Pregestational Diabetes: Consequences for Pregnancy

Frequent readers of The Pulse are well aware of gestational diabetes, diabetes mellitus that begins during pregnancy and then resolves, which is the most common type of diabetes among pregnant women. But today’s topic is pregestational diabetes. This condition is less common than gestational diabetes, but has become much more common than it used to be and continues to strike a growing number of women. Pre-gestational diabetes is any diabetes mellitus that exists prior to the onset of pregnancy, so it can be diabetes type 1 or diabetes type 2. Just to review some vocabulary, the term diabetes mellitus refers to the disorder involving blood sugar and the hormone insulin. This is in contrast with diabetes insipidus, whose cause involves either the kidneys or the hormones that help the kidneys decide how much water to keep in the body and does not involve sugar or insulin.

Not to give away too much of the ending, but pregestational diabetes is worse than gestational diabetes, since the complications of the latter are fairly limited. It’s also worse, because, as noted above, the prevalence of pregestational diabetes is growing. It’s growing on account of a growing prevalence specifically of type 2 pregestational diabetes. Where as nearly all pregestational diabetes used to be diabetes type 1, the type that usually begins in childhood, the proportion of type 2 cases is growing. Type 2 is the kind of diabetes associated with being overweight or obese or having metabolic syndrome. Increasing prevalence of pregestational diabetes therefore correlates with the epidemic of obesity.

The basics of diabetes mellitus can begin with our recent article on the endocrine system and how it changes during pregnancy. If you are comfortable with that material, let’s move on by talking about blood sugar and insulin. Blood sugar, glucose, is the main source of energy for body cells. Numerous body tissues pull glucose from the blood, but a great deal of glucose goes into skeletal muscle (the muscle throughout your body that you can control) because there is so much of it. A good amount of glucose also moves from the blood into fat cells and into the liver, because the liver can store glucose. While glucose is vital to the brain, most brain cells receive glucose from the blood without help from the hormone insulin. However, insulin, which is produced by the pancreas, is what enables cells of the liver, muscles, and fat to receive glucose from the blood. If adequate amounts of insulin are not available, or if cells of body tissues do not respond to insulin, the cells will not have enough glucose, while the concentration of glucose in the blood will rise. When the concentration of sugar in blood exceeds a certain level, the kidneys excrete glucose and it pulls a lot of water with it. Thus, the person has to urinate a lot. Excessive urination is the meaning of the term diabetes, while mellitus refers to the sugar in the urine. Even without reaching a concentration of sugar in the blood high enough to cause sugar in the urine, however, a person is considered diabetic, if her blood glucose is just a little higher than normal on average, or if it takes longer than normal for the concentration of glucose in the blood to decrease after a meal.

To evaluate a patient’s blood glucose status over expended periods of time, laboratory medicine doctors measure the abundance of a certain type of hemoglobin. Hemoglobin is the molecule that fills red blood cells and carries oxygen in the blood, but hemoglobin exists as a variety of types. One type, called hemoglobin A1c (HbA1c), has glucose attached to it. Once a glucose molecule attaches to a hemoglobin molecule, it doesn’t disconnect easily, even when the concentration of glucose in the blood drops. HbA1c thus lasts about as long as a red blood cell lasts, about 110 to 120 days at most. Consequently, if you have not eaten a lot of sugar in the day prior to a blood test, such that your blood glucose reading is normal, but if you have been eating a lot of sweets over the past 2-4 months, your HbA1c will reveal that sugary diet that your blood sugar test did not reveal. While the short-term blood glucose levels contribute to the diagnosis of diabetes and are vital to calculating dosages and schedules for insulin and for pills that lower blood sugar, diagnosis of diabetes and prediabetes depends primarily on HbA1c. Since HbA1c is one of several types of hemoglobin, the HbA1c value is measured as a percentage. Nobody has zero percent HbA1c, but in most laboratories the normal value ranges from 4 percent to 5.6 percent. Readings of 5.7 percent up to 6.4 percent HbA1c indicate prediabetes, while 6.5 percent and higher mean diabetes.

The HbA1c percentage is important also for pregestational diabetes —diabetes that starts prior to pregnancy— because people have HbA1c values a lot higher than 6.5 percent and when we get into the double digits this correlates with a very high incidence of what doctors call adverse pregnancy outcomes.  Some studies have reported risks of adverse outcomes as high as 14 percent in women with HbA1c in the high single digits (7-9 percent) and 25 percent risk with HbA1c above 12 percent. Regarding one category of adverse outcomes, birth defects, a recent study reported that an HbA1c of 10 percent entails a 10 percent risk of birth defects.

The birth defect risk includes neural tube defects, which means that women expectant mothers with pregestational diabetes must be even more careful to consume enough folic acid in their diets or to take pregnancy vitamins that include adequate folic acid. Other abnormalities that may affect the fetus include congenital heart malformations, intrauterine growth restriction (the fetus doesn’t grow enough in the womb), problems with the lungs, liver, pituitary, thyroid, polycythemia (too many red blood cells), and spontaneous abortion (miscarriage). This is only a partial list and we also should mention macrosomia (the baby is unusually big) and shoulder dystocia (baby’s shoulder is injured during vaginal delivery, because the baby is so large). These latter two things also can occur in gestational diabetes.

Complications specific to the mother that occur more often in those with pregestational diabetes include preeclampsia and eclampsia, very serious pregnancy complications whose connection with diabetes may have to do with problems with blood vessels of the placenta. Along with various complications that can strike any diabetic, women with pregestational diabetes also are at risk for infections and hemorrhage.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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