B Y T TRNG I HC DC H NI NGUYN KHNH LY KHO ST TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR TI BNH VIN BCH MAI KHA LUN TT NGHIP DC S H NI - 2014 B Y T TRNG I HC DC H NI NGUYN KHNH LY KHO ST TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR TI BNH VIN BCH MAI KHA LUN TT NGHIP DC S Ngi hng dn:1.TS. Nguyn Thnh Hi2.ThS. L Vn Anh Ni thc hin: 1.B mn Dc Lm Sng trng H Dc H Ni 2.Bnh vin Bch Mai H NI - 2014 LI CM N Vi lng knh trng v bit n su sc, ti xin by t li cm n chn thnh ti TS.DS.NguynThnhHigingvinbmnDclmsngtrngihc Dc H Ni ngi thy tn tnh hng dn v gip ti trong qu trnh hc tp, tin hnh nghin cu v hon thnh lun vn. Ti xin chn thnh cm n ThS.DS. L Vn Anh Dc s ti khoa Dc Bnh vin Bch Mai gip v to mi iu kin thun li cho ti trong qu trnh thc hin v hon thnh lun vn. hon thnh kha lun tt nghip ny, ti cng v cng bit n s gip nhit tnh ca: ThS.BSNguynThHngVnbcskhmbnhtiKhoaKhmbnh Bnh vin Bch Mai. ThS.BS V Thy Thanh bc s khm bnh ti Khoa Khm bnh Bnh vin Bch Mai. Cui cng, ti xin c gi li cm n ti ban gim hiu, cc thy c gio trong b mn Dc Lm Sng, gia nh v bn b lun gip ti trong qu trnh thc hin kha lun. Do s hn ch v trnh cng nh thi gian, kha lun khng trnh khi sai st, mong thy c v cc bn thng cm v ng gp kin. Ti xin trn trng cm n! H Ni, ngy 13 thng 5 nm 2014 Sinh vin Nguyn Khnh Ly MC LC DANH MC CC K HIU, CH VIT TT DANH MC CC BNG, HNH V, BIU T VN ................................................................................................................ 1 CHNG I: TNG QUAN V I THO NG ............................................. 3 1.1. I CNG V I THO NG ............................................................... 3 1.1.1.nh ngha ............................................................................................................ 3 1.1.2.c im dch t ca bnh i tho ng .......................................................... 3 1.1.3.Phn loi ............................................................................................................... 4 1.1.4.C ch bnh sinh .................................................................................................. 4 1.1.5.Tiu chun chn on........................................................................................... 5 1.1.6.Cc bin chng thng gp.................................................................................. 6 1.1.7.iu tr ................................................................................................................. 8 1.1.7.1.Mc tiu iu tr ............................................................................................. 8 1.1.7.2.Phng php iu tr ...................................................................................... 9 1.2.CC THUC IU TR I THO NG TYP 2 .................................... 10 1.2.1.Insulin ................................................................................................................. 10 1.2.2.Cc thuc iu tr i tho ng typ 2 dng ung .......................................... 12 1.2.2.1.Nhm Biguanid .............................................................................................. 13 1.2.2.2.Nhm Thiazolidindion ................................................................................... 14 1.2.2.3.Nhm Sulfonylure .......................................................................................... 15 1.2.2.4.Nateglinid v Meglitinid ............................................................................... 16 1.2.2.5.Nhm thuc nh hng n s hp thu glucose ........................................... 16 1.2.2.6.Nhm cc thuc Incretin ............................................................................... 