In part 1 of this Exclusive Interview, Dr. Mary Loeken talks with Diabetes in Control Publisher Steve Freed during the ADA meeting in San Diego, CA about maternal diabetes and birth defects and her work to understand what happens to embryos in women with diabetes.
Mary Loeken, PhD is an Associate Professor of Medicine at Harvard Medical School and an Investigator at Joslin Diabetes Center.
Transcript of this video segment:
Steve: This is Steve Freed with Diabetes In Control and we are here in San Diego with American Diabetes Association 77th Scientific Sessions. Today we have a unique person we will be interviewing. Instead of being an MD doctor, she is a PhD investigator that does research, so maybe we can get some inside scoops on the cure of diabetes.
Tell us a little about yourself and what you do?
Dr. Loeken: I am a basic researcher. I am very interested in understanding how normal cells function and what goes wrong when there are disease situations. Related to my research at the Joslin Diabetes Center, several years ago, when I was a new faculty member, I recognized that based on the work of Priscilla White who had been an early doctor at Joslin Diabetes Center soon after insulin was discovered, she took care of children with diabetes and also young women who now were surviving their diabetes with the availability of insulin. What she noticed when they were pregnant, it was particularly challenging to treat them and there was a large loss of life of the women with diabetes even during their pregnancies, so obviously even their fetuses would not survive either. By about the mid 1930’s, she had actually improved the care of women with diabetes enough that the survival of the women was very high. But, she noticed that there was high rate of birth defects in their offspring, so there was a high rate of perinatal and neonatal loss from the malformations. Now she made a lot of improvements in the care of women during pregnancy during her career, and she’s known among the specialists in diabetic pregnancy internationally for having really laid the groundwork for caring for women with diabetes during their pregnancies.
What I thought in the early ‘90s, a few years into setting up my own lab, was that the time was right for understanding on a molecular level what happens to the early developing embryo as a result of the mother’s diabetes leading to congenital malformations. Part of the reason why I thought this was a good time was because there had been a lot of genes that control formation of organ systems that had been identified from animals as far back as fruit flies but as recent as mice and there were methods to study how they might be regulated in a diabetic setting leading to congenital malformations. So, we set up a mouse model of diabetic pregnancy. And what we saw with very high frequency is one of the most common malformations in human diabetic pregnancy, which are neural tube defects. We also see some cardiac defects, which are also very common. We set out to study how it is that mother’s diabetes interferes with expression of the genes that would control the formation of the brain and the spinal cord and some structures in the heart. What is it about the increased glucose metabolism, as a result of the mother’s glucose going to the embryo that causes abnormal expression of genes. And really trying to identify are there particular pathways that we can say are crucial leading to malformations and might there eventually be strategies to prevent the malformations from occurring.