countries who were given a 75-gram, two-hour OGTT. Results clearly demonstrated strong and continuous associations between maternal glucose and adverse outcomes such as increased birth weight, C-section delivery, and neonatal hypoglycemia. The continuous associations between glucose and outcome meant that translating the HAPO results into clinical practice would be challenging. Recognizing that, the study investigators called for a re-defining of the criteria used to diagnose GDM. As a result, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) convened to establish new diagnostic criteria for the diagnosis of GDM.

Ultimately, this group settled on diagnostic cutoffs that reflected an odds ratio of 1.75 times the mean for the outcomes of increased neonatal body fat, large for gestational age infants, and an umbilical cord serum C-peptide concentration greater than the 90th percentile. They also recommended that a universal, one-step, two-hour, 75-gram OGTT be performed during pregnancy and that the diagnosis of GDM be made when any single cutoff on the two-hour OGTT was met or exceeded.

It was immediately recognized that use of the IADPSG cutoffs would likely double the incidence of women diagnosed with GDM, and this alone lessened an enthusiastic adoption of the new protocol. The loudest critic was the American College of Obstetricians and Gynecologists (ACOG), which continued to support the two-step approach to screening and diagnosis and recommended that additional studies be performed before changes to GDM diagnostic criteria were adopted. Notably, the Endocrine Society, the WHO, and the American Diabetes Association (ADA) have accepted the one-step approach. (The ADA also accepts the two-step approach and so is somewhat noncommittal on the controversy.)

To be clear, all experts agree that screening pregnant women for GDM is an important part of obstetrical care. Indeed, the United States Preventative Services Task Force has recommended screening all pregnant women for GDM. The controversy centers on how to best screen for the condition. Several studies have now been conducted that evaluate outcomes when GDM is identified via the one-step or two-step approach. Perhaps not surprisingly, the conclusions of these various studies are not in agreement with each other. As expected, all studies report an increased number of women diagnosed with GDM using the one-step test. However, the outcomes of these pregnancies are reported as improved in some studies, while others describe no improvements compared to GDM cases diagnosed by the two-step test. The debate, therefore, continues, as it remains unclear if the increased number of women identified as having GDM by the one-step approach have truly benefited from treatments for GDM or if they have been subjected to unnecessary (and potentially harmful) interventions. A uniform approach to identifying GDM is needed, but more data and more studies will be necessary before a consensus opinion on one that produces the greatest benefits with the least risks will be achieved.

David Grenache, PhD, is a professor of pathology at the University of Utah School of Medicine and section chief of clinical chemistry at ARUP Laboratories. He is board-certified by the American Board of Clinical Chemistry and is a fellow in the National Academy of Clinical Biochemistry. He also maintains a blog, “The Pregnancy Lab” (, focused on the laboratory tests performed during pregnancy.