17 1.2.2.7.Thuc khc .................................................................................................... 18 1.2.3.Phi hp thuc trong iu tr i tho ng typ 2 ........................................... 18 1.2.3.1.Phi hp insulin v cc thuc iu tr i tho ng typ 2 dng ung...18 1.2.3.2.Phi hp cc thuc iu tr i tho ng typ 2 dng ung ..................... 19 CHNG II: I TNG V PHNG PHP NGHIN CU ...................... 21 2.1.I TNG NGHIN CU .............................................................................. 21 2.1.1.Thi gian v a im nghin cu ...................................................................... 21 2.1.2.Tiu chun la chn ........................................................................................... 21 2.1.3.Tiu chun loi tr ............................................................................................. 21 2.2. PHNG PHP NGHIN CU ....................................................................... 21 2.2.1.Thit k nghin cu ............................................................................................ 21 2.2.2.Mu nghin cu .................................................................................................. 21 2.3. CC NI DUNG NGHIN CU ....................................................................... 23 2.3.1.Mt s c im ca bnh nhn trong nghin cu ............................................ 22 2.3.2.Tnh hnh s dng thuc trong iu tr i tho ng typ 2 trn bnh nhn ngoi tr.. .................................................................................................................. 23 2.3.3.S thay i nng glucose mu lc i v tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr ........................................................ 23 2.4. CC TIU CHUN NH GI ........................................................................ 24 2.5. PHNG PHP PHN TCH V X L S LIU ..................................... 25 CHNG III: KT QU NGHIN CU ............................................................... 26 3.1. MT S C IM CA BNH NHN TRONG NGHIN CU ............. 26 3.1.1.Mt s c im chung ca bnh nhn trong nghin cu .................................. 26 3.1.2.Cc ch s cn lm sng khc ti thi im bt u nghin cu ........................ 28 3.2. TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR .............................................................. 29 3.2.1.T l bnh nhn ti khm .................................................................................... 29 3.2.2.Danh mc cc thuc iu tr i tho ng typ 2 gp trongnghin cu....30 3.2.3.Tnh ph hp ca vic la chn phc iu tr ti thi im ban u vi Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, Hng dn iu tr ca Hip hi i tho ng Hoa K nm 2014 (ADA 2014), Hng dn s dng thuc dnh cho cn b y t ca EMC (EMC) ................................................. 31 3.2.4.Danh mc cc thuc iu tr bnh mc km Tng huyt p vRi lon lipid mu. ............................................................................................................................... 32 3.3. S THAY I NNG GLUCOSE MU LC I V TNH AN TON KHI S DNG THUC IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR ................................................................................................... 33 3.3.1.S thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr ........................................................................... 33 3.3.2.Tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr......................................................................................................................... 34 3.3.2.1.Cc bin c bt li (AE) gp trong qu trnh nghin cu ............................ 