Pregnancy Complicated by Diabetes Mellitus

Screening and Diagnosis

Screening and diagnosing GDM have a long history of controversy, related mainly to significant implications on health care costs, the effect on obstetric interventions, and whether diagnosis and treatment of GDM will improve maternal and perinatal outcomes. In 2001, the American College of Obstetricians and Gynecologists (ACOG) recommended that all pregnant women should be screened for GDM, whether by patient history, clinical risk factors, or a glucose challenge test. The latter is comprised of a “two step” method consisting of a 50-g, 1-hour glucose challenge test (GCT) and a 100-g, 3-hour oral glucose tolerance test (OGTT) for a definitive diagnosis. However, in 2003, the US Preventive Services Task Force (USPSTF) and the Cochrane Collaboration found insufficient evidence to recommend for or against screening for GDM, similar to the conclusions reached in 2008; namely, that insufficient evidence exists to balance between the benefits and harms of screening for gestational diabetes. In the same year, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Group published the results of a large, multicenter observational study designed to examine the relationship between maternal hyperglycemia less severe than overt GDM and adverse pregnancy outcome. This study clearly demonstrated a relationship between increased maternal blood glucose and birth weight, cord blood C-peptide (a measure for intrauterine fetal hyperinsulinemia), neonatal hypoglycemia, and delivery by cesarean section.

The International Association of Diabetes in Pregnancy Study Group recommended in 2007 a simplified “one step” approach to the screening and diagnosis of GDM with a 75-g, 2-hour glucose tolerance test. Although implementation of these guidelines would presumably double the number of patients diagnosed with GDM, no evidence exists that this will lead to clinically significant improvement in maternal and neonatal outcomes. Regardless of these reservations, universal screening for GDM was adopted by more than 90% of practices.

In the sequential “two step” testing, a 50-g GCT is performed in pregnant women between 24 and 28 weeks’ gestation unless a high risk for developing GDM exists (glycosuria, diabetes in first-degree relative, history of glucose intolerance, previous GDM, marked obesity, and previous infant with macrosomia). At-risk women should be screened by the 50-g GCT at their first prenatal visit. Screening cutoff values are 130 mg/dL (7.20 mmol/L; 90% sensitivity) or 140 mg/dL (7.75 mmol/L; 80% sensitivity). Random or fasting glucose measurement is not recommended for screening because of poor specificity.

In women who screen positive, a 100-g, 3-hour OGTT is used to diagnose GDM. Gestational diabetes is diagnosed if two or more plasma glucose measurements are abnormal. The World Health Organization and the American Diabetes Association recommend simultaneous screening and diagnosis using a 75-g OGTT ( Table 18.1 ).

The interested reader will find more information about the controversial diagnosis of GDM elsewhere.

Antenatal Management

Despite uncertainty regarding the clinical value of treating GDM, data strongly suggest that treatment may reduce adverse maternal and neonatal outcomes. The Australian Carbohydrate Intolerance Study in Pregnant Women randomized patients to receive either routine care or treatment for GDM. Primary fetal outcomes included death, shoulder dystocia and its consequences such as bone fracture, and nerve palsy. Primary maternal outcomes were induction of labor and cesarean delivery. Infants of women in the treatment group had significantly fewer perinatal complications (RR 0.33; 95% CI 0.14, 0.75). There were more labor inductions in the treatment group (RR 1.36; 95% CI 1.15, 1.62), but the number of cesarean deliveries was similar in both groups. Further evidence of possible adverse effects associated with even mild maternal hyperglycemia comes from the HAPO trial. The results of this trial point to a linear correlation between increasing maternal glucose levels and increasing birth weight, primary cesarean delivery, fetal C-peptide levels, and neonatal hypoglycemia. Most clinicians use glucose targets as defined by the Fifth International Workshop-Conference on Gestational Diabetes Mellitus ( Table 18.2 ).

Diabesity is a relatively new term denoting the combination of diabetes and obesity. In a recent large population based study, Blickstein et al. found that the ill-effect of pregravid obesity is greater than that of GDM. Obesity, with and without GDM, increased the odds of having chronic hypertension, whereas preeclampsia appears to be influenced by obesity only, as were the risk of births at <33 weeks’ gestation, of birth weight >4000 g, low 5-minute Apgar scores, and neonatal intensive care unit (NICU) admissions. They concluded that obesity (without diabetes) is more frequently associated with adverse perinatal outcomes than GDM in nonobese mothers. They argued that a campaign to decrease pregravid obesity should have at least the same priority as any campaign to control GDM. Interestingly, this effect of diabesity was not found in twin pregnancies.

Treatment

First-line therapy for women with gestational diabetes (the so-called GDM-A1) is nutritional and lifestyle modification; however, the impact on patient outcome has not been conclusively demonstrated in large randomized controlled trials. Pharmacotherapy is indicated when nutritional control is inadequate (the so-called GDM-A2), especially in patients with elevated fasting glucose levels, since diet is largely ineffective in this metabolic presentation. The ACOG and the American Diabetes Association recommends insulin therapy for women in whom the fasting glucose level exceeds 95 mg/dL, 1-hour postprandial glucose level is greater than 130-140 mg/dL, or 2-hour postprandial glucose level is greater than 120 mg/dL (6.65 mmol/L). Intermediate- and short-acting insulins served as the first-line therapy for GDM for many years; however, long-acting insulin was approved for use during pregnancy with its clear advantages in measures of patient compliance.

A safe and effective oral agent for the treatment of gestational diabetes is highly desired. Research efforts have focused on the effectiveness, safety, and placental metabolism of sulfonylurea glyburide. Despite a large number of studies, the absolute number of patients is relatively small and currently glyburide is classified as FDA class C (i.e., animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks). Nevertheless, glyburide therapy is a viable alternative for women who are unable or unwilling to take insulin, and it is used in many practices as first-line therapy.

Metformin (Glucophage) may be another option for women with GDM. Although metformin clearly crosses the placenta, it is classified as FDA class B (i.e., animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women).

Further research is needed to establish the role of oral hypoglycemic medications in the treatment of GDM either as a first-line therapy or in addition to insulin.

Fetal Surveillance

Gestational diabetes mellitus is associated with increased perinatal morbidity and mortality. In an attempt to reduce the risk of adverse outcome, prenatal surveillance, including assessment of fetal well-being and growth as well as screening for congenital anomalies, is recommended.