Exposure to per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals due to their persistence in the environment and human body, may increase diabetes risk in midlife women, according to data from the Study of Women’s Health Across the Nation (SWAN).
Findings were published in Diabetologia and led researchers to conclude that “reduced exposure to these ‘forever and everywhere chemicals’ may be an important preventative approach to lowering population-wide diabetes risk.”
PFAS are synthetic compounds used in both industrial and consumer products and have been hypothesized to function as potential diabetogens based on their structural similarity to fatty acids, authors explained.
The chemicals can be found in everything from food packaging and carpeting to firefighting foams, and studies have revealed their presence in blood of almost all those tested in the United States.
Previous research also indicated an association between these chemicals, as well as long-chain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), with preeclampsia, increased serum lipids, low birth weight, and decreased antibody response to vaccines.
To better elucidate any association between serum PFAS concentrations and incident diabetes, investigators assessed data from SWAN, which was initiated to characterize menopausal transition and its association with subsequent health endpoints.
However, “the SWAN-Multi-Pollutant Study (MPS) was initiated to evaluate the roles of multiple environmental pollutants in chronic diseases during and after the menopausal transition,” researchers wrote. “Environmental chemical exposure assessment, including PFAS, was conducted using repository serum and urine samples from the third SWAN follow-up (MPS baseline, 1999–2000, n = 2694).”
In the current analysis, a total of 1237 women followed from 1999/2000 through 2017 were assessed. Although the type of diabetes was not determined, “most of the incident cases of diabetes at this life stage can be assumed to be type 2," authors said.
At baseline, participants had a median (IQR) age of 49.4 (47.4-51.5) years; 51.7% of participants were White, 19.2% were Black, 13.3% were Chinese, and 15.8% were Japanese. In addition, during the 17,005 person-years of follow-up, 102 individuals developed incident diabetes, amounting to an incidence of 6 per 1000 person-years. Researchers used quantile-based g-computation to evaluate joint effects of PFAS mixtures.
Analyses adjusted for race/ethnicity, education, smoking status, and other factors revealed the following HRs for diabetes risk, comparing the lowest with highest exposure tertile:
- 1.67 (95% CI, 1.21-2.31) for n-PFOA (Ptrend = .001)
- 1.58 (95% CI, 1.13-2.21) for PFHxS (Ptrend = .003)
- 1.36 (95% CI, 0.97-1.90) for Sm-PFOS (Ptrend = .05)
- 1.85 (95% CI, 1.28-2.67) for MeFOSAA (Ptrend = .0004)
- 1.64 (95% CI, 1.17-2.31) for the sum of 4 common PFAS (n-PFOA, PFNA, PFHxS, and total PFOS) (Ptrend = .002)
Furthermore, “exposure to 7 PFAS as mixtures was associated with an HR of 2.62 (95% CI, 1.12 to 6.20), comparing the top with the bottom tertiles for all 7 PFAS.” This finding indicates a potential additive effect of multiple PFAS on diabetes risk, authors noted. An HR of 2.62 is similar in magnitude to the HR of overweight on diabetes risk observed in the analysis (2.89), and greater than that of smoking (2.3).
Current evidence on sex-dependent associations of PFAS exposure with diabetes in humans is lacking, although a murine study found female mice exhibited greater hepatic responses to PFOA exposure than male mice. Additional research is needed to support these findings and to better elucidate the underlying biological mechanisms of the association.
Observed associations could have been due to residual confounding, and findings may not be generalizable to boys and men or to women in a different age range, marking limitations to the study.
“Our findings suggest that PFAS may be an important risk factor for diabetes that has a substantial public health impact,” authors wrote. “Despite the population-wide reduction in serum concentrations of PFOS and PFOA, almost all people are still exposed to these known ‘forever chemicals’ as well as innumerable alternatives and substitutes (eg short-chain PFAS) through drinking water, foods, air and consumer products including cosmetics.”
The extreme stability of carbon-fluorine bonds makes PFAS extremely difficult to break down, with this persistence leading to accumulation in the natural environment, humans, and animals, where they can remain for years.
Individuals who live near industrial sites, military bases, or wastewater treatment plants may be at particularly high risk of greater PFAS exposure and diabetes incidence, researchers explained, noting that cutting down on exposure even before midlife could help reduce these risks.
“Policy changes around drinking water and consumer products could prevent population-wide exposure,” they wrote.
“Recent literature suggests that regulations that focus on a few specific PFAS may be ineffective and therefore persistent PFAS may need to be regulated as a class. It is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects,” the authors concluded.
Park SK, Wang X, Ding N, et al. Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the study of women’s health across the nation (SWAN). Diabetologia. Published online April 11, 2022. doi:10.1007/s00125-022-05695-5