Povezanost plazmatskih koncentracija kemokina s metaboličkim komplikacijama šećerne bolesti tipa 1 i pretilosti u djece

doctoral thesis

• Title (english): Association of plasma levels of chemokines with metabolic complications of type 1 diabetes and obesity in children
• Author: Anita Špehar Uroić
• Mentor: Danka Grčević (mentor)
• Committee member: Marija Jelušić (predsjednik povjerenstva)
• Committee member: Nevena Krnić (član povjerenstva)
• Committee member: Hrvoje Lalić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Physiology and Immunology); Zagreb
• Defense date and country: 2025-03-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Universal decimal classification (UDC): 612 - Physiology

Abstract

U djece sa šećernom bolešću tipa 1 i pretilošću, dobi 12 do 18 godina, analizirali smo profil kemokina i kemokinskih receptora u perifernoj krvi s ciljem usporedbe sa zdravim ispitanicima te utvrđivanja povezanosti s kardiometaboličkim čimbenicima rizika. Koncentracija kemokina CCL2 povišena je u djece s loše reguliranim šećernom bolešću, kemokina CXCL11 snižena je u značajno pretilih, dok je kemokina CXCL12 snižena u obje skupine bolesnika. Uočene su brojne značajne korelacije kemokina i kemokinskih receptora s kardiometaboličkim i upalnim parametrima. U šećernoj bolesti se izdvaja pozitivna korelacija monocita CCR2+ s krvnim tlakom, limfocita B CCR2+ i CXCR3+ s trigliceridima, kemokina CCL2 s udjelom HbA1c i kemokina CXCL12 s omjernom albumina i kreatinina u urinu (ACR), uz negativnu povezanost subpopulacija CCR2+ s ACR. U pretilih dominira pozitivna povezanost kemokina CXCL12 s više metaboličkih parametara, negativna povezanost monocita CCR4+ i CXCR3+ s omjerom ACR te monocita s vrijednostima HOMA-IR. U obje bolesti nalazimo negativnu povezanost subpopulacija CXCR4+ s omjerom ACR i limfocita T CXCR3+ s lipidogramom te pozitivnu povezanost limfocita T CCR4+ s krvnim tlakom. Iako različiti rezultati sugeriraju imunoregulaciju specifičnu za pojedinu bolest, između šećerne bolesti i pretilosti postoje i preklapajući obrasci koji povezuju kemokinske signale s metaboličkom i vaskularnom disfunkcijom te predstavljaju moguće zajedničke terapijske ciljeve.

Abstract (english)

We compared peripheral blood chemokine/receptor profiles in children and adolescents (12-18 years) with type 1 diabetes mellitus (T1D) or obesity to healthy controls and analyzed associations of chemokine network with cardiometabolic risk factors. The level of CCL2 was higher in poorly controlled T1D, CXCL11 was lower in severe obesity and CXCL12 was lower in both diseases. Numerous significant associations were found for chemokine/receptor profiles and cardiometabolic/inflammatory parameters. In T1D we can emphasize positive associations of CCR2+ monocytes with blood pressure, CCR2+ and CXCR3+ B lymphocytes with triglycerides, CCL2 levels with HbA1c and CXCL12 levels with urine albumin-to-creatinine ratio (ACR), and inverse association of CCR2+ subsets with ACR. Major findings in obesity are positive associations of CXCL12 with metabolic parameters, inverse association of CCR4+ and CXCR3+ monocytes with ACR, and CXCR4+ monocytes with HOMA-IR. Both diseases share inverse associations of CXCR4+ subsets with ACR and CXCR3+ T lymphocytes with lipid profile, and positive associations of CCR4+ T lymphocytes with blood pressure. Although different results indicate disease-specific immunoregulation, overlapping patterns found in T1D and obesity suggest shared associations of chemokine axes with metabolic and vascular disfunction. Thus, chemokine axes might present potential common therapeutic targets for disease-related morbidity.

• Keywords: Pretilost/ Morbidno; Kreatinin; Dijabetes melitus/ tip 1; Glikirani hemoglobin; Krvni tlak; Kardiometabolički čimbenici rizika; Kardiovaskularne bolesti
• Keywords (english): Obesity/ Morbid; Creatinine; Diabetes Mellitus/Type 1; Glycated Hemoglobin; Blood Pressure; Cardiometabolic Risk Factors; Cardiovascular Diseases
• Language: croatian
• URN:NBN: urn:nbn:hr:105:733915
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 104 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-03-19 14:43:18