Treating two: Effective management of gestational diabetes

Growing rates of adult obesity and updated diagnosis guidelines have recently put gestational diabetes mellitus (GDM) in the spotlight.

The American Diabetes Association (ADA; www.diabetes.org) defines GDM as a condition affecting pregnant women who have never had diabetes before but have high blood glucose levels during pregnancy. GDM develops when the body is unable to make and use all the insulin that is essential for pregnancy. According to ADA estimates, it affects 18% of pregnancies.

If not properly controlled, GDM doesn't just present a health risk for the patient; it also puts the unborn child at risk and, according to experts, can cause macrosomia (excessive birth weight) or birth trauma. Under some circumstances, it could require a cesarean delivery.

"This is not your typical diabetic patient, because there is another person involved," said Jamie Terrell, PharmD, assistant professor at the ULM College of Pharmacy–Shreveport Campus, Louisiana. "If you are just treating someone with type 2 diabetes, you are just treating them. If you treat someone with gestational diabetes, you are not only treating them, you are treating the baby, as well."

Diagnosing the disease

Although physicians’ offices may differ somewhat in their testing practices, Terrell said, it is recommended that pregnant women with certain characteristics be tested for the disease as a matter of course.

These factors include an age of more than 25 years, obesity, a family history of diabetes, a previous stillbirth or delivery of an infant weighing more than 4 kg (8.8 lbs), a history of glucose intolerance, current glycosuria (glucose excreted into the urine), or membership in certain ethnic groups.

Recommendations for how patients are tested for the disease changed in 2011, when the ADA updated its diagnostic criteria for GDM to support the use of a two-hour, 75-g glucose challenge.

"It actually has more stringent guidelines, so they think that they will capture more people with diabetes," Terrell said.

Previously, ADA had recommended a one-hour, 50-g challenge, followed by a three-hour, 100-g challenge for those women who failed the initial test.

The new testing guidelines aren't always being used in practice, Terrell said.  

"From what I understand, the reason that many physicians are still doing the 3-hour (challenge) as opposed to just the two-hour (challenge) is because the American College of Obstetricians and Gynecologists does not support the two-hour as of yet," she said.

Women are diagnosed with GDM if they fall into any one of three categories: those with a fasting plasma glucose value ≥ 92 mg/dL, a one-hour glucose value ≥180 mg/dL, or a two-hour glucose value ≥153 mg/dL.

Therapy goals

The primary goal of therapy for patients with GDM is to reduce for both mother and infant the possible risks associated with the disease.

"You are going to want to keep them as close to normal as you can," says Tibb Jacobs, PharmD, BCPS, a clinical associate professor at the ULM College of Pharmacy–Shreveport Campus.

She said a reasonable glycemic goal for patients should be a fasting glucose value of approximately 80 mg/dL to 130 mg/dL or a postprandial glucose level <180 mg/dL. If patients aren't able to reach reasonable levels through diet alone, she said medication may be necessary.

Identifying and treating GDM during a pregnancy is central to reducing the overall risks to both mother and unborn baby. For instance, if the GDM is undiagnosed or not treated, Terrell said the baby could develop macrosomia, becoming excessively larger than average. She said babies who develop macrosomia are not only large; they also have disproportional fat distribution, which leads to a large shoulder and chest area that can create a risk of trauma to the baby during birth or cause the need for a caesarean section.

According to Terrell, some research has found that hemoglobin A1c (HbA1c) greater than 12 in a pregnant woman carries a risk of fetal malformation or birth defects equal to that of certain teratogens.

"It's a very serious thing that you want to get under control," she said.

Babies can also have hypoglycemia after the delivery, so testing the baby after birth is essential.

The risks associated with GDM don't just end after pregnancy. According to information from the National Diabetes Information Clearinghouse (diabetes.niddk.nih.gov), women who have had GDM have a 35% to 60% chance of developing type 2 diabetes mellitus over the next 10 to 20 years. The diagnosis also increases the infant’s risk of developing diabetes at some point in its life, Terrell said.

Effect of obesity

Both obesity and GDM have been found to increase the risk of adverse pregnancy outcomes in patients, but when the two are combined, the risks are even greater.

“They are going to be considered more high-risk pregnancy,” said Jacobs, adding that women who are both obese and have GDM are at greater risk of having a larger baby or having more pregnancy complications than those without GDM.

There is no definitive standard for the amount of weight these patients should gain during pregnancy. Typically, Jacobs said, obese patients are counseled to gain anywhere from 11 to 20 pounds during pregnancy, but that is a fairly large range, she said, and the numbers often differ, depending on the physician.

It is likely that obese patients who also have gestational diabetes will be given calorie restrictions, Terrell said, to prevent them from gaining too much weight during pregnancy and raising their risk of complications.

Treatment options

Patients’ daily self-monitoring of blood glucose levels is recommended, to enable better tracking of patients with GDM; however, Terrell and Jacobs said, the frequency of monitoring has not been definitively established.

"I think that's probably doctor-specific," said Terrell, who was diagnosed with GDM herself during her first pregnancy. "Ideally, if they are on insulin, [patients should test] three or four times a day, probably."

Before moving to medication, doctors usually try to control GDM through medical nutrition therapy. This involves restricting a patient’s sugar and carbohydrates each day as would be done with a type 2 diabetes patient. It also could include calorie restriction for those patients who are considered obese.

"Most doctors are trying to control it with diet as much as they can, and with your patients that are very contentious you can do that, but it's hard," Jacobs said.

Drug therapy

When diet alone fails to control GDM, physicians move to medication therapy. There is no standard for when to add medication, Jacobs said, but it's typically done when a patient is consistently unable to stay within the optimal glycemic levels her doctor has established.

While an oral agent such as metformin is often a starting point for newly diagnosed patients with type 2 diabetes, Terrell said, it is not typically used with pregnant patients, owing to a potential risk to the fetus and a lack of available safety data.

For GDM, insulin is typically the primary treatment and the one for which the most safety data is available.

"It's a naturally occurring hormone that your body makes anyway, so there's no risk to the fetus, other than hypoglycemia in the mother," Terrell said.

Most of the data for using insulin in GDM patients centers around neutral protamine Hagedorn (NPH), Jacobs said.

"Normally, you'll start with once- or twice-daily NPH dose and then adjust from the blood glucose levels," she said. "You wouldn't have to add the shorter-acting right away, if you didn't need to."

While research did not initially focus on short-acting insulin agents, Jacobs said, research has recently been conducted with insulin analogues such as insulin lispro and insulin aspart, and both drugs are now considered in the pregnancy category B.

Whether a patient is prescribed a long-acting or a short-acting insulin, the exact dosage amount varies according to the patient.

"Insulin is completely patient-specific," Terrell said. "Some patients might need only 5 or 10 units, some patients might need 100 units. An adjustment would be based on their checking their blood glucose."

Glyburide, a second-generation sulfonylurea, is also a choice for GDM patients, although there isn't as much data available on its use in pregnancy, Terrell said.

"Some patients don't want insulin. They don't want to inject themselves, even though that is the safest drug, so glyburide is used for some patients," she said.

Post-pregnancy

GDM resolves in most patients after birth, but, according to data from the Centers for Disease Control and Prevention, about 5% to 10% of women who had GDM are found to have diabetes immediately after birth.

For this reason, it's important to continue monitoring a patient's glucose levels immediately after pregnancy. Terrell said it is recommended that patients who have had GDM be screened for overt diabetes between 6 and 12 weeks postpartum.

Jill Sederstrom is a freelance writer in Kansas City.