Distinct association patterns of chemokine profile and cardiometabolic status in children and adolescents with type 1 diabetes and obesity

Scientific paper - Original scientific paper

• Author: Anita Špehar Uroić
• Author: Maša Filipović
• Author: Alan Šućur
• Author: Tomislav Kelava
• Author: Nataša Kovačić
• Author: Danka Grčević
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy)
• Author's institution: University of Zagreb; School of Medicine; (Department of Physiology and Immunology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy

Abstract (english)

Objective: We compared peripheral blood (PBL) chemokine ligand/receptor profiles in children and adolescents with type 1 diabetes mellitus (T1D) or obesity (OB) (both involving inflammation and vascular complications) to identify their associations with cardiometabolic risk factors.

Materials and methods: PBL samples from children and adolescents (12-18 years) included: healthy controls (n=29), patients with T1D (n=31) and OB subjects (n=34). Frequency of mononuclear cell populations and chemokine receptor expression (CCR2, CCR4, CXCR3, CXCR4) were determined by flow cytometry. Chemokine levels of CCL2, CCL5, CXCL10 and CXCL11 were measured by bead-based assay and CXCL12 by ELISA. Data were correlated with cardiovascular, metabolic and inflammatory parameters.

Results: The proportion of CD14+ monocytes was higher in T1D, whereas the proportion of CD19+ B lymphocytes was higher and CD3+ T lymphocytes was lower in OB. The level of CCL2 was higher in T1D (241.0 (IQR 189.6-295.3) pg/mL in T1D vs 191.5 (IQR 158.0-254.7) pg/mL in control, p=0.033), CXCL11 was lower in OB (6.6 (IQR 4.9-7.7) pg/mL in OB vs 8.2 (IQR 6.9-11.3) pg/mL in control, p=0.018) and CXCL12 was lower in both diseases (2.0 (IQR 1.8-2.5) ng/mL in T1D, 2.1 (IQR 1.9-2.4) ng/mL in OB vs 2.4 (IQR 2.2-2.5) ng/mL in control, p=0.016). Numerous significant associations were found for chemokine ligand/receptor profiles and clinical data. Among these, we are suggesting the most important indicators of cardiometabolic risk in T1D: positive associations of CCR2+ monocytes with blood pressure and CCL12 levels with urine albumin-to-creatinine ratio (ACR), inverse association of CXCR3+ B lymphocytes with AST but positive with triglycerides; and OB: positive associations of CXCL12 levels with triglycerides and AST/ALT, inverse association of CCR4+ and CXCR3+ monocytes with ACR. Both diseases share positive associations for CCR4+ T lymphocytes and blood pressure, inverse associations of CXCR4+ subsets with ACR and CXCR3+ T lymphocytes with lipid profile.

Conclusion: Significantly changed chemokine ligand/receptor profiles were found in both T1D and OB even at a young age. Although different associations with cardiometabolic risk factors indicate disease-specific changes, overlapping pattern was found for the associations between CCR4+ T lymphocytes and vascular inflammation, CXCR4+ subsets and albuminuria as well as CXCR3+ T lymphocytes and dyslipidemia. Thus, chemokine axes might present potential therapeutic targets for disease-related morbidity.

• Keywords (english): Adolescent; Biomarkers / blood; Cardiometabolic Risk Factors; Cardiovascular Diseases / blood; Cardiovascular Diseases / metabolism; Case-Control Studies; Chemokines / blood; Chemokines / metabolism; Child; Diabetes Mellitus, Type 1 / blood; Diabetes Mellitus, Type 1 / metabolism; Female; Humans; Male; Obesity / blood; Obesity / complications; Obesity / metabolism; Pediatric Obesity / blood; Pediatric Obesity / metabolism
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Frontiers in Endocrinology
• Numbering: vol. 15, 1335371
• e-ISSN: 1664-2392
• DOI: https://doi.org/10.3389/fendo.2024.1335371
• URN:NBN: urn:nbn:hr:105:290007
• Publication: 2024-07-23
• Document URL: https://www.frontiersin.org/articles/10.3389/fendo.2024.1335371/full
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-03-31 11:12:18