Research Reveals How Diabetes in Pregnancy Affects Baby’s Heart

Source: University of California at Los Angeles

Summary: Researchers discovered how high glucose levels keep heart cells from maturing normally which explains why babies born to women with diabetes are more likely to develop congenital heart disease.

Congenital heart disease (CHD) is a defect in the structure of the heart at the time of birth and affects nearly 1 in 100 children born in the U.S., making it the most common birth defect. Although genetics plays a key role in the development of CHD, a mother with diabetes during pregnancy leads the non-genetic risk factor for the disease. Babies are 2-5 times are more likely to develop CHD, those who are born to women with diabetes during pregnancy. Until now the precise effect of glucose on the developing fetus is not well understood. Researchers from the University of California at Los Angels discovered how high glucose levels keep heart cells from maturing normally, which explains why babies born to women with diabetes are more likely to develop the CHD. The research findings were published in the journal eLife.

Cardiomyocytes when exposed to high levels of glucose they don't mature

Human heart cells grown from stem cells show less robust muscle fibers (green) in high glucose conditions (left) compared to reduced glucose conditions (right). Credit: UCLA Broad Stem Cell Research Center/eLife

Human embryonic stem cells were used to grow heart muscle cells (cardiomyocytes) in the lab and exposed to different levels of glucose. The research team found that, when developing heart cells are exposed to small amounts of glucose, they matured normally. But when exposed to high levels of glucose, they matured late or failed to mature, instead generated more immature cells. In the presence of extra glucose, the cardiomyocytes generate more building blocks of DNA through pentose phosphate pathway (a cellular process involved in nucleotide biosynthesis) than usual and led the cells to continue reproducing rather than mature. The findings could lead to better methods of making cardiomyocytes from stem cells. Targeting the pentose phosphate pathway could help generate more mature cells for regenerating heart cells or for research purposes.

Assoc Prof. Haruko Nakano said, “High blood sugar levels are not only unhealthy for adults; they’re unhealthy for developing fetuses”, “Understanding the mechanism by which high blood sugar levels cause disease in the fetus may eventually lead to new therapies.”

More Information: Haruko Nakano et al, “Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis”, eLife (2017). DOI: 10.7554/eLife.29330

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