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

Area of Science:

• Proteomics
• Biomarker Discovery
• Diabetes Mellitus Complications

Background:

• Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM).
• Current diagnostic methods for DCM lack specificity and effectiveness for early detection.
• There is a critical need for reliable biomarkers to identify DCM in its early stages.

Purpose of the Study:

• To identify novel plasma biomarkers for the early diagnosis of diabetic cardiomyopathy.
• To investigate proteomic and glycation modification patterns in controls, diabetes mellitus (DM) patients, and DCM patients.
• To explore the potential of specific peptides and glycation sites as diagnostic indicators for DCM.

Main Methods:

• Integrated proteomic and nonenzymatic glycation analysis using data-dependent and data-independent acquisition.
• Construction of a plasma-specific spectral library.
• Validation of candidate biomarkers using parallel reaction monitoring.
• Receiver operating characteristic (ROC) analysis to assess diagnostic capacity.

Main Results:

• Significant disparities in protein abundance and glycation modification patterns were observed among controls, DM patients, and DCM patients.
• Differentially expressed proteins and modified peptides were primarily associated with immune responses, inflammation, and metabolic pathways.
• Specific peptides of complement 5 and glycation modifications on human serum albumin showed high accuracy (AUC=0.97) in discriminating DCM from DM.

Conclusions:

• Integrated proteomic and glycation analysis successfully identified potential biomarkers for DCM diagnosis.
• Complement 5 peptides and human serum albumin glycation sites show promise as early diagnostic biomarkers for DCM.
• The findings offer new insights into the pathogenesis of diabetic cardiomyopathy.