Identifying Diabetic Cardiomyopathy Biomarkers via Proteomic and Glycation Modification Analysis Using DIA and PRM

Diabetic cardiomyopathy (DCM), a severe complication of type 2 diabetes mellitus (T2DM), lacks specific and effective biomarkers for early diagnosis. This study constructed a plasma-specific spectral library by integrating proteomic and nonenzymatic glycation data from eight pretreatment workflows via data-dependent acquisition. Data-independent acquisition was then applied to profile plasma proteomes and glycation modifications in controls, DM patients, and DCM patients, revealing clear disparities in protein abundance and glycation modification patterns among the three groups. Functional enrichment analysis indicated that these differentially expressed proteins and modified peptides were involved primarily in immune responses, inflammatory processes, and metabolic pathways. Subsequently, parallel reaction monitoring was used to validate the proteins and glycation sites with significant changes. Specific peptides of complement 5 and specific glycation modifications on human serum albumin demonstrated a strong capacity to discriminate DCM from DM, achieving the highest area under the curve values of 0.97 in receiver operating characteristic analyses, underscoring their promising potential as DCM biomarkers. In conclusion, integrated proteomic and glycation modification analysis revealed candidate biomarkers for DCM diagnosis and offered novel insights into DCM pathogenesis.