Gene Mutation Explains Why Some Kids Get Fat After Mom’s Diabetes

A genetic twist of fate may determine which children become obese after exposure to diabetes in the womb. New research reveals that specific variations in the GLP-1R gene—the same target of popular weight-loss drugs like Ozempic and Wegovy—can dramatically increase a child’s risk of weight gain when their mother had gestational diabetes during pregnancy.

The discovery helps explain a medical mystery that has puzzled doctors for decades: why some children exposed to maternal diabetes develop obesity while others maintain healthy weights.

The Gestational Diabetes Puzzle

Gestational diabetes affects up to 10% of pregnancies and has long been recognized as a strong predictor of childhood obesity and diabetes. But the connection isn’t absolute, leaving researchers scratching their heads about the missing pieces.

“Some children with in utero exposure to gestational diabetes never develop obesity,” explained lead author Kylie Harrall, who conducted the research at the University of Colorado Anschutz Medical Campus before joining the University of Florida.

To crack this puzzle, researchers turned their attention to the GLP-1R gene, which regulates both insulin production and appetite control. This gene has gained attention recently as the target of blockbuster medications like semaglutide (Ozempic, Wegovy) that help people lose weight by mimicking natural hormones.

Following 464 Children for Years

The research team analyzed data from 464 children participating in the EPOCH study, a long-term project tracking families to understand how gestational diabetes affects children’s metabolic health. Scientists performed genetic testing when the children were around 10 years old, then tracked their weight patterns through adolescence.

What they discovered was striking. Children exposed to gestational diabetes who carried specific variations of the GLP-1R gene showed markedly different weight trajectories compared to those without these genetic changes.

The study identified three key genetic polymorphisms that modified how gestational diabetes exposure affected childhood weight:

• rs10305420 and rs1042044: Children with minor allele variants (CT/TT or CA/AA) showed higher average BMI when exposed to gestational diabetes
• rs6923761: Children who were major allele homozygotes (GG genotype) had significantly higher BMI than all other participants when exposed to gestational diabetes

Beyond Simple Genetics

The findings reveal something more complex than a simple genetic predisposition to obesity. Instead, they demonstrate what scientists call a “gene-environment interaction”—where genetic variations only matter in the presence of specific environmental exposures.

“Our hypothesis was that there were mutations in this receptor that made kids prone to higher BMI,” said senior author Dana Dabelea, associate dean of research at the Colorado School of Public Health and director of the Lifecourse Epidemiology of Adiposity & Diabetes Center.

The research showed that these genetic variations specifically amplified the effects of gestational diabetes exposure on weight gain. Children with the risk variants gained weight faster and maintained higher BMI trajectories compared to their peers.

Clinical Implications

Perhaps most significantly, the study found no evidence that these genetic polymorphisms affected glucose-insulin homeostasis markers during adolescence. This suggests the gene variants specifically influence weight regulation rather than broader metabolic dysfunction—a finding absent from typical coverage of this research.

This distinction could prove crucial for developing targeted interventions. Rather than focusing solely on blood sugar control, clinicians might need different approaches for children carrying these genetic variants.

“This is important because it highlights a joint effect of a genetic mutation and of an environmental exposure,” Dabelea noted. The research demonstrates how genetic predisposition combines with prenatal environmental factors to influence childhood obesity risk.

Future Treatment Possibilities

The discovery opens intriguing possibilities for personalized medicine approaches to childhood obesity prevention. Could doctors someday test children exposed to gestational diabetes for these genetic variations to identify those at highest risk?

“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,” Dabelea suggested.

The connection to GLP-1R makes this possibility particularly tantalizing, given the proven effectiveness of GLP-1 receptor agonists for weight management in adults. However, research into pediatric applications of these medications remains in early stages.

The Bigger Picture

This research adds another layer to our understanding of obesity’s complex origins. Rather than viewing childhood weight gain as simply a matter of calories consumed versus calories burned, the findings highlight how genetic architecture can modify environmental influences from the earliest stages of life.

“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 explained.

The study’s implications extend beyond individual patient care to public health strategies. As gestational diabetes rates continue rising globally, understanding which children face the greatest long-term risks could help target limited prevention resources more effectively.

Future research will need to replicate these findings in larger, more diverse populations while exploring the biological mechanisms underlying these gene-environment interactions. The ultimate goal: turning genetic insights into practical tools for protecting children’s health from their very first breath.