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Mary Loeken Part 6, Results From Research of Diabetes Birth Defects

Jan 12, 2018
 

In part 6 of this Exclusive Interview, Dr. Mary Loeken talks with Diabetes in Control Publisher Steve Freed during the ADA meeting in San Diego, CA about the research to reduce the risk of birth defects and other potential risks of 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: Has your research led to any treatments or changes in diabetes care that could reduce the risk of birth defects in pregnancies of diabetic women?

Dr. Loeken:  Our results support the recommendations of, for example, the American Diabetes Association and The International Association for the Diabetic Pregnancy Study Group that  recommends planning of pregnancies, good glycemic control prior to pregnancy.  What hasn’t necessarily been advanced yet is what can we do with technology to improve control of diabetes in pregnancy. Now, since the time I have been working in this field, I’s has been more common for women to use insulin pumps and to do continuous glucose monitoring.  I think that our evidence that you need to have glucose in a relatively narrow range; you don’t want it to be getting close to the level where you’re going to be getting a lot of transport of glucose via Glut2, so if you can have a real-time sensing of glucose levels, I think that would be ideal. Even with our best technology, we don’t have the kinetics of insulin release, even from insulin pumps in the forms of insulin that adequately mimic what a normal functioning pancreas can do.  So, I think that we need to get that technology, so that what the fetal circulation is seeing is more like what a normal non-diabetic pregnancy would be seeing.

Steve: Sometimes research doesn’t pan out for what you are looking for, but sometimes it opens the door for other types of research.  In your research findings, from your lab, have any implications for other problems associated with diabetes been found?

Dr. Loeken: There are some of the same biochemical pathways that are activated in response to high glucose transport in embryo cells that also occur in other tissues that are affected by diabetic complications. We don’t know if the Glut2 transporter might be involved in any of those complications. If Glut2 is involved, if it is expressed in progenitor stem cells, or particular stages of regeneration, it may be involved in wound healing. So, that’s research that still needs to be done to see if the particular rates of glucose uptake via Glut2 could be involved in maybe some of the failure of other diabetic complications to improve. One of the things we have found, however, we know that a gene that we focused on that needs to be turned on for normal neural tube for brain and spinal cord development is inhibited by high glucose. We’ve shown that that’s due to a particular modification of the DNA that occurs in cells where the gene isn’t turned on and it fails to be removed when the gene needs to turn on. This is called DNA methylation, or it’s an epigenetic regulation. I think there may be DNA methylation effects involved in other diabetic complications that may be more involved in failure of the tissues once injured to repair themselves. But again further research needs to test that. One area though I think that could be useful in the future is most of the work we have done up to this point has involved our model of mice diabetic pregnancy and mice embryos, but for various reasons we have been using mice embryonic stem cells that we’ve derived under conditions that they can respond to high glucose levels like the mice embryo does, and we can form neuronal precursors from them, like the cells that would form the neural tube. We’ve shown that Glut2 seems to be very important for responsiveness of these cells to high glucose. But that the normal function of Glut2, seems to be, under normal glucose concentrations, to transport another sugar that then stimulates growth.  If human progenitor cells, either induce pluripotent stem cells that you would make in the dish or are endogenous stem cells that are involved in, for example, wound repair in vivo, if they also express a transporter that could take up the sugar and lead to improved growth, this may give us more therapeutic strategies for other diabetic complications.

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