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The Role of Pharmacogenetics in the Treatment of Diabetes Mellitus / ULOGA FARMAKOGENETIKE U LEČNJU DIJABETES MELITUSA

E. Topić

Published 2013 in Unknown venue

ABSTRACT

Summary Diabetes mellitus is a heterogeneous group of disorders in which particular disease phenotypes can be characterized by a specific etiology and/or pathogenesis of the disease, but in many cases its classification is greatly impeded due to significant phenotype overlapping. Diabetes is a wordwide epidemic with significant health and economic consequences. The frequency of type 2 diabetes (T2D) is much higher than type 1 diabetes (T1D). In adults, around 285 million people suffer from T2DM with a projected rise to 438 million in the next 20 years. A variety of pharmacological treatments exist for patients with T2D, in addition to dietary and physical activity. Pharmacologically, diabetes is treated with nine major classes of approved drugs, including insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, a-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Treatment strategy for T2D is based mostly on oral hypoglycemic drug (OHD) efficacy assessed usually by HbA1c and/or fasting plasma glucose. The patients are often treated with more than one OHD in combination with the purpose to receive more effective treatment. Characterization of drug response is expected to substantially increase the ability to provide patients with the most effective treatment strategy. If pharmacogenetic testing for diabetes drugs could be used to predict treatment outcome, appropriate measures could be taken to treat T2D more efficiently. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs, the most used OHD. A comprehensive review of the pharmacogenetic studies of specific OHD is presented in this article. Understanding the pharmacogenetics of these drugs will provide critical baseline information for the development and implementation of a genetic screening program into therapeutic decision making, enabling a personalized medicine approach for T2D patients. Kratak sadržaj Dijabetes melitus predstavlja heterogenu grupu pore mećaja u kojoj određeni fenotip može karakterisati spe cifična etiologija i/ili patogeneza bolesti, ali u mnogim slučajevima njegova klasifikacija je vrlo otežana zbog značajnog fenotipskog pre klapanja. Dijabetes je globalni epidemiološki problem sa značajnim zdravstvenim i ekonomskim posledicama. Učes talost tipa 2 dijabetesa (T2D) mno go je veća od tipa 1 dijabetesa. Kod odraslih, oko 285 miliona osoba boluje od T2D, s predviđenim rastom do 438 miliona u sledećih 20 godina. Za pacijente s dijabetesom tipa 2, uz ishranu i fizičku aktivnost, postoji niz farmakoloških lekova. Devet glavnih vrsta lekova odobreno je za lečenje T2D bolesnika: insulin i njegovi analozi, sulfonilureje, bi gvanidi, tiazolidindioni, meglitinidi, inhibitori a-glukozidaze, analozi amilina, mimetici inkretin hormona i inhibitori dipeptidil-peptidaze 4. Strategija lečenja T2D se temelji uglavnom na učinkovitosti oralnih hipoglikemijskih lekova merenjem HbA1c i/ili glukoze natašte. Bolesnici se često leče kombinacijom više oralnih hipoglikemika kako bi se postigla što uspeš nija terapija. Karakterizacija odgovora na lek obezbediće, kako se očekuje, mogućnost uspešnijeg lečenja, odnosno, da se bolesniku omogući strategija najbo ljeg lečenja. Ako bi se farmakogenetskim testiranjem dija be tičkih bolesnika mogao predvideti ishod lečenja, odgovarajuće merenje moglo bi se pri meniti za mnogo uspešnije lečenje dijabetesa. Do sada, glavne farmakogenetske studije fokusirale su se na istra ži vanje odgovora na terapiju sulfo nil urejama, bigvanidima i tiazolidindionima, najčešće ko riš ćenim oralnim hipo glikemij skim lekovima. Ovaj članak predstavlja sažeti pregled farmakogenetskih studija specifičnih navedenih oralnih hipo glikemijskih lekova. Razumevanjem farmakogenetike ovih lekova dobiće se temeljne informacije za razvoj i primenu programa genetskog pretraživanja pri odluci o lečenju, koji bi omogućio pristup personalizovane medicine bolesnicima s dijabetesom tipa 2.

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