Diabetes mellitus (DM) complicates approximately 6–7% of all pregnancies in the United States. The American Diabetes Association has classified glucose intolerance into three different types (Table 28.1). Gestational diabetes mellitus (GDM), or carbohydrate intolerance with onset or recognition during pregnancy, represents 90% of cases [1]. The White classification is another system for classifying diabetes in pregnancy (Table 28.2). White classification class A1 diabetes (GDMA1) represents pregnant women with gestational diabetes mellitus who are able to maintain glucose control with exercise and diet alterations. White classification class A2 diabetes (GDMA2) represents pregnant women with gestational diabetes who require medication therapy in order to maintain adequate glucose control.

Classification	Mechanism of disease	No insulin required	Insulin required	Insulin required for survival
Type I diabetes mellitus	Immunologic destruction of pancreas
Type II diabetes mellitus	Resistance of pancreatic cells
Gestational diabetes mellitus	Glucose intolerance not present prior to pregnancy

The remaining 10% include both Type 1 and Type 2 diabetes mellitus. This cohort accounts for over eight million women in the US alone at any given time. Type 1 pregestational DM (DM1) occurs as the result of an autoimmune process that destroys pancreatic B cells, leading to a need for insulin therapy [2]. Type 2 pregestational DM (DM2) is characterized by peripheral insulin resistance and insufficiency. The rising epidemic of DM2 is associated with the increasing rate of obesity and metabolic syndrome.

1. 2. What causes gestational diabetes?

Insulin resistance increase in pregnancy is largely related to an increase in placental hormones such as human placental lactogen (promotes lipolysis and decreased glucose uptake), prolactin, cortisol (insulin antagonist), tumor necrosis factor α, leptin, and placental growth hormone. Estrogen and progesterone further disrupt mechanisms of glucose and insulin [3]. Insulin sensitivity is greatest at the end of the first trimester, with the greatest risk of maternal hypoglycemia, and lowest insulin sensitivity in the third trimester, the time of greatest insulin requirement. A decrease in maternal exercise and an increase in caloric intake and altered adipose deposition compound glucose intolerance in pregnancy.

1. 3. In pregnant patients, what are the best strategies for screening for diabetes?

All pregnant women who do not have a diagnosis of pregestational diabetes should be routinely screened for gestational diabetes at 24–28 weeks gestation. However, some debate exists over the optimal screening approach. The International Association of Diabetes and Pregnancy Study Groups (IADPSGs) recommend a one‐step testing approach using the 75 g two‐hour oral glucose tolerance test (GTT). A positive test results occurs if any single threshold is abnormal: fasting value 92 mg ml⁻¹, one‐hour value 180 mg dl⁻¹, two‐hour value 152 mg dl⁻¹.

The American College of Obstetricians and Gynecologists (ACOG) recommends the two‐step approach. This involves a 50 g oral glucose challenge test (GCT), followed by a 100‐g three‐hour oral GTT in screen positive women (Table 28.3). A threshold of ≥130 mg dl⁻¹ (7.5 mmol l⁻¹) to ≥140 mg dl⁻¹ (7.8 mmol l⁻¹) may be used to determine candidates for the 3‐hour oral GTT dependent on institutional preference [2]. If a patient has a value of ≥200 mg dl⁻¹, they do not require the 3‐hour test for confirmation and are diagnosed with GDM.

For women at high risk of pregestational diabetes but who do not carry this diagnosis upon initiation of prenatal care, consideration should be given to screening for diabetes in the first trimester. Women with risk factors including obesity, known impaired glucose tolerance or a past history of GDM are candidates for early screening [4].

Early screening may include A1C analysis. A value >6.5% (>48 mmol mol⁻¹) is diagnostic of T2DM. In addition, a fasting glucose of >126 mg dl⁻¹ or a GCT of >200 mg dl⁻¹ are also diagnostic of T2DM [5].

1. 4. What are the potential adverse effects of diabetes on the fetus and how should the fetus be monitored?

Adverse outcomes associated with DM in pregnancy include pre‐eclampsia, hydramnios, macrosomia, or large for gestational age infant, maternal or infant birth trauma, operative delivery, neonatal respiratory problems, and metabolic complications such as hypoglycemia, hyperbilirubinemia, hypocalcemia, and erythremia, and fetal demise. In addition, if a mother is hyperglycemic during organogenesis, there is significantly increased risk of miscarriage and congenital anomalies [6–8].

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