The Interplay of Systemic Inflammation and Oxidative Stress in Connecting Perirenal Adipose Tissue to Hyperuricemia in Type 2 Diabetes Mellitus: A Mediation Analysis

Background: Emerging evidence suggests that increased perirenal adipose tissue (PAT) may trigger systemic inflammation and oxidative stress, potentially contributing to hyperuricemia (HUA). This study aimed to explore the link between PAT and HUA risk, and the potential mediating role of inflammation and oxidative stress.

Methods: This study recruited 903 participants with T2DM. Monocyte to high-density lipoprotein cholesterol ratio (MHR) was computed to assess systemic inflammation and oxidative stress. Perirenal fat thickness (PrFT) was measured by unenhanced abdominal CT, indicating PAT mass. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association correlation of HUA risk with PrFT and MHR. Meanwhile, adjusted mediation analysis based on bootstrapping calculations was performed to evaluate the direct impact of PrFT on HUA risk and the indirect effect mediated by MHR.

Results: Participants in the HUA group exhibited markedly higher levels of PrFT and MHR than the non-HUA group (P < 0.001). Serum uric acid presented a positive correlation with PrFT (β=0.368, P<0.001) and MHR (β=0.188, P<0.001) following adjustments for confounding factors. PrFT and MHR demonstrated an independent association with HUA risk after full adjustment for confounding factors in Model 3, with the ORs (95% CI) at 1.24 (95% CI:1.19-1.30, P<0.001) and 1.32 (95% CI:1.14-1.53, P<0.001), respectively. RCS analysis confirmed a non-linear association between PrFT, MHR, and HUA risk (P for nonlinear and overall< 0.001). Furthermore, MHR accounted for a mediated proportion of 11.29% in this association (P<0.001).

Conclusion: Increased PAT was an independent factor in HUA risk, with systemic inflammation and oxidative stress mediating this relationship.