What Do You Need to Know About Diabetes and Pregnancy?
Rebecca Morey, MD, and Kim A. Carmichael, MD—Series Editor
Morey R, Carmichael KA. What do you need to know about diabetes and pregnancy? Consultant. 2019;59(4):106-107.
Diabetes is a common condition and affects approximately 7% of all US pregnancies, of which 86% are in women with gestational diabetes mellitus (GDM).1 This article answers common questions among primary care providers.
Q. What preconception counseling should women with diabetes get?
A. The American Diabetes Association (ADA) recommends preconception counseling as part of routine care for girls of childbearing potential starting at puberty.2 Preconception visits should include topics such as vaccination, folic acid supplementation, and smoking cessation. Women should be counseled on the risk of congenital malformations associated with poor glycemic control, especially in the first trimester. The ADA recommends checking hemoglobin A1c, thyrotropin, creatinine, and urinary albumin-to-creatinine ratio.
Patients with preexisting diabetes are at increased risk for diabetic retinopathy onset or progression.3 Good preconception glycemic control is associated with lower risk of progression. Dilated eye examinations are recommended prior to pregnancy or in the first trimester and should be repeated in the second trimester, in the third trimester, and at 1 year postpartum.1
Women with poorly controlled preexisting diabetes are at higher risk of congenital malformations. The relative risk of fetal malformation is about 2 per each percent increase in A1c above 7%.4 Congenital malformation rates of approximately 2% to 3% occur in women with A1c levels below 6%, which is approximately the same rate as in the general population. This is in contrast to a rate of 22% in women with A1c levels above 9.5%.5
Angiotensin-converting enzyme inhibitors (ACEIs) are associated with impaired fetal kidney function and related complications, including oligohydramnios, pulmonary hypoplasia, fetal growth restriction, and fetal death.6 The Food and Drug Administration (FDA) issued a black box warning about the risk of fetal injury and death when ACEIs are used in pregnancy. This risk is greatest in the second and third trimesters. A 2017 review of Medicaid claims related to more than 1.3 million pregnancies demonstrated no associated risk between ACEI use in the first trimester and major congenital malformations.7
The use of statins has been linked to birth defects, including limb defects and central nervous system anomalies. A 2015 review of Medicaid data from more than 800,000 completed pregnancies did not show a statistically significant teratogenic effect of statin use in the first trimester.8 Several studies have shown the absolute risk of teratogenicity with statins to be small or not statistically significant.9 However, given the potential teratogenicity of statins, the ADA recommends avoiding their use in women of childbearing age without effective contraception.6
Q: What is GDM, and what are its causes?
A. The ADA defines GDM as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation.6
In early pregnancy, women can have enhanced insulin sensitivity and lower insulin requirements.6 As pregnancy progresses, maternal metabolism undergoes several changes to ensure the fetus has adequate metabolic fuel. These changes include elevations in serum insulin levels, insulin resistance, and plasma lipids. Abundant maternal carbohydrates are shielded from maternal metabolism by insulin resistance for use by the growing fetus. Maternal energy needs are met largely through lipolysis, a sort of “accelerated starvation.”10 This process is driven by human placental growth hormone, which reduces insulin receptors and glucose transport. Cortisol, glucagon, and other hormones may also play a part in gestational insulin resistance.10
Q: Who should be screened for GDM, and when?
A. The US Preventive Services Task Force recommends that all asymptomatic pregnant women be screened for GDM after 24 weeks of gestation.11 The ADA recommends screening women without a prior diagnosis of diabetes at 24 to 28 weeks of gestation.6
The ADA also recommends screening for diabetes at the first prenatal visit for women with risk factors.6 These include a first-degree relative with diabetes, overweight (body mass index ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans), sedentary lifestyle, hypertension (≥140/90 mm Hg or on medication), cardiovascular disease, polycystic ovarian syndrome (PCOS), clinical conditions associated with insulin resistance, a high-density lipoprotein cholesterol level below 35 mg/dL, or a triglyceride level above 250 mg/dL. Women of certain ethnicities also are at increased risk, including African Americans, Asian Americans, Hispanics, Native Americans, and Pacific Islanders.1 The American College of Obstetricians and Gynecologists (ACOG) includes the above as risk factors and adds a history of GDM, a history of a large for gestational age fetus (>4 kg), or previous elevated glycemic measures.1
Q: How should we screen women without known diabetes?
