For gestational diabetes, one step or two?

The HAPO study clearly showed that women who had a normal glucose tolerance test rate based on IADPSG criteria had a lower frequency of all adverse outcomes compared with women who had one abnormal glucose value. “Every single one of these adverse outcomes was lower in women below the threshold compared to women who had one or more abnormal values,” Dr. Brown said.

A HAPO follow-up study looked at long-term outcomes in more than 4,500 mothers and offspring 10 to 14 years after the HAPO study, with children and mothers undergoing a 75-g two-hour OGTT. The study found continuous linear associations between maternal glucose during pregnancy with childhood adiposity, skin-fold thickness, percent body fat, waist circumference, and markers of childhood glucose metabolism. “There is a strong relationship between the mother’s metabolic status in pregnancy and the offspring’s metabolic status 10 to 14 years later,” Dr. Brown said (Scholtens DM, et al. Diabetes Care. 2019;42[3]:381–392).

When researchers dichotomized the subjects based on post hoc diagnosis of maternal GDM by IADPSG criteria, in which 14.3 percent of the mothers had GDM versus mothers who did not have GDM, “they found that children of those mothers were more likely to have impaired glucose tolerance, higher 30-minute, one-hour, and two-hour glucose levels on a 75-g two-hour OGTT, and reduced insulin sensitivity and oral disposition index,” she said. The children also had higher odds ratio of obesity, body fat percent, waist circumference, and skin fold thickness than children of mothers who did not have GDM.

“For the mothers, the odds ratio was 3.44 for long-term diabetes or prediabetes,” she said. “In terms of absolute numbers, 52 percent of the mothers who made criteria by IADPSG criteria had either diabetes or prediabetes, and 20 percent of mothers who did not have gestational diabetes had diabetes or prediabetes.”

Dr. Brown referred to her published report of the prevalence of GDM by country, which showed that the IADPSG criteria “does definitely increase the prevalence of gestational diabetes” (Brown FM, et al. Curr Diab Rep. 2017;17[10]:85).

To sum up, she presented a comparison of the 1964 study of 762 patients at a single center, “at a time when the prevalence of diabetes was 1.24 percent,” with the HAPO studies, in which there were 23,000 women and more than 4,500 pairs in the follow-up from multiple centers across the globe. “Both demonstrated increased maternal risk for diabetes in the population, but only the one-step method looked at pregnancy, neonatal, and long-term offspring outcomes.”

Amy Valent, DO, a maternal fetal medicine specialist and assistant professor of obstetrics and gynecology, Oregon Health and Science University, and director of the OHSU diabetes in pregnancy program, defended the two-step method to screen for gestational diabetes.

“We have these two diagnostic methods, and they’re both appropriate per the guidelines of several of our major groups,” Dr. Valent said. “What will it take for us to change and choose one or the other?”

Dr. Valent said she advises her patients to think of their gestational diabetes diagnosis as “a crystal ball into your future metabolic health” because more than 50 percent of women with GDM develop type two diabetes in the five to 10 years after diagnosis.

She called the HAPO study a “wakeup call to providers to realize that women were at higher risk for adverse pregnancy outcomes—not necessarily type two diabetes—in the future, at lower glycemic targets than we previously thought. Before 2008, we didn’t have this recognition, and HAPO homed in on that to make us realize that even at lower glycemic ranges, women are still at higher risk.”

The one-step IADPSG criteria that uses the 1.75 odds ratio came out in 2010, and while the method increases the prevalence of GDM diagnoses, “the [2013] NIH consensus of experts didn’t think that the cost was justified with the potential improvement in outcomes,” she said. The U.S. Preventive Services Task Force, however, recognized through evidence that there was enough of a risk factor of GDM among women and in 2014 recommended universal screenings at 24 weeks of gestation.

“Where are we now?” she asked.

The two-step approach is a nonfasting 50-g oral glucose challenge test. “You can use the Carpenter-Coustan criteria of 135, but most institutions will use population-based prevalence to determine if they’re using a 130, 135, or 140 cutoff.”

Women who fail this step continue to the diagnostic standard of a fasting 100-g OGTT. The Carpenter and Coustan or the NDDG criteria, both of which use plasma, can be used.

An effective screening test must detect a condition in a high proportion of the population, be safe and reasonably cost-effective, and demonstrate improved health outcomes, Dr. Valent noted.

The two-step method, using the Carpenter and Coustan criteria, has demonstrated relatively good sensitivity between 85 and 99 percent, and a specificity between 77 and 86 percent, Dr. Valent said. “Of course, your population prevalence drives your positive predictive values, so that can vary. But it has very high negative predictive values” of 98 to 100 percent.

The two-step approach is more immediately cost-effective, she said, since the majority of women are not diagnosed with GDM. By increasing GDM diagnoses threefold, the one-step approach would result in increased interventions, maternal and neonatal evaluations, loss in productivity, and anxiety and stress for the patient. “We have to consider the costs of testing supplies and medications, clinic time, provider time, patient time, social work time, dietician, ultrasounds, and then antenatal surveillance because they are at a higher risk for stillbirth.”

Does the test identify a problem, and if the problem is treated, are the outcomes better? The Maternal-Fetal Medicine Units Network study demonstrated improved outcomes for mother and baby with treatment of mild GDM. A secondary analysis of the MFMU Network study demonstrated decreased rates of pregnancy-induced hypertension, macrosomia, and large-for-gestational-age neonates among women treated after diagnosis of GDM with Carpenter and Coustan or NDDG criteria, suggesting that using Carpenter and Coustan criteria, a more sensitive test than NDDG, has the ability to reduce maternal and neonatal risks and is more commonly used.

The Diabetes Prevention Program trial of the National Institute of Diabetes and Digestive and Kidney Diseases studied men and women at high risk for type two diabetes, and among them was a group of 350 women with a previous diagnosis of GDM, and 1,400 pregnant women who did not have diabetes in their pregnancies but had elevated BMI and impaired fasting glucose levels. Participants were randomized to receive either intense lifestyle intervention, metformin, or placebo. Women with a history of GDM who had lifestyle intervention or used metformin had similar reductions of 35 to 40 percent in the incidence of type two diabetes over 10 years, Dr. Valent said.

By identifying women during pregnancy who are at risk for developing type two diabetes in the near future, following up with them and providing preventive care, “we can make an impact on their development of type two diabetes.”

“We have to think about physiology,” Dr. Valent said. “How do lipids, adiponectin, leptin, and other things influence women who have gestational diabetes? Should it change our glucose-centric focus on how we treat women with diabetes to a more broad, individualized health care program?”

In summary, the two-step approach was designed to detect women at high risk for the development of type two diabetes, she said. “If we consider the women diagnosed with gestational diabetes, those are women who have the potential for developing type two diabetes. If we intervene now, that is called primary prevention.”

Thinking about the fetus, “which is the part that I love about my job because I get to think about two people,” she said, “then I have primary preventive capacity for that fetus if I can help improve the overall health condition of the mother.”

Treating GDM improves perinatal outcomes. But a screening test is supposed to be followed up on, and the challenge is that only 40 percent of women diagnosed with GDM return after delivery for a GTT. Whether they follow up with their primary care physicians is unknown. “We have a huge potential to be able to make an impact on these women if we can follow them a little more closely,” Dr. Valent said.

Amy Carpenter Aquino is CAP TODAY senior editor. This session was also presented at the American Diabetes Association annual meeting in June.