By Ahizechukwu C. Eke, MD, PhD, MPH
Associate Professor of Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
In 2023, the Centers for Diseases Control and Prevention (CDC) estimated that approximately 2% to 10% of all pregnancies were complicated by gestational diabetes mellitus (GDM), a condition characterized by glucose intolerance with onset or first recognition during pregnancy, characterized by pancreatic β-cell dysfunction that cannot meet the body’s insulin needs.1,2 Although minority race and ethnic groups, including Blacks, Hispanics, and Native Americans, are disproportionately affected by GDM, the prevalence of GDM rates continues to increase among all race and ethnicity subgroups and across all age groups.3
Early detection of GDM allows for the implementation of appropriate interventions to reduce the adverse effects of uncontrolled hyperglycemia, making GDM screening an integral part of prenatal care. However, the question of whether to adopt universal or selective (risk-based) screening for GDM has been a subject of ongoing debate and lacks a clear international consensus.
Although countries such as the United States, Canada, Australia, and the United Kingdom recommend universal screening of all pregnant women for GDM between 24-28 weeks of gestation, other countries such as the Netherlands, Switzerland, Sweden, Norway, and Nigeria recommend risk-based GDM screening based on risk factors, including a prior history of GDM, age > 25 years, obesity, family history of diabetes, and ethnicity.4 Ultimately, the choice between selective and universal screening should consider prevalence rates, available resources, local context, and the goal of optimizing maternal and fetal health outcomes.
Screening and Diagnosis
International agreement on GDM screening and diagnosis criteria has been unclear because of divergent views regarding the degree of maternal hyperglycemia that correlates with adverse outcomes. The original set of diagnostic criteria for GDM were introduced by O’Sullivan and Mahan in 1964 based on a 100-g, three-hour oral glucose tolerance testing (OGTT) threshold.5 These testing criteria were mod-ified by the National Diabetes Data Group (NDDG) in 1982 (by introducing a two-step approach); and by Carpenter and Coustan in 1999 (by lowering glucose thresholds and simplifying the diagnostic process).6
In 2010, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) proposed new criteria for GDM by a one-step 75-g, two-hour OGTT, that was later endorsed by the American Diabetes Association (ADA) and the World Health Organization (WHO).7-9 The current American College of Obstetricians and Gynecologists (ACOG) GDM testing algorithm involves an initial screening with a 50-gram, one-hour OGTT (non-fasting), followed by a 100-mg, three-hour OGTT testing (for those who fail the one-hour test).10
New Management Techniques
Advances in diabetes management have led to the use of continuous glucose monitors (CGMs) for real-time monitoring of maternal plasma glucose levels during pregnancy.11 CGMs have the advantage of improved patient satisfaction, enhanced user acceptability, and improved ability of providers to remotely monitor patients while on anti-diabetic therapy.12 Studies have demonstrated mixed results with the use of CGMs during pregnancy.
Although some studies showed improved pregnancy-specific glucose target time-in-range (TIRp), improved glycemic control, reduced rates of macrosomia, and improved neonatal outcomes with CGM compared with conventional glucose monitoring, others did not.11,13-17 The GlucoMOMS study, a multicenter randomized controlled trial (RCT) published in 2018, found that, although CGM offered accurate information on glycemic fluctuations, its usage did not decrease the incidence of fetal macrosomia or lead to better pregnancy outcomes.18 One critique of the GlucoMOMS study is that insulin targets did not consistently fall within the TIRp of 63 mg/dL to 140 mg/dL, as recommended by the international consensus on time-in-range, a critical factor directly linked to maternal and neonatal outcomes.19
In the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT), pregnant women using CGM spent more time within the TIRp of 63 mg/dL to 140 mg/dL by 34 to 35 weeks of gestation compared to pregnant women using self-monitoring of blood glucose (SMBG).20 Additionally, there were shorter newborn intensive care unit stays, decreased rates of fetal macrosomia, and reduced rates of neonatal hypoglycemia in women randomized to the CGM arm of CONCEPTT compared to those using SMBG. Although the CONCEPTT trial confirmed the benefits of CGM, glycemic and neonatal outcomes remained suboptimal.