34 3.3.2.2.Tng tc thuc gp trong mu nghin cu gia cc thuc iu tr i tho ng typ 2 vi cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu ................................................................................................................................ 35 CHNG IV: BN LUN ........................................................................................ 36 4.1. MT S C IM CA BNH NHN TRONG NGHIN CU... ......... 36 4.2. TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR .............................................................. 38 4.2.1. T l bnh nhn ti khm ................................................................................... 38 4.2.2. Danh mc cc thuc iu tr i tho ng typ 2 gp trong nghin cu ....... 39 4.2.3.Tnh ph hp ca vic la chn phc iu tr ti thi im ban u theo Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, Hng dn iu tr ca Hip hi i tho ng Hoa K nm 2014 (ADA 2014), Hng dn s dng thuc dnh cho cn b y t ca EMC (EMC) ................................................. 40 4.2.4. Danh mc cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu ................................................................................................................................ 43 4.3. S THAY I NNG GLUCOSE MU LC I V TNH AN TON KHI S DNG THUC IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR ....................................................................................... 44 4.3.1. S thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr....................44 4.3.2. Tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr.........45 4.3.2.1. Cc bin c bt li (AE) gp trong nghin cu.......................45 4.3.2.2. Tng tc thuc gp trong nghin cu gia cc thuc iu tr i tho ng typ 2 vi cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu ................................................................................................................................ 46 4.4. NGHA V HN CH CA NGHIN CU ............................................... 47 KT LUN V KIN NGH .................................................................................... 49 KT LUN .................................................................................................................. 49 1.V c im ca bnh nhn trong mu nghin cu ................................................... 49 2.V tnh hnh s dng thuc trong iu tr i tho ng typ 2 ............................... 49 3.V s thay i nng glucose mu lc i v tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr ........................................................ 50 KIN NGH ................................................................................................................. 51 TI LIU THAM KHO PH LC 1 PH LC 2 PH LC 3 DANH MC CC K HIU, CH VIT TT ADAAmerican Diabetes Association (Hip hi i tho ng Hoa K) AECc bin c bt li BMIBody Mass Index (Ch s khi c th) BNBnh nhn Ti tho ng EASDEuropean Association for the Study of Diabetes (Hip hi nghin cu i tho ng Chu u) EMCElectronic Medicines Compendium (Thng tin hng dn s dng thuc ca Anh) HbA1cGlycosylated Haemoglobin (Hemoglobin gn glucose) HDL-CHigh Density Lipoprotein Cholesterol IDFInternational Diabetes Federation (Lin on i tho ng Quc t) LDL-CLow Density Lipoprotein Cholesterol PPhc TDKMMTc dng khng mong mun THATng huyt p TZDNhm Thiazolidindion RLLPRi lon lipid mu UKPDSThe U.K prospective diabetic study (Nghin cu tin cu v i tho ng ca Anh) GLP 1Glucagon-like peptid (GLP - 1) GIPGlucose-dependent Insulinotropic Polypeptid DPP - 4Dipeptidyl peptidase IV enzym DANH MC BNG, HNH V, BIU Bng 1.1: Mc tiu iu tr T typ 2 theo B Y t 2011 ............................................ 