Diabetes mellitus (DM) is a growing global health concern that affects millions of individuals worldwide. In 2019, an estimated 463 million adults were diagnosed with DM globally, and this number is expected to increase to 700 million by 2045 (Saeedi et al., 2019). The increasing DM prevalence worldwide coincides with increased global exposure to various environmental chemicals, particularly persistent organic pollutants, which suggests that environmental exposure to these chemicals might be a risk factor for DM (Patrick, 2020). Given the adverse health effects of DM, such as cardiovascular disease, nephropathy, neuropathy, and retinopathy (Saeedi et al., 2019; Sophausvaporn et al., 2023), identifying modifiable environmental risk factors and developing effective prevention strategies are essential to address this growing public health concern.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in various industrial and consumer products. These include food packaging materials, fabrics treated for stain resistance, nonstick cookware, and foams used in firefighting. (Glüge et al., 2020). Because of their extensive use and environmental persistence, people are exposed to these contaminants in their living environment through drinking water, dietary intake, and contact with PFAS-containing products and household dust (Agency for Toxic Substances and Disease Registry, 2018). Consequently, PFAS are detectable in the blood of most of the general population (Fisher et al., 2013; He et al., 2018; Park et al., 2022). Owing to their persistent nature, PFAS accumulate in the human body, raising concerns regarding potential adverse health outcomes, including testicular and kidney cancer, dyslipidemia, thyroid disease, ulcerative colitis, and pregnancy-induced hypertension (Agency for Toxic Substances and Disease Registry, 2018).

Multiple studies have been conducted to assess the association between PFAS exposure and DM; however, the epidemiological evidence is inconclusive (Agency for Toxic Substances and Disease Registry, 2018; Gui et al., 2023). Although some studies have found a potential positive association between PFAS exposure and the risk of DM (Cardenas et al., 2019; Duan et al., 2021; Sun et al., 2018; Zeeshan et al., 2021), other studies have found the opposite (Fisher et al., 2013; Liu et al., 2018). Notably, a recent meta-analysis including small number of studies reported a positive relationship between PFAS and risk of DM in prospective cohort studies but inconsistent results in case-control and cross-sectional studies (Gui et al., 2023). Possibly, these discrepant results in the previous studies are because of post-diagnostic changes in lifestyle and physiology. DM diagnosis may have influenced serum concentrations of PFAS through lifestyle changes related to PFAS exposure and physiological changes related to PFAS excretion, such as glomerular hyperfiltration (Jain and Ducatman, 2019). This could have led to biased estimates of the association among individuals with a DM diagnosis. Race is another possible factor that can influence the risk of DM. Koreans are recognized as having a relatively high susceptibility to diabetes compared with Western populations. This genetic predisposition, characterized by a higher frequency of risk alleles linked to impaired β-cell function, contributes to the limited insulin secretory capacity observed in Koreans (Kwak and Park, 2018). Despite their susceptibility to DM, only one prospective cohort study with a limited sample size of 100 has assessed the association between PFAS exposure and the risk of DM in the Korean population (Chung et al., 2022).

In this context, to avoid the potential influence of post-diagnostic changes in lifestyle and physiology, in this study, we focused on the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population.