Newer CGM studies, conducted following CONCEPTT, show that pregnant women with diabetes spent 60% to 70% of their TIRp within the recommended glucose targets during the third trimester of pregnancy.21,22 Since many women with GDM now are monitoring their blood sugars through a continuous approach, a multidisciplinary approach that uses the expertise of the obstetricians, the nutritionists, and the diabetes team (endocrinologist, diabetes nurse specialist) to optimize treatment regimens and improve pregnancy outcomes in women with diabetes is becoming increasingly important.
Closed-Loop Therapy
The use of hybrid closed-loop (HCL) systems (CGM with automated insulin delivery via a pump) is increasingly being used in obstetric care for management of diabetes. Recently published small randomized crossover studies have demonstrated that median percent TIRp was increased from approximately 60% during CGM with insulin pump therapy (self-adjusted) to 75% during HCL therapy.23,24
In a 2023 automated insulin delivery among pregnant women with type 1 diabetes (AiDAPT) multicenter RCT comparing automated HCL with standard insulin delivery, HCL significantly improved maternal hyperglycemia, with a 10.5% higher TIRp from 16 weeks of gestation until the time of delivery compared to standard insulin pump delivery.25 Additionally, HCL was associated with fewer episodes of maternal hypoglycemia, optimal weight gain, and better hemoglobin A1c values compared to standard insulin pump therapy.25 More data are needed on the efficacy, safety, and feasibility of closed-loop therapy in women with GDM.
Postpartum Testing
The debate over postpartum type 2 diabetes screening in women who had GDM highlights the intricate relationship between clinical evidence, resource distribution, and customized patient care. Postpartum screening for type 2 diabetes in women with a history of GDM with a fasting 75-g, two-hour OGTT is recommended by both ACOG and the ADA. Recent studies have demonstrated that an earlier timing (within one week of delivery) for the 75-g, two-hour OGTT has similar diagnostic value when compared to the four- to 12-week postpartum OGTT in predicting type 2 diabetes, although the majority of women dropped out of care and did not complete the recommended four- to 12-week postpartum OGTT.26
The optimal timing for the 75-g, two-hour OGTT depends on various factors, including the population being studied, available resources, and the balance between early detection and potential false negatives. Both immediate and four- to 12-week postpartum OGTT testing have their merits, and the choice may be influenced by practical considerations and the specific goals of diabetes prevention and management in a given healthcare setting or population.
Future Cardiovascular Risk
Gestational diabetes has long been established as a risk factor for future cardiovascular disease based on consistent evidence of the associations between GDM and subsequent development of chronic hypertension, dyslipidemia, vascular dysfunction, atherosclerosis, and other markers of cardiometabolic risk.27 According to the longest follow-up data, up to 50% of women may develop type 2 diabetes within a span of 20 to 30 years from GDM diagnosis.28
A recent systematic review and meta-analysis demonstrated that GDM is associated with two times the risk of future cardiovascular disease (risk ratio 2.0; 95% confidence interval, 1.6 to 2.5) when compared to women without GDM.29 In a retrospective cohort study, the risk of future cardiovascular events was 9.9 higher times in African American women with GDM and 6.3 times higher in Asian women with GDM compared to controls without GDM.30 Future studies with continuous follow-up of these women are warranted to evaluate longer-term cardiovascular implications of GDM diagnosis.
REFERENCES
- Centers for Disease Control and Prevention. Gestational diabetes and postpartum depression. Last reviewed April 6, 2023. https://www.cdc.gov/diabetes/library/features/gestational-diabetes-depression.html
- Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest 2005;115:485-491.
- Shah NS, Wang MC, Freaney PM, et al. Trends in gestational diabetes at first live birth by race and ethnicity in the US, 2011-2019. JAMA 2021;326:660-669.
- Dłuski DF, Ruszała M, Rudzinski G, et al. Evolution of gestational diabetes mellitus across continents in 21st century. Int J Environ Res Public Health 2022;19:15804.
