Earlier Detection of GDM Via OGTT: Is It Helpful?

Amy Valent; David A. Price


J Clin Endocrinol Metab. 2021;106(2):e1048-e1049. 

Gestational diabetes (GDM) is a growing public health concern, affecting 1 in 10 pregnancies. It is a condition with hyperglycemia that is first recognized during pregnancy and is associated with adverse perinatal outcomes and developmental origins of adult-onset diseases such as obesity, type 2 diabetes mellitus, and cardiovascular disease in the offspring.[1] Although controlling glycemia with diet, behavioral modifications, and pharmacotherapies have improved adverse outcomes such as large-for-gestational age (LGA) and preeclampsia,[2] our current management approaches have not fully mitigated adverse perinatal outcomes or prevention of long-term metabolic health risks. Lesser degrees of hyperglycemia below the diagnostic threshold for GDM diagnosis have been demonstrated to be associated with similar rates of adverse perinatal outcomes as pregnancies complicated by overt GDM.[3,4] This is further supported with increased rates of hypertensive spectrum disorders, LGA, macrosomia, cesarean delivery, and neonatal hypoglycemia/hyperinsulinemia with dysglycemia diagnosed in early gestation. These findings emphasize the potential importance of early recognition of relative hyperglycemia. However, beyond the recommendation for universal screening at 24 to 28 weeks, many knowledge gaps exist, including the role and degree of abnormal maternal glycemia on fetal metabolic programming, efficacy of current diagnosing and management strategies, and if early recognition and treatment of dysglycemia would reduce the potential perinatal or long-term adverse effect on the mother and her offspring.[5]

In a recent issue of The Journal of Clinical Endocrinology and Metabolism, Liu and colleagues[6] have taken the science in the right direction to investigate the correlation of glycemia tested at an earlier gestational age (18–20 weeks) to the standard testing window (24–28 weeks) among low-risk pregnant women, using the oral glucose tolerance test (OGTT). They characterized the participants' glycemic state as early GDM (diagnosis based on earlier gestation testing only), late GDM (diagnosis based on later testing only), GDM (abnormal testing in both periods), or normal glucose tolerance, using glycemic thresholds developed during 24 to 28 weeks' gestation.[7] Each of the 4 glycemic categories was associated with rates of adverse maternal and neonatal outcomes, which resulted in a few notable findings. First, the reproducibility between earlier and standard OGTT (~75%) was similar to other previously reported studies but as expected in a low-risk population the positive predictive value was low (~28%). Pregnancy is not a static physiologic state. Therefore, it may be of limited value to investigate reproducibility of a test 4 to 6 weeks apart. The study results, however, highlight the importance of understanding dysglycemia that occurs across gestation with the second noteworthy finding; the early GDM group represented the largest cohort (~16%) and met diagnostic GDM criteria predominantly because of elevated fasting glucose. Because the incidence of adverse neonatal outcomes was very low in this early GDM cohort, the significance and risk of GDM diagnosis earlier in gestation cannot be concluded from this study. Using diagnostic criteria developed in mid-trimester (24–28 weeks' gestation) to predict adverse perinatal outcomes earlier in gestation poses challenges resulting from the physiologic decline of fasting glucose with advancing gestation and the dynamic hormonal and biologic changes that influence insulin sensitivity during this period. Accordingly, other diagnostic criteria may need to be developed if GDM is screened for earlier in pregnancy. Last, women that had sustained hyperglycemia and met GDM criteria with both the early and the later OGTTs had higher rates of LGA, macrosomia, neonatal hyperinsulinemia, neonatal hypoglycemia, and time in the neonatal intensive care unit compared with the group with normal glucose tolerance.

The fetal pancreas is responsive to maternal glycemia as early as 12 weeks' gestation. Testing in early pregnancy is currently recommended to rule out undiagnosed type 2 diabetes mellitus but diagnostic glucose thresholds or optimal testing method(s) for early diagnosis of GDM is unknown.[8] Liu et al demonstrated in a low-risk population that age and body mass index are not predictive of the development of GDM. Moreover, the early and late GDM cohorts had similar rates of adverse neonatal outcomes as the normoglycemic group, highlighting the metabolic heterogeneity that makes the GDM phenotype difficult to clinically stratify.

To advance our care for patients with GDM and improve outcomes, it is imperative that future studies evaluate "normal" metabolic physiology in early and across gestation and to determine the (1) role and degree of dysglycemia and (2) relationship of glucose and other metabolic risk factors such as lipids in contributing to adverse perinatal outcomes. The OGTT involves an undesirable glucose beverage, overnight fasting, meticulous and timely sample handling, only 3 individual time points, and does not reflect the day-to-day diet, activity, sleep, or stress variability (i.e., real life). Therefore, alternate methods such as metabolic biomarkers and continuous glucose monitoring (CGM) are available tools that can potentially help characterize the dynamic metabolic biology during pregnancy, help provide individualized assessments, and contribute to glycemic optimization strategies.

At least 2 large studies are now in progress or development that aim to characterize glucose levels across gestation with CGM. The Glycemic Levels Across Maternity study, cofunded by United Health Group and the Helmsley Charitable Trust, is being coordinated by the Jaeb Center for Health Research and United Health Group; the Glycemic Observation and Metabolic Outcomes in Mothers and Offspring study is being funded by the NIH. Glycemic Levels Across Maternity and Glycemic Observation and Metabolic Outcomes in Mothers and Offspring will both attempt to correlate CGM-based glucose metrics to results of other diagnostic tests, to the use of hypoglycemic medications, to maternal and fetal outcomes, and to economic data. The studies may help researchers develop CGM-based criteria to predict adverse pregnancy outcomes in mothers and their newborns. Moreover, future studies including these trials are needed to determine the role of CGM to complement or potentially replace an OGTT during different points in pregnancy for diagnosing GDM as well as use for glycemic optimization to improve outcomes. Earlier identification of women and neonates at risk from dysglycemia presents an opportunity for prevention and potential interruption of the transgenerational dysmetabolic cycle.