Diabetic pregnancies linked to increased risk of congenital heart disease

Children born to diabetic mothers are up to five times more likely to be diagnosed with congenital heart disease, University of California, Los Angeles (UCLA) researchers reported this week in a novel study linking diabetic pregnancies and fetal heart conditions.

Congenital heart disease is often tied to genetics, Atsushi Nakano, MD, PhD, and colleagues wrote in the eLife-published study, but the leading non-genetic risk factor for the condition is maternal diabetes. If a pregnant woman records higher-than-average levels of blood glucose, that extra sugar inhibits heart cells from maturing fully rather than feeding their growth. In babies, this translates to a two- to five-percent increased risk of developing a congenital heart condition.

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

Diabetic pregnancies are also linked to maternal complications like vasculopathy, neuropathy and insulin resistance, Nakano and co-authors wrote in the study, which could also potentially affect fetal heart development.

Nakano and his team in California used human embryonic stem cells to replicate cardiomyocytes in a lab setting and exposed those heart cells to varying levels of glucose, according to the study. Cells exposed to regular glucose levels matured at a normal pace, the researchers found, but those in high-glucose environments either matured late or not at all.

When mixed with high amounts of glucose, the authors found, cardiomyocytes overactivated the chemical pentose phosphate pathway, which is responsible for churning out nucleotides. By overstimulating the pathway, high blood sugar prompted the heart cells to continue reproducing, creating an excess of nucleotides rather than full, mature cells.

“More nutrition is generally thought to be better for cells, but here we see the exact opposite,” Nakano said. “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 and colleagues found similar patterns in pregnant, diabetic mouse models.

According to the study, an estimated 60 million diabetic women are currently at an age where they could carry children, and nearly one in 100 babies born suffer from a congenital heart defect. Though medicine has advanced the lifespan of pediatric heart patients exponentially, the 60-million figure is expected to double by 2030.

“With the advances in fetal diagnosis and surgical techniques, the number of CHD (congenital heart disease) patients who survive childhood, and so have adult CHD, is growing rapidly by nearly 5 percent per year,” Nakano et al. wrote. “Our findings will lay a foundation for understanding how the glucose environment regulates cardiogenesis and how disturbance of non-genetic factors affects the genetic program during the pathological development of the heart.”