Genetic factors influence obesity risk in children exposed to gestational diabetes

Children exposed to gestational diabetes in utero with a specific variation of a common gene are at a higher risk of becoming overweight or obese during childhood, according to a new study by researchers at the University of Colorado Anschutz Medical Campus.

The study was published today in the journal Diabetes Care.

Scientists have long known that exposure to gestational diabetes is a strong predictor for both childhood obesity and diabetes.

"But it's not infallible," said the study's lead author Kylie Harrall, PhD, who did the research while at CU Anschutz but is now an assistant research professor at the University of Florida in Gainesville. "Some children with in utero exposure to gestational diabetes never develop obesity."

To understand why, the researchers focused on a receptor gene known as GLP-1R, the same gene activated by the weight loss drugs Ozempic and Wegovy. It regulates insulin and appetite.

Previous studies have shown that polymorphisms or common variations of the gene were associated with body mass index (BMI) trajectories across childhood, insulin sensitivity and insulin secretion.

The researchers examined 464 children from the EPOCH study group, a collection of parents and their offspring monitored by researchers to determine the effects of gestational diabetes on the metabolic health of children.

"Our hypothesis was that there were mutations in this receptor that made kids prone to higher BMI," said the study's senior author Dana Dabelea, MD, PhD, associate dean of research at the Colorado School of Public Health and director of the Lifecourse Epidemiology of Adiposity & Diabetes Center (LEAD) on the CU Anschutz Medical Campus.

Dabelea and Harrall found that children exposed to gestational diabetes with a polymorphism of the GLP-1R gene gained weight faster and had a higher than average BMI compared to other children.

This is important because it highlights a joint effect of a genetic mutation and of an environmental exposure. It also shows how children can become overweight. In the future, clinicians can possibly test kids exposed to gestational diabetes for these genetic polymorphisms. They could then be good candidates for pharmacological interventions."

Dana Dabelea, MD, PhD, associate dean of research, Colorado School of Public Health 

Harrall agreed and said the study results show that GLP-1R variations help explain why some children exposed to gestational diabetes are more prone to a higher BMI than others.

"This knowledge could help clinicians identify children who are at the highest risk for rapid BMI growth, which would allow for earlier intervention and potentially decrease the risk for childhood development of type 2 diabetes," Harrall said.