What is gestational diabetes?

Gestational diabetes mellitus (GDM) is the development of abnormal blood glucose levels during pregnancy as a result of increasing insulin resistance due to hormones made by the placenta and pancreatic beta cell function being insufficient to overcome the insulin resistance.^1,2 The American Diabetes Association (ADA) classifies GDM as diabetes that is first develops during pregnancy with no clear indication of prior type 1 or type 2 diabetes mellitus (T1DM and T2DM).^3,4 However, some women diagnosed with gestational diabetes may not have true gestational diabetes but rather have previously undiagnosed diabetes.^1,5 By definition, GDM is only present during pregnancy and is understood to resolve after birth. In 2016, 6% of pregnant people were diagnosed with GDM, with the number growing to 8.3% in 2021.⁶

Diagnostic Criteria

In 2010, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) produced broad recommendations for diagnosis and classification of hyperglycemia in pregnancy based on results from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study, a large-scale multinational cohort study of more than 23,000 pregnant individuals.^7,8 These recommendations are based on adverse perinatal outcomes rather than thresholds established for diagnosis of impaired glucose tolerance outside of pregnancy. IADPSG guidelines recommend universal early screening for preexisting diabetes in pregnant people at <15 weeks gestation during their first prenatal visits using the same diagnostic criteria as those for nonpregnant patients. The IADPSG threshold for GDM diagnosis is a fasting plasma glucose (FPG) ≥92 mg/dL, 1-hour oral glucose tolerance test (OGTT) ≥180 mg/dL, or 2-hour OGTT ≥153 mg/dL. If negative for this early screening, then patients are recommended to undergo an OGTT between gestational weeks 24 and 28 with the same diagnostic cutoffs. Because only one positive test is required for diagnosis, these criteria have high diagnostic sensitivity.⁹

The 2024 ADA clinical practice guidelines endorse these diagnostic criteria but do not agree with the need for early screening.⁴ They recommend that diagnosis of GDM should occur between gestational weeks 24 and 28.

The American College of Obstetricians and Gynecologists (ACOG) similarly does not agree for early screening, advising that there is not consistent evidence of benefit for early diagnosis and treatment of GDM, and so does not recommend routine screening for GDM before 24 weeks.¹⁰ ACOG specifically recommends the two-step approach to diabetes diagnosis, with a 50-gram nonfasting screen followed by a 100-gram 3-hour OGTT, although the one-step 75-g OGTT can also be appropriate for certain populations. The ACOG threshold for GDM diagnosis is slightly different from the IADPSG thresholds at FPG ≥95 mg/dL, 1-hour OGTT ≥180 mg/dL, 2-hour OGTT ≥155 mg/dL, 3-hour OGTT ≥140 mg/dL.

GDM is a predictor of adverse maternal and neonatal outcomes and has increased across all race, ethnic, and age groups.^11,12 GDM can increase the risk of large-for-gestational-age birth weight, neonatal and pregnancy complications, long-term maternal T2DM, and abnormal glucose metabolism of offspring in childhood.

A population-based study of singleton births in Germany from 2013-2019 (n=4,991,275, 283,210 with GDM) found that GDM is associated with an increased risk of premature birth (7.4% vs 6.6%), large-for-gestational-age birth weight (14.4% vs 9.2%), cesarean section (37.6% vs 29.8%), and transfer of newborn to the perinatal unit (14.1% vs 9.2%).¹³

While GDM is associated with a number of perinatal complications, treatment can reduce risk.¹⁴ A randomized control trial taking place from 1993-2003 of 1,000 mothers and their 1,030 infants examined the relationship between treatment of GDM and rates of complications. Women were randomly assigned to receive standard care or an intervention of individualized coaching and treatment. In the intervention group, the rate of serious perinatal outcomes (defined as one or more of the following: death, shoulder dystocia, bone fracture, and nerve palsy) was significantly lower than in the control group (1% vs 4%, p=0.01). More infants in the control group were admitted to the neonatal intensive care unit (NICU, 71% vs 61%, p=0.01).

