Endocrine Disruptors in Type 2 Diabetes: A Translational Analysis of the Influence of BPA and BPS on Metabolic Parameters and Skeletal Muscle Insulin Resistance

Background: Bisphenol-A and -S (BPA and BPS, respectively) are used in the manufacturing of food and beverage packaging, primarily in the form of plastic linings in cans. These chemicals can be ingested via packaged and processed food intake. Epidemiological studies indicate that high BPA and BPS exposure leads to the development of type 2 diabetes (T2D). BPA and BPS are endocrine disruptors that induce insulin resistance. Decrease in skeletal muscle glucose transporter (GLUT4) and mitochondrial dysfunction underlying insulin resistance in skeletal muscle. This study aims to identify dietary exposures linked to high BPA/BPS exposure and assess their impact on T2D management, skeletal muscle mitochondria biogenesis, and GLUT4 expression. Methods: Plasma samples from T2D patients (n=298) were obtained from a randomized control clinical trial, “Investigating medication adherence intervention in patients with T2D,” and levels of BPA and BPS were assessed by ELISA assay. Results for these chemicals were associated with existing data from the parent study, such as glycated hemoglobin (A1C), blood glucose, insulin, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides and dietary behavior (self-reported Connor Diet Habit Survey). Associations were tested using Pearson correlation or Kendall Tau's b-test, and metabolic predictors were assessed by multivariate regression on SPSS statistical software. The impact of BPA and BPS on mitochondria dysfunction and GLUT4 expression was evaluated in human skeletal muscle cells (HsMC) by incubating these chemicals (200nM) for 7 days. MtDNA copy number and GLUT4 were assessed by real-time rtPCR. Results: No associations were found between dietary behavior and BPA or BPS levels in individuals with T2D (p<0.05). BPA level in plasma was positively associated with triglycerides (r= 0.131, p=0.024), and BPS level was positively associated with A1C (r=0.12, p=0.045). High saturated fat intake was associated with high levels of A1C (r=0.2, p=0.02) and total cholesterol (r=0.1, p=0.021). Multivariate regression confirmed that BPS levels and saturated fat intake were predictors of A1C (p=0.003 and p=0.044, respectively) in T2D. Exposure to BPA decreased levels of GLUT4 mRNA expression by over 50% in HsMC, while exposure to BPS decreased mtDNA copy number by over 35%. Conclusion: The results of the present study indicate that BPA and BPS impair distinct cellular pathways in skeletal muscle, which affect distinct metabolic parameters key to T2D management. While no dietary behaviors could predict levels of bisphenols in T2D, high BPS levels, and high saturated fat intake are linked to high levels of A1C in T2D individuals. Controlling BPS and BPS exposure via diet is challenging, but it could represent a valuable therapeutic approach to managing various metabolic outcomes in individuals with T2D. Diabetes Action Research and Education Foundation, Center for Research and Education Pilot/Feasibility Program training grant University of Pittsburgh. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.