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5.2 1HPYHPKHVV]XNiN ... 37

5.3 Magzatok ... 38

6. gVV]HIRJODOiV ... 41

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(5)

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(6)

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(7)

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$ YHPKHVVpJ PHVWHUVpJHVHQ LV IHQQWDUWKDWy SURJHV]WHURQQDO $ SURJHV]WHURQ NRQFHQWUiFLyQDN QJPO IHOHWW NHOO OHQQLH D YHKHP PHJPDUDGiViKR] H] EL]WRVtWMD D]

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YHPKHVpVQHPYHPKHVV]XNiNEDQLVPHJILJ\HOWpNPHO\QHNHUHGPpQ\HNpQWFXNRUEHWHJVpJLV kialakulhat (VERSTEGEN-ONCLIN - VERSTEGEN, 2008). Az inzulin pU]pNHQ\VpJ NE 43%-NDO FV|NNHQ D YHPKHVVpJ NpVHL V]DNDV]iEDQ V]XNiNEDQ (JOHNSON, 2008). Az anyai inzulin-UH]LV]WHQFLD YHPKHVVpJ DODWW VRN IDMQiO NHUOW NLPXtaWiVUD EHOHpUWYH D] HPEHUW pV D NXW\iW ispVQDJ\KDWiVVDOYDQDPDJ]DWLIHMOĘGpVUH(FALL, et al., 2008).

(J\ WDQXOPiQ\ V]HULQW D WHUKHVVpJ DODWW a Langerhans szigetek sejtjeinek W|PHJpQHN Q|YHNHGpVH HJ\ DGDSWtY YiODV] D] LQ]ulin-rezisztenFLD OHN]GpVH pUGHNpEHQ $ SURODNWLQ XJ\DQLVQ|YHOQLWXGMDDEpWD-VHMWHNSUROLIHUiFLyMiWpVD]LQ]XOLQV]HNUpFLyt in vitro.tVpUOHWHW YpJH]WHNDQQDNIHOGHUtWpVpUH, hogy a prolaktin receptor (PRLr) PHQQ\LEHQKDWiUR]]D meg a QRUPiO DQ\DL JONy] KRPHRV]Wi]LVW D WHUKHVVpJ DODWW $ NtVpUOHW DODSMiQ LQWUDSHULWRQHiOLV JONy]-WROHUDQFLDWHV]WHWKDMWRWWDNYpJUH35/UpVKHWHUR]LJyWD35/U- vemhes egereken a 0., 15., 18. napon. $] HUHGPpQ\HN V]HULQWa PRLr +/- egyedekEHQ NiURVRGRWW D JNy]

NOtUHQV] FV|NNHQW D JONy] VWLPXOiOWD LQ]XOLQ NLERFViWiV PDJDVDEE JONy] pV DODFVRQ\DEE LQ]XOLQ V]LQW YROW MHOOHP]Ę. A PRLr +/+ HJHUHNEHQ MHOHQWĘVHQ Q|YHNHGHWW D V]LJHWVHMWHN GHQ]LWiVDpVDEpWD-VHMWHNV]iPDDYHPKHVVpJVRUiQHOOHQWpWEHQD35/U- szemben. A PRLr HJHUHNEHQHUĘWHOMHVHEEEpWD-VHMWSUROLIHUiFLy]DMORWWPtJQHPYROWNO|QEVpJD]DSRSWy]is V]HPSRQWMiEyO D NpW JHQRWtSXV N|]|WW (] D] HOVĘin vivo GHPRQVWUiFLyMD DQQDN KRJ\ D YHPKHVVpgi hormonok a PRLr-RQ NHUHV]WO KDWiVVDO YDQQDN D EpWD-VHMWHNUH tJ\az anyai JONy]KRPHRV]Wi]isra (HUANG, et al., 2009).

A GDM alatt, KDDEpWD-VHMWHNW~OPĦN|GpVHQHPYH]HWD]RNNLIiUDGiViKR]DNNor van HVpO\DIHOJ\yJ\XOiVUD(llenben, hDW~O]RWWYROWDNRPSHQ]iFLyV PĦN|GpVNpVQDJ\UpV]N HOSXV]WXOW D YHPKHVVpJ XWiQa FXNRUEHWHJVpJ iOODQGyVXOhat (]pUW D N|YHWNH]Ę YHPKHVVpJ DONDOPiYDOQDJ\D]HVpO\D]LQ]XOLQ-dependens DM kialakuliViUD(Feldman - Nelson, 2004).

2007-EHQ -XQ\LQJ +DQ pV PXQNDWiUVDL NtVpUOHWHNHW YpJH]WHN SDWNiQ\RNEDQ DQQDN kiGHUtWpVpUH KRJ\ D] DQ\DL FXNRUEHWHJVpJ PLO\HQ KDWiVVDO YDQ D] ~MV]O|WWHN KDVQ\iOPLULJ\pQHNEpWD-VHMWMHLUH$]DQ\DSDWNiQ\RNFXNRUEHWHJVpJpWVtreptozotocinnal (STZ) LGp]WpNHOĘDPHO\HJ\EpWD-VHMWNiURVtWy YHJ\OHW$]HUHGPpQ\HNV]HULQWD]DQ\iNYpUFXNRU NRQFHQWUiFLyMDQHPPXWDWRWWMHOHQWĘVNO|QEVpJHWDQHPNH]HOWNRQWUROOFVRSRUWpKR]NpSHVW KDEiUDYHPKHVVpJYpJpQKLSHUJOLNpPLDDODNXOWNLamely az ellpVXWiQPHJLVV]Ħnt. Az STZ- YHONH]HOWSDWNiQ\RNWHVWV~O\DD]RQEDQMHOHQWĘVHQFV|NNHQWDYHPKHVVpJpVKHWpUH$]

