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Mary Loeken Part 4, Preventing A Diabetes Birth Defect

Jan 12, 2018
 

In part 4 of this Exclusive Interview, Dr. Mary Loeken talks with Diabetes in Control Publisher Steve Freed during the ADA meeting in San Diego, CA about what can be done towards preventing a diabetes birth defect 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: What can diabetic women or their doctors do to reduce the risk that a birth defect will occur?

Dr. Loeken: So as I said, plan pregnancies, make sure that HbA1cs are in an advisable range, taking folic acid as would be advised for any women planning a pregnancy, and try to avoid unplanned pregnancies. But then just really be up on your cycles and if you might be pregnant to monitor your blood glucose frequently and try to keep the levels in a healthy range. You don’t want to be hypoglycemic either, and you certainly don’t want to avoid hyperglycemia.

Steve: Can you speak of the use of metformin and glyburide in pregnancy?

Dr. Loeken: Women may be taking either glyburide or metformin if they have type 2 diabetes, not type 1 diabetes.  Many women, who are not necessarily diabetic but have polycystic ovarian syndrome, may be taking metformin with or without other drugs to try to improve their glucose tolerance, but also to normalize their menstrual cycles and their symptoms of polycystic ovarian syndrome. One of the reasons that we looked at metformin, and that’s the reason that I will be speaking about metformin here, is that one of the pathways that we’ve shown to be activated by high glucose in the embryo, leading to abnormal gene expression, is an enzyme that can be stimulated by metformin in the liver. So, we asked whether or not this enzyme might be stimulated in mouse embryos if you give their mothers metformin.  And we gave them a dose that would be approximately the higher end of the dose that women might be taking.  Although we did see that metformin may be stimulating this enzyme in the mouse mothers’ livers, we did not see any effect on the embryo.  We didn’t see any stimulation of the enzyme and we didn’t see any malformations. What we think that’s due to is the fact that just as glucose has  transporters that get it into the cells, there are transporters for metformin that get it into cells also. It looks like the early embryo, at least during the stage of development when malformations can occur, express very low levels of metformin transporters.  So, they are not at risk, which is good.  We know that having high glucose levels are increasing risks for malformations and we didn’t want to counteract the beneficial effects of increasing good glucose control by having a drug, metformin, that might counteract due to stimulation of the enzyme that high glucose regulates. So, it looks like metformin does not have that risk, at least in mice embryos. Obviously, you can’t do those same studies in human embryos.  Looking at later pregnancy, there are still a lot of unanswered questions. Again. there are beneficial effects to the outcome of pregnancy from studies looking at metformin. Many women find is easier to take metformin, if they gave gestational diabetes or type 2 diabetes later in pregnancy, than insulin injections. But, those studies are still ongoing and I am not going to speak to recommendations there.

With regard to glyburide, so glyburide does not cross the placenta, not at meaningful levels.  However, the embryo at the stage of development when malformations can occur doesn’t have a placenta, so glyburide could be exposed to the embryo. We know that the way that glyburide works is by binding to a protein that regulates the potassium channel, and that is expressed on pancreatic beta cells and not a lot of other tissues. The embryo at this stage of development doesn’t have pancreatic beta cells.  So, if a mother is taking glyburide and becomes pregnant, I’m not saying that it is advisable, but we don’t have basic science evidence that there are cellular responses in the embryo that could be activated by glyburide.

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