Concentrations of the vitamin D metabolite 1,25(OH)₂D and odds of metabolic syndrome and its components

Aim Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)₂D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)₂D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D. Methods Participants from two completed clinical trials of colorectal neoplasia with available metabolic syndrome data and blood samples for measurement of 1,25(OH)₂D (n = 1048) and 25(OH)D (n = 2096) were included. Cross-sectional analyses of the association between concentrations of 1,25(OH)₂D, 25(OH)D, metabolic syndrome, and its components were conducted. Results A statistically significant inverse association was observed for circulating concentrations of 1,25(OH)₂D and metabolic syndrome, with adjusted ORs (95% CIs) of 0.73 (0.52-1.04) and 0.52 (0.36-0.75) for the second and third tertiles of 1,25(OH)₂D, respectively (p-trend < 0.001). Significant inverse relationships were also observed between 1,25(OH)₂D and high triglycerides (p-trend < 0.001), and low high-density lipoprotein (p-trend < 0.001). For 25(OH)D concentrations, significant inverse associations were found for metabolic syndrome (p-trend < 0.01), high waist circumference (p-trend < 0.04) and triglyceride levels (p-trend < 0.01). Participants with 25(OH)D ≥ 30 ng/ml and in the highest tertile of 1,25(OH)₂D demonstrated significantly lower odds of metabolic syndrome, with an OR (95% CI) of 0.38 (0.19-0.75) compared to those in the lowest category for both metabolites. Conclusion These results provide new evidence that the relatively rarely-studied active hormonal form of vitamin D, 1,25(OH)₂D, is associated with metabolic syndrome and its components, and confirm prior findings for 25(OH)D. The finding that 1,25(OH)₂D is related to high-density lipoprotein, while 25(OH)D is not, suggests that there may be an independent mechanism of action for 1,25(OH)₂D in relation to metabolic dysregulation.