Scientists from the University of Michigan discovered that exposure to widely used ‘forever chemicals’ increases the risk of diabetes in middle-aged women.
This study, recently published in Diabetologia, revealed that exposure to per and polyfluoroalkyl substances (PFAS) – a large and diverse group of industrial chemicals discovered in many everyday products – is associated with an increased risk of developing diabetes in middle-aged women.
Dr Sung Kyun Park led the study with colleagues at the Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
What are PFAS?
PFAS are a group of more than 4,700 synthetic chemicals, that were first developed in the 1940s and are widely utilised industrially as well as in consumer products, such as non-stick cookware, water and stain-repellent coatings, food packaging, carpeting, firefighting foam, and even cosmetics.
Their molecular structure is based on a linked chain of carbon atoms with one or more fluorine atoms attached, and it is the extreme stability of those carbon-fluorine bonds that make PFAS highly resistant to being broken down. Thus, this durability causes PFAS to persist and accumulate in the environment as well as in the bodies of humans and animals where they can remain for years, which is why they are referred to as ‘forever chemicals.’
Why are PFAS becoming a public health concern?
Their ubiquity and persistence in both the environment and the human body has led to PFAS exposure becoming a serious public health concern, resulting in restrictions and even bans on their use.
At least one type of PFAS was present in the blood samples of nearly every American tested by the US Biomonitoring Program, and they were also detected in the drinking water supply of more than 200 million people in the USA. A recent review of possible health effects of these chemicals suggests that exposure to some may be associated with pre-eclampsia, altered levels of liver enzymes, increased blood fats, decreased antibody response to vaccines, an increased risk of developing diabetes, and low birth weight, although causal relationships have yet to be established.
Why do PFAS lead to an increased risk of developing diabetes?
Many PFAS have molecular structures, which resemble those of naturally occurring fatty acids, resulting in them having similar chemical properties and effects on the human body. Fatty acids act on a class of protein molecules discovered in cells called peroxisome proliferator-activated receptors (PPARs), which act as fat and insulin sensors and are the main regulators of the formation and development of new adipocytes (fat cells) as well as the control of the body’s fat and glucose levels.
Thus, structurally and chemically similar PFAS compounds could potentially interact with the same PPARs, disrupting their regulatory behaviour and suggesting that these substances lead to an increased risk of developing diabetes.
Experimental studies with cell cultures reveal that exposure to the high levels of PFAS discovered in some humans may interfere with PPAR function, leading to increased production of fat cells, changes to fat and sugar metabolism, an increased risk of developing diabetes, and abnormal inflammatory responses.
What was involved in conducting this experiment?
The sample group for the study was selected from the Study of Women’s Health Across the Nation (SWAN), an ongoing multi-site, multi-ethnic, community-based prospective cohort study of midlife women to characterise the menopausal transition and its association with subsequent health endpoints.
A total of 3,302 premenopausal participants aged 42-52 years who met the selection criteria for SWAN were recruited from seven different locations in the USA from 1996 to 1997 and given a baseline clinical examination that was repeated annually.
The SWAN-Multi-Pollutant Study (SWAN-MPS) was initiated in 2016 to evaluate the roles of environmental pollutants in chronic diseases during and after the menopausal transition. It analysed the stored blood and urine samples from 1,400 of the study participants, which had been collected by SWAN from the third follow-up (1999-2000) onwards. These were tested for the presence of environmental chemicals including seven PFAS.
After excluding women who had diabetes at SWAN-MPS baseline, as well as participants for whom insufficient data was available, the authors were left with a final sample of 1,237 women with a median age of 49.4 years who had been monitored from 1999-2000 through to 2017. During the 17,005 person-years of follow-up, there were 102 cases of incident diabetes: a rate of six cases per 1,000 person-years.
What did the results of this study reveal about the increased risk of developing diabetes?
When scientists compared the results to participants who remained free of the disease, it was revealed that those who developed diabetes were more likely to be black, from Southeast Michigan (a more socioeconomically disadvantaged area), less educated, less physically active, have a larger energy intake, and higher BMI at baseline.
The authors explained: “Higher serum concentrations of certain PFAS were associated with a higher risk of incident diabetes in midlife women. The joint effects of PFAS mixtures were greater than those for individual PFAS, suggesting a potential additive or synergistic effect of multiple PFAS on the risk of developing diabetes.”
Serum concentrations of PFAS were categorised into high/middle/low exposure groups (tertiles), and a hazard ratio (HR) for incident diabetes was calculated by comparing the incidence rate in the ‘high’ or ‘middle’ tertiles to that in the lowest tertile (reference group).
Researchers discovered that combined exposure to the seven different PFAS had a stronger association with diabetes risk than what was observed with individual compounds. Women in the ‘high’ tertile for all seven had an increased risk of developing diabetes – they were 2.62 times more likely to develop the disease than those in the ‘low’ category, while increased risk associated with each PFAS ranged from 36% to 85%, suggesting a potential additive or synergistic effect of multiple PFAS on diabetes risk.
The strength of the association between combined exposure and incident diabetes rates also suggests that PFAS may have substantial clinical impacts on diabetes risk. The authors point out the 2.62 times increased risk was roughly equivalent to the magnitude of having overweight or obesity (BMI between 25 kg/m2 and 30 kg/m2) compared with having normal weight [(BMI less than 25 kg/m2 (HR 2.89)], and even greater than that for current smokers vs never smokers (HR 2.30) observed in their study population.
Researchers said: “Given the widespread exposure to PFAS in the general population, the expected benefit of reducing exposure to these ubiquitous chemicals might be considerable.”
What was the conclusion of this study?
Scientists noted that the prospective cohort study supports the hypothesis that exposure to PFAS, individually and as mixtures, leads to an increased risk of developing diabetes among middle-aged women.
Although, the effect sizes in men and other populations not included in the study are unknown. If these results are also applicable to men as well as to individuals of all ages and ethnicities regardless of location, then approximately 370,000 cases (around 25%) – out of the 1.5 million Americans newly diagnosed with diabetes each year – could be attributable to PFAS exposure.
Thus, these findings suggest that PFAS may be an important risk factor for diabetes and have a substantial public health impact.
Scientists concluded: “Reduced exposure to these ‘forever and everywhere chemicals’ even before entering midlife may be a key preventative approach to lowering the risk of diabetes. Policy changes around drinking water and consumer products could prevent population-wide exposure.”
Thus, researchers advise that regulations that focus on a few specific compounds may be ineffective, and persistent PFAS may be required to be regulated as a ‘class’. Additionally, they also noted that clinicians ought to be aware of PFAS as unrecognised factors that lead to an increased risk of developing diabetes and to be prepared to counsel patients about sources of exposure and potential health effects.
