# The Linkage Between Inflammation and the Progression of Type 2 Diabetes Mellitus

**Authors:** Lucy Baldeón-Rojas, Valeria Alulema, Francisco Barrera-Guarderas, Diana Aguirre-Villacís, Cristina Cañadas-Herrera, Ricardo Bedón-Galarza, Francisco Pérez-Tasigchana, Jorge Pérez-Galarza

PMC · DOI: 10.3390/cimb47100859 · 2025-10-17

## TL;DR

This study explores how inflammation contributes to type 2 diabetes progression and identifies biomarkers that could help monitor and predict the disease.

## Contribution

The study identifies novel biomarkers like leptin, IL-8, and miR-146a for predicting and monitoring T2D progression in an Ecuadorian population.

## Key findings

- Leptin and IL-8 were the strongest predictors of T2D, with high odds ratios.
- miR-146a was upregulated in T2D patients, contrasting with serum-based findings.
- Adiponectin distinguished uncontrolled T2D from diabetic kidney disease.

## Abstract

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder in which inflammation plays a central role in its onset, progression, and complications. Identifying reliable biomarkers is essential to improve risk prediction, disease monitoring, and early intervention. A total of 169 Ecuadorian participants were stratified into four clinical groups: non-diabetic controls (NDC), controlled T2D (C-T2D), uncontrolled T2D (NC-T2D), and diabetic kidney disease (DKD). Circulating levels of cytokines (IL-6, IL-8, TNF-α), adipokines (leptin, adiponectin), and PBMC-derived microRNAs (miR-146a, miR-155) were quantified. Associations with disease stage were evaluated using ROC curve analysis and logistic regression. Leptin showed the strongest association with T2D (OR = 13.76, 95% CI: 6.47–29.26), followed by IL-8 (OR = 6.73, 95% CI: 3.30–13.70) and IL-6 (OR = 4.43, 95% CI: 2.26–8.97). Adiponectin distinguished NC-T2D from DKD (OR = 4.15, 95% CI: 1.77–9.71), underscoring its potential as an indicator of renal complications. Interestingly, TNF-α levels declined across disease stages, possibly reflecting subclinical inflammation in Ecuadorian NDC with high rates of obesity and dyslipidemia. PBMC-derived miR-146a was upregulated in T2D patients, contrasting with prior serum-based studies and emphasizing the importance of compartment-specific analysis. miR-155 was elevated in C-T2D, suggesting a compensatory immune-regulatory mechanism that diminishes with poor glycemic control and advanced disease. Inflammatory cytokines, adipokines, and microRNAs act in distinct yet complementary ways in T2D. Leptin, IL-6, and IL-8 emerge as strong predictors of disease, while miR-146a and miR-155 provide additional insight into immune-inflammatory regulation. Integrated biomarker panels may enhance patient stratification and support personalized monitoring of T2D progression.

## Linked entities

- **Proteins:** IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), TNF (tumor necrosis factor), lepa (leptin a)
- **Diseases:** Type 2 diabetes mellitus (MONDO:0005148), diabetic kidney disease (MONDO:0005016), obesity (MONDO:0011122), dyslipidemia (MONDO:0002525)

## Full-text entities

- **Genes:** LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** metabolic disorder (MESH:D008659), T2D (MESH:D003924), diabetic (MESH:D003920), dyslipidemia (MESH:D050171), DKD (MESH:D003928), renal complications (MESH:D007674), Inflammation (MESH:D007249), obesity (MESH:D009765)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12562427/full.md

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Source: https://tomesphere.com/paper/PMC12562427