The Science of Diabetes and Pregnancy
Here's a peek at how human physiology and modern medicine join forces to help a mom with diabetes nurture a new life
A pregnant woman's body is a cyclone of hormones, blood, and glucose, with a growing baby nestled in the eye of the storm. It's also an extraordinary example of complicated biological engineering.
From the first few days after conception, a woman's body is already beginning to change. Pregnancy hormones swiftly transform the body's daily operations: Temperatures rise, the heart beats faster and stronger, the kidneys work harder, metabolic priorities shift, and the body, of course, gradually expands.
Whether a woman has diabetes or not, pregnancy naturally changes her body's insulin production and use. Insulin is the hormone that ushers glucose from the blood into body cells, where it can be used as energy or stored as fat. In the first trimester, the body wants to bulk up in advance of the energy-draining second and third trimesters, when the fetus will have its turn to grow. "Metabolically, you are eating to grow your own nutrient stores," says Patrick Catalano, MD, a professor in the Department of Obstetrics and Gynecology at Case Western Reserve University. To pack on pounds, the body releases growth hormones that spur the insulin-making beta cells to increase production.
Of course, women with type 1 diabetes have lost most of their beta cells to an autoimmune attack. And yet, amazingly, some women with type 1 begin to produce some or more insulin during pregnancy. This could be the result of these powerful growth factors and the concomitant dampening of the immune system (which is naturally suppressed during pregnancy to help the mother host what is basically a foreign body for nine months).
The newly pregnant body not only makes more insulin but also becomes more sensitive to insulin, at first. These changes are particularly noteworthy for women with diabetes who inject insulin. The greater availability of and sensitivity to insulin can cause the blood glucose of a pregnant woman with diabetes to go too low during her first trimester. That risk is also increased because nausea may keep women from eating as much as usual during this early phase of pregnancy.
As the baby develops, so, too, does the placenta, the temporary organ grown by the pregnant body to broker the transfer of nutrients (including glucose) and waste between maternal and fetal blood. The placenta also produces hormones and other substances that help direct important resources to the fetus, shifting the balance from the mother's growth in early pregnancy to the fetus's growth nearer the end.
One side effect of pregnancy is making a woman more insulin resistant. "Every pregnant woman has an increase in insulin resistance late in pregnancy," says Steven Gabbe, MD, the CEO of the Ohio State University Medical Center. Insulin resistance will drive blood glucose levels up after a meal, which gives the baby access to more nutrients. It's not entirely clear how the placenta's secretions make the mother more insulin resistant. "We think insulin resistance in pregnancy is related to inflammation and cytokines," says Catalano. The placenta releases cytokines, small proteins that are known to trigger inflammation. This theory likens insulin resistance in pregnancy to that in type 2 diabetes, which is thought to be caused, in part, by inflammation. Hormonal changes in pregnancy, such as an increase in progesterone, may also boost insulin resistance.
Even for women without preexisting diabetes, the pregnant body's strategy for nourishing a growing baby can sometimes lead to blood glucose levels that are higher than normal. This can result in gestational diabetes, which develops in some nondiabetic women during pregnancy. While gestational diabetes usually resolves after childbirth, women who experience it have an increased risk of developing type 2 later in life.
For moms-to-be with preexisting diabetes, all of these attacks on the body's insulin sensitivity make blood glucose control more challenging. "Women on insulin end up needing two to three times as much during pregnancy," according to Erin Keely, MD, FRCPC, a professor in the Department of Obstetrics and Gynecology at the University of Ottawa.
Throughout pregnancy, getting the appropriate amount of glucose from mother to baby is of the utmost importance. But while the growing fetus is excellent at taking in glucose, it is not so good at knowing when enough is enough.
The developing baby absorbs its mother's glucose in two ways: passively and actively. The passive route sends glucose from mother to fetus via diffusion across the placenta that separates maternal and fetal blood, with the goal of equalizing maternal and fetal blood glucose levels. The other route pushes the glucose across the placenta from mother to child, regardless of the mom's blood glucose levels.
The fetus's skill at siphoning off glucose is particularly noticeable after the mother hasn't eaten for a while. "During the night, the fetus and placenta use up the glucose and cause the glucose levels to fall," says Gabbe. This is why fasting blood glucose levels are lower in pregnant women. The fetus keeps eating even when the mom doesn't. This, plus the tight blood glucose control needed in pregnancy, considerably ups the risk of maternal hypoglycemia.
Going a little low once in a while probably won't hurt the baby, though. Babies are "quite well protected," says Keely. "They get their glucose no matter what." It's too much glucose that can cause serious problems for the baby, including heart defects. "In early pregnancy, the goal is organogenesis"—the development of the baby's organs—"it isn't necessarily growth," says Catalano. "If your glucose concentrations are high early on, it increases your [baby's] risk of having a birth defect."
In later pregnancy, the issue is size. Larger babies can experience trauma during delivery and have a greater chance of poor health both early in life and later on. In a huge trial called the Hyperglycemia and Adverse Pregnancy Outcome Study, the researchers found "a continuous relationship between the mother's glucose and how large the baby was, how fat the baby was, and what the cord-blood insulin was. That's the baby's insulin," says Gabbe. The study showed the extreme sensitivity of developing babies to high blood glucose, even in pregnant women who had not been diagnosed with preexisting or gestational diabetes and whose blood glucose was lower than levels previously linked to health problems.
The more glucose a fetus gets from the mother, the more insulin the fetus must produce to regulate its blood glucose levels. Newborns who make a lot of insulin can actually become hypoglycemic once they are deprived of their mother's glucose supply at birth. Some researchers believe that those exposed to high blood glucose in the womb are at greater risk of obesity and diabetes as adults.
Next: Other Systems
The work of creating a new life also has significant effects on other organs of the body. "Your heart is working harder throughout pregnancy," says Keely. "It's like being on a treadmill for nine months." Along with greater cardiac output, blood volume and flow rate are amplified, too. "The baby's got to grow, so you need more blood going to the uterus to deliver the nutrients," says Catalano. "The mother needs to increase blood volume to clear fetal waste." The extra blood also helps a mother during delivery, which may involve substantial blood loss. But for a pregnant woman with heart disease, these increased strains can be harmful.
Pregnancy also places increased demands on the kidneys, though healthy kidneys can handle the burden. However, a common diabetes complication is kidney disease (nephropathy), and it can worsen during pregnancy. "Because there's more blood going through the kidneys [during pregnancy]," says Keely, "sometimes pregnancy can damage the kidneys because they are working harder."
The changes in kidney function and blood flow also tend to increase blood pressure in the third trimester. "The real concern is that women with diabetes have a risk of preeclampsia," says Catalano, which is compounded by high blood pressure and kidney dysfunction. Preeclampsia is a condition characterized by high blood pressure and protein in the urine during pregnancy. Another diabetes complication that can worsen in pregnancy is retinopathy, damage to blood vessels in the eye.
Most of the roughly 160,000 women with diabetes who have babies each year in the United States have gestational diabetes. But more and more women with preexisting diabetes are becoming moms. The metamorphosis of pregnancy may seem dizzying in its complexity, especially for women with diabetes, who have so many additional concerns. The reward of a healthy baby, though, is well worth the challenge.