Comparative proteomic exploration of plasma proteins in different levels of vitamin D with type 2 diabetes mellitus using iTRAQ-coupled LC-MS/MS.

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Due to the variety of modern diet and lifestyle changes, China has become the world's largest number of people with T2DM. How to prevent and cure T2DM has become one of the urgent public health events in China. Numerous studies have demonstrated vitamin D (VitD) was independently correlated with insulin sensitivity and β cells function. VitD deficiency occurs in about 70% to 80% of patients with T2DM. However, the reason of T2DM patients suffering from VitD deficiency is not very clear. The aim of this project is to identify biomarkers to explore potential mechanism of VitD deficiency in patients with T2DM. We used the iTRAQ-coupled LC-MS/MS technique to screen differential expression proteins between VitD deficiency group and VitD sufficiency group in T2DM patients. Then we carried out hierarchical clustering analysis, Gene Ontology classification and enrichment analysis, KEGG pathway enrichment analysis, protein-protein interaction network (PPI) analysis and ELISA validation. We identified 63 differentially expressed proteins, 17 proteins were up-regulated and 46 proteins were down-regulated (VitD sufficiency vs. VitD deficiency). We ultimately selected four proteins, Podocalyxin (PODXL), ICAM3, MMP9, ApoF for further verification. As a result, the level of MMP9 and ICAM3 was higher in VitD sufficiency group than VitD deficiency group. Our study provided a solid theoretical foundation for the study of biomarkers and their mechanisms in most patients with T2DM who suffer from vitamin D deficiency. In addition, MMP9 and ICAM3 may play critical roles in the process of VitD deficiency in T2DM. The online version contains supplementary material available at 10.1007/s40200-024-01456-w.