The modulatory role of white matter lesions in the mediation between BMI, lipids, blood pressure, and glucose levels

Introduction: Cardiometabolic alterations affect glycemic control, but the modulatory role of cerebral white matter lesions in these associations is not yet fully understood. Objective: To evaluate whether the presence of cerebral white matter lesions moderates the relationship between BMI and glucose through cardiometabolic markers. Materials and Methods: Analytical secondary data study (n = 1904) of patients undergoing clinical evaluations and brain MRI. The independent variable was BMI and fasting glucose the dependent variable; mediators included LDL, triglycerides (TG), and systolic blood pressure (SBP); and the moderator was the presence of cerebral white matter lesions. Hayes’ PROCESS model 59 was used to assess direct, indirect, and moderated effects. The causal model was visualized with a directed acyclic graph. Results: The effect of BMI on LDL (β = 1.47; p < 0.001), TG (β = 10.13; p < 0.001), and SBP(β = 1.45; p < 0.001) was attenuated in the presence of lesions, with significant negative interactions (LDL: β = −0.86; p = 0.036; TG: β = −3.89; p = 0.003; SBP: β = −0.81; p = 0.001). In the glucose model, BMI (β = 1.36; p < 0.001), TG (β = 0.015; p = 0.003), and SBP (β = 0.11; p = 0.004) showed positive associations. Lesions had no significant direct effect (β = 11.58; p = 0.12) but moderated the BMI-glucose (interaction: β = −0.49; p = 0.048) and TG-glucose (interaction: β = 0.058; p < 0.001) relationships. The indirect effect of BMI on glucose via triglycerides was greater in the presence of lesions (β = 0.45; 95%CI: 0.25–0.75) than in their absence (β = 0.15;95%CI: 0.01-0.40). Mediation through SBP was significant in both groups (no lesions: β = 0.15; with lesions: β = 0.07). Conclusions: The indirect effects of BMI on glucose are modulated by the presence of cerebral white matter lesions, highlighting the modulatory role of brain damage in the pathways linking adiposity and glycemic control.