July 26th, 2020
Gestational diabetes melitus (GDM) is chronic hyperglycemia that is first recognized during pregnancy. This hyperglycemia, in most cases, is the result of impaired glucose tolerance secondary to pancreatic β-cell dysfunction, on a background of chronic insulin resistance.
GDM tends to develop during the second or third trimester. It is most often diagnosed during the universal screening for GDM conducted at 24-28 weeks of gestation.
Risk factor: age
A maternal age ≥40 years is associated with an increased risk of impaired glucose tolerance during pregnancy.
Risk factor: ethnicity
Women of African-American, Hispanic, Middle-Eastern, Native American, Pacific Islander, and South Asian origin are more likely to develop GDM.
Risk factor: past GDM
Around one-third of women with GDM develop the condition in a future pregnancy.
Risk factor: positive family history
The presence of a first-degree relative with diabetes mellitus or a sister with GDM increases the risk of developing GDM.
Risk factor: sedentary lifestyle
An inactive lifestyle and westernized diet are both modifiable risk factors for GDM.
Risk factor: dysglycemic medications
Regular treatment with corticosteroids, antipsychotics, or other medications with an anti-insulin effect is another modifiable risk factor for GDM.
Risk factor: high gestational weight gain
During the period of gestation, maternal weight gain >22 lb/year (>10kg/year) confers a more than two-fold increased risk for GDM.
Elevated body mass index
Obesity is a major modifiable risk factor for GDM.
High blood pressure
Both essential hypertension and gestational hypertension confer an increased risk for GDM. Conversely, women with GDM are at increased risk for preeclampsia.
Reasons for the development of hypertension include the increased weight gain secondary to hyperinsulinemia, and increased renal sodium retention.
Increased symphysis-fundal height
During routine antenatal care, symphysis-fundal height (SFH) estimation may be higher than expected for the gestational age, because of macrosomina, polyhydramnios, or both.
Macrosomia is due to fetal hyperinsulinemia secondary to maternal hyperglycemia and a continuous high transplacental flow of glucose.
Polyhydramnios occurs when the fetal hyperglycemia results in osmotic diuresis and polyuria; this disrupts the delicate balance between amniotic fluid production and resorption.
Signs of metabolic syndrome
These include signs such as acanthosis nigricans, abdominal obesity, and hypertension. The presence of these findings should prompt evaluation for GDM.
This is because GDM shares common features with metabolic syndrome, including insulin resistance, dyslipidemia, and endothelial dysfunction.
Signs of polycystic ovarian syndrome
Signs of polycystic ovarian syndrome (PCOS) include acne and hirsutism. Where present, these should prompt evaluation for GDM.
Importantly, while PCOS is not a risk factor for GDM, these patients have a 2.4-fold likelihood of developing GDM, versus women without PCOS. This is possibly because both conditions are related to being overweight.
Previously undiagnosed diabetes mellitus can be unmasked during pregnancy and be clinically and biochemically indistinguishable from GDM.
However, these patients will test positive for diabetes during the first trimester itself, and demonstrate persistent hyperglycemia even after the postpartum period. The presence of microvascular or macrovascular complications of diabetes immediately indicates this diagnosis.
Gestational impaired glucose tolerance
Gestational impaired glucose tolerance (GIGT) refers to impaired glucose tolerance that does not meet the diagnostic criteria for GDM. Other differences include relatively lower blood pressures and little or no dysfunction of lipid metabolism, versus patients with GDM.
Polyhydramnios due to other conditions
While GDM is a major cause of polyhydramnios, it is not the only cause. Fetal malformations (unrelated to the maternal diabetes), genetic anomalies, and fetal anemia are other potential causes.
First trimester screening
Screening for diabetes in the first trimester should be opportunistic and conducted as early as the first antenatal visit, especially in women considered to be at high-risk for diabetes.
GDM can be diagnosed if the fasting plasma glucose (FPG) is ≥92 mg/dL (≥5.1 mmol/L) but <126 mg/dL (<7 mmol/L). Note that a FPG ≥126 mg/dL during the first trimester indicates overt diabetes mellitus.
Second-trimester screening: one-step
Second trimester screening for GDM can be performed via the one-step approach. This involves administration of 75g oral glucose, followed by plasma glucose estimation at 0-hours, 1-hour and 2-hours. GDM can be diagnosed if at least one measurement is elevated as follows:
- 0-hour glucose: ≥92 mg/dL (≥5.1 mmol/L)
- 1-hour glucose: ≥180 mg/dL (≥10.0 mmol/L)
- 2-hour glucose: ≥153 mg/dL (≥8.5 mmol/L)
The one-step approach is preferred in patients who are at high-risk for GDM, as missed or delayed diagnosis of this group can increase the likelihood of adverse events. It is also recommended in patients fear frequent investigations, or if follow-up care is uncertain.
Second-trimester screening: two-step
Second trimester screening for GDM can also be performed via the two-step approach. In this, a 50g non-fasting oral glucose challenge test (OGCT) is first administered, followed by a 100g fasting oral glucose tolerance test (OGTT) test for women with a positive screening result.