~MV]O|WWHNV]iPDWHVWV~O\Dalacsonyabb voOWPLQWDNRQWUROOFVRSRUWp$NH]HOWDQ\iNXWyGDL NH]GHWEHQ KLSRJOLNpPLiVDN YROWDN PHO\ D YiODV]WiV XWiQ QRUPDOL]iOyGRWW $] ~MV]O|WWHN LQ]XOLQ HOYiODV]WiViQDN YL]VJiODWiUD NpW NO|QE|]Ę PHQQ\LVpJĦ JONy]W DGDJROWDN D] L]ROiOW KDVQ\iOPLULJ\ V]|YHWKH] $] DODFVRQ\ NRQFHQWUiFLyM~ JONy] DGiVDNRU QHP WDSDV]WDOWDN

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MHOHQWĘVHOWpUpVWDNpWFVRSRUWN|]|WW0DJDVDEEJONy]NRQFHQWUiFLyHVHWpQYLV]RQWMHOHQWĘVHQ FV|NNHQW D] LQ]XOLQ HOYiODV]WiV D NRQWUROOFVRSRUWKR] NpSHVW $ NH]HOW ~MV]O|WW iOODWRN KDVQ\iOPLULJ\pEHQ D JONy]-IHOKDV]QiOiV LV FV|NNHQW DKRJ\ D JONy] PHWDEROL]PXVipUW IHOHOĘVHQzimek NRQFHQWUiFLyMDLV$KDVQ\iOPLULJ\PRUIROyJLDLODJQHPPXWDWRWWHOWpUpVWDNpW FVRSRUW N|]|WW 9DOyV]tQĦ KRJ\ D FV|NNHQW HQ]LP DNWLYLWiV WHKHWĘ IHOHOĘVVp D EpWD-sejtek GLV]IXQNFLyMipUW(HAN, et al., 2007).

$ PDJ]DWRW EXUNROy DPQLRQEXURN HSLWHOVHMWHNEĘO pV PH]HQFKLPiOLV VHMWHNEĘO iOO DPHO\HN PXOWLSRWHQV VHMWHN tJ\ GLIIHUHQFLiOyGy NpSHVVpJN QDJ\ In vitro NtVpUOHWWHO LJD]ROWiNKRJ\D]DPQLRQHSLWHOVHMWHNNpSHVHNLQ]XOLQWHUPHOĘVHMWHNNpGLIIHUHQFLiOyGQLIn vivo STZ-YHO NH]HOW GLDEpWHV]HV HJHUHNEH OWHWYH DPQLRQ HSLWHOVHMWEĘO iOOy LPSODQWiWXPRW D]RNYpUFXNRUNRQFHQWUiFLyMDQRUPDOL]iOyGRWWDEHOWHWpVXWiQQpKiQ\KpWWHO(]EL]RQ\tWMD KRJ\ D] DPQLRQ HSLWHOVHMWQHN PHJYDQ D]RQ NpSHVVpJH KRJ\ LQ]XOLQ V]HNUHWiOy EpWD-VHMWWp GLIIHUHQFLiOyGMon (WEI, et al., 2003).

$ SDWNiQ\NtVpUOHWHNEHQ D FXNRUEHWHJ DQ\iNWyO V]iUPD]y XWyGRN KDVQ\iOPLULJ\pQHN EpWD-VHMWHLWHNLQWHWpEHQHOpJHOOHQWPRQGiVRVHUHGPpQ\HNV]OHWWHN(J\LNNtVpUOHWV]HULQWHJ\

eQ\KH FXNRUEHWHJ DQ\iQDN D] XWyGDLEDQ D] DQ\DL KLSHUJOLNpPLD YiOWRWWD NL D KDVQ\iOPLULJ\

EpWD-sejtjeinek PDJDVVHMWV]iPiWPtJDV~O\RVFXNRUEHWHJDQ\DXWyGDLEDQDEpWD-VHMWHNV]iPD FV|NNHQWYROWpVDVHMWHNGHJUDQXOiOWDN(J\PiVLNNtVpUOHWEHQDIHOQĘWWXWyGRNDWYL]VJiOWiN Az enyhe cukorbeteg anyD IHOQĘWW XWyGDLEDQ FV|NNHQW LQ]XOLQ V]HNUpFLy PtJ D V~O\RV FXNRUEHWHJ DQ\iEyO V]iUPD]y IHOQĘWW XWyGokEDQ PHJQ|YHNHGHWW LQ]XOLQ V]HNUpFLy YROW D MHOOHP]Ę $] HUHGPpQ\HN QHP HJ\pUWHOPĦHN D] D]RQEDQ NLMHOHQWKHWĘ KRJ\ D] DQ\DL FXNRUEHWHJVpJ V]iPRV PHWDEROLNXV pV IXQNFLRQiOLV EHWHJVpJHW RNR]KDW D] XWyGRN KDVQ\iOPLULJ\pEHQDPHO\N|]UHPĦN|GKHWHJ\IHOQĘWWNRULNIDDM NLDODNXOiViEDQ(HAN, et al., 2007).

pVQDSRVSDWNiQ\PDJ]DWRNJONy]UDDGRWWLQ]XOLQYiODV]iWYL]VJiOWiNin utero. Az DQ\iNQDN DGRWW JONy] LQI~]Ly KLSHUJOLNpPLiW RNR]RWW D PDJ]DWRNEDQ D QDSUD GH D YpUFXNRUNRQFHQWUiFLyMXNVRVHPKDODGWDPHJD]DQ\MXNpW$JONy]LQI~]LyKDWiViUDDSOD]PD LQ]XOLQ NRQFHQWUiFLyja LV PHJQĘWW PLQG D] DQ\iEDQ PLQG D PDJ]DWRNEDQ $] LQ]XOLQ NRQFHQWUiFLy Q|YHNHGpVH PiU D QDSRQ PpUKHWĘ YROW pV D QDSLJ Q|YHNHGHWW (KERVRAN - GIRARD, 1974).

$ NRUDL HPEULy VWiGLXPEDQ SDWNiQ\RNRQ EL]RQ\tWRWWiN KRJ\ D JOLNROt]LV DQDHURE PyGRQPHJ\YpJEH$KRJ\DQXNOHLQVDYHOOiWiVEL]WRVtWRWWiYiOLNDSHQWy]-IRV]IiW-ciklus is DNWtYYi YiOLN HEEHQ D SHULyGXVEDQ .pVĘEE D JONy] IHOKDV]QiOiVVDO DUiQ\RVDQ FV|NNHQ D ODNWiW WHUPHOpV DKRJ\ D] DQDHURE JOLNROt]LVW IHOYiOWMD D] DHURE .UHE¶V FLNOXV (] D PDJ]DWL

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YpUNHULQJpVNLIHMOĘGpVpQHNN|V]|QKHWĘDPHO\D]R[LJpQWV]iOOtWMD3DWNiQ\PDJ]DWHVHWpEHn a PDJ]DWLYpUNHULQJpVNLIHMOĘGpVHNEQDSRVNRUUDW|UWpQLNPHJSHEPARD, et al., 1997).

(]WEL]RQ\tWMDD]DNtVpUOHWLVDPHO\SDWNiQ\HPEULyNJONy]PHWDEROL]PXViWYL]VJiOWDD pV D YHPKHVVpJL QDSRQ LQWDNW HPEULyNRQ pV L]ROiOW HPEULyNRQ LV illetve azok DPLQRQEXUNiQ $] DQDHURE JOLNROt]LV KiQ\DGD PDJDV YROW D QDSRQ D] HPEULyEDQ pV D burokEDQLVDPHO\DQDSUDHJ\KDUPDGiUDFV|NNHQW$JOLNROt]LVPLQGLJMHOHQWĘVHEEvolt a EXUNRNEDQPLQWPDJiEDQD]HPEULykEDQ$]R[LGDWtYJOLNROt]LVDODFVRQ\YROWDQDSRQpV QDSUD MHOHQWĘVHQ PHJQĘWW D KiQ\DGD D] DQDHURE JOLNROt]LVKH] NpSHVW $ SHQWy]-IRV]IiW FLNOXVLVKDVRQOyNpSSHQDODNXOWPLQWD]DHUREJOLNROt]LV$]HUHGPpQ\HND]WPXWDWMiNKRJ\D PDJ]DWLYpUNHULQJpVDYHPKHVVpJLQDSRQIHMOĘGLNNL(AKAZAWA, et al., 1994). 3DWNiQ\

HPEULy DPQLRQ IRO\DGpNiW YL]VJiOYD PHJiOODStWRWWiN KRJ\ QDSRV NRUEDQ D JONy]

NRQFHQWUiFLy1,5 mmol/l 0,089 mmol/l, pVH]DQDSLJQĘPDMGKLUWHOHQOHFV|NNHQ pVQDSRVHPEULyNDWYL]VJiOWDN 0 ϶&pV϶&LQNXEiFLyDODWW϶C-RQDpVQDSRV HPEULyEDQLOOHWYH϶C-RQDQDSRVHPEULyEDQQHPPpUWHNMHOHQWĘVJONy]NRQFHQWUiFLy FV|NNHQpVW(OOHQEHQ 38 ϶C-RQDQDSRVHPEULyDPQLRQIRO\DGpNiEDQSHUFDODWWPtJD QDSRV HPEULy DPQLRQ IRO\DGpNiEyO SHUF DODWW NLPXWDWKDWDWODQQi YiOW D JONy]

konceQWUiFLy (]HN D PpUpVHN D]W PXWDWMiN KRJ\ D QDSRV HPEULy JONy] IHOKDV]QiOiVD MHOHQWĘVDPHO\IRNR]DWRVDQFV|NNHQnapos korig (PARK - SHEPARD, 1994).

Az amnion IRO\DGpN |VV]HWpWHOH nagyon fonWRV D] LGHJUHQGV]HU QRUPiOLV NLIHMOĘGpVH V]HPSRQWMiEyO $] DPQLRQ IRO\DGpNEDQ OpYĘ JONy], illetve annak metabolizmusa elengedhetetlen a magzat IHMOĘGpVpKH]$OHJQDJ\REEJONy]IHOKDV]QiOiVDSDWNiQ\PDJ]DW UpV]pUĘO-16 napos korban jelentkezLNDPLNRUDQHXUDOL]iFLyD]LGHJUHQGV]HUNLIHMOĘGpVH W|UWpQLN3$5., 1997).

In vitro SDWNiQ\ HPEULyNRQ YpJ]HWW NtVpUOHWHN LJD]ROWiN KRJ\ D KLSHUJOLNpPLiV N|UQ\H]HWEHQ D JONy] IHOKDV]QiOiV pV D ODNWiW termHOpV QDJ\IRN~ $] HPEULyN IRO\DPDWRV anaerob gliNROt]LVW IRO\WDWQDN (]HNHW D] HPEULyNDW KLSRJOLNpPLiV N|UQ\H]HWEH KHO\H]YH IHMOĘGpVL UHQGHOOHQHVspJHW PXWDWWDN D JOLNROt]LV DODFVRQ\ KDWiVIRND PHOOHWW AKAZAWA, 2005).

3DWNiQ\PDJ]DWRN*1*-UHYDOyNpSHVVpJpWYL]VJiOWiN$NtVpUOHWOpQ\HJHD]YROWKRJ\

18-QDSRVYHPKHVSDWNiQ\RNDWpKH]WHWHWWHNyUiQiWPDMGMHO|OWJONy]]DOLQIXQGiOWiN ĘNHW$FpOD]YROWKRJ\PHJiOODStWViNDzt, hogy a PDJ]DWYpUFXNRUNRQFHQWUiFLyMDHOWXG-e NO|QOQLD]DQ\ipWyOpKH]pVVRUiQ pVtJ\ IHQntartani a normiOPDJ]DWLYpUFXNRUV]LQWHW$

NRUiEEL NtVpUOHWHN LJD]ROWiN KRJ\ PDJ]DWL NRUEDQ D PiM QHP NpSHV D *1*-UH (]XWiQ D

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PpKOHSpQ\WYL]VJiOWiNPHJLO\HQV]HPSRQWEyOGHEHEL]RQ\RVRGRWWKRJ\DSODFHQWiEDQQHP WDOiOKDWyPHJDIRV]IRHQROSLUXviW-NDUER[LNLQi]DPHO\HQ]LPSHGLJ elengedhetetlen a GNG- hez$MHOHQNtVpUOHWVRUiQPLQLPiOLVIRN~JOLNRJHQROt]LVWYpOWHNIHOIHGH]QLDPDJ]DWLPiMEDQ DPHO\D]RQEDQQHPHOHJHQGĘDPDJ]DWLYpUFXNRUV]LQWIHQQWDUWiViKR]ËJ\PiVJONy]IRUUiVW J\DQtWDQDNDPHO\D]DQ\DpKH]pVHIRO\DPiQDPDJ]DWRWYpGLDYpUFXNRUV]LQWFV|NNHQpVpWĘO (BOSSI - GREENBERG, 1972).

$ *1* NpSHVVpJpQHN D NLIHMOĘGpVH V]pOHV N|UEHQ YL]VJiOW WpPD $ UiJFViOyNUyO Q\XODNUyOpVMXKRNUyONpV]OWWDQXOPiQ\RND]WiOOtWMiNKRJ\D*1*IHMOĘGpVHMyO|VV]HKDQJROW folyamat, mely D VSHFLILNXV V]DEiO\R]y HQ]LPHN JHQHWLNDL WUDQV]NULSFLyMiYDO pV NLIHMH]ĘGpVpYHO V]DEiO\o]RWW (]HNQHN D] HQ]LPHNQHN D NLIHMH]ĘGpVH PHJKDWiUR]RWW LGĘSRQWKR] N|WKHWĘ (PLDWW KDEiU D PDJ]DW NpSHV OHQQH D *1*-re, a piruviWEyO W|UWpQĘ JONy] NpS]pVpKH] V]NVpges foszfoenolpiruviW-NDUER[LNLQi] HQ]LP V]LQWMH OLPLWiOW D V]OHWpVLJ$]RQEDQDKXPiQNtVpUOHWHNDOiWiPDV]WMiND]WDWpQ\WPLV]HULQWDV]OHWpVXWiQD

*1* NpSHVVpJH KDPDU NLIHMOĘGLN pV HOpUL D JONy] SURGXNFLy -t is (KALHAN - PARIMI, 2000).

$] HOVĘ OpSpV D JONy] IHOKDV]QiOiViKR] D] LQWUDFHOOXOiULV WUDQV]SRUW PHO\ JONy]- WUDQV]SRUWHUHQ NHUHV]WO YDOyVXO PHJ. A GLUT-4 egy inzulin-IJJĘ transzporter a Yi]L]RPVHMWHNHQ a V]tYVHMWHNHQ pV a ]VtUVHMWHNHQ GH PLQGHQ VHMWHQ PHJWDOiOKDWy NLV PHQQ\LVpJEHQ A YpUFXNRU V]LQW Q|YHNHGpVpYHO D] LQ]XOLQ V]HNUpFLy IRNR]yGLN PLiOWDO D JONy]LQWUDFHOOXOiULVWUDQV]SRUWMDN|QQ\HEEpYiOLNpVtJ\FV|NNHQDYpUFXNRUV]LQW$PLNRU az energia-V]NVpJOHWDODFVRQ\DJONy]JOLNRJpQNpQWYDJ\]VtUNpQWWiUROyGLND]VtUVHMWHNEen, PiMEDQ L]RPEDQ $ODFVRQ\ YpUFXNRU V]LQW D] LQ]uOLQ V]HNUpFLyW HOQ\RPMD pV D JOXkagon, DGUHQDOLQ QRUDGUHQDOLQ Q|YHNHGpVL KRUPRQ NRUWL]RO NRQFHQWUiFLyMiW Q|YHOL DPHO\ iOWDO HOĘVHJtWLDOLSROt]LVWJONRQHRJHQH]LVWJOLNRJHQROt]LVWDPLQHNVRUiQQĘD YpUFXNRUV]LQWD V]DEDG]VtUVDYV]LQWpVDNHWRQNRQFHQWUiFLyDYpUEHQ

A vemKHVVpJ hatiVVDO YDQ D JONy]-V]DEiO\R]y PHFKDQL]PXVRNUD az inzulin rezisztHQFLDNLDODNXOiVD UpYpQ DPHO\ D JONy] LQWUDFHOOXOiULV WUDQV]SRUWMiWHOQ\RPMD H]iOWDO UHODWtY LQWUDFHOOXOiULV HQHUJLD-KLiQ\W RNR]YD pV Q|YHOYH D YpUFXNRUV]LQWHW 6]pOVĘVpJHV esetben GDM alakulhat ki. Ebben a folyamatban fontos szerepe van a progeszteronnak,

|V]WUDGLROQDN Q|YHNHGpVL KRUPRQQDN SODFHQWiOLV ODNWRJpQQHN FLWRNLQHNQHN (] D UHODWtY in]XOLQ KLiQ\ RNR]]D D ]VtUVHMWHNEĘO YDOy ]VtUVDY PRELOL]iFLyW pV D KHSDWLNXV ]VtUVDY V]LQWp]LVWĘOD]R[LGiFLyKR]YDOyHOPR]GXOiVWLOOHWYHDNHWRJHQH]LVW$*'0N|YHWNH]WpEHQ alakul ki inzulin-UH]LV]WHQFLD D Yi]L]RP VHMWHNHQ pV ]VtUVHMWHNEHQ PtJ D PiMVHMWek inzulin pU]pNHQ\VpJHpSPDUDG$PROHNXOiULVKiWWHUHD]LQ]XOLQUH]LV]WHQFLiQDNQHPWLV]Wi]RWWPLYHO

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a GLUT-WUDQV]SRUWHUYiOWR]DWODQPDUDGWWHUKHVQĘNHVHWpEHQpVD]LQ]XOLQ-UHFHSWRUKR]YDOy N|WĘGpVLVpSnek bizonyult. Emiatt egy poszt-receptRULiOLVGHIHNWXVWIHOWpWHOH]QHN DKiWWpUEHQ, ami az LQ]XOLQKDWiViWEORNNROMDJOHNSON, 2008).

Az inzulin UH]LV]WHQFLDYHOHMiUyMDDYHPKHVVpJQHN.pWIDNWRUVHJtWLHOĘDSURJHV]WHURQ pV D Q|YHNHGpVL KRUPRQ DPHO\HN KDVRQOy NRQFHQWUiFLyEDQ YDQQDN MHOHQ YHPKHV pV Qem vemhes PHW|V]WUXV]RV V]XNiEDn is, KDEiU D YHPKHV V]XNiNEDQ QDJ\REE PpUWpNEHQ jelentkezik a rezisztencia. Ennek N|YHWNH]WpEHQ D0 IHMOĘGKHW NL DONDOPDQNpQW D met|V]WUXV]RVQHPYHPKHVV]XNiNEDQ)HOGPDQV]HULQWNXW\iEyONXW\DHVHWpEHQ ÈOWDOiQRVDQ HOIRJDGRWW Qp]HW V]HULQW D *'0 QHP J\DNRUL D YHPKHV V]XNiNEDQ 7|EE PDJ\DUi]DWV]OHWHWWDUUDKRJ\PLpUWNHYHVHEEDGLDJQRV]WL]iOW*'0VzXNiNEDQPLQWQĘN HVHWpEHQ (]HN HJ\LNH KRJ\ KDEiU D QĘN HVHWpEHQ J\DNUDQ WQHWPHQWHV D EHWHJVpJ GH D rendszeres WHUKHVVpJL NRQWUROO IHOIHGL D EHWHJVpJHW PtJ V]XNiN HVHWpEHn csDN DNNRU NHUO PHJiOODStWiVUDDPLNRUPiUMHOHQWNH]QHNDWQHWHN(FALL, et al., 2008).

$'0NLDODNXOiViQDNIRO\DPDWDPHW|V]WUXV]RVV]XNiNEDQQDJ\KDVRQOyViJRWPXWDWD QĘN*'0-valDPHO\IJJDNRUWyOpVWHVWV~O\WyO LV$PLNRUDYpUJONy]NRQFHQWUiFLyHOpULD maximiOLV reabV]RUSFLyVNDSDFLWiVWDSUR[LPiOLVYHVHWXEXOXVRNEDQJONy]~ULDpVR]PRWLNXV GLXUp]LV DODNXO NL (] D] ~Q NV]|E pUWpN 10 mmol/l YpUFXNRU koncentUiFLyQDN IHOHO PHJ Emiatt pROL~ULDpVDYHOHMiUyNRPSHQ]iFLyV polidipszia a leggyakoribb klinikai jele a DM- QDN$SROLIiJLDpVDV~O\YHV]WpVDPiVLNNHWWĘJ\DNRULWQHWHKDEiUH]YHPKHVV]XNiNEDQ QHP IHOWĦQĘ PHUW D] pWYiJ\ Q|YHNHGpVH YHOHMiUyMD D YHPKHVVpJnek. 9pJVĘ HVHWEHQ PiV WQHWHNGRPLQiOQDNLO\HQSpOGiXODJ\HQJHVpJa OHWDUJLDDKiQ\iV1pKiQ\HVHWEHQNHWyzis is HOĘIRUGXO. $ *'0 GLDJQy]LVD D NyUHOĘ]PpQ\L pV IL]LNiOLV DGDWRNNDO IHOWpWHOH]KHWĘmelyet PHJHUĘVtW D IRO\DPDWRV KLSHUJOLNpPLD pV JONy]~ULD WpQ\HA DM sok metabolikus zavart RNR] DPHO\HNHW PLQG IHO NHOO WiUQL D VLNHUHV NH]HOpV pUGHNpEHQ EHOHpUWYH D GHKLGUiFLyW NHWy]LVWDFLGy]LVWpVD]HOHNWUROLWHJ\HQV~O\]DYDUiW5HMWHWWK~J\V]HUYLIHUWĘ]pV±DPLV]LQWpQ KR]]iMiUXlhat az inzulin-UH]LV]WHQFLD NLDODNXOiViKR] ± J\DNRUL FXNRUEHWHJ NXW\iNEDQ H]pUW indokolt a vizelet-YL]VJiODW.

$]DQ\DLEHWHJVpJHNQHNEiUPHO\LNIDMWiMDKiWUiQ\RVDQKDWKDWDPDJ]DWRNHJpV]VpJpUH (PEHUHN HVHWpEHQ D *'0 Q|YHOL D] DQ\DL PDJ]DWL pV ~MV]O|WW NRUL PRUELGLWiVW pV PRUWDOLWiVW $ W~O]RWW PDJ]DWL Q|YHNHGpV PDNros]yPLD J\DNRUL pV KR]]iMiUXO D FViV]iUPHWV]pVKH] pV D V]OHWpVL WUDXPiNKR] $ YHOHV]OHWHWW IHMOĘGpVL UHQGHOOHQHVVpJHN gyakoriEEDNKDDYHPKHVVpJNRUDLV]DNDV]iEDQDODNXONLD*'0GHN|]pSLGĘVvemhesen YDJ\NpVĘEENLDODNXOy*'0NHYpVEpMiUXOKR]]iDIHMOĘGpVLUHQGHOOHQHVVpJHNNLDODNXOiViKR]

(JOHNSON, 2008).

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$*'0QĘN HVHWpEHQ 2-12%-EDQIRUGXOHOĘ+DEiUQĘNQpOD*'0iOWDOiEDQQHPMiUD DM MHOOHJ]HWHV NOLQLNDL WQHWHLYHO GH D N|YHWNH]PpQ\HL MHOHQWĘVHN OHKHWQHN ~J\ PLQW makros]yPLDFViV]iUPHWV]pV~MV]O|WWNRULKLSRJOLNpPLD$*'0 iOWDOiEDQPHJROGyGLND V]OpVXWiQGHDNpVĘEELHNEHQQ|YHOLD]HVpO\pWDWtSXV~'0NLDODNXOiViUD(FALL, et al., 2008).

$ KXPiQ *'0 HOĘIRUGXOiViQDN J\DNRULViJD D] HOP~OW - pYEHQ D NpWV]HUHVpUH emelkedett. $ *'0 VRUiQ D] LQ]XOLQ V]HNUpFLy QLQFV HJ\HQV~O\EDQ D] LQ]XOLQ pU]pNHQ\VpJ FV|NNHQpVpYHODPLYpJOKLSHUJOLNpPLiKR]YH]HW$]LQ]XOLQ-UH]LV]WHQFLDNLIHMOĘGpVHD*'0 patRIL]LROyJLiMiQDN OHJIRQWRVDEE |VV]HWHYĘMH $ NRUDL WHUKHVVpJ DODWW D] LQ]XOLQ V]HNUpFLy Q|YHNHGpVpYHO D] LQ]XOLQ pU]pNHQ\VpJ YiOWR]DWODQ YDJ\ Q|YHNHGHWW PtJ D NpVĘL WHUKHVVpJ VRUiQD]LQ]XOLQ-UH]LV]WHQFLDNLDODNXOiViYDOD]pU]pNHQ\VpJOHFV|NNHQpVD]LQ]XOLQPHGLiOWD JONy]IHOYpWHO-60 %-kDOFV|NNHQDWHUKHVVpJHOĘWWL LGĘV]DNKR]NpSHVWBARBOUR, et al., 2007).

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+DVRQOy HUHGPpQ\HN V]OHWWHN QĘN WHUKHVVpJpQHN YL]VJiODWD VRUiQ LV $] HOVĘ WULPHV]WHUEHQPHJQ|YHNHGHWWLQ]XOin-pU]pNHQ\VpJHWMyOWNU|]LD]DYL]VJiODW, miszerint az 1.

ttSXV~GLDEpWHV]HVWHUKHVQĘNLQ]XOLQV]NVpJOHWHiWPHQHWLFV|NNHQpVWMHOH]D]HOVĘWULPHV]WHU alatt. Ahogy a terhesVpJ KDODG HOĘUH D] LQ]XOLQ-pU]pNHQ\VpJ ~J\ FV|NNHQ YpJO LQ]XOLQ- UH]LV]WHQFLDDODNXONLDWHUKHVVpJXWROVyV]DNDV]iEDQ(]D]LQ]XOLQ-rezis]WHQFLDPLQGQĘNEHQ PLQGSDWNiQ\RNEDQD]LQ]XOLQ-PHGLiOWJONy]IHOYpWHO-60 %-RVFV|NNHQpVpWRNR]]DDNRUDL

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14

WHUKHVVpJKH]YDJ\DQHPWHUKHViOODSRWKR]NpSHVW+DEiUD]LQ]XOLQUH]LV]WHQFLDNLDODNXOiVD YHPKHVVpJ VRUiQ MyO GRNXPHQWiOW D] DODS PHFKDQL]PXVt ± DPHO\ D ]VtUV]|YHW LQ]XOLQ- pU]pNHQ\VpJpWPHJYiOWR]WDWMDDYHPKHVVpJDODWW ± QHPLVPHUMN(J\HVNtVpUOHWHNV]HULQWD]

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SĮ DOHJ\VpJpQHN D K3*+ iOWDO PHJQ|YHNHGHWW H[SUHVV]LyMiKR] NDSFVROyGLN D Yi]L]RPzatEDQ$SĮDOHJ\VpJQHJDWtYNRPSHWtWRUNpQWKDWD3,-3-NLQi]SDOHJ\VpJJHO YDOyKHWHURGLPpUUpYDOyDODNXOiViEDQtJ\JiWROMDD3,-3-NLQi]DNWLYLWiViW(BARBOUR, et al., 2007).

$ ]VtUVHMWHN iOWDO WHUPHOW IDNWRURN PLQW DGLSRNLQHN YiOWDN LVPHUWWp .|]pMN WDUWR]LN W|EEHN N|]|WW D] DGLSRQHNWLQa leptin, a TNF-Į $ 71)-Į HJ\ FLWRNLQ PHO\QHN V]LQWMH HOKt]RWW iOODWRNEDQ pV HPEHUHNEHQ ± D NtVpUOHWHN DODSMiQ ± SR]LWtY NRUUHOiFLyW PXtatott a hipeULQ]XOLQpPLDV]LQWMpYHO)URVWpV/DQJ in vitro SDWNiQ\pVHPEHULYi]L]RPVHMWHNHQ LQ]XOLQUH]LV]WHQFLDQ|YHNHGpVpWWDSDV]WDOWiN71)-ĮLQIXQGiOiVDXWiQ.

A TNF-Į D] LQ]XOLQ UHFHSWRU V]XEV]WUiW ,56-1 szerin foszfoULOiFLyMiW Q|YHOL pV D]

inzulin receptor (IR) tirozin-NLQi] DNWLYLWiViW FV|NNHQWL .RUiEEL WDQXOPiQ\RN DODSMiQ PHJiOODStWRWWiN KRJ\ D 71)-Į SOD]PD NRQFHQWUiFLyMD NRUUHOiOW D] LQ]XOLQ pU]pNHQ\VpJ YiOWR]iViYDODNRUDLWHUKHVVpJWĘONH]GĘGĘHQDNpVĘLWHUKHVVpJLJ.,5:$1 et al., 2002).

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:LQNOHU pV PXQNDWiUVDL (2002) D V]pUXP 71)-Į NRQFHQWUiFLyMiW KDVRQOtWRWWiN |VV]H harminc GDM-HVQĘKDUPLQF|WHJpV]VpJHVWHUKHVQĘpVKXV]RQ|W HJpV]VpJHVQHPWHUKHVQĘ HVHWpEHQ $] HUHGPpQ\HN V]HULQW D] HJpV]VpJHV WHUKHV QĘN WULPHV]WHUpEHQ PpUW pUWpN PDJDVDEEYROWPLQWD]WULPHV]WHUEHQPpUWLOOHWYHDQHPWHUKHVQĘNQpOPpUWNRQFHQWUiFLyN A GDM-HVQĘNQpOPLQGLJPDJDVDEENRQFHQWUiFLyWPpUWHNPLQWDPiVLNNpWFVRSRUWHVHWpEHQ -HOHQWĘV SR]LWtY NRUUHOiFLyW WDOiOWDN D WHUKHVVpJL GLDEpWHV] pV D QHP GLDEpWHV]HV WHUKHV QĘN V]pUXP71)-ĮV]LQWMHN|]|WWWINKLER, et al., 2002).

$] DGLSRNLQHN N|]O D] DGLSRQHNWLQt NL]iUyODJ D ]VtUVHMWHN V]LQWHWL]iOMiN $ SOD]PD DODFVRQ\ DGLSRQHNWLQ NRQFHQWUiFLyMD NRUUHOiO D] LQ]XOLQ UH]LV]WHQFLD PpUWpNpYHO HOKt]RWW pV WHUKHVVpJL GLDEpWHV]HV QĘN HVHWpEHQ &6(+, et al. $] DGLSRQHNWLQ HJ\ HQGRJpQ inzulin-pU]pNHQ\tWĘKRUPRQNpQWIRJKDWyIHODPHO\IRNR]]D DJONy]-IHOYpWHOWDYi]L]RPEDQ, pV FV|NNHQWL D KHSDWLNXV JONy] WHUPHOpVW $] DGLSRQHNWLQ NRQFHQWUiFLyMiQDN D FV|NNHQpVH

*'0 HVHWpEHQ PiU EL]RQ\tWRWW $ 71)-Į pV PiV J\XOODGiVNHOWĘ PHGLiWRURN JiWOy KDWiViW LJD]ROWiND]DGLSRQHNWLQWUDQV]NULSFLyMiEDQDPLPDJ\DUi]DWRWDGKDWD]DODFVRQ\DGiponektin NRQFHQWUiFLyUDD*'0-es egyedekben (BARBOUR, et al., 2007).

$] LQ]XOLQ PHGLiOWD JONy] IHOYpWHOW YL]VJiOWiN KXPiQ Yi]L]RP URVWRNRQin vitro. A YL]VJiODWEDQWHUKHVQHPWHUKHVpV*'0-HVQĘNEĘOV]iUPD]yYi]L]RPV]|YHWHWKDV]QiOWDN$]

HUHGPpQ\HN V]HULQW D WHUKHV QĘNEĘO V]iUPD]y L]RPV]|YHWEHQ %-kal cs|NNHQW D JONy]

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%LUQEDXP HUHGPpQ\HLYHO DPHO\EHQ L]ROiOW JHV]WiFLyV GLDEpWHV]HV pV WHUKHV QĘNEĘO V]iUPD]y]VtUVHMWHNJONy]WUDQV]SRUWMiWYL]VJiOWiN (BARBOUR, et al., 2007).

$]LQ]XOLQUHFHSWRUEDQDEpWD-aOHJ\VpJIRV]IRULOiFLyMiWVWLPXOiOMDD]LQ]XOLQN|WĘGpVHD]

alfa-DOHJ\VpJKH] *'0 HVHWpEHQ D IRV]IRULOiFLy W|NpOHWOHQ KDEiU D] ,5 V]iPD pV D UHFHSWRUKR] YDOy N|WĘGpV QHP WpU HO Dz HJpV]VpJHV YHPKHV QĘNEHQ WDSDV]WDOWDNKR] NpSHVW (Shao, HWDO(PLDWWHJ\UHFHSWRURQEHOOL defektus az oka az inzulin receptor FV|NNHQW pU]pNHQ\VpJpQHN$EL]RQ\tWpNRNDOiWiPDV]WMiNKRJ\DWLUR]LQ-fRV]IDWi]FV|NNHQWDNWLYLWiVD PLQWD],5IRV]IRULOiFLyMiWV]DEiO\R]yHQ]LPRNR]KDWMDDFV|NNHQWpU]pNHQ\VpJHWD]LQ]XOLQ LUiQWHPEHUHNEHQpViOODWRNEDQLVBARBOUR, et al., 2007).

Az inzulin receptorokat DONDOLNXVIRV]IDWi]]DONH]HOYH D]WWDSDV]WDOWiNKogy az inzulin PROHNXOD NpSHVVpJH D WLUR]LQ IRV]IRULOiFLyMiQDN DNWLYiOiViUD YLVV]DWpUW D QRUPiOLV V]LQWUH WHUKHVQĘNEHQ*'0HVHWpEHQSHGLJMHOHQWĘVHQMDYXOW$71)-ĮJiWROQLNpSHVD],5WLUR]LQ IRV]IRULOiFLyMiWH]]HOLQ]XOLQUH]LV]WHQFLiWNLYiOWYD (SHAO, et al., 2000).

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an\DJFVHUpEHQ IHOLVPHUW OHJIULVVHEE HUHGPpQ\HN DODSMiQ D PHJHOĘ]Ę LQWp]NHGpVHNQHN D]

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29

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30

4. (UHGPpQ\HN

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9HPKHVVpJLKHWHN *ONy]iWODJ6' (mmol/l)

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JO

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SD (ng/ml)

1. 4,7 0,077 _

2. 3,7

3.

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5.

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7.

8.

9.

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31

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32

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(mmol/l)

Inzulin iWODJ6'

JO

Progeszteron iWODJ6' (ng/ml)

20 napos 5,16 _ _

30 napos 2,93 0,015 0,58

50 napos 1,83 0,020 0,52

(33)

33 ALLANTOIS *ONy]iWODJ6'

(mmol/l)

Inzulin iWODJ6'

JO

Progeszteron iWODJ6' (ng/ml)

20 napos 4,86 _ _

30 napos 3,68 0,117 0,75

50 napos 2,11 0,158 2,70

6$9Ï

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30 napos 6,66 0,035 1,13

50 napos 12,23 0,055 1,48

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34

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35

(r =0 LOOHWYH D JONy] pV SURJHV]WHURQ N|]|WW U WDSDV]WDOKDWy V]RURVDEE

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