Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis

Gui, Si-Yu; Qiao, Jian-Chao; Li, Ze-Lian; Chen, Yue-Nan; Wu, Kejia; Jiang, Zhengxuan; Hu, Chengyang

doi:10.1038/s41370-022-00464-3

Cited by 30 publications

(12 citation statements)

References 90 publications

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“…PFAS exposure in laboratory animal studies and human cohorts is associated with small decreases in birth weight [ 25 , 26 ], and decreased birth weight is listed by the CDC/ATSDR on its document on the health effects of PFAS [ 27 ](ATSDR 2023). Also, multiple studies of associations of PFAS with diabetes have been conducted with mixed results [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

PFAS Modulate Osmotic Signaling Independent of Gravimetric Changes in the Rat Uterus

Dixon,

Rowan,

Yackley

et al. 2024

Toxics

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Various PFAS have been identified as potential endocrine-disrupting chemicals due to estrogen receptor activation, impacts on puberty timing, or impacts on hormonally sensitive endpoints in fish. This study screened multiple PFAS in the rat uterotrophic assay to determine potential estrogenic effects on the uterus with PFAS exposure. This study also explored PFAS-dependent uterine signaling with an osmotic stress mRNA gene expression array. Briefly, Sprague–Dawley rats (26–39 days old) were ovariectomized, and uterine tissue was allowed to regress for a 3-week period of recovery. Animals were then exposed daily via oral gavage to PFAS for 4 days, and then uterine weight was determined. In contrast to the positive control estrogens, the PFAS tested (4:2, 6:2, and 8:2FTOH; perfluorooctanesulfonamide (PFOSA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), nafion byproduct 2 (NBP2), 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol) and 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol)) caused no significant changes in the uterine weight. Hormonally active compounds can act as carcinogens, and because earlier rodent work has demonstrated that chronic PFOA exposure is associated with increased risk of uterine cancer, uterine mRNA gene expression was explored with an osmotic stress RT-qPCR array. PFAS exposure significantly upregulated multiple genes across the array, with PFOSA being the compound most similar to the reference estrogens (estradiol benzoate and ethinyl estradiol) in its expression pattern. Also, across all PFAS, pathway analysis revealed that the paxillin pathway, a pathway important in tumor suppressor gene SHP-2 signaling, was significantly upregulated with PFAS exposure. These results demonstrate that in vitro estrogen screens or impacts in fish may show different responses from direct impacts on mammalian uterine weight as assessed with the uterotrophic assay. This study also builds out new mechanisms that may contribute to understanding of carcinogenic changes seen in the uterus after PFAS exposure.

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Section: Discussionmentioning

confidence: 99%

PFAS Modulate Osmotic Signaling Independent of Gravimetric Changes in the Rat Uterus

Dixon,

Rowan,

Yackley

et al. 2024

Toxics

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“…A recent meta-analysis of 22 studies examining associations between PFAS and T2DM reported that statistically significant, positive associations between PFAS body burden and risk were consistently reported for cohort studies, with less consistent results reported for case-control and cross-sectional studies. 79…”

Section: Pfas and Cvd Risk Factorsmentioning

confidence: 99%

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Schlezinger,

Gokce

2024

Circulation Research

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Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are man-made chemicals that are extensively used in industrial and consumer products worldwide and in aqueous film-forming foam utilized in firefighting. As such, our exposure to PFAS is essentially ubiquitous. Given the long half-lives of these degradation-resistant chemicals, virtually, all people are carrying a body burden of PFAS. Health concerns related to PFAS are growing such that the National Academies of Sciences, Engineering and Medicine has recommended standards for clinical follow-up of individuals with high PFAS blood levels, including prioritizing screening for dyslipidemia. The link between PFAS and dyslipidemia has been extensively investigated, and evidence for associations is compelling. However, dyslipidemia is not the only cardiovascular risk factor with which PFAS is associated. Here, we review the epidemiological evidence for links between PFAS of concern identified by the National Academies of Sciences, Engineering and Medicine and risk factors for cardiovascular disease, including overweight/obesity, glucose intolerance, hypertension, dyslipidemia, and hyperuricemia. Moreover, we review the potential connections of PFAS with vascular disease and atherosclerosis. While observational data support associations between the National Academies of Sciences, Engineering and Medicine PFAS and selected cardiac risk factors, additional research is needed to establish causation and better understand how exposure to PFAS leads to the development of these conditions.

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“…1 However, a recent meta-analysis indicates a potential overall increased risk of incident T2D in relation to PFAS exposure. 28 Furthermore, nonmonotonic associations have been found such as inverse U-shaped associations, which could explain differences between studies with different PFAS exposure levels. 29 T A B L E 3 Summary of key articles for underlying mechanisms related to PFAS exposure and cardiometabolic risk factors.…”

Section: T2dmentioning

confidence: 99%

“…Associations of PFAS with T2D are similarly inconsistent as different studies have reported higher risk, lower risk and null associations 1 . However, a recent meta‐analysis indicates a potential overall increased risk of incident T2D in relation to PFAS exposure 28 . Furthermore, non‐monotonic associations have been found such as inverse U‐shaped associations, which could explain differences between studies with different PFAS exposure levels 29 …”

Section: Epidemiological Evidence and Considerationsmentioning

confidence: 99%

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Schillemans,

Donat‐Vargas,

Åkesson

2023

Basic Clin Pharma Tox

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Per‐ and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi‐omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

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Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis

Cited by 30 publications

References 90 publications

PFAS Modulate Osmotic Signaling Independent of Gravimetric Changes in the Rat Uterus

PFAS Modulate Osmotic Signaling Independent of Gravimetric Changes in the Rat Uterus

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

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