Higher PFAS levels reduce blood sugar improvements after teen bariatric surgery

A new USC study shows teens with higher blood levels of per- and polyfluoroalkyl substances (PFAS) measured before bariatric surgery had smaller improvements in blood sugar over five years, including fasting glucose and hemoglobin A1c (HbA1c), which measures average blood sugar levels over the past 60-90 days. Blood sugar is a key marker of the surgery's success-and the differences were large enough that the metabolic benefits of the surgery could fade within a decade. The results, published in the journal Environmental Endocrinology, suggest that PFAS exposure may help explain why metabolic outcomes differ among patients.

PFAS are a class of industrial chemicals used in consumer products that accumulate in the body over time. They have been detected in the blood of nearly all U.S. adults and have been linked to a number of health problems, including kidney and liver problems and several types of cancer. A growing body of evidence now suggests that PFAS could also play a role in metabolic conditions such as type 2 diabetes.

The study was led by researchers at the Keck School of Medicine of USC's Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention (ShARP) Center, which is funded by the National Institute of Environmental Health Sciences to identify the health effects of hazardous chemicals and use those insights to drive prevention and policy.

Recent findings from the USC team showed that teens with higher blood levels of PFAS also tend to regain more weight after bariatric surgery. Broadly, the team is studying what factors influence why some patients do better than others. Their research could help guide a more targeted approach to treatment, taking into account how environmental toxins like PFAS may affect patient outcomes. For example, screening for PFAS before surgery could identify patients who need extra monitoring or additional interventions to keep their blood sugar healthy over time.

Our findings show that it's important for environmental epidemiologists and physicians to collaborate. Targeted precision medicine based on our growing knowledge of PFAS and environmental health may help ensure patients have the greatest success with this weight loss intervention."

Brittney Baumert, PhD, MPH, postdoctoral research fellow in population and public health sciences, Keck School of Medicine and study's joint first author

Reversing blood sugar progress

Patient data for the study came from the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS), which tracks outcomes among adolescents who have undergone the weight loss procedure. In 186 teens, aged 19 or younger, the researchers measured levels of eight types of PFAS before patients had surgery.

After surgery, the researchers tracked each patient's metabolic health at six months, 12 months, 36 months and five years. To measure short- and long-term blood sugar levels, they collected data on fasting glucose and HbA1c. They also measured insulin and estimated insulin resistance, or how hard the body has to work to keep blood sugar under control.

Overall, most Teen-LABS patients had significant improvements in metabolic health after surgery. But teens with higher exposure to all eight PFAS together showed a smaller improvement in long-term blood sugar, with their HbA1c rising, on average, 0.27 percentage points three years after surgery. (For context, a normal HbA1c is under 5.7%, so this increase is considerable.)

One PFAS in particular, perfluorohexanesulfonic acid (PFHxS), had an outsized impact. Teens with higher PFHxS exposure before surgery had average annual increases of 0.15 percentage points in HbA1c, a rate that could move someone from normal blood sugar to prediabetes-or from prediabetes to type 2 diabetes-within a few years.

PFHxS was also linked to rising fasting glucose, about one milligram per deciliter (mg/dL) per year. At that rate, a patient who initially improved by 10 mg/dL after surgery could see those gains reversed within a decade. Researchers did not observe a clear association between pre-surgery PFAS levels and post-surgery insulin levels and say more research is needed on that link.

Linking PFAS to metabolic health

The Teen-LABS study allowed researchers to explore metabolic outcomes related to diabetes, even though diabetes was not its primary focus. Future research could build on these findings by including gold-standard diabetes tests, detailed dietary data and larger patient populations, the researchers said.

"This is another step toward understanding the relationship between PFAS and type 2 diabetes, including differences between types of PFAS and the role of patient age, sex and lifestyle. But many questions remain unanswered," said joint first author Elizabeth Costello, PhD, a research scientist at the Brown University School of Public Health who was a postdoctoral researcher at the Keck School of Medicine when the study was done.

Baumert is now leading a follow-up study to investigate biological mechanisms that may explain why some patients have better outcomes after bariatric surgery. She will use metabolomics and proteomics, which measure small molecules and proteins in the body, to understand how PFAS exposure might influence metabolism and recovery.

This study adds to growing evidence that PFAS can interfere with the body's ability to regulate glucose, even after substantial weight loss, said last author Vaia Lida Chatzi, MD, PhD, professor of population and public health sciences and pediatrics and director of the ShARP Center at the Keck School of Medicine. The findings underscore that metabolic recovery is shaped not only by clinical treatment but also by environmental factors. The ShARP Center aims to uncover these hidden barriers and generate solutions that protect metabolic health during the critical period of adolescence.