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

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.