Guarding the Next Generations from Diabetes
Joslin scientists analyze what can go wrong in diabetic pregnancies, and the nongenetic ways in which risk of diabetes can be handed down.
Mary Loeken, Ph.D.
Mary Loeken, Ph.D., has found crucial clues to the causes of birth defects that may occur in pregnancies of women with diabetes. Her research follows in the legacy of Joslin’s Dr. Priscilla White, a trailblazer in improving the health of women with diabetes during their pregnancies and the health of their babies. Dr. Loeken’s work may help in learning how to better manage any form of diabetes in pregnancy (including gestational diabetes) and eventually in detecting and treating birth defects at an early stage.
The Loeken lab has shown how high blood glucose levels can decrease production of a key protein called Pax3, and that this event can trigger problems in forming the brain and spinal cord and the heart. Recently, she and her colleagues have discovered that Pax3 helps to control another protein called p53 that plays
a crucial role in cell life and death. This suggests a scenario in which less Pax3 is produced and p53 then becomes more active and helps to kill cells needed in normal development.
Additionally, Dr. Loeken investigates why the offspring of women with gestational or long-term diabetes are at increased risk of eventually developing obesity and type 2 diabetes. Her lab developed a mouse strain that is genetically diabetic. During pregnancy, their fetuses are exposed to high blood glucose levels. As the offspring of these mice age, they develop characteristics of type 2 diabetes, and the researchers are investigating how this process occurs.
Dr. Mary-Elizabeth Patti looks at the effects of poor maternal nutrition on the babies' risks for diabetes and obesity.
Another Joslin scientist, Mary-Elizabeth Patti, M.D., studies the causes of type 2 diabetes. As part of her work, she pursues a different angle in exploring how the risk of developing the disease can be handed down to following generations in ways that are not based simply on copying parental DNA.
In one effort, “we examine the effects of poor maternal nutrition on their babies’ risks for diabetes and obesity,” Dr. Patti says. “Many factors contribute to this increased risk, including problems in muscle, fat and pancreatic islets. We’ve been largely interested in how obesity develops, because it occurs very early in life. Human babies exposed to an abnormal intrauterine environment are already fat, and they have less muscle in relation to fat.”
In a recent project, Dr. Patti examined the role of muscle stem cells in this heightened risk of disease down the road. Mice born after poor maternal nutrition or given an overly rich diet as newborns produce a smaller number of muscle stem cells, setting the stage for reduced muscle mass, which in turn may be linked to later development of diabetes as well as obesity.
“There’s an important public health message here about maternal nutrition and fitness,” Dr. Patti comments. “We know that obesity begets obesity. If you are planning to become pregnant, you really want to try to improve your health as much as possible before the pregnancy, so your baby is exposed to a healthy metabolic environment. Fortunately, women in pregnancy are very open to ideas.”