PFAS "Forever Chemicals" Linked to 31% Increased Risk of Type 2 Diabetes
Key Insights
A nested case-control study of 360 participants found that each tertile increase in PFAS (search) mixture exposure was associated with a 31% higher likelihood of developing type 2 diabetes (search).
The research identified specific metabolic disruptions, including altered levels of sulfolithocholylglycine (search) and other metabolites that may link PFAS (search) exposure to diabetes risk.
PFAS (search) exposure appears to disrupt key metabolic pathways including glutamate metabolism, arginine and proline metabolism, and drug metabolism via cytochrome P450 (search) enzymes.
A new study has revealed that exposure to per- and polyfluoroalkyl substances (search) (PFAS (search)), commonly known as "forever chemicals," may significantly increase the risk of developing type 2 diabetes (search) through metabolic disruptions. The research, published in eBioMedicine, found that each tertile increase in PFAS mixture exposure was associated with a 31% higher likelihood of developing type 2 diabetes (OR, 1.31; 95% CI, 1.01-1.70).
Study Design and Population
The nested case-control study was conducted 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. After excluding individuals with type 2 diabetes (search) at baseline, researchers identified 180 incident type 2 diabetes 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 (search) compounds and conducted untargeted metabolomic profiling.
Key Findings on Metabolic Disruption
The analysis revealed that perfluorooctane sulfonate (search) contributed most strongly to the association between PFAS (search) exposure and diabetes risk. Several metabolites were linked to both higher PFAS exposure and increased odds of type 2 diabetes (search), including 5-hydroxytryptophan (search), glucoheptulose (search), and sulfolithocholylglycine (search). The association involving sulfolithocholylglycine remained statistically significant after correcting for multiple comparisons.
"PFAS (search) are synthetic chemicals that resist heat, oil, water, and stains, and are found in countless everyday consumer products," said Vishal Midya, PhD, MStat, corresponding author and assistant professor of environmental medicine at the Icahn School of Medicine at Mount Sinai. "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."
Pathway Analysis Reveals Metabolic Mechanisms
Pathway enrichment analysis revealed that PFAS (search) exposure and type 2 diabetes (search) shared disrupted metabolic pathways, including glutamate metabolism, arginine and proline metabolism, and drug metabolism via cytochrome P450 (search) enzymes. The research suggests that PFAS may alter people's metabolism of amino acids, carbohydrates and some drugs.
Specifically, PFAS (search) appeared to alter people's levels of sulfolithocholyglycine, described as a key signaling molecule for coordinating and regulating metabolism of fats, blood sugar, drugs and energy.
Study Limitations and Future Directions
The researchers acknowledged several limitations, including a small sample size that limited detection of sex- or ancestry-specific effects and the ability to assess newer short-chain PFAS (search). 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. Additionally, residual confounding factors such as diet or reproductive history may have influenced results.
Clinical and Public Health Implications
Despite these limitations, the findings suggest a potential metabolic mechanism through which PFAS (search) may influence diabetes risk. PFAS compounds have been used in consumer products since the 1940s, including fire extinguishing foam, nonstick cookware, food wrappers, stain-resistant furniture and waterproof clothing.
"This research leverages an exposomics framework to characterize environmental impacts and associated metabolic alterations contributing to the development of type 2 diabetes (search) in vulnerable US populations," said Damaskini Valvi, MD, PhD, MPH, senior author and associate professor of public health and environmental medicine at the Icahn School of Medicine at Mount Sinai. "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 (search) are a risk factor for several chronic diseases, such as obesity, liver disease, and diabetes."