One in six live births (16.8%) are to women with some form of hyperglycemia in pregnancy. The majority (84%) of these cases are due to gestational diabetes mellitus (GDM), with the remainder due to preexisting type 1 and type 2 diabetes.2
Pregnancies complicated by diabetes are at increased risk for maternal and neonatal morbidities including spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, and neonatal hypoglycemia.3
Glycemic control is the cornerstone of management of any diabetic pregnancy. Insulin is a traditional, safe, and effective medication used for this purpose. Rapid, intermediate, and long-acting insulin are all considered safe for use in pregnancy.4
Although not recommended for use because of concern about possible teratogenic effects, glyburide and metformin are often used in pregnancy due to patient request or physician discretion. Neither metformin nor glyburide is U.S. Food and Drug Administration (FDA) approved for use in pregnancy.5
Neither drug has been associated with birth defects or short-term adverse neonatal outcomes. However, data on long-term metabolic effects on children with in utero exposure are limited.4
Insulin is considered the first-line therapy for the treatment of diabetes in pregnancy.5
Gestational Diabetes Mellitus
Although controversial, GDM has been defined as “glucose intolerance with onset or first recognition in pregnancy.”6
The prevalence of GDM varies between 1% and 28%, and GDM is a strong risk factor for subsequent permanent diabetes development in the mother.2,6
Maternal risk factors for GDM have been identified (Table 6.1
All pregnant women should be screened for diabetes early in the pregnancy and receive oral glucose tolerance testing between 24 and 28 weeks of gestation. Management of GDM begins with nonpharmacologic approaches such as dietary modifications, exercise, and glucose monitoring. Studies show that 70% to 85% of women diagnosed with GDM can control it with lifestyle modification alone.3
If lifestyle modification fails to achieve glucose control, insulin is the first line of therapy. Metformin and glyburide may be considered in special circumstances.2
Diabetic ketoacidosis (DKA) has been reported to complicate 0.5% to 3% of diabetic pregnancies.7
It usually occurs in patients with type 1 diabetes mellitus, especially of new onset, but may also affect women with type 2 diabetes and rarely women with GDM. It most commonly occurs in the first trimester, although it may occur at any point throughout the pregnancy. Pregnancies complicated by DKA have a 9% to 36% rate of fetal loss.7
Pregnant women are at greater risk for DKA than nonpregnant diabetic women. Factors predisposing the pregnant patient to DKA include increased production of hormones that are insulin antagonists—human placental lactogen, prolactin, and cortisol, an accelerated starvation state, and decreased buffering capacity due to the compensatory respiratory alkalosis of pregnancy. The nausea that frequently accompanies pregnancy may also lead to decreased caloric intake. Common precipitants of DKA in pregnancy include hyperemesis gravidarum, a concomitant viral or bacterial infection, noncompliance with insulin dosing, and concurrent use of medications such as beta-sympathomimetic agents for tocolysis, and steroids used for fetal lung maturation.
The metabolic profile of DKA is the result of an exaggerated counterregulatory response to a perceived lack of glucose. Without adequate insulin availability, cells enter a state of starvation, which in turn activates energy-producing pathways (Figure 6.1
). The symptoms of DKA in pregnancy are no different from those experienced by nonpregnant women, except that they tend to develop more rapidly in pregnancy. Patients typically present with malaise, nausea, vomiting, polydipsia, polyuria, tachypnea, and physical signs of dehydration such as dry mucous membranes, tachycardia, and hypotension. The classic fruity smell of acetone may be noted on the breath. Because perfusion may be compromised resulting in ischemia, patients may present with
abdominal pain. In severe cases, patients may present with altered consciousness, usually in the setting of extreme hyperglycemia.
TABLE 6.1 Risk Factors for Gestational Diabetes Mellitus
Gestational diabetes mellitus in previous pregnancy
Macrosomia in previous pregnancy
Body mass index > 30 kg/m2
Weight gain of more than 5 kg since 18 years of age
Excessive gestational weight gain
Polycystic ovarian syndrome
Maternal age older than 35 years
Diabetes in first-degree relative
Asian, Native American, Pacific Islander, Black, Hispanic
Figure 6.1: Pathophysiology of diabetic ketoacidosis in pregnancy.
Laboratory evaluation of DKA is characterized by the triad of hyperglycemia, anion gap metabolic acidosis, and ketosis. Initial testing should include a complete blood cell count, urinalysis, serum glucose, electrolytes, blood urea nitrogen, creatinine, and ketones. Serum pH should be measured by arterial or venous blood gases if serum ketones are present or if there is an elevated anion gap. The presence of serum ketones and an arterial pH < 7.30 with an anion gap greater than 12 mEq/L is characteristic of DKA. Falsely normal or elevated serum potassium levels may be present; however, most patients have a low total body potassium that will become apparent with treatment. Blood urea nitrogen and creatinine levels may be elevated as a result of dehydration and renal dysfunction. The serum glucose level is usually higher than 300 mg/dL, but lower levels are not uncommon during pregnancy. Euglycemic ketoacidosis is a rare phenomenon that has been described in pregnancy. In this condition, ketoacidosis occurs in the absence of pronounced hyperglycemia.
TABLE 6.2 Management of Diabetic Ketoacidosis in Pregnancy
0.9% sodium chloride 1-2 L/h × 2 h, then 250 mL/h
In cases of hypernatremia, use 0.45% sodium chloride
Potassium: if normal or low, replace at a rate of 15-20 mEq/h; if high, wait until it drops to within normal range, then replace at a rate of 20-30 mEq/h
Bicarbonate: only indicated if serum pH < 7. Infuse at a rate of 44 mEq/h
Infuse intravenously at a rate of 0.1 units/kg/h. May bolus with 10-15 units before beginning the infusion
Begin infusion of 5% dextrose when glucose levels drop <250 mg/dL
The management principles for DKA in pregnancy are the same as in the nonpregnant patient (Table 6.2
). Aggressive volume replacement, intravenous insulin therapy, correction of acidosis as well as electrolyte abnormalities, and management of the underlying pathology are the cornerstones of treatment. The serum glucose levels should be checked every hour and serum electrolytes and ketones checked every 2 hours during treatment. All pregnancies beyond 24 weeks’ gestation should have continuous fetal monitoring during treatment.