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

• Published in: Frontiers in endocrinology (Lausanne) 2024-07, Vol.15, p.1335371
• Main Authors: Špehar Uroić, Anita, Filipović, Maša, Šućur, Alan, Kelava, Tomislav, Kovačić, Nataša, Grčević, Danka
• Format: Article
• Language: English
• Subjects: Adolescent; Biomarkers - blood; Cardiometabolic Risk Factors; Cardiovascular Diseases - blood; Cardiovascular Diseases - metabolism; Case-Control Studies; chemokine receptors; chemokines; Chemokines - blood; Chemokines - metabolism; Child; children; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Endocrinology; Female; Humans; Male; obesity; Obesity - blood; Obesity - complications; Obesity - metabolism; Pediatric Obesity - blood; Pediatric Obesity - metabolism; type 1 diabetes mellitus
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2024.1335371

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. 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. 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. 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.