Gene mutations explain why some children gain weight after their mothers have diabetes

The genetic distortion of fate may determine which children are obese after exposure to diabetes in the uterus. New research shows that specific changes in the GLP-1R gene (Ozempic and Wegovy) are the same targets of popular weight loss drugs that can greatly increase the risk of children gaining weight when they have gestational diabetes during pregnancy.

This discovery helps explain a medical mystery that has plagued doctors for decades: why some children are exposed to maternal diabetes, while others maintain a healthy weight.

Gestational diabetes problem

Gestational diabetes affects up to 10% of pregnancy and has long been considered a strong predictor of childhood obesity and diabetes. But this connection is not absolute, allowing researchers to capture the lost work.

“Some children exposed to gestational diabetes in the uterus will never develop obesity,” explains lead author Kylie Harrall.

To solve this puzzle, the researchers turned their attention to the GLP-1R gene, which regulates insulin production and appetite control. The gene has recently attracted attention, a target for blockbuster drugs like Semaglutide (Ozempic, Wegovy) that can help people lose weight by mimicking natural hormones.

464 children over the years

The team analyzed data from 464 children who participated in the Epoch study, a long-term project that tracks families to understand how gestational diabetes affects children’s metabolic health. When the child is about 10 years old, scientists perform genetic tests and then track their weight patterns through puberty.

What they found was amazing. The weight trajectory of children exposed to fetal diabetes was significantly different compared to gestational diabetes without these genetic changes.

The study identified three key genetic polymorphisms that alter the weight of gestational diabetes exposure to children:

• RS10305420 and RS1042044: Children with secondary allelic variants (CT/TT or CA/AA) showed higher mean BMI when exposed to gestational diabetes
• RS6923761: When exposed to gestational diabetes

Beyond simple genetics

These findings reveal something more complex than the simple genetic tendency of obesity. Instead, they demonstrate what scientists call “gene environment interactions”, in which case genetic variation is important only when a particular environment is exposed.

“Our hypothesis is that there are mutations in this receptor that make children vulnerable to higher BMI,” said Dana Dabelea, associate dean of research at the Colorado School of Public Health and director of Vital Epidemiology at the Center for Obesity and Diabetes.

Studies have shown that these genetic variants specifically amplify the effect of gestational diabetes on weight gain. Children with risk mutation gained faster weight and maintained a higher BMI trajectory compared to their peers.

Clinical significance

Perhaps most importantly, studies have found no evidence that these genetic polymorphisms affect the homeostasis of glucose insulin during adolescence. This suggests that gene variants specifically affect weight regulation rather than broader metabolic dysfunction, which is found from the typical coverage of this study.

This distinction may be crucial for setting target interventions. Clinicians not only focus on blood sugar control, but may also require different methods to carry these genetic variants in children.

“This is important because it highlights the joint role of genetic mutations and environmental exposure,” Dabelea notes. The study shows how genetic susceptibility is combined with prenatal environmental factors to affect the risk of childhood obesity.

Future treatment possibilities

This discovery opens interesting possibilities for personalized medical approaches to prevent personalized medical approaches. Can doctors test the genetic variants of children with gestational diabetes to identify those at the highest risk?

“In the future, clinicians may be exposed to children with gestational diabetes for these genetic polymorphism tests. They may then be good candidates for pharmacological interventions,” Dabelea suggested.

Given the proven effectiveness of GLP-1 receptor agonists in adult weight management, the association with GLP-1R makes this possibility especially tempting. However, research on pediatric applications of these drugs is still in its early stages.

Larger pictures

This study adds another layer to our understanding of the complex origins of obesity. Instead of gaining childhood weight into the problem of calories consumed versus calories burned relative to calories, these findings highlight how genetic structures change environmental impacts from the earliest stages of life.

“This knowledge can help clinicians identify children with the highest risk of rapid BMI growth, which will allow for earlier interventions and potentially reduce the risk of development in children with type 2 diabetes,” Harrall explained.

The implications of this study are beyond the scope of individual patient care for public health strategies. As gestational diabetes rates continue to rise worldwide, understanding which children face the greatest long-term risks can help target limited preventive resources more effectively.

Future research will require replicating these findings in larger, more diverse populations, while exploring the biological mechanisms of interactions between these gene environments. The ultimate goal is to transform genetic insights into practical tools to protect children’s health from first breathing.