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Early lipid and inflammatory markers of atherosclerosis in children with type 1 diabetes mellitus: effects of metabolic control and comorbidities

dc.contributor.advisorSpasojević-Kalimanovska, Vesna
dc.contributor.otherVekić, Jelena
dc.contributor.otherNinić, Ana
dc.contributor.otherMilenković, Tatjana
dc.creatorBojanin, Dragana
dc.date.accessioned2020-10-12T14:18:23Z
dc.date.available2020-10-12T14:18:23Z
dc.date.issued2020
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=7586
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:22516/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=18003465
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/17432
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3702
dc.description.abstractCilj ove disertacije je bio određivanje lipidnih i inflamatornih markera ateroskleroze kod dece sa tipom 1 dijabetes melitusa (T1DM) (N=201) i zdrave dece (N=141), ispitivanje njihove međusobne povezanosti, kao i uticaja metaboličke kontrole i komorbiditeta na analizirane parametre. To je uključilo određivanje standardnog lipidnog profila, veličine i raspodele subfrakcija lipoproteina niske (LDL) i visoke (HDL) gustine, koncentracije proprotein konvertaze subtilisin keksin tip 9 (PCSK9), koncentracije i genske ekspresije receptora za krajnje produkte uznapredovale glikacije (RAGE) i transformišućeg faktora rasta β1 (TGF-β1) u mononuklearnim ćelijama periferne krvi. U grupi sa T1DM bilo je 30 pacijenata sa pridruženim autoimunskim tireoiditisom i 15 sa pridruženom celijačnom bolešću. Koncentracije HDL-holesterola su bile više kod dece sa T1DM u odnosu na zdravu decu, dok se drugi parametri lipidnog profila nisu značajno razlikovali. Pacijenti sa neadekvatnom metaboličkom kontrolom su imali više koncentracije PCSK9 i veće udele malih HDL subfrakcija. U grupi sa dobrom metaboličkom kontrolom je utvrđena negativna korelacija između koncentracija PCSK9 i udela malih LDL čestica. Ekspresija gena za RAGE i TGF-β1 je bila značajno niža, a koncentracije značajno više kod dece sa T1DM. Koncentracije TGF-β1 u plazmi pacijenata sa T1DM su pozitivno korelirale sa udelom malih HDL subfrakcija, a genska ekspresija sa povećanom ekskrecijom albumina. Pacijenti sa pridruženom celijačnom bolešću su imali najniže koncentracije HDL-holesterola, najmanje dijametre HDL čestica i najveći indeks ateroskleroze. Rezultati su ukazali na značaj određivanja lipidnih i inflamatornih markera i ranog povećanja ekskrecije albumina u prevenciji dijabetesnih komplikacija.sr
dc.description.abstractThe aim of this thesis was to determine lipid and inflammatory markers of atherosclerosis in children with type 1 diabetes mellitus (T1DM) (N=201) and healthy children (N=141), to investigate their mutual relationships and the effects of metabolic control and comorbidities on examined markers. Standard lipid profile, low-density (LDL) and high-density (HDL) size and subclasses distribution, concentration of proprotein convertase subtilisin kexin type 9 (PCSK9), and concentrations and gene expression of receptor for advanced glycation end-products (RAGE) and transforming growth factor β1 (TGF-β1) in peripheral blood mononuclear cells were determined. In T1DM group 30 patients had associated autoimmune thyroiditis and 15 patients had celiac disease. HDL-cholesterol (HDL-C) levels were higher in children with T1DM, while other lipid status parameters did not differ between the groups. Patients with inadequate metabolic control had increased PCSK9 levels and higher proportion of small HDL subfractions. In the group with good metabolic control an inverse association between PCSK9 level and proportion of small LDL particles was found. Gene expression of RAGE and TGF-β1 was significantly lower and plasma concentrations were significantly higher in children with T1DM. TGF-β1 levels in plasma of T1DM patients were positively associated with the proportion of small HDL subfractions, and higher gene expression was associated with increased albumin excretion. Patients with associated celiac disease had the lowest concentrations of HDL-C, the smallest diameter of HDL particles, and the highest index of atherosclerosis. The results indicated importance of lipid and inflammatory markers and early increase of albumin excretion determination for prevention of diabetic complications.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.rightsAutorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
dc.rightsopenAccess
dc.sourceУниверзитет у Београдуsr
dc.subjectTip 1 dijabetes melitus, ateroskleroza, inflamacija, dislipidemija, metabolička kontrola, PCSK9, TGF-β1, RAGE, komorbiditetsr
dc.subjectType 1 diabetes mellitus, atherosclerosis, inflammation, dyslipidemia, metabolic control, PCSK9, TGF-β1, RAGE, comorbidityen
dc.titleRani lipidni i inflamatorni markeri ateroskleroze kod dece sa tipom 1 dijabetes melitusa: uticaj metaboličke kontrole i komorbiditetasr
dc.title.alternativeEarly lipid and inflammatory markers of atherosclerosis in children with type 1 diabetes mellitus: effects of metabolic control and comorbiditiesen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractСпасојевић-Калимановска, Весна; Миленковић, Татјана; Нинић, Aна; Векић, Јелена; Бојанин, Драгана; Рани липидни и инфламаторни маркери атеросклерозе код деце са типом 1 дијабетес мелитуса: утицај метаболичке контроле и коморбидитета; Рани липидни и инфламаторни маркери атеросклерозе код деце са типом 1 дијабетес мелитуса: утицај метаболичке контроле и коморбидитета;
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8296/IzvestajKomisije23254.pdf
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8295/Disertacija.pdf
dc.type.versionpublishedVersion


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