| Abstract | Dijabetes mellitus u trudnoći utječe na nastanak dijabetičke embriopatije i fetopatije. Dijabetička embriopatija obuhvaća kongenitalne malformacije nastale poremećajem organogeneze u prvih 8 tjedana razvoja. Kongenitalne malformacije su dva do četiri puta češće u trudnica s dijabetesom i mogu zahvatiti jedan ili više organskih sustava, a najčešće je zahvaćen srčani, mišićno-koštani i središnji živčani sustav. U trudnica dijabetičarki također je veća učestalost rijetkih sindroma. Dijabetes je karakteriziran hiperglikemijom te obuhvaća poremećaj metabolizma ugljikohidrata, masti i bjelančevina. Poremećaj odvijanja metaboličkih procesa uzrokuje promjene u intrauterinom miljeu u kojem se razvija fetus. Nastaju različiti metaboliti i aktiviraju se različiti procesi koji mogu djelovati teratogeno. Osim hiperglikemije, u majčinoj se cirkulaciji teratogeni utjecaj povezuje s povećanom razinom β-hidroksibutirata, aminokiselina razgranatih lanaca i masnih kiselina. U fetalnoj cirkulaciji mogući teratogeni utjecaj ima snižena razina inozitola, arahidonske kiseline, prostaglandina i folne kiseline te povećana razina sorbitola. Istraživanja pokazuju kako se teratogeni utjecaj različitih metabolita očituje putem povećanog odvijanja procesa oksidativne fosforilacije i nastanka slobodnih radikala. Oksidativni stres, uz direktni utjecaj hiperglikemije, uzrokuje ER stres, lipidnu peroksidaciju i nitrozativni stres. Promijenjeno djelovanje raznih kinaza, PKC, JNK1/2 i AMPK dovodi do povećane apoptoze. Epigenetske promjene uzrokuju promijenjenu ekspresiju gena NCAM, PGP9.5, Bmp4, Msx1, Pax3 koji utječu na poremećenu migraciju i proliferaciju stanica te gena Bax i Bcl-2 koji aktiviraju kaspaze i posljedično uzrokuju apoptozu. Brojni faktori utječu na normalan embrionalni razvoj i nastanak kongenitalnih malformacija. Učestalost kongenitalnih malformacija u trudnica s dijabetesom moguće je smanjiti dobrom predkoncepcijskom obradom i regulacijom glikemije tijekom trudnoće. |
| Abstract (english) | Diabetes mellitus causes diabetic embryopathy and fetopathy in pregnancy. Diabetic embryopathy is a spectrum of congenital malformations caused by an interruption of organogenesis during the first 8 weeks of development. Diabetes is associated with a two-to fourfold increase in the rate of congenital malformations. Diabetes-induced malformations may affect one or more organ systems. The most commonly affected organ systems are the cardiac, musculoskeletal, and central nervous systems. Also, the fetuses of diabetic pregnant women have higher rates of rare syndromes. Diabetes is characterized by hyperglycemia, which affects metabolism of carbohydrates, fats, and proteins. Maternal metabolic dysregulation causes alterations in the intrauterine milieu. Formation of many metabolites and activation of different processes may have a teratogenic effect. Besides hyperglycemia, increased levels of beta-hydroxybutyrate, acetoacetate, branched-chain amino acids, triglycerides, and fats in the maternal circulation might act as teratogens. In the fetal circulation, decreased levels of inositol, arachidonic acid, prostaglandins, and folic acid, as well as an increased level of sorbitol may have a possible teratogenic effect. Studies showed teratogenic effect on embryonal development through increased oxidative phosphorylation, which leads to increased levels of reactive oxygen species. The synergistic effect of oxidative stress and hyperglycemia result in ER stress, lipid peroxidation, and nitrosamine stress. There is also alteration in the activity of many different kinases like PKC, JNK1/2, and AMPK, which lead to increased apoptosis. Epigenetic modifications change the expression of several genes, NCAM, PGP9.5, Bmp4, Msx1, and Pax3, which affect normal migration and proliferation of the cells. Also, a changed expression of Bax and Bcl-2 causes increased activation of caspaze and, consequently, apoptosis. There are many different teratogenic factors which interrupt normal embryogenic development and cause congenital malformations. Good preconception care and adequate glycemia regulation during pregnancy diminish the incidence of congenital malformations in the fetuses of diabetic pregnant women. |
