(1) Background: Observational studies have established that vitamin D-binding protein (DBP) and 25-hydroxyvitamin D3 (25(OH)D) concentrations are the major factors affecting the bioavailability of 25(OH)D. It has also been shown that poor 25(OH)D bioavailability elevates the risk of obesity and its related cardio-metabolic disorders. However, the relationship between 25(OH)D and DBP concentrations with cardio-metabolic risk factors in overweight and obese cohorts has not been established. Consequently, we evaluated the association between DBP and 25(OH)D concentrations with lipid profile, blood pressure (BP), and body composition in overweight and obese women. (2) Methods: In this cross-sectional study of 236 overweight and obese women, DBP and 25(OH)D concentrations were measured using an enzyme-linked immunosorbent assay. Body composition was assessed via bioelectrical impedance analysis. Lipid profile and BP were assessed by an auto-analyzer and digital BP monitor, respectively. The associations were examined by multivariate logistic regression. (3) Results: The indicated showed an inverse relationship between DBP and high-density lipoprotein (HDL) (p = 0.010) concentrations (where individuals with higher DBP had lower HDL) which, after adjusting for possible cofounders, remained significant (p = 0.006). Moreover, DBP concentration was positively associated with fat mass index (FMI) after adjustment (p = 0.022). No significant relationships were observed among 25(OH)D and target variables. (4) Conclusions: In conclusion, lower concentrations of HDL and higher values of FMI are associated with higher concentrations of DBP in overweight and obese women. These findings present novel awareness regarding the association of DBP with some metabolic and body composition variables in overweight and obese women. However, a two-way causal relationship between DBP and target variables should be considered.
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