Diabetes Forecast January 2004

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FOR GESTATIONAL

Research Profile

Gestational Diabetes
Are Prediction And Prevention Possible?
by Terri Kordella

Jeffrey L. Ecker, MD, believes that low levels of a certain sex hormone early in pregnancy may predict the development of gestational diabetes.	Jeffrey L. Ecker, MD Occupation Assistant Professor of Obstetrics, Gynecology, and Reproductive Study at the Massachusetts General Hospital and Harvard Medical School Professional Focus Obstetrics Outside Interests Time with his family, reading, running Research Funding ADA Clinical Research Award

Each year, about 4 percent of pregnant women in the United States develop gestational diabetes. Gestational diabetes occurs much like type 2 diabetes, arising when the body is not able to make and use all the insulin it needs. In fact, women with gestational diabetes are at much higher risk for developing type 2 diabetes in the future.

Gestational diabetes, however, can also cause immediate problems. When you have gestational diabetes, your pancreas pumps out a lot of insulin, but your blood glucose (also know as blood sugar) remains high. In turn, your blood glucose can cross the placenta, where it enters the baby's bloodstream. In response, the baby's pancreas pumps out a lot of insulin, too. However, because the baby is getting more energy than it needs by metabolizing all of that extra glucose, as well as an extra dose of other substances the pancreas makes, it can grow very large. This can lead to complications during labor and delivery. For example, you might need a Caesarean section. Or, if you deliver your baby vaginally, the bones and nerves of his or her arm or shoulders might be injured.

Babies born to mothers who had gestational diabetes are also more likely to become overweight or obese and more likely to develop type 2 when they get older.

If you are diagnosed with gestational diabetes, it may seem like a no-brainer to get treatment. Current treatment involves changes in diet, increased activity, insulin, or any combination thereof. But it's a controversial subject in medicine.

"It is difficult to demonstrate that screening for gestational diabetes during pregnancy and treating women as appropriate improves pregnancy outcomes," says Jeffrey L. Ecker, MD, Assistant Professor of Obstetrics, Gynecology, and Reproductive Study at the Massachusetts General Hospital and Harvard Medical School in Boston, Mass. "It's especially difficult to demonstrate that treatment decreases the rate of Caesarean sections and birth trauma."

Ecker has an idea about why this is so, and he is using funds from an American Diabetes Association Clinical Research Award to test his theory. He thinks it's a matter of timing.

"Women are usually tested for gestational diabetes in the beginning of the third trimester," Ecker explains. "By then there's only a little time left to treat the problem, and the gestational diabetes may have already begun to affect the fetus. Maybe we're just looking for it too late for our interventions to make a difference."

Predicting Risk

Could treatment early in the course of gestational diabetes have a positive effect on your pregnancy and your baby's health? Possibly. But that hasn't been studied yet.

"The truth is, during pregnancy most people don't care about their blood sugars," Ecker says. "They care about their health and their baby's health. We'd like to screen women for gestational diabetes earlier, but they want to know how it's going to make their pregnancies better, and I have a hard time justifying it with current science."

If recent studies indicate that treatment doesn't necessarily cut the risk of complications—even though these studies only account for gestational diabetes diagnosed late in pregnancy—it might be more practical to look beyond treatment altogether and look at prevention instead.

This is where Ecker's work comes in. He thinks it might be possible to determine who is at risk for gestational diabetes before it actually develops, so that it might be possible to prevent it. If you prevent gestational diabetes, there is no need to worry about the complications associated with it.

According to Ecker, one way to predict risk is to look for a marker in the blood.

"Earlier research in a small number of women indicates that low levels of a protein called sex hormone binding globulin (SHBG) early in pregnancy are related to increased risk of gestational diabetes," he says. "If your SHBG is in the lowest third of the range, your risk of gestational diabetes may be three to four times higher."

The larger the study, the less room there is for error, however, so Ecker and his team are studying SHBG in a much larger population of women. Each year, more than 1,700 women enroll in the Massachusetts General Hospital Obstetrical Maternal Study (MOMS), an ongoing research program at the Harvard Medical School. The women allow researchers to freeze leftover blood from routine blood tests at the beginning of their pregnancies so that the blood can be studied later. The blood tests are taken during the first prenatal visit, in the first trimester, usually between the 10th and 13th weeks of pregnancy.

"Later, after delivery, we track the outcomes using our computerized patient records. We look for things like gestational diabetes, high blood pressure, Caesarean sections, and other complications," Ecker explains. "Then we thaw out the blood, run analyses such as SHBG levels, and see if anything in the blood correlates to those conditions.

"If we see that many of the women who have low levels of SHBG at about 12 weeks go on to develop gestational diabetes, SHBG could be a predictor," he adds. "If we can identify who is at risk that early in pregnancy, we would have an added 16 to 20 weeks in which to try to intervene with things like diet and exercise. It would be left to a future study to show whether those interventions will have an effect."