Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort

Environ Res. 2024 Dec 1;262(Pt 2):119938. doi: 10.1016/j.envres.2024.119938. Epub 2024 Sep 4.

Abstract

Objective: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation.

Methods: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed.

Results: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05).

Conclusions: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Keywords: Dinitroaniline herbicide; Glucose dysregulation; Lifestyle; Polygenic risk score.

MeSH terms

  • Adult
  • Aged
  • Aniline Compounds* / toxicity
  • Blood Glucose* / analysis
  • China
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Environmental Exposure / adverse effects
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease*
  • Herbicides* / toxicity
  • Humans
  • Life Style*
  • Longitudinal Studies
  • Male
  • Middle Aged

Substances

  • Herbicides
  • Blood Glucose
  • Aniline Compounds