Scientists reveal how gestational diabetes affects a baby’s heart

by Barbara Hewitt on December 19, 2017

New research has revealed how diabetes in pregnancy affects a baby’s heart by preventing cells from maturing normally and making them more prone to congenital heart disease.

High glucose levels that are found in gestational diabetes affect the developing heart cells of the baby, according to the scientists from the Eli and Edythe Broad Centre of Regenerative Medicine and Stem Cell Research at the University of California in the United States.


They discovered that the cells generate more building blocks of DNA than usual, which leads the cells to continue reproducing rather than mature.

‘High blood sugar levels are not only unhealthy for adults, they’re unhealthy for developing foetuses. Understanding the mechanism by which high blood sugar levels cause disease in the foetus may eventually lead to new therapies,’ said Atsushi Nakano, associate professor of molecular, cell and developmental biology.

Although genetics plays a large role in the development of congenital heart disease, the leading non-genetic risk factor for the disease is a mother having diabetes during pregnancy. Babies born to women with high levels of glucose in their blood during pregnancy are two to five times more likely to develop the disorder than other babies. However, researchers have never been able to define the precise effect of glucose on the developing foetus.

Nakano and his colleagues used human embryonic stem cells to grow heart muscle cells, or cardiomyocytes, in the laboratory and then exposed them to varying levels of glucose. Cells that were exposed to small amounts of glucose matured normally. But cardiomyocytes that had been mixed with high levels of glucose matured late or failed to mature altogether, and instead generated more immature cells.

The researchers discovered that, when exposed to extra glucose, the cardiomyocytes over activated the pentose phosphate pathway, a cellular process that, among other things, generates nucleotides, the building blocks of DNA. In cells with high glucose levels, the pentose phosphate pathway made more nucleotides than usual. The scientists showed that the excess of building blocks kept the cells from maturing.

‘More nutrition is generally thought to be better for cells, but here we see the exact opposite. By depleting glucose at the right point in development, we can limit the proliferation of the cells, which coaxes them to mature and makes the heart muscle stronger,’ Nakano explained.

Nakano’s group observed the same thing at work in pregnant mice with diabetes. The heart cells of foetuses divided quickly but matured slowly. He believes that the finding could lead to better methods of making cardiomyocytes from stem cells. Today, most protocols for generating cardiomyocytes in the lab lead to immature cells, but targeting the pentose phosphate pathway could help generate more mature cells for regenerating heart cells or for research purposes.

Congenital heart disease affects nearly one in 100 children born in the US, making it the most common birth defect. The severity of the symptoms it causes varies, ranging from a slightly weakened heart muscle and no symptoms to severe heart deformations that require surgery.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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