Analysis of Plasma Extracellular Vesicles in Normal-Weight and Overweight Type 2 Diabetes Mellitus Using Multimodal...

Area of Science:

• Biochemistry
• Genomics
• Metabolomics

Background:

• Type 2 diabetes mellitus (T2DM) exhibits significant heterogeneity, impacting clinical presentation and treatment response.
• Normal-weight diabetes represents a distinct T2DM subtype requiring further molecular characterization.
• Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication and potential biomarkers in metabolic diseases.

Purpose of the Study:

• To characterize subtype-associated heterogeneity in T2DM using extracellular vesicle (EV)-associated molecular features.
• To investigate molecular differences in EVs from clinically stratified T2DM patients, focusing on normal-weight diabetes.
• To establish a framework for studying T2DM heterogeneity through multimodal EV profiling.

Main Methods:

• EVs were isolated from plasma of T2DM patients stratified by BMI and race/ethnicity.
• Multimodal analysis included surface-enhanced Raman spectroscopy (SERS) and EV-RNA sequencing.
• EV isolation and characterization were validated using transmission electron microscopy, nanoparticle tracking analysis, flow cytometry, and Western blotting.

Main Results:

• SERS identified distinct spectral fingerprints differentiating T2DM subgroups based on BMI and race/ethnicity.
• EV-RNA sequencing revealed differential microRNA expression, with specific miRNAs elevated in Asian overweight (A-OWD) and Asian normal-weight (A-NWD) T2DM subgroups.
• Unsupervised analysis indicated overlapping EV molecular features between A-NWD and White normal-weight (W-NWD) T2DM, suggesting BMI alone may not fully define metabolic states.

Conclusions:

• Multimodal EV profiling successfully identified subgroup-associated spectral and miRNA features in clinically stratified T2DM.
• These findings provide a framework for understanding T2DM heterogeneity at the molecular level.
• The study highlights specific molecular patterns associated with normal-weight diabetes, paving the way for targeted research.