What is gestational diabetes?

[Note: This article is being published in draft form for use in an active research study. Its contents may be adjusted as we recieve feedback from collaborating health care professionals.]

Gestational diabetes mellitus (GDM) is the development of abnormal blood glucose levels during pregnancy as a result of increasing insulin resistance due to defective β-cells.^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).^3-5 However, some women diagnosed with gestational diabetes may not have true gestational diabetes but rather have previously undiagnosed diabetes.^1,6 By definition, GDM is only present during gestation and is understood to resolve after birth. In 2016, 6% of pregnant people were diagnosed with GDM, with the number growing to 6.3% in 2021.⁷

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.^8,9 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 an FPG ≥92 mg/dL, 1-hour 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.¹⁰

The 2024 ADA clinical practice guidelines endorse these diagnostic criteria but differ on the timetable.⁴ They advise that diagnosis of GDM should occur between gestational weeks 24 and 28, not at earlier screenings.

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 and an increased risk of long-term maternal T2DM and abnormal glucose metabolism of offspring in childhood.⁵ Offspring with exposure to untreated GDM have reduced insulin sensitivity and β-cell compensation and are more likely to have impaired glucose tolerance in childhood.¹³

Higher Birth Weight and Abnormal Offspring Glucose Metabolism

GDM increases risk for large-for gestational-age birth weight.⁵ One recent study conducted between November 2019 and November 2021 in India, found that children of women with GDM had a higher BMI.¹⁴ Of the children analyzed, 11.3%, 1.3% and 1.3% were overweight, obese, and severely obese, respectively. The same study found impaired fasting glucose (3.8%) and impaired glucose tolerance (16.9%) after an oral glucose tolerance test.

Another study in China showed that women with GDM produced large for gestational age offspring with an odds ratio of 1.3.¹⁵

Perinatal complications

GDM is also associated with a number of complications during perinatal complications, but treatment reduces risk.¹⁶ A clinical trial characterizing the following perinatal complications associated with GDM; death, dystocia, bone fracture, and nerve palsy as well as admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety and depression.¹⁶ They found that treatment of GDM reduces risk of serious morbidity.

Another study characterizing births in Germany also concluded that GDM is associated with an increased risk of premature birth, cesarean section, and transfer of newborn.¹⁷

Type 2 Diabetes Risk

A history of GDM increases the 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.¹⁸ 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.⁶ The ADA further recommends postdelivery lifestyle interventions to further reduce risk of T2DM development.

References

1. Feig DS, Zinman B, Wang X, Hux JE. Risk of development of diabetes mellitus after diagnosis of gestational diabetes. Canadian Medical Association Journal. 2008;179(3):229-234. doi:10.1503/cmaj.080012
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
5. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. Jan 1 2022;45(Suppl 1):S17-s38. doi:10.2337/dc22-S002
6. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2024. Diabetes Care. Jan 1 2024;47(Suppl 1):S282-s294. doi:10.2337/dc24-S015
7. Cdcmmwr. QuickStats: Percentage of Mothers with Gestational Diabetes, by Maternal Age — National Vital Statistics System, United States, 2016 and 2021. MMWR Morb Mortal Wkly Rep. 2023 2023;72doi:10.15585/mmwr.mm7201a4
8. 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
9. 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
10. 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
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. 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
14. Malik N, Ahmad A, Ashraf H. Metabolic Profile of Offspring of Mothers with Gestational Diabetes Mellitus. Indian Journal of Endocrinology and Metabolism. 2024/04//Mar 2024;28(2):192. doi:10.4103/ijem.ijem_211_23
15. He L-R, Yu L, Guo Y. Birth weight and large for gestational age trends in offspring of pregnant women with gestational diabetes mellitus in southern China, 2012-2021. Front Endocrinol (Lausanne). 2023 2023;14:1166533. doi:10.3389/fendo.2023.1166533
16. 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
17. 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
18. 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