UF researcher links diabetes receptor gene to increased childhood obesity

Certain genetic variations, gestational diabetes linked to unhealthy weight gain in children

A new study led by a University of Florida College of Medicine researcher has found that certain genetic variations of a receptor targeted by popular weight loss drugs are associated with a higher risk of obesity for children who were also exposed to gestational diabetes in the womb.

Findings from the study, co-led by researchers at UF and the University of Colorado, could help improve obesity prediction by spotlighting a genetic variant that may interact with gestational diabetes exposure, said study author Kylie Harrall, Ph.D., a research assistant professor in the Department of Health Outcomes and Biomedical Informatics.

If a child who was exposed to gestational diabetes also has one of the variations of the glucagon-like peptide 1 receptor, or GLP-1R gene, Harrall said, earlier weight-loss interventions might be possible.

Gestational diabetes exposure is one of the best predictors of childhood obesity and Type 2 diabetes, although not all children exposed develop either condition.

“While gestational diabetes is an excellent predictor for childhood obesity, it’s not an infallible predictor,” Harrall said.

Harrall completed the study, published last week in the journal Diabetes Care, as part of her doctoral dissertation under senior author Dana Dabelea, M.D., Ph.D., the associate dean of research and the Conrad M. Riley Distinguished Professor at the Colorado School of Public Health.

“While gestational diabetes is an excellent predictor for childhood obesity, it’s not an infallible predictor.”

In the study, researchers analyzed genetic data from more than 450 participants in the National Institutes of Health-funded Exploring Perinatal Outcomes Among Children, or EPOCH, study, and found that certain variations in GLP-1R, along with exposure to gestational diabetes while in the womb, led to faster rates of body mass index growth and higher average body mass index among children ages 2-17. BMI is a calculated measure of weight in relation to height.

“Even when controlling for diet and physical activity, some people are just metabolically different, and one child may be a healthy weight while another is obese,” Harrall said. “If kids who are identified as being at a higher genetic risk of obesity could be nurtured more to try and keep them off that path, it would help them have better health outcomes not only in childhood, but later in life as well because once a child has obesity, it’s likely they’re going to continue to have obesity into adulthood.”

The GLP-1R gene has been widely studied in adult diabetes and weight gain, and the receptor has been successfully targeted for weight loss drugs including Ozempic and Mounjaro. These new findings, however, offer a novel approach to the problem, Harrall said.

“Further investigations will need to take place to study this in a larger sample size before we can draw conclusions,” she said.

Harrall’s upcoming work at UF will continue to explore these relationships and other areas related to child health outcomes.