A 2009 multicenter randomized control trial (n=958) had similar findings, with treatment significantly reducing mean birth weight (3,302 vs 3,408 g), neonatal fat mass (427 vs 464 g), large-for-gestational-age infants (7.1% vs 14.5%), shoulder dystocia (1.5% vs 4.0%), and cesarean delivery (26.9% vs 33.8%).¹⁵

Type 2 Diabetes Risk

Children whose mothers had GDM have reduced insulin sensitivity and β-cell compensation and are more likely to have impaired glucose tolerance.¹⁶ The Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study (HAPO FUS) collected data from 4,160 children aged 10-14 from 2013-2016. Children whose mothers had GDM were found to have higher rates of impaired glucose tolerance (10.6% vs 5.0% for children of mothers without GDM).

Birthing parents with a history of GDM have increased risk of later developing T2DM. In a 2008 population-based study in Ontario, Canada, 18.9% of women with GDM went on to develop T2DM within nine years post-partum. This is compared to 1.95% of women without GDM developing T2DM post-partum.¹ The most significant risk factor for the development of T2DM was previous GDM.

A 2020 meta-analysis of 20 observational studies published from 2002-2019 assessed incidence of T2DM in women with GDM.¹⁷ Every study included showed a greater risk for T2DM in women with GDM, with a pooled T2DM incidence of 18.5% among women with GDM compared to 1.9% among controls.

The ADA recommends that women with GDM be tested on their glycemic status at least 4-12 weeks after delivery and continue to have lifelong screening every 1-3 years depending on an individual’s risk factors.⁵ ACOG also advises that testing in the immediate postpartum period prior to hospital discharge is a good strategy to ensure postpartum testing is done and can provide reliable results.¹⁰ The ADA further recommends postdelivery lifestyle interventions to further reduce risk of T2DM development.⁵

References

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2. Kleinwechter H, Schäfer-Graf U, Bührer C, et al. Gestational diabetes mellitus (GDM) diagnosis, therapy and follow-up care: Practice Guideline of the German Diabetes Association(DDG) and the German Association for Gynaecologyand Obstetrics (DGGG). Exp Clin Endocrinol Diabetes. 2014/07// 2014,122(7):395-405. doi:10.1055/s-0034-1366412
3. American Diabetes A. Gestational Diabetes Mellitus. Diabetes Care. 2004,27(suppl_1):s88-s90. doi:10.2337/diacare.27.2007.S88
4. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. Jan 1 2024,47(Suppl 1):S20-s42. doi:10.2337/dc24-S002
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6. QuickStats: Percentage of Mothers with Gestational Diabetes, by Maternal Age — National Vital Statistics System, United States, 2016 and 2021. Morbidity and Mortality Weekly Report. 2023 2023,72doi:10.15585/mmwr.mm7201a4
7. 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. Mar 2010,33(3):676-82. doi:10.2337/dc09-1848
8. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Int J Gynaecol Obstet. Jul 2002,78(1):69-77. doi:10.1016/s0020-7292(02)00092-9
9. Egan AM, Vellinga A, Harreiter J, et al. Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe. Diabetologia. 2017/10/01/ 2017,60(10):1913-1921. doi:10.1007/s00125-017-4353-9
10. ACOG Clinical Practice Update: Screening for Gestational and Pregestational Diabetes in Pregnancy and Postpartum. Obstetrics & Gynecology. 2024,144(1):e20-23. doi:10.1097/AOG.0000000000005612
11. Akinyemi OA, Weldeslase TA, Odusanya E, et al. Profiles and Outcomes of Women with Gestational Diabetes Mellitus in the United States. Cureus. 15(7):e41360. doi:10.7759/cureus.41360
12. 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. 2021/08/17/ 2021,326(7):660-669. doi:10.1001/jama.2021.7217
13. Reitzle L, Heidemann C, Baumert J, et al. Pregnancy Complications in Women With Pregestational and Gestational Diabetes Mellitus. Dtsch Arztebl Int. 2023/02// 2023,120(6):81-86. doi:10.3238/arztebl.m2022.0387
14. Crowther Caroline A, Hiller Janet E, Moss John R, McPhee Andrew J, Jeffries William S, Robinson Jeffrey S. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. New England Journal of Medicine. 2005 2005,352(24):2477-2486. doi:10.1056/NEJMoa042973
15. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. Oct 1 2009,361(14):1339-48. doi:10.1056/NEJMoa0902430
16. Lowe WL, Jr., Scholtens DM, Kuang A, et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care. Mar 2019,42(3):372-380. doi:10.2337/dc18-1646
17. Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ (Clinical research ed). 2020:m1361. doi:10.1136/bmj.m1361