Proteomic Signatures of Cardiac Dysfunction Among People With Diabetes: The Atherosclerosis Risk in Communities Study

Area of Science:

• Cardiovascular Research
• Metabolomics
• Proteomics

Background:

• Diabetes mellitus significantly increases the risk of heart failure (HF).
• The specific biological mechanisms driving this elevated HF risk in diabetic individuals remain largely unknown.
• Understanding these mechanisms is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To identify proteomic signatures associated with heart failure (HF) in individuals with diabetes.
• To uncover novel protein markers that specifically predict HF risk in the context of diabetes.
• To explore the underlying biological pathways involved in diabetes-related HF.

Main Methods:

• Utilized a large cohort (ARIC study) of 10,189 participants, including those with and without diabetes, to discover protein-HF associations.
• Employed Cox regression analysis to identify plasma proteins linked to HF, stratified by diabetes status.
• Performed internal validation within the ARIC study and external validation using the MESA study cohort to confirm findings.
• Conducted pathway analyses to understand the biological functions of identified proteins.

Main Results:

• Identified 19 proteins associated with HF in individuals with diabetes in the discovery phase.
• Validated 6 proteins in an independent cohort, with 5 proteins specifically associated with HF in the diabetes subgroup.
• Four novel proteins (tyrosine-protein kinase 7, chondroadherin, LRRIG1, fibulin-5) and one known protein (CLIP2) were uniquely linked to HF risk in diabetes.
• Pathways implicated included lipid metabolism, inflammation, and brown adipose tissue function.

Conclusions:

• Discovered five proteomic markers, four of which are novel, that are uniquely associated with heart failure risk in individuals with diabetes.
• These findings provide new insights into the specific molecular mechanisms underlying heart failure in the diabetic population.
• The identified novel markers may serve as potential biomarkers for early detection or therapeutic targets for diabetes-related heart failure.