Diagnosing GDM in the first trimester

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The only evidence critical to this discussion is that “fasting plasma glucose at the first antenatal visit is not always consistent with fasting plasma glucose at 24 to 28 weeks,” Dr. Sacks said, referencing a study of 13 hospitals in China (Zhu WW, et al. Diabetes Care. 2013;36[3]:586–590). “The average of the first visit for these data was about 13.4 weeks, and it is a very large study, more than 17,000 individuals.”

With the cutoff of 92 mg/dL, “the sensitivity in this study showed subsequent gestational diabetes was only 0.24,” Dr. Sacks said. “The specificity was better, 0.92, but the positive predictive value was only 0.39.”

What is unknown about glucose in early pregnancy is whether glucose concentrations in women with GDM increased in early pregnancy, and, if so, when is the onset of maternal hyperglycemia. How soon after conception?

Data from the same study in China show the fasting plasma glucose level drops substantially from five weeks of gestation to just over 20 weeks.
Other unknowns: Are the current GDM diagnostic criteria for glucose valid before 24 weeks of gestation, and, if not, what cutoff values should be used?
A study conducted in New Zealand found that an HbA1c threshold of 5.9 percent was the best predictor of GDM at less than 24 weeks of gestation (Hughes RCE, et al. Diabetes Care. 2014;37[11]:2953–2959).

As with fasting plasma glucose, HbA1c is complicated, Dr. Sacks said. Data published in 2018 by Cuilin Zhang, MD, PhD, MPH, senior investigator, National Institute of Child Health and Human Development, Division of Intramural Population Health Research, NIH, showed changes in HbA1c concentrations at four different stages of pregnancy: enrollment (eight to 13 weeks of gestation), first study visit (16 to 22 weeks of gestation), second study visit (24 to 29 weeks of gestation), and just before delivery (34 to 37 weeks of gestation) (Hinkle SN, et al. Sci Rep. 2018;8[1]:12249). HbA1c concentrations fell between enrollment and the first study visit, then rose through the final study visit. This happens in women diagnosed with GDM and in those who did not subsequently develop GDM. “But at all time periods, HbA1c is higher in the women who subsequently develop gestational diabetes,” Dr. Sacks said.
Dr. Zhang and colleagues found that the optimal HbA1c threshold for diagnosing GDM in the first trimester was 5.7 percent, slightly lower than the 5.9 percent cutoff reported in the New Zealand study.

The diagnostic value of glycated albumin, which represents average glycemia over the preceding 14 to 21 days, has also been considered. “In theory, it is potentially useful in diagnosing gestational diabetes including the first trimester,” Dr. Sacks said, though further studies are needed.

The unknown issues regarding glycated proteins in early pregnancy are as follows: What are the reference intervals for HbA1c and glycated albumin in pregnancy, are these tests realistic alternatives to glucose measures for early diagnosis of GDM, is the predictive value of HbA1c for GDM useful in early pregnancy, and does HbA1c and/or glycated albumin predict adverse outcomes in GDM?

“The important question is, does predicting gestational diabetes in the first trimester make a difference? As of August 2019,” Dr. Sacks said at the meeting, “the answer is, Who knows? Nobody knows.”

He cited four limitations of the data on early identification of GDM, the first of which is that no criteria had been validated. Second, in most of the published studies, the outcome is usually GDM at 24 to 28 weeks, “but not maternal or fetal outcomes, which is the important question.” Third, there is no consensus on whether one should test or how to test, and, fourth, there is no evidence that testing has clinical value, “which at this stage is the important issue.”

The National Institute of Diabetes and Digestive and Kidney Diseases published an executive summary of a workshop that examined research gaps in GDM (Wexler DJ, et al. Obstet Gynecol. 2018;132[2]:496–505). It identified two gaps: therapy and early pregnancy diagnosis and treatment. “Clearly, this has been identified by the NIH as a very important topic,” Dr. Sacks said.

At the workshop, unanswered questions were identified: Which techniques should be used to identify GDM in early pregnancy? Is diagnosis of GDM early in pregnancy of clinical value? Will identification and/or treatment of GDM in early pregnancy improve outcomes for the mother and baby? Several studies of early diagnosis and/or treatment of GDM are ongoing, he said, “so presumably these questions will be answered in the not-too-distant future.”

Dr. Sacks’ take-home message: There is no consensus or evidence regarding the important issues surrounding predicting GDM early in pregnancy, which are how to identify individuals with GDM in the first trimester and whether prevention or treatment is effective. The latter is the key question, he said, and “until it can be answered, it will be hard to justify screening.” And last: Can it make a difference in outcome?

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