8 Bng 1.2: Mc tiu iu tr T typ 2 theo Hip hi T Hoa K nm 2014 ............ 8 Bng 1.3: Mt s dng insulin.......................................................................................11 Bng 2.1: Ch tiu nh gi glucose mu lc i, HbA1c, lipid mu, huyt p........... 24 Bng 2.2: Ch tiu nh gi s khi c th BMI...........................................................24 Bng 3.1: c im chung ca bnh nhn ti thi im bt u nghin cu .............. 26 Bng 3.2: Cc ch s cn lm sng khc ti thi im bt u nghin cu .................. 28 Bng 3.3: Danh mc cc thuc iu tr T typ 2 gp trong nghin cu ................... 30 Bng 3.4: La chn phc iu tr ti thi im ban u .......................................... 31 Bng 3.5: La chn phc c Insulin ti thi im ban u ..................................... 32 Bng 3.6: Danh mc cc thuc iu tr bnh mc km THA v RLLP ....................... 32 Bng 3.7: S thay i nng glucose mu sau tng thng iu tr ........................... 33 Bng 3.8: Mc kim sot glucose mu sau tng thng iu tr ............................... 34 Bng 3.9: Cc AE gp trong qu trnh nghin cu ....................................................... 34 Bng 3.10: Tng tc thuc gp trong nghin cu ...................................................... 35 Hnh 2.1: Cc bc tin hnh thu thp s liu ......................................................... ....22 Biu 3.1: T l bnh nhn ti khm .......................................................................... 29 1 T VN i tho ng (T), l mt trong bn bnh khng ly nhim dn n t vong nhiu nht trn th gii [55], trong bnh T typ 2 chim khong 85 - 95% trong tng s bnh nhn T [50]. S lng ngi mc T trn ton th gii t nm 1980 n nm 2008 tng t 153 triu n 347 triu ngi [44]. Nu m hnh nhn khu hc ny tip tc c duy tr th trong vng mt th h na s c hn 592 triu ngi b nh hng bi T. C th thy bnh T ang c xu hng ngy cng pht trin v l mt thch thc i vi tt c cc nc trn ton th gii [50]. Bnh T nu khng c qun l v kim sot cht ch s dn n xut hin cc bin chng nng n trn nhiu h thngv cc c quan trong c th nh: tim, mch mu, mt, thn v thn kinh. Mt iu ng ch l cc bin chng ny cng l mt trong nhng nguyn nhn gy gim cht lng cuc sng ca ngi bnh v dn n tvong.T c xp lmt trong nhng bnhmn tnh, iu ng ngha vi vicbnh nhn Tphi s dngthuc sut i lmgim cc triu chng v bin chng do tng glucose mu gy ra. Do , bnh nhn T phi tn mt chi ph iu tr bnh khng h nh, y qu thc l mt gnh nng khng ch vi bnh nhn ni ring m c ton x hi ni chung. Hinnay,huhtccbnhnhnsaukhicchnonTthngc iu tr bnh ngoi tr bng cch kt hp gia vic dng thuc, ch n v luyn tp. C th thy vic dng thuc iu tr T ng mt vai tr quan trng v thit yu trong vic qun l v kim sot bnh T. Cng vi s pht trin ca Y dc hc, ngy cng c nhiu thuc iu tr T c a vo s dng, phong ph v a dng v dc cht, dng bo ch cng nh gi c, mang li nhiu thun li trong vic iu tr bnh song cng l mt thch thc khng h nh trong vic la chn v s dng thuc mt cc hp l m bo: hiu qu, an ton v kinh t. Bnh vin Bch Mai l mt bnh vin a khoa trung ng, hng c bit hay cn c gi l bnh vin tuyn cui, trung bnh mi ngy tip n t 2.000 3.000 lt bnh nhn n khm t khp cc ni trn c nc. Hin nay, Khoa Khm bnh Phng Ni tit v i tho ng ca Bnh vin ang qun l theo di iu tr ngoi 2 tr cho mt lng ln bnh nhn T, ch yu l T typ 2. Tuy nhin vic kho st v tnh hnh s dng cc thuc iu tr T trn nhng bnh nhn ny t nhiu nm nay vn cha c thc hin. Xut pht t thc tin ny, chng ti tin hnh ti: Kho st tnh hnh s dng thuc trong iu tr i tho ng typ 2 trn bnh nhn ngoi tr ti Bnh vin Bch Mai vi hai mc tiu sau: 1.Kho st tnh hnh s dng thuc trong iu tr i tho ng trn bnh nhn i tho