Cystic fibrosis related diabetes mellitus

Cistična fibroza (CF) je najčešća autosomno-recesivno nasljedna bolest u ljudi bijele rase koja bitno skraćuje životni vijek. Posljednjih smo desetljeća došli do brojnih novih saznanja i bolje razumijemo patofiziologiju bolesti, što nam je pomoglo u dijagnostici i metodama liječenja, ali je također otkrilo složenost bolesti. CF je progresivna bolest koja se liječi od trenutka postavljanja dijagnoze do kraja života, a oboljeli s vremenom razvijaju različite i u pravilu sve složenije kliničke slike. Posljedica mutacije gena za CF je disfunkcija proteina - transmembranskog regulatora provodljivosti (CFTR protein) koji služi kao kloridni kanal, a nalazi se na epitelnim stanicama u egzokrinim žlijezdama i drugdje u tijelu. Iako su najrazorniji simptomi CF povezani s plućima, bolest zahvaća više organskih sustava, a gotovo polovica svih bolesnika s CF razvija i dijabetes koji se zove šećerna bolest pridružena cističnoj fibrozi (CFRD). To je posebni oblik šećerne bolesti, izravna posljedica CF, i dijeli karakteristike s dijabetesom tipa 1 i tipa 2. Ovaj rad pregled je trenutnog razumijevanja patogeneze CFRD-a, opisuje kliničku prezentaciju, metode probira i dijagnoze te suvremene metode liječenja. Primarni uzrok CFRD-a je relativna inzulinska insuficijencija uzrokovana uništenjem Langerhansovih otočića gušterače. Početna faza bolesti često je asimptomatska zbog čega se u oboljelih od CF od desete godine života nadalje preporučuje aktivno tragati za bolešću, odnosno jednom godišnje učiniti oralni pokus opterećenja glukozom. Kako CFRD povećava morbiditet i smrtnost u oboljelih od CF-a važno ga je što ranije prepoznati i početi provoditi terapiju da bi se spriječili nepovoljni klinički ishodi. Terapija CFRD-a uključuje praćenje razine glukoze u krvi i održavanje tih razina u granicama normale. Ovo se najčešće postiže inzulinom i primjerenom prehranom koja se bitno razlikuje od prehrane za druge vrste dijabetesa.Cystic fibrosis (CF) is the most common autosomal recessive disorder among Caucasians that significantly shortens life expectancy. In recent decades we have gained an abundance of new insights and better understand the pathophysiology of the disease. This enabled improved diagnostic and therapeutic approaches, but also revealed the complexity of the disease. CF is a progressive disease that is treated from the moment of diagnosis to the end of a person’s life, and over time, patients develop different and overall more complex clinical presentations. The consequence of gene mutation in CF is the dysfunction of a protein – cystic fibrosis transmembrane conductance regulator (CFTR), a protein that acts as a chloride channel and is expressed on epithelial cells in the exocrine glands and elsewhere in the body. Although the most severe symptoms of CF are related to the lungs, the disease affects multiple organ systems, and nearly half of all CF patients develop a type of diabetes called cystic fibrosis related diabetes (CFRD). It is a distinct form of diabetes, a direct consequence of CF, and shares some of its characteristics with both type 1 and type 2 diabetes. This thesis reviews the current understanding of CFRD pathogenesis, describes clinical presentation, screening and diagnostic methods as well as modern treatment methods. The primary cause of CFRD is relative insulin insufficiency caused by the destruction of the pancreatic islets of Langerhans. The initial phase of the disease is often asymptomatic, thus active screening for the disease in CF patients is recommended from the age of ten onwards, performing oral glucose tolerance test once a year. As CFRD increases morbidity and mortality in CF patients, early recognition and therapy initiation are important to prevent adverse clinical outcomes. CFRD therapy involves monitoring blood glucose levels and keeping those levels within normal limits. This is most often achieved with insulin and an appropriate diet that is significantly different from the diet for other types of diabetes