A 1-hour OGCT plasma glucose level >140 mg/dL (>7.8 mmol/L) indicates a positive screening result. For OGTT positivity, at least two of the following threshold criteria must be met:
- 0-hour glucose: ≥95 mg/dL (≥5.3 mmol/ L)
- 1-hour glucose ≥180 mg/dl (≥10.0 mmol/L)
- 2-hour glucose ≥155 mg/dl (≥8.6 mmol/L)
- 3 hour glucose ≥140 mg/dl (≥7.8 mmol/ L)
The two-step approach is currently preferred by the American College of Obstetricians and Gynecologists (ACOG) and National Institutes for Health (NIH).
Prenatal ultrasound may show a fetus that is large for gestational age (LGA), i.e. with a length that is above the 90th percentile for its gestational age.
Urine glucose testing
Urine glucose testing is no longer recommended for screening, as physiological glycosuria is seen in around half of all pregnant women.
Once GDM has been diagnosed, ultrasound surveillance should commence at 28–30 weeks and continue until the late third trimester.
This aims to assess fetal growth and detect if it becomes large for gestational age (LGA). Fetal abdominal circumference is the most sensitive parameter in this regard.
Non-stress cardiotocography (CTG) should be performed in the third trimester, in patients with GDM severe enough to require pharmacological therapy. In patients with GDM responsive to diet alone, CTG is only indicated if additional complications are present.
Ideally, women should be educated regarding GDM once they reach childbearing age. This will help them make well-informed decisions regarding modifiable risk factors for the condition.
Lifestyle interventions are a key element of the management. These include: counselling on nutrition and exercise, a diet that has a low glycemic index, regular exercise, and self-monitoring of weight.
Good glycemic control
Target glucose values include:
- A fasting plasma glucose (FPG) that is ≤95 mg/dL (≤5.3 mmol/ L);
- A 1-hour postprandial glucose (PPG) that is ≤140 mg/dL (≤17.8 mmol/L); and,
- A 2-hour PPG that is ≤120 mg/ dL (≤6.7 mmol/L).
Self-monitoring of blood glucose levels is key to good glycemic control; the intensity of monitoring should be decided on case-to-case basis.
Patients should be weighed at every antenatal visit and evaluated for excessive gestational weight gain; the latter is an independent risk factor for fetal macrosomia and a major predictor of adverse pregnancy outcomes.
In general, induction of labour should not occur before 39 weeks, unless glycemic control is poor or there are other indications for delivery.
Cesarean section is preferred for fetuses who weigh ≥4500g; vaginal delivery is preferred in fetuses who are ≤4000g in weight.
Peripartum glucose monitoring
During the peripartum period the mother's plasma glucose levels should be monitored to ensure euglycemia. While GDM disappears almost immediately after birth, monitoring should continue until glycemic values have normalized.
Following birth, regular monitoring of neonatal plasma glucose levels is also important, to minimize the risk of neonatal hypoglycemia; the latter can result in severe and permanent neurological compromise.
Following birth, these women should be treated for persistent hyperglycemia at 4-12 weeks peripartum, via a 75g oral glucose tolerance test (OGTT).
Even where this is negative, these patients are at an increased lifetime risk for diabetes, and should be tested in this respect every 1-3 years, and screened for GDM in the first trimester of future pregnancies.
Pharmacologic therapy is indicated if:
- more than two values (at the same meal) during a two-week period are above target by >10 mg/dL (>0.6 mmol/L) despite lifestyle interventions; or,
- when 50% of the values in one week are found to be elevated despite lifestyle interventions.
Some experts recommend metformin as a first-line hypoglycemic agent. While the drug crosses the placenta, there are no reports of teratogenicity. Suitable candidates are women who refuse to take insulin, patients diagnosed with GDM for the first time, and individuals with a lower BMI.
Around half of all women treated with metformin eventually require supplemental insulin to achieve their glycemic targets.
Sulfonylureas (e.g., glyburide) are alternate first-line agents; they also have a lower failure rate vis-a-vis metformin. However, they are associated with higher birth weights and rates of neonatal hypoglycemia, possibly due to their insulin-secreting effects on the fetal pancreas.
Ideal candidates include women who refuse to take insulin, patients who are further along in their pregnancy (i.e., ≥25 weeks), and individuals with a singleton pregnancy.
Other anti-diabetic drugs
Metformin and sulfonlylureas are the only anti-diabetic drugs that have been proven to be safe in pregnancy. The use of other oral or injected agents is not currently recommended.
Insulin is required in women with uncontrolled hyperglycemia, despite lifestyle changes and/or oral medications, and in women who elect to avoid a trial of oral medications. It does not cross the placenta and it is safe for use in pregnancy.
Insulin requirements vary, but tend to plateau at 36–38 weeks. Currently, there is no evidence that any specific form of insulin is superior to the others; neither is there evidence favoring any particular insulin regimen.