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.