Sexual Dimorphism in the Association Between Vitamin D and Depressive Symptoms in Diabetic Patients and the Mediating Role of BMI: A Cross-Sectional Study

Background: The interplay between vitamin D deficiency, obesity, and depressive symptoms in type 2 diabetes remains poorly understood. Potential sex-specific differences in these associations have not been fully explored. Methods: We conducted a cross-sectional analysis of patients with type 2 diabetes (N = 917) from the NHANES 2017–2018 cycle. Restricted cubic spline models were used to assess potential non-linear associations between serum 25-hydroxyvitamin D3 and PHQ-9 depression scores. Regression-based mediation analysis was performed to estimate total, direct, and indirect associations, with body mass index (BMI) considered as a potential mediator. Models were adjusted for relevant demographic and cardiometabolic covariates. Results: In the overall diabetic cohort, higher vitamin D levels were modestly associated with lower depressive symptom scores. Mediation analysis suggested that this association was statistically accounted for by BMI. In sex-stratified analyses, significant total and indirect associations were observed among men, with a remaining direct association after adjustment for BMI, whereas no statistically significant associations were detected among women. Formal interaction testing supported differential association patterns by sex. Conclusions: Among adults with type 2 diabetes, serum vitamin D levels were inversely associated with depressive symptoms, with evidence suggesting sex-specific association patterns. These findings warrant further investigation in prospective studies to clarify potential underlying mechanisms and clinical implications.