A. The ADA recommends either a 1-step or a 2-step screening strategy. The 1-step strategy uses the 75-g oral glucose tolerance test (OGTT) in women at 24 to 28 weeks of gestation and measures fasting (normal, <92 mg/dL), 1-hour (normal, <180 mg/dL), and 2-hour (normal, <153 mg/dL) blood glucose levels. The 1-step strategy is more sensitive, since it requires only 1 abnormal value to make the diagnosis of GDM.6
The National Institutes of Health and ACOG recommend a 2-step approach with an initial 1-hour 50-g glucose load test (GLT). The cutoff for a normal test varies, ranging from 130 to 140 mg/dL depending on desired sensitivity. This first step does not require fasting. If GLT results are abnormal, the woman undergoes a 3-hour 100-g OGTT. Fasting blood glucose levels are measured at 1, 2, and 3 hours. The ADA requires at least 2 values to be abnormal to make the diagnosis of GDM. While ACOG previously had required only 1 abnormal value to diagnose GDM, a 2018 update softened this stance without clearly defining the new position. Cutoff values for the 100-g OGTT are summarized in the accompanying Table.1,6
Q: What are the treatment options and goals?
A. First-line treatment of GDM is healthy diet and exercise.12 Most women with GDM can manage their disease through these methods alone.6
The ADA recommends fasting and postprandial blood glucose checks in women with diabetes.2 Preprandial surveillance is also recommended for women who would have mealtime insulin dosing affected. The ADA and ACOG agree on the following blood glucose target ranges for patients with GDM: fasting, ≤95 mg/dL; 1-hour postprandial, ≤140 mg/dL; and 2- hour postprandial, ≤120 mg/dL.
ACOG and the ADA disagree on the use of metformin in the management of GDM. The ADA states that insulin is the preferred medication for treating hyperglycemia in GDM because it does not cross the placenta to a measurable extent.”2 The ADA lists metformin and glyburide as second-line agents, because both cross the placenta. The ADA recommends that metformin, even if used to treat PCOS, should be discontinued once a pregnancy is confirmed.2 Oral antidiabetes drugs are not FDA-approved for use in GDM.
The ACOG, on the other hand, supports metformin as a first-line treatment option in women who decline insulin, are not able to safely administer insulin, or cannot afford insulin.1 ACOG agrees with the ADA that glyburide is associated with higher rates of fetal hypoglycemia and should not be used as a first-line antidiabetes agent in pregnancy.1
Q: What about postpartum counseling, follow-up, and treatment?
A. Erratic sleeping and eating schedules may put women who take insulin at higher risk of hypoglycemia.6 After delivery of the placenta, insulin resistance characteristic of pregnancy typically rapidly returns to prepregnancy levels.
Women with a history of GDM are at higher risk of developing diabetes in the future. Approximately 70% of women reportedly will develop type 2 diabetes in the decades following pregnancy.1
The ADA recommends diabetes screening 4 to 12 weeks postpartum using a 75-g OGTT and nonpregnancy criteria. If OGTT results are normal, the woman should be screened every 1 to 3 years using any traditional glycemic test. This screening should be lifelong.6
Rebecca Morey, MD, is a clinical fellow in the Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, at Washington University School of Medicine in St Louis, Missouri.
Kim A. Carmichael, MD, is a professor of medicine in the Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, at Washington University School of Medicine in St Louis, Missouri.
1. Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64.
2. American Diabetes Association. 14. Management of diabetes in pregnancy: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(suppl 1):S165-S172.
3. Chew EY, Mills JL, Metzger BE, et al; National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Metabolic control and progression of retinopathy: the Diabetes in Early Pregnancy Study. Diabetes Care. 1995;18(5):631-637.
4. Inkster ME, Fahey TP, Donnan PT, Leese GP, Mires GJ, Murphy DJ. Poor glycated haemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: systematic review of observational studies. BMC Pregnancy Childbirth. 2006;6:30.
5. Endocrine disorders. In: Beckmann CRB, Ling FW, Herbert WNP, et al. Obstetrics and Gynecology. 7th ed. Philadelphia, PA: Wolters Kluwer Lippincott Williams & Wilkins; 2014:chap 20.
6. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(suppl 1):S13-S28.
7. Bateman BT, Patorno E, Desai RJ, et al. Angiotensin-converting enzyme inhibitors and the risk of congenital malformations. Obstet Gynecol. 2017;129(1):174-184.
8. Bateman BT, Hernandez-Diaz S, Fischer MA, et al. Statins and congenital malformations: cohort study. BMJ. 2015;350:h1035.
9. Taguchi N, Rubin ET, Hosokawa A, et al. Prenatal exposure to HMG-CoA reductase inhibitors: effects on fetal and neonatal outcomes. Reprod Toxicol. 2008;26(2):175-177.
10. Berga SL, Nitsche JF, Braunstein GD. Endocrine changes in pregnancy. In: Melmed S, Polonski KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016:chap 21.
11. Gestational diabetes mellitus, screening. US Preventive Services Task Force. https://www.uspreventiveservicestaskforce.org/Page/
Document/UpdateSummaryFinal/gestational-diabetes-mellitus-screening. January 2014. Accessed April 1, 2019.
12. Gestational diabetes. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/basics/gestational.html. Reviewed July 25, 2017. Accessed April 1, 2019.