Associations between per-and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden
Open accessAbstract
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis. METHODS: In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose. RESULTS: In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: β: -0.03, p = 0.02, PFUnDA: β: -0.03, p = 0.03). IMPACT: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research. CONCLUSIONS: PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.
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Adults and the elderly are more vulnerable to metabolic, cardiovascular, and bone diseases from PFAS exposure.
“adults and the elderly are more vulnerable to metabolic, cardiovascular, and bone diseases.”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [223]
The Results (EpiHealth cross-sectional analyses; page unavailable) examine PFAS and diabetes but report no overall significant association after adjustment and no age interaction. The Discussion (Sex-specific effects; page unavailable) mentions links between PFAS and markers of carotid artery atherosclerosis. The paper does not establish that adults or elderly people are more vulnerable to these conditions, and the passages found do not address bone disease. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPFAS exposure alters glucose and lipids and is associated with diabetes, with high risk and long-term metabolic disorders.
“| Metabolic Effects | Alters glucose, lipids, diabetes. | High | Both | Long-term metabolic disorders | [223] |”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [223]
The Results report associations between PFAS levels and fasting glucose over 10 years, and an inverse association with prevalent diabetes in women; they found no overall association with diabetes. The paper does not establish altered lipids, a generally high risk of diabetes, or long-term metabolic disorders as outcomes. (LLM, conf=0.88)
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- Authors
- Dunder, L., Salihovic, S., Elmståhl, S., Lind, P. M., & Lind, L.
- Affiliations
- Uppsala University (SE)
- Lund University (SE)
- Corresponding author
- Dunder, Linda
- Venue
- Journal of Exposure Science & Environmental Epidemiology
- Published
- 2023-03-24
- Volume
- 33
- Issue
- 5
- Pages
- 748-756
- ISSN
- 1559-0631 (ISSN-L)
- 1559-064X
- PMC
- PMC10541316
- OpenAlex
- W4360826438
- Cited by
- 41
- References
- 48
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 10 · 2023: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Exposure Science & Environmental Epidemiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Vetenskapsrådet
- Akademiska Sjukhuset
- Uppsala Universitet
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
- Keywords
- per- and polyfluoroalkyl substances, PFAS exposure, diabetes mellitus, perfluorooctanoic acid, PFOS, PFHxS, fasting blood glucose, sex differences, non-monotonic dose-response, metabolic disorders, PIVUS study, older adults, non-alcoholic fatty liver disease, obesity, endocrine disruptors
- MeSH terms
- Caprylates, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Environmental Pollutants, Fatty Acids, Female, Fluorocarbons, Glucose, Humans, Longitudinal Studies, Male, Obesity, Sulfonic Acids, Sweden, Alkanesulfonic Acids, Non-alcoholic Fatty Liver Disease
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