Ethylene oxide exposure increases impaired glucose metabolism in the US general population: a national cross-sectional study

Abstract

Background: Current experimental evidence supports that ethylene oxide (EO) exposure-related pathophysiologies may affect glucose metabolism, but few population-based studies have explored the potential links.

Methods: This study used cross-sectional data from 15560 participants in the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. EO exposure levels were calculated by testing hemoglobin adducts of EO (HbEO) via a modified Edman reaction. We focused on the association of EO exposure with prediabetes and diabetes as well as indicators of impaired glucose metabolism and further analyzed the potential pathogenic mechanisms. Statistics included logistic regression, generalized additive model fitting, penalized spline method, two-piecewise linear regression, recursive algorithm, mediation analysis, and Pearson’s analysis.

Results: EO exposure was associated with changes in glucose metabolic indicators and increased prevalence of prediabetes and diabetes, showing age-consistency and being more pronounced in obese and non-smoking populations. For each one pmol/g Hb, one SD, or two-fold SD increase in log2-HbEO, the risk of prediabetes increased by 12%, 16%, and 33%, with an increased risk of diabetes by 18%, 26%, and 61%, respectively. Dose-response curves revealed that this positive correlation was approximately linear with prediabetes and “J” shaped with diabetes. When log2-HbEO > 8.03 pmol/g Hb, the risk of diabetes would be further increased. Pearson’s correlation revealed that EO exposure was associated with reduced fasting insulin and elevated HbA1c in the prediabetic stage. While in the diabetes stage, EO exposure was correlated with elevated fasting glucose, HbA1c, and HOMA-IR, suggesting an exacerbation of diabetes progression by EO exposure. A potential mechanism that the early stages of impaired glucose metabolism may be initiated by EO-related inflammation and oxidative stress damaging pancreatic β-cells, resulting in decreased insulin secretion. These speculations were partially supported by mediation analysis and mediators’ Pearson analysis.

Conclusion: Elevated ethylene oxide exposure increases the incidence of impaired glucose metabolism in the general U.S. population and a potential intervention may be to effectively suppress inflammation and oxidative stress imbalances.