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Exposure to synthetic chemicals known as per- and polyfluoroalkyl substances (PFAS), colloquially known as “forever chemicals,” has been shown to significantly increase the risk for type 2 diabetes (T2D) in a nested case-control study recently published in eBioMedicine. Individuals in the study were approximately 31% more likely to develop diabetes, with the risk escalating at an equal pace as exposure levels climbed, and within the mixtures of PFAS studied, perfluorooctane sulfonate (PFOS) had the highest contributions to this association.

Study Design and Execution

The study, led by a team of researchers from the Icahn School of Medicine at Mount Sinai Health System in New York City, made use of existing data within BioMe, a large, electronic health record-linked research database comprising records of more than 70,000 study participants who have sought care at Mount Sinai Hospital since 2007. From the more than 53,000 individuals enrolled in BioMe as of March 31, 2020, the survey team excluded those who already had diabetes when they first sought treatment, those with an uncertain diabetes status, and those who were diagnosed with T2D within 1 year of their initial measurement, reducing the number of case-control pairs to 779.

From this cohort, 180 case-control pairs were selected for the study’s in-depth PFAS and metabolomics analysis, evenly divided among African American, Hispanic American, and European American pairs. Budgetary restrictions limited the sample size analyzed.

The BioMe biobank contains plasma samples, and the survey team analyzed those samples from the selected records at the time of those individuals’ initial admission to the biobank to assess a baseline for exposure to PFAS. More than 650 metabolic features were also assessed, using ultrahigh-resolution mass spectrometry. The data were then subjected to a variety of machine learning algorithms and statistical analyses.

Those who ultimately developed T2D were more likely to be smokers and had higher BMI measurements at the time of enrollment.

Alarming Correlation With Omnipresent Chemicals

As noted, the results of the study indicated that exposure to PFAS may cause as much as a 31% increase in the likelihood of developing T2D. Vishal Midya, PhD, corresponding author and assistant professor of environmental medicine at the Icahn School of Medicine, said the amount of PFAS in the blood can be used to predict the risk for diabetes as far out as 4-5 years before diagnosis, which is especially worrisome considering the population examined in the study.

“I think one of the novel aspects of our study was to look at a population of people who are usually healthy. I mean, they’ll go to the hospital for a checkup but nothing crazy. That was the concerning part that we saw,” Midya said. “Even in normal, everyday New Yorkers, even then we see this pattern.”

The study provided evidence that the connection between metabolites created by exposure to PFAS and the development of diabetes is through dysregulations in amino acid biosynthesis and drug metabolism pathways. The chemicals create a disturbance that has a domino effect in the body, according to Midya.

“PFAS can somehow predict the amount of these metabolites. And this amount of these metabolites are also predictive of type 2 diabetes,” he explained. “PFAS affects some metabolism and that metabolism leads to type 2 diabetes.”

“It’s like a chain reaction in that sense,” he said.

Forever Chemicals Have a Lasting Effect

PFAS are known as “forever chemicals” because they take an incredibly long time to break down in both the environment and within living organisms, including the human body. This is because these chemicals are made up of carbon-fluorine bonds, the strongest bond in organic chemistry.

Medya said that once an individual ingests or absorbs a PFAS, it can take 3-4 years, or even decades, to break down and exit the body. These chemicals continue to affect the body during the entirety of that time — for example, by slowly affecting metabolism, as this study suggests.

Research indicates that PFAS are detected in the blood of 98% of people in the United States and elsewhere. They are found in drinking water, and their water- and grease-resistant properties make them popular for use in food packaging, from which they then leach into their contents.

PFAS are also found in household items like nonstick cookware and cleaning products; consumer items, including clothing and cosmetics; and a wide variety of industrial products, from textile coatings to fire-fighting foams.

The study found the leading PFAS contributor to the risk for T2D to be PFOS. This chemical is especially effective at putting out petroleum-based fires, so it is a leading component of fire-fighting foams — for example, those used at airports. It’s also a key component of commercial and household products used to protect fabrics and upholstery from stains and water damage and is used for metal plating and in the semiconductor industry. While major manufacturers began phasing out the production of PFOS in the early 2000s, this chemical’s durability means it continues to have legacy effects on people, animals, and the environment. Additionally, it may have been replaced in some products by other dangerous PFAS.

More Research To Come

Due to the size of this study, it is not possible to make calculations regarding factors like increased risk by age, sex, or ethnicity. Midya and the Mount Sinai team are at work on a larger study that will enable them to analyze these factors.

“We have already started the sample collections, and I am guessing by the end of next year, it should be able to publish,” Midya said. “Our main population for the data is going to be the Mount Sinai biobank, but also we have a collaboration with University of Southern California where we will also work with them so that we can see if these results are also translatable there.”

Midya estimated that the forthcoming study will look at more than 1000 samples to gain some granularity on niche variables within the population.

Avoiding PFAS: Is It Possible?

In this study, the research team noted that its findings underscore the importance of preventing PFAS exposures to promote public health, and that they can inform about potential mechanisms underlying PFAS effects on human metabolism in multiethnic populations. While policy and clinical analysis catch up, Midya said there are some things that individuals can do to reduce exposure to PFAS and thus mitigate their susceptibility to developing diabetes — at least with respect to this particular factor.

“I drink water from a filter that can filter the PFAS out, and I’m also mindful of which household products that I’m using — for example, reducing my use of nonstick cookware, and then choosing PFAS free cleaning products,” he said. “Many products are actually labeled as PFAS free. That’s the best option I have right now.”