Normal pregnancy can be characterized as a state of increased insulin resistance that helps ensure a steady stream of glucose delivery to the developing fetus. Thus, both mild fasting hypoglycemia and postprandial hyperglycemia are physiologic. These metabolic changes are felt to be hormonally mediated with likely contributions from human placental lactogen, estrogen, and progesterone.
A. Gestational Diabetes Mellitus
Gestational diabetes mellitus is abnormal glucose tolerance in pregnancy and is generally believed to be an exaggeration of the pregnancy-induced physiologic changes in carbohydrate metabolism. Alternatively, pregnancy may unmask an underlying propensity for glucose intolerance, which will be evident in the nonpregnant state at some future time if not in the immediate postpartum period. Indeed, at least 50% of women with gestational diabetes are diagnosed with overt diabetes at some point in their lifetime. During the pregnancy, the principal concern in women identified to have gestational diabetes is excessive fetal growth, which can result in increased maternal and perinatal morbidity. Shoulder dystocia occurs more frequently in infants of diabetic mothers because of fetal overgrowth and increased fat deposition on the shoulders. Cesarean delivery and preeclampsia are also significantly increased in women with diabetes, both gestational and overt.
All asymptomatic pregnant women should undergo laboratory screening for gestational diabetes after 24 weeks’ gestation. The diagnostic thresholds for glucose tolerance tests in pregnancy are not universally agreed upon, and importantly, adverse pregnancy outcomes appear to occur along a continuum of glucose intolerance even if the diagnosis of gestational diabetes is not formally assigned. A two-stage testing strategy is recommended by the American College of Obstetricians and Gynecologists, starting with a 50-g screening test offered to all pregnant women at 24–28 weeks’ gestation. If this test is abnormal, the diagnostic test is a 100-g oral glucose tolerance test (Table 19–4).
Table 19–4.Screening and diagnostic criteria for gestational diabetes mellitus. ||Download (.pdf) Table 19–4. Screening and diagnostic criteria for gestational diabetes mellitus.
Screening for gestational diabetes mellitus
50-g oral glucose load, administered between 24 and 28 weeks, without regard to time of day or time of last meal.
Venous plasma glucose measured 1 hour later.
Value of 140 mg/dL (7.8 mmol/L) or above in venous plasma indicates the need for a diagnostic glucose tolerance test.
Diagnosis of gestational diabetes mellitus
100-g oral glucose load, administered in the morning after overnight fast lasting at least 8 hours but not more than 14 hours, and following at least 3 days of unrestricted diet (> 150 g carbohydrate) and physical activity.
Venous plasma glucose is measured fasting and at 1, 2, and 3 hours. Patient should remain seated and should not smoke throughout the test.
The diagnosis of gestational diabetes is made when two or more of the following venous plasma concentrations are met or exceeded: fasting, 95 mg/dL (5.3 mmol/L); 1 hour, 180 mg/dL (10 mmol/L); 2 hours, 155 mg/dL (8.6 mmol/L); 3 hours, 140 mg/dL (7.8 mmol/L).
Women in whom gestational diabetes is diagnosed should undergo nutrition counseling, and medications are typically initiated for those with persistent fasting hyperglycemia. Insulin has historically been considered the standard medication used to achieve glycemic control. Oral hypoglycemic agents, principally glyburide and metformin, have been evaluated in short-term clinical trials and appear to achieve similar degrees of glycemic control to insulin without increasing maternal or neonatal morbidity. These medications, however, have not been approved by the US Food and Drug Administration for this indication; the long-term safety of oral agents has not been adequately studied in the women or in their offspring, and study quality of these agents has been poor. The current standard of care is insulin, unless circumstances preclude its use. In those cases, metformin is a reasonable choice. Insulin regimens commonly include multiple daily injections of a split-dose mix of intermediate-acting and short-acting agents. Regular and NPH insulins, as well as insulin lispro and aspart, do not cross the placenta. Once therapy is initiated, blood glucose surveillance is important to assess for adequacy of glycemic control. Capillary blood glucose levels should be checked four times per day, once fasting and three times after meals. Euglycemia is considered to be 60–90 mg/dL (3.3–5.0 mmol/L) while fasting and less than 120 mg/dL (6.7 mmol/L) 2 hours postprandially. Intensive therapy with dietary modifications or insulin therapy, or both, has been demonstrated to decrease rates of macrosomia, shoulder dystocia, and preeclampsia. Because of the increased prevalence of overt diabetes in women identified to have gestational diabetes, they should be screened at 6–12 weeks’ postpartum with a fasting plasma glucose test or a 2-hour oral glucose tolerance test (75-g glucose load).
B. Overt Diabetes Mellitus
Overt diabetes is diabetes mellitus that antedates the pregnancy. There is an inverse relationship between glycemic control and the occurrence of fetal malformations, and women whose periconceptional glycosylated hemoglobin levels are at or near normal levels have rates of malformations that approach baseline. In gestational diabetes, fetal overgrowth from inadequately controlled hyperglycemia remains a significant concern because of the increased maternal and perinatal morbidity that accompany macrosomia. Women with overt diabetes are subject to a number of other complications as well. Spontaneous abortions and third-trimester stillbirths occur with increased frequency in these women. There is also at least a twofold to threefold increased risk for fetal malformations, as hyperglycemia during organogenesis is teratogenic. The most common malformations in offspring of diabetic women are cardiac, skeletal, and neural tube defects. For the mother, the likelihood of infections and pregnancy-related hypertension is increased.
Preconception counseling and evaluation in a diabetic woman is ideal to maximize the pregnancy outcomes. This provides an opportunity to optimize glycemic control and evaluate for evidence of end-organ damage. The initial evaluation of diabetic women should include a complete chemistry panel, HbA1c determination, 24-hour urine collection for total protein and creatinine clearance, funduscopic examination, and an ECG. Hypertension is common and may require treatment. Optimally, euglycemia should be established before conception and maintained during pregnancy with daily home glucose monitoring by the patient. A well-planned dietary program is a key component, with an intake of 1800–2200 kcal/day divided into three meals and three snacks. Insulin is given subcutaneously in a split-dose regimen as described above for women with gestational diabetes. The use of continuous insulin pump therapy may be helpful for some patients (see Chapter 27).
Throughout the pregnancy, diabetic women should be seen every 2–3 weeks and more frequently depending on the clinical condition. Adjustments in the insulin regimen may be necessary as the pregnancy progresses to maintain optimal glycemic control. A specialized ultrasound is often performed around 20 weeks to screen for fetal malformations. Symptoms and signs of infections should be evaluated and promptly treated. In the third trimester, fetal surveillance is indicated, and women with diabetes should receive serial antenatal testing (usually in the form of a nonstress test or biophysical profile). The timing of delivery is dictated by the quality of diabetic control, the presence or absence of medical complications, and fetal status. The goal is to reach 39 weeks (38 completed weeks) and then proceed with delivery. Confirmation of lung maturity may be appropriate if preterm delivery is contemplated.
American College of Obstetricians and Gynecologists. Practice Bulletin No. 201: Pregestational Diabetes Mellitus. Obstet Gynecol. 2018 Dec;132(6):e228–48.
American College of Obstetricians and Gynecologists. Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018 Feb;131(2):e49–64.
et al. Diabetic ketoacidosis complicating pregnancy. J Neonatal Perinatal Med. 2017;10(1):17–23.
et al. Induction of labor before 40 weeks is associated with lower rate of cesarean delivery in women with gestational diabetes mellitus. Am J Obstet Gynecol. 2016 Mar;214(3):364.e1–8.