Nonlinear Relationship Between Monocyte‐to‐Lymphocyte Ratio and Bone Mineral Density in Type 2 Diabetes Mellitus: Mediating Role of Fat Distribution

ABSTRACT Objective The objective of study is to clarify the relationship between monocyte‐to‐lymphocyte ratio (MLR) and lumbar spine bone mineral density (BMD) in type 2 diabetes mellitus (T2DM), and analyse the mediating role of fat distribution, providing a new indicator for the early diagnosis of osteoporosis in T2DM. Methods A total of 430 T2DM patients over 50 years were included. Subjects were divided into T1, T2 and T3 three groups based on MLR. The adjusted regression models, subgroup analysis, generalised additive model (GAM), smoothed curve fitting, and mediated effects analysis methods were used. Results The results indicated a significant negative correlation between MLR and lumbar spine BMD in T2DM ( β = −0.701; 95%CI: −0.112, −0.290). Subgroup analysis, smoothed curve fitting and threshold effect analysis showed a nonlinear relationship between MLR and BMD, with an optimal inflection point at an MLR value of 0.1266. Additionally, the ratio of visceral to subcutaneous fat area (VSR) was negatively correlated with lumbar spine BMD ( β = −0.775; 95%CI: −1.007, −0.504). Mediation effect analysis of VSR between MLR and lumbar spine BMD showed that the total effect estimate was −0.0717, the direct effect estimate was −0.0524, the mediation effect estimate was −0.0193, with the mediated proportion accounting for 26.88% of the total effect. Conclusion MLR is significantly associated with lumbar spine BMD in T2DM. Higher MLR levels correlated with reduced BMD. VSR plays a significant mediating role in this relationship, highlighting MLR's potential utility in osteoporosis diagnosis and importance of fat management for bone health.