Association of vitamin D Status with immune-associated serum protein pathways in overweight French-Canadian adults with hyperinsulinemia in the Quebec City metropolitan area, Canada

Deficiency in vitamin D can increase the risk of type 2 diabetes (T2D). Yet, the association between 25-hydroxyvitamin D (25(OH)D) levels and the serum proteome in subjects at risk of T2D remains unknown This proteomic analysis aimed to examine the correlations between serum proteins and 25(OH)D levels stratified as insufficient (<50 nmol/L), adequate (50-74.9 nmol/L), and optimal (≥75 nmol/L); and (2) to identify biological pathways linked to these proteins that may reduce T2D risk. In this crossover study, 25 hyperinsulinemic French-Canadian adults from the Quebec City metropolitan area (Canada) were evaluated at four timepoints: before and after 6 weeks of either adequate dairy intake (∼2 servings/day) or high dairy intake (≥4 servings/day). Serum 25(OH)D concentrations were measured using an immunoassay and serum protein profiling was performed using liquid chromatography-tandem mass spectrometry. Gene ontology analysis identified biological pathways. Dairy intake did not significantly change 25(OH)D serum levels. Nevertheless, in ten subjects with optimal 25(OH)D levels, positively correlated proteins were mainly involved in immunoglobulin-mediated immune response, regulation of blood coagulation, acute-phase response, and adaptive immunity. Negatively correlated proteins were enriched in classical complement activation, innate immune response, acute-phase response, and proteolysis. In six subjects with adequate 25(OH)D levels, correlated proteins were associated mainly with innate immune responses. No significant biological pathway enrichment was observed in subjects with insufficient 25(OH)D. Overall, individuals with higher or optimal serum 25(OH)D levels exhibit a greater number of proteins enriched in various immune system response pathways, processes known to influence T2D development.