Povezanost inkretinske terapije i nealkoholne steatoze jetre u bolesnika sa šećernom bolesti tipa 2

master's thesis

• Title (english): Association between incretin therapy and non-alcoholic fatty liver disease in patients with diabetes mellitus type 2
• Author: Anamarija Lončar
• Mentor: Lea Smirčić-Duvnjak (mentor)
• Committee member: Darko Kaštelan (predsjednik povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Committee member: Lea Smirčić-Duvnjak (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2016-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Nealkoholna masna bolest jetre (NAFLD – Non-alcoholic fatty liver disease) nastaje prekomjernim nakupljanjem masti u hepatocitima u odsutnosti konzumacije alkohola u količinama štetnim za jetru. Može se manifestirati različitim oblicima, od jetrene steatoze kao masne infiltracije jetre do nealkoholnog steatohepatitisa (NASH-a) praćenog upalom. Oba stanja mogu rezultirati ozbiljnim hepatalnim komplikacijama poput fibroze, ciroze i hepatocelularnog karcinoma. Zahvaća do 30% svjetske populacije i vodeći je uzrok kronične jetrene bolesti u Zapadnim zemljama. Unatoč visokoj prevalenciji, NAFLD nema univerzalno prihvaćenu farmakološku terapiju. Prema nekim istraživanjima, 43% bolesnika sa šećernom bolesti tipa 2 ima NAFLD. Upravo šećerna bolest tipa 2 (DMT2), uz metabolički sindrom i pretilost, predstavlja najveći rizik za razvoj NAFLD-a. Iako patogeneza NAFLD-a nije do kraja razjašnjena, poznato je da je povezana s perifernom i hepatalnom inzulinskom rezistencijom koja uzrokuje steatozu zbog povećane dopreme slobodnih masnih kiselina (SMK) u jetru. Dvije su terapijske opcije bazirane na inkretinima: GLP analozi i inhibitori dipeptidil petidaze (DPP-4).GLP analozi, poput eksenatida i liraglutida, inkretinski su mimetici koji se često koriste u liječenju bolesnika sa DMT2. Smanjuju razinu šećera u krvi poticanjem sekrecije inzulina i inhibicijom sekrecije glukagona ovisno o razini glukoze. Djelujući putem GLP-receptora smještenih na humanim hepatocitima, GLP analozi djeluju izravno na smanjenje jetrene steatoze poboljšavajući inzulinsku osjetljivost, lipidni metabolizam i zaustavljajući oksidativni stres u hepatocitima. Osim izravnoga učinka, GLP analozi pokazuju i neizravni učinak na smanjenje masti u jetri i jetrenih upalnih biomarkera djelujući na supresiju apetita u hipotalamusu, smanjenje tjelesne težine i HbA1c-a. Također, smanjuju krvni tlak i pokazuju brojne poželjne kardiovaskularne učinke. GLP analog liraglutid terapija je izbora u bolesnika s NAFLD-om i DMT2, dok se DPP-4 inhibitori koriste samo kod bolesnika s DMT2.

Abstract (english)

Non-alcoholic fatty liver disease (NAFLD) represents an excessive accumulation of fat in hepatocytes in the absence of alcohol abuse. It can manifest with a wide range of disorders,from non-alcoholic fatty liver as a simple steatosis to non-alcoholic steatohepatitis (NASH) accompanied by inflammation. Both disorders can result in serious conditions as cyrosis and hepatocellular carcinoma. It affects up to 30% people worldwide and has become the leading cause of chronic liver damage in Western countries. Despite its high prevalence, there are no universally accepted pharmacological therapies. According to some researches, even up to 43% of patients with diabetes mellitus type 2 have NAFLD. Diabetes mellitus type 2, besides metabolic syndrome and obesity, represents the highest risk of developing NAFLD. Although its mechanism remains unclearified, it is well-known that NAFLD is associated with peripheral and hepatic insulin resistance which causes steatosis due to higher delivery of free fatty acids (FFA) to the liver. There are two therapeutic options based on incretins: GLP analogues and dipeptidyl peptidase - 4 (DPP-4) inhibitors.GLP-1 analogues, like exenatide and liraglutide, are incretin mimetics widely used in patients with diabetes mellitus type 2 (DMT2). They lower blood glucose by enhancing the secretion of insulin and inhibiting the secretion of glucagon in glucose - dependent manner. By binding to GLP-receptors presented on human hepatocytes, GLP analogues exert their direct effects on lowering hepatic steatosis by improving insulin sensitivity, lipid metabolism and inhibition of oxidative stress. GLP analogues also show indirect effects on the decrease of liver fat and hapatic biomarkersby suppressing appetite, lowering of the body weight and Hb1Ac. They also decrease blood pressure and show cardiovascular benefits. GLP analogue liraglutide has been therapy of choice in patients with NAFLD and DMT2, while DPP-4 inhibitors are used only in patients with DMT2.

• Keywords: nealkoholna masna bolest jetre (NAFLD); šećerna bolest tipa 2; GLP-analozi; inhibitori DPP-4; inzulinska rezistencija
• Keywords (english): non-alcoholic fatty liver disease (NAFLD); diabetes mellitus type 2 (DMT2); GLPanalogues; DPP-4 inhibitor; insulin resistance
• Language: croatian
• URN:NBN: urn:nbn:hr:105:792685
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-08-10 11:14:16