- O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964;13:278-285.
- Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-773.
- International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-682.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33 Suppl 1:S62-S69.
- Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus; Seino Y, Nanjo K, Tajima N, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 2010;1:212-228.
- [No authors listed]. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol 2018;131:e49-e64.
- Murphy HR, Rayman G, Lewis K, et al. Effectiveness of continuous glucose monitoring in pregnant women with diabetes: Randomised clinical trial. BMJ 2008;337:a1680.
- Yu Q, Aris IM, Tan KH, Li LJ. Application and utility of continuous glucose monitoring in pregnancy: A systematic review. Front Endocrinol (Lausanne) 2019;10:697.
- Yu F, Lv L, Liang Z, et al. Continuous glucose monitoring effects on maternal glycemic control and pregnancy outcomes in patients with gestational diabetes mellitus: A prospective cohort study. J Clin Endocrinol Metab 2014;99:4674-4682.
- Paramasivam SS, Chinna K, Singh AKK, et al. Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: A randomized controlled trial. Diabet Med 2018;35:1118-1129.
- Secher AL, Ringholm L, Andersen HU, et al. The effect of real-time continuous glucose monitoring in pregnant women with diabetes: A randomized controlled trial. Diabetes Care 2013;36:1877-1883.
- Kestilä KK, Ekblad UU, Rönnemaa T. Continuous glucose monitoring versus self-monitoring of blood glucose in the treatment of gestational diabetes mellitus. Diabetes Res Clin Pract 2007;77:174-179.
- Petrovski G, Dimitrovski C, Bogoev M, et al. Is there a difference in pregnancy and glycemic outcome in patients with type 1 diabetes on insulin pump with constant or intermittent glucose monitoring? A pilot study. Diabetes Technol Ther 2011;13:1109-1113.
- Voormolen DN, DeVries JH, Sanson RME, et al. Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial. Diabetes Obes Metab 2018;20:1894-1902.
- Battelino T, Danne T, Bergenstal RM, et al. Clinical targets for continuous glucose monitoring data interpretation: Recommendations from the international consensus on time in range. Diabetes Care 2019;42:1593-1603.
- Feig DS, Donovan LE, Corcoy R, et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): A multicentre international randomised controlled trial. Lancet 2017;390:2347-2359.
- Tundidor D, Meek CL, Yamamoto J, et al. Continuous glucose monitoring time-in-range and HbA1c targets in pregnant women with type 1 diabetes. Diabetes Technol Ther 2021;23:710-714.
- O’Malley G, Ozaslan B, Levy CJ, et al. Longitudinal observation of insulin use and glucose sensor metrics in pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps: The LOIS-P study. Diabetes Technol Ther 2021;23:807-817.
- Stewart ZA, Wilinska ME, Hartnell S, et al. Closed-loop insulin delivery during pregnancy in women with type 1 diabetes. N Engl J Med 2016;375:644-654.
- Stewart ZA, Wilinska ME, Hartnell S, et al. Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: A randomized controlled crossover trial. Diabetes Care 2018;41:1391-1399.
- Lee TTM, Collett C, Bergford S, et al. Automated insulin delivery in women with pregnancy complicated by type 1 diabetes. N Engl J Med 2023;389:1566-1578.
- Carter EB, Martin S, Temming LA, et al. Early versus 6-12 week postpartum glucose tolerance testing for women with gestational diabetes. J Perinatol 2018;38:118-121.
- Tobias DK, Stuart JJ, Li S, et al. Association of history of gestational diabetes with long-term cardiovascular disease risk in a large prospective cohort of US women. JAMA Intern Med 2017;177:1735-1742.
- Sivaraman SC, Vinnamala S, Jenkins D. Gestational diabetes and future risk of diabetes. J Clin Med Res 2013;5:92-96.
- Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: A systematic review and meta-analysis. Diabetologia 2019;62:905-914.
- Xiang AH, Li BH, Black MH, et al. Racial and ethnic disparities in diabetes risk after gestational diabetes mellitus. Diabetologia 2011;54:3016-3021.
