The presence of synthetic chemicals known as per- and polyfluoroalkyl substances (PFAS) may significantly raise the risk of developing type 2 diabetes (T2D) by causing metabolic disruptions.1
The nested case-control study was published in eBioMedicine.
Elevated levels of “forever chemicals” may be associated with metabolic disruptions potentially leading to type 2 diabetes, according to one study. | Image credit: Vodkaz – stock.adobe.com
“PFAS are synthetic chemicals that resist heat, oil, water, and stains, and are found in countless everyday consumer products,” Vishal Midya, PhD, MStat, corresponding author and assistant professor of environmental medicine at the Icahn School of Medicine at Mount Sinai, said in a statement.1 “Because they don’t break down easily, PFAS accumulate in the environment—and in human bodies. Our study is one of the first to examine how these chemicals may disrupt the body’s metabolism in ways that increase diabetes risk—particularly in diverse US populations.”
The researchers conducted an analysis within BioMe, a large, electronic health record-linked biobank of over 65,000 patients who have received primary care at Mount Sinai Hospital since 2007.2 After excluding individuals with T2D at baseline, the team identified 180 incident T2D cases, which were equally distributed among Black, Hispanic, and White participants. Cases were matched by age, sex, and ancestry to 180 diabetes-free controls.
Using plasma samples collected approximately 6 years before diagnosis, the researchers measured levels of seven PFAS compounds and conducted untargeted metabolomic profiling.
The analysis found that each tertile increase in PFAS mixture exposure was associated with a 31% higher likelihood of developing T2D (OR, 1.31; 95% CI, 1.01-1.70), with perfluorooctane sulfonate contributing most strongly to this association. Several metabolites, including 5-hydroxytryptophan, glucoheptulose, and sulfolithocholylglycine, were linked to both higher PFAS exposure and increased odds of T2D, with the association involving sulfolithocholylglycine remaining statistically significant after correcting for multiple comparisons.
Pathway enrichment analysis revealed that PFAS exposure and T2D shared disrupted metabolic pathways, including glutamate metabolism, arginine and proline metabolism, and drug metabolism via cytochrome P450 enzymes.
However, the researchers acknowledged some limitations, including a small sample size that limited detection of sex- or ancestry-specific effects and the ability to assess newer short-chain PFAS. Because PFAS and metabolomic data were collected at the same time, causality could not be established. The researchers also noted that pathway analyses should be interpreted with caution due to database limitations and potential false discoveries. Lastly, residual confounding, such as diet or reproductive history, may also have influenced results.
Despite these limitations, the researchers believe the findings suggest a potential metabolic mechanism through which PFAS may influence diabetes risk.
“This research leverages an exposomics framework to characterize environmental impacts and associated metabolic alterations contributing to the development of type 2 diabetes in vulnerable US populations,” Damaskini Valvi, MD, PhD, MPH, senior author of this paper and associate professor of public health and environmental medicine at the Icahn School of Medicine at Mount Sinai, said in a statement.1 “Findings can help us design more effective interventions for the early prevention of type 2 diabetes in the future, taking into account individuals’ exposures to environmental chemicals along with other well-known genetic, clinical, and lifestyle factors implicated in diabetes development. Mounting research suggests that PFAS are a risk factor for several chronic diseases, such as obesity, liver disease, and diabetes.”
References
1. “Forever chemicals” linked to higher risk of type 2 diabetes. Mount Sinai Health System. News release. July 20, 2025. Accessed July 29, 2025. https://www.newswise.com/articles/forever-chemicals-linked-to-higher-risk-of-type-2-diabetes
2. Midya V, Yao M, Colicino E, et al. Exposure to per- and poly-fluoroalkyl substances in association to later occurrence of type 2 diabetes and metabolic pathway dysregulation in a multiethnic US population. eBioMedicine. July 20, 2025. Accessed July 29, 2025. https://www.thelancet.com/journals/EBIOM/article/PIIS2352-3964(25)00282-8/fulltext