Role of Liver Enzymes in the Relationship Between Particulate Matter Exposure and Diabetes Risk: A Longitudinal Cohort Study

Abstract

Context: Particulate matter (PM) is an important risk factor for diabetes. However, its underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored this in the association between PM and diabetes.

Objective: We investigated the role of liver enzymes in mediating the relationship between PM exposure and diabetes.

Methods: We included a total of 7963 participants from the China Multi-Ethnic Cohort. Residential exposure to PM was assessed using a validated spatial-temporal assessment method. Diabetes was diagnosed according to the criteria from American Diabetes Association. Associations between PM, liver enzyme [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (GGT)], and diabetes were estimated using multivariable regression models. The function of liver enzymes in the relationship between PM and diabetes was assessed using mediation analysis.

Results: PM exposure was positively associated with the odds of diabetes, with odds ratios of 1.32 (95% CI 0.83, 2.09), 1.33 (95% CI 1.07, 1.65), and 1.18 (95% CI 1.02, 1.36) for every 10-μg/m3 increment in ≤1 μm (PM1), ≤2.5 μm (PM2.5), and ≤10 μm (PM10) PM, respectively. ALT (4.47%) and GGT (4.78%) exhibited statistically significant mediation effects on the association between PM2.5 and diabetes, and the ALT (4.30%) also had a mediating role on PM10. However, none of the liver enzymes had a significant mediating effect on PM1.

Conclusion: The relationship between PM and diabetes is partially mediated by liver enzymes, suggesting that lipid accumulation, oxidative stress, and chronic inflammation in the liver may be involved in its pathogenesis.

Keywords: biomarkers; diabetes; liver; mechanisms; mediation; particulate matter.