ng typ 2 c iu tr ngoi tr ti Bnh vin Bch Mai.2.Bc u nh s thay i nng Glucose mu lc i v tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr ti Bnh vin Bch Mai. Trn c s , chng ti a ra cc xut nhm gp phn nng cao vic s dng thuc an ton, hiu qu v hp l trong iu tr bnh i tho ng typ 2 ngoi tr ti Khoa Khm bnh Phng Ni tit v i tho ng Bnh vin Bch Mai. 3 CHNG I: TNG QUAN V I THO NG 1.1. I CNG V I THO NG 1.1.1.nh ngha ithong(T)lbnhrilonchuynhadonhiunguynnhn, bnh c c trng bi tnh trng tng glucose mu mn tnh phi hp vi ri lon chuyn ha carbonhydrat, lipid v protein do thiu ht ca tnh trng tit insulin, tc dng ca insulin hoc c hai [20], [42]. 1.1.2.c im dch t ca bnh i tho ng T l mt bnh ri lon chuyn ha ang c tc pht trin nhanh. Theo thng bo ca t chc Y t th gii WHO, nm 2000 s lng ngi mc T trn th gii l 171 triu ngi v d on n nm 2035 s lng ngi mc i tho ng s l 366 triu ngi. Tuy nhin tnh t nm 1980 n nm 2008 th con s ny tng t 153 triu n 347 triu ngi [44]. Theo Hip hi i tho ng Hoa K (ADA), nm 2013, s lng ngi mc T trn th gii l 382 triu ngi vt ngng s lng ngi c d on s mc T vo nm 2035 ca WHO trc y. Tuy nhin, mt iu ng ch l 46% s bnh nhn khng bit mnh mc T v khng nhn thc c nhng hu qu lu di m bnh gy ra; ch tnh trong nm 2013 c 5,1 triu ngi cht do T v 548 t la c chi cho cn bnh ny [50].Vit Nam nm trong khu vc Chu Thi Bnh Dng, l khu vc c s lng ngi mc T ng nht trong cc khu vc trn th gii [50]. Theo nghin cu ton quc nm 2002 2003 ca T Vn Bnh v cng s th t l mc T ton quc l 2,7%, n chim 3,7%, nam chim 3,3%; t l ri lon dung np glucose ton quc l 7,3%; t l ri lon glucose mu khi i ton quc l 1,9% [3]. Theo ti liu nghin cu tnh cht dch t bnh T, th t l bnh tng ln hng nm, c 15 nm th t l bnh tng ln 2 ln, T c xp vo mt trong ba bnh gy tn ph v t vong nht (x va ng mch, ung th, T) [18]. Trong , bnh i tho ng typ 2 chim 85 - 95% [50]. 4 y u l nhng con s ng kinh ngc cho thy T v ang tr thnh mt i dch, mt vn ln ca Y t ton cu. Tt c cc quc gia d giu hay ngho u ang phi chu tc ng khng h nh ca cn bnh ny v Vit Nam cng khng phi l mt ngoi l. 1.1.3.Phn loi Bnh i tho ng c phn loi nh sau: -i tho ng typ 1: Do t bo ca tuyn ty b ph v, thng dn n thiu ht insulin tuyt i. -i tho ng typ 2: Do qu trnh gim tit insulin trn nn tng khng vi insulin. -Cc typ c hiu khc: T do nhng nguyn nhn khc: Khim khuyt v gen lin quan n chc nng t bo hay tc ng ca insulin Bnh tuyn ty ngoi tit (nh x nang ty) T do thuc hoc ha cht : thuc iu tr HIV/AIDS v thuc chng thi ghp. -ithongthaik:Tphthintrongthigiancthai,khngphi T thc s [23], [30]. 1.1.4.C ch bnh sinh i tho ng typ 1 c trng ca T typ 1 l s thiu ht insulin tuyt i. Cc t bo tuyn ty ch yu b ph hy bi cht trung gian min dch, him trng hp l T typ 1 v cn hoc t pht [30]. T typ 1 thng xut hin nhng ngi c h gen nhy cm,90%cctrnghpdngtnhvikhngnguynHLA-DR3vHLA-DR4 [25]. Cc du hiu ch im cho bnh gm c: cc t khng th khng t bo o ty, t khng th khng insulin, t khng th khng glutamic acid decarboxylase (GAD), t khng th khng tyrosin phosphatase IA -2 v IA 2 [18], [31]. 5 i tho ng typ 2 C 2 yu t c bn ng vai tr quan trng trong c ch bnh sinh ca T typ 2 l khng insulin v ri lon tit insulin kt hp vi nhau [29]: -Ri lon tit insulin: Ngha l t bo o ty b ri lon v kh nng sn xut insulin bnh thng v mt s lng cng nh cht lng m bo cho chuyn ha glucose bnh thng. Nhng ri lon c th l: Bt thng v nhp tit v ng hc bi tit insulin Bt thng v s lng tit insulin [2]. -Tnh trng khng insulin c th c thy hu ht cc i tng T typ 2 v tng glucose mu xy ra khi kh nng bi xut insulin ca cc t bo o ty khng p ng tha ng nhu cu chuyn ha [20]. Hnh thc khng insulin cng rt phong ph bao gm, gim kh nng c ch sn xut glucose (gan), gim kh nng thu np glucose ( m ngoi vi) v gