Associations between Exposures to Perfluoroalkyl Substances and Diabetes, Hyperglycemia, or Insulin Resistance: A Scoping Review

Abstract

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental pollutants that are commonly found in the human body due to exposures via drinking water, surfactants used in consumer materials, and aqueous film-forming foams (AFFFs). PFAS exposure has been linked to adverse health effects such as low infant birth weights, cancer, and endocrine disruption, though increasingly studies have demonstrated that they may perturb metabolic processes and contribute to dysfunction. This scoping review summarizes the chemistry of PFAS exposure and the epidemiologic evidence for associations between exposure to per- and polyfluoroalkyl substances and the development of diabetes, hyperglycemia, and/or insulin resistance. We identified 11 studies on gestational diabetes mellitus, 3 studies on type 1 diabetes, 7 studies on type 2 diabetes, 6 studies on prediabetes or unspecified diabetes, and 15 studies on insulin resistance or glucose tolerance using the SCOPUS and PubMed databases. Approximately 24 reported positive associations, 9 negative associations, 2 non-linear associations, and 2 inverse associations, and 8 reported no associations found between PFAS and all diabetes search terms. Cumulatively, these data indicate the need for further studies to better assess these associations between PFAS exposure and diabetes.

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

“…Using an experimental mouse model of autoimmune diabetes, Bodin and co-workers showed that PFUnDA exposure of female mice from conception and up to 30 weeks of age exacerbated pancreatic insulitis development, a potential early marker for type 1 diabetes (T1D), but did not accelerate diabetes development [ 192 ]. A recent scoping review included three epidemiological studies examining associations between different PFAS and T1D, but no clear trends could be identified [ 193 ].…”

Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer

“…While there is strong evidence supporting the direct activation of PPARs, there is less evidence that PFAS directly activate endocrine receptors, including estrogen (ER) and androgen receptors (AR). Hence, the mechanism of endocrine disruption mediated by PFAS remains unclear, suggesting that indirect mechanisms, including epigenetic and/or metabolic reprogramming, may play roles in disrupting the production and secretion of endocrine hormones during critical windows of exposure [ 44 , 96 ] ( Figure 2 ). In turn, early-life exposure to EDCs has been associated with epigenetic reprogramming that manifests later in life [ 97 ].…”

Exposure to per- and polyfluoroalkyl substances (PFAS) and type 2 diabetes risk

“…PFAS have been associated with multiple chronic diseases in epidemiological studies including immunotoxicity, cardiometabolic disease, developmental and reproductive effects, and cancer (36)(37)(38)(39)(40). More recent studies have begun to explore associations between PFAS exposure and diabetes (14,15). However, the link between PFAS exposure and the development of diabetes continues to be a disputed area of study, with conflicting data having been reported from various epidemiological studies.…”

“…In addition, little physical activity, a poor diet, smoking, stress, and high body mass index have all been attributed in the promotion of T2D prevalence and incidence (10). However, studies have begun to investigate additional environmental factors that potentially impact on the development of diabetes, such as exposure to environmental contaminants acting as endocrine-disrupting chemicals, including per-and polyfluoroalkyl substances (13)(14)(15).…”