Study Examines How Diabetes in Pregnancy Affect's Baby's Heart

Researchers at the University of California in Los Angeles (UCLA) have found that high glucose levels in babies can keep heart cells from maturing normally. These findings help explain why babies born to women with diabetes are more likely to develop congenital heart disease. Study results were published in the journal eLife.

The study, conducted at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, was led by Atsushi Nakano, associate professor of molecular, cell, and developmental biology at UCLA and a member of the Broad Stem Cell Research Center.

Developing heart cells exposed to high levels of glucose generate more DNA building blocks than usual.

This phenomenon causes the cells to reproduce rather than mature, which inhibits heart development and maturity. "High blood sugar levels are not only unhealthy for adults; they're unhealthy for developing fetuses," Nakano said in a release. "Understanding the mechanism by which high blood sugar levels cause disease in a fetus may eventually lead to new therapies."

The leading non-genetic factor in the development of congenital heart disease is a diabetic mother during pregnancy. Until now, however, researchers have not been able to define what effect glucose has on a developing fetus.

Nakano and his team used human embryonic stem cells to grow heart muscle cells in the lab. They then exposed them to varying levels of glucose. Cells exposed to small amounts of glucose developed normally whereas those mixed with high levels of glucose matured late or did not mature at all, generating more immature cells instead.

Further research found that the cells exposed to high levels of glucose over-activated the pentose phosphate pathway. This is a cellular process that generates nucleotides, the building blocks of DNA. This higher level of activated pentose phosphate pathway activation caused more nucleotides to be made, creating an excess of building blocks, lowering cell development. The same effect was seen in pregnant mice with diabetes and their developing fetuses.

Nakano's group noted that depleting glucose at the right point in development stopped this process, leading to normal heart cell development. A side-effect, the team noted, is that cardiomyocytes could be developed to be more mature in the lab--something that has hitherto not been possible. This would lead to more developed research in the lab.

Source: UCLA