Inflammatory Proteomic Heterogeneity Beyond Glycemia Status in Severe Obesity

Area of Science:

• Metabolomics
• Immunology
• Obesity Research

Background:

• Chronic low-grade inflammation is linked to obesity and dysglycemia.
• Significant variation in inflammatory responses exists across glycemic statuses (normoglycemia, prediabetes, type 2 diabetes mellitus).
• Understanding inflammatory protein profiles may define patient phenotypes beyond current classifications.

Purpose of the Study:

• To investigate if circulating inflammatory protein profiles identify distinct patient phenotypes in severe obesity.
• To explore inflammatory protein signatures in relation to glycemic status (normoglycemia, prediabetes, T2DM).

Main Methods:

• Cross-sectional analysis of 142 individuals with severe obesity.
• Plasma inflammatory proteins quantified using Olink proximity extension assay.
• Differential expression analysis and unsupervised topological data analysis (TDA) applied to identify patient subgroups.

Main Results:

• Several inflammatory proteins, including IL-8, Flt3L, and CDCP1, were upregulated in prediabetes and T2DM compared to normoglycemia.
• TDA identified seven distinct inflammatory protein-based clusters.
• One cluster showed coordinated upregulation of IL-8, Flt3L, CDCP1, and other immune proteins, enriched in T2DM patients.

Conclusions:

• Inflammatory proteomic profiling reveals glycemia-associated protein changes and distinct phenotypes in severe obesity.
• These inflammatory phenotypes transcend conventional glycemic classification.
• Findings support a framework for future studies on proteomic patterns in obesity-related dysglycemia.