12. Management of Diabetes in Pregnancy

For guidelines related to the diagnosis of gestational diabetes mellitus (GDM), please refer to Section 2. Classification and Diagnosis of Diabetes.

Recommendations

• Provide preconception counseling that addresses the importance of tight control in reducing the risk of congenital anomalies with an emphasis on achieving A1C <7%, if this can be achieved without hypoglycemia. B

• Potentially teratogenic medications (ACE inhibitors, statins, etc.) should be avoided in sexually active women of childbearing age who are not using reliable contraception. B

• GDM should be managed first with diet and exercise, and medications should be added if needed. A

• Women with pregestational diabetes should have a baseline ophthalmology exam in the first trimester and then be monitored every trimester as indicated by degree of retinopathy. B

• Due to alterations in red blood cell turnover that lower the normal A1C level in pregnancy, the A1C target in pregnancy is <6% if this can be achieved without significant hypoglycemia. B

• Medications widely used in pregnancy include insulin, metformin, and glyburide; most oral agents cross the placenta or lack long-term safety data. B

Diabetes in Pregnancy

The prevalence of diabetes in pregnancy has been increasing in the U.S. The majority is GDM with the remainder divided between pregestational type 1 diabetes and type 2 diabetes. Both pregestational type 1 diabetes and type 2 diabetes confer significantly greater risk than GDM, with differences according to type as outlined below.

Preconception Counseling

All women of childbearing age with diabetes should be counseled about the importance of strict glycemic control prior to conception. Observational studies show an increased risk of diabetic embryopathy, especially anencephaly, microcephaly, and congenital heart disease, that increases directly with elevations in A1C. Spontaneous abortion is also increased in the setting of uncontrolled diabetes. While observational studies are confounded by the relationship between elevated periconceptional A1C and other poor self-care behaviors, the quantity and consistency of data are convincing, and the recommendation remains to aim for an A1C <7% prior to conception to minimize risk (1,2). There are opportunities to educate adolescents of reproductive age with diabetes about the risks of unplanned pregnancies and the opportunities for healthy maternal and fetal outcomes with pregnancy planning (3).

Targeted preconception counseling visits should include routine rubella, rapid plasma reagin, hepatitis B virus, and HIV testing as well as Pap smear, cervical cultures, blood typing, and prescription of prenatal vitamins (with at least 400 μg of folic acid). Diabetes-specific management should include A1C, thyroid-stimulating hormone, creatinine, and urine albumin-to-creatinine ratio testing; review of the medication list for potentially teratogenic drugs (i.e., ACE inhibitors, statins); and referral for an ophthalmologic exam.

Specific risks of uncontrolled diabetes include fetal anomalies, preeclampsia, macrosomia, intrauterine fetal demise, neonatal hypoglycemia, and neonatal hyperbilirubinemia, among others. In addition, diabetes in pregnancy increases the risk of obesity and type 2 diabetes in offspring later in life (4,5).

Glycemic Targets in Pregnancy

The goals for glycemic control for GDM are based on recommendations from the Fifth International Workshop-Conference on Gestational Diabetes Mellitus (6) and have the following targets for maternal capillary glucose concentrations:

• Preprandial ≤95 mg/dL (5.3 mmol/L) and either

• One-hour postmeal ≤140 mg/dL (7.8 mmol/L) or

• Two-hour postmeal ≤120 mg/dL (6.7 mmol/L)

For women with preexisting type 1 diabetes or type 2 diabetes who become pregnant, the following are recommended as optimal glycemic goals if they can be achieved without excessive hypoglycemia (7):

• Premeal, bedtime, and overnight glucose 60–99 mg/dL (3.3–5.4 mmol/L)

• Peak postprandial glucose 100–129 mg/dL (5.4–7.1 mmol/L)

• A1C <6.0%

Metabolic physiology of pregnancy is characterized by fasting hypoglycemia due to insulin-independent glucose uptake by the placenta, postprandial hyperglycemia, and carbohydrate intolerance as a result of diabetogenic placental hormones. In addition, insulin resistance increases exponentially during the second trimester and levels off toward the end of the third trimester.

Reflecting this physiology, pre- and postprandial monitoring of blood glucose is recommended to achieve metabolic control. The American College of Obstetricians and Gynecologists (ACOG) recommends the following targets: fasting <90 mg/dL, preprandial <105 mg/dL, 1-h postprandial <130–140 mg/dL, and 2-h postprandial <120 mg/dL. If women cannot achieve these targets without significant hypoglycemia, the American Diabetes Association (ADA) suggests consideration of slightly higher targets: fasting <105 mg/dL, 1-h postprandial <155 mg/dL, and 2-h postprandial <130 mg/dL. Until harmonization of these guidelines is achieved, the ADA recommends setting targets based on clinical experience, individualizing care, as needed.

Due to increases in red blood cell turnover associated with pregnancy, A1C levels fall during pregnancy. Additionally, as A1C represents an average, it may not fully capture physiologically relevant glycemic parameters in pregnancy. A1C should be used as a secondary measure, next to self-monitoring of blood glucose. The recommended A1C target in pregnancy is <6% if this can be achieved without hypoglycemia. Given the alteration in red blood cell kinetics during pregnancy, A1C levels may need to be monitored more frequently than usual (e.g., monthly).

Pregnancy and Antihypertensive Drugs

In a pregnancy complicated by diabetes and chronic hypertension, target blood pressure goals of systolic blood pressure 110–129 mmHg and diastolic blood pressure 65–79 mmHg are reasonable, as they contribute to improved long-term maternal health. Lower blood pressure levels may be associated with impaired fetal growth. During pregnancy, treatment with ACE inhibitors and angiotensin receptor blockers is contraindicated because they may cause fetal damage. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, diltiazem, clonidine, and prazosin. Chronic diuretic use during pregnancy has been associated with restricted maternal plasma volume, which may reduce uteroplacental perfusion (8).

Management of Gestational Diabetes Mellitus

As highlighted in Section 2. Classification and Diagnosis of Diabetes, GDM is characterized by increased risk of macrosomia and birth complications, without a risk threshold (9). Treatment starts with medical nutrition therapy, exercise, and glucose monitoring aiming for the targets described previously. A total of 70 to 85% of women diagnosed with GDM under older criteria can control GDM with lifestyle modification alone; it is anticipated that this number will increase using the lower International Association of the Diabetes and Pregnancy Study Groups (IADPSG) thresholds. Treatment has been demonstrated to improve perinatal outcomes in randomized studies and in a U.S. Preventive Services Task Force review (10). Historically, insulin has been the recommended treatment for GDM in the U.S. Randomized controlled trials support the efficacy and short-term safety of glyburide (11) (pregnancy category B) and metformin (12,13) (pregnancy category B) for the treatment of GDM. However, both agents cross the placenta, and long-term safety data are not available (14). Insulin also may be used and should follow the guidelines below.

Management of Pregestational Type 1 Diabetes and Type 2 Diabetes in Pregnancy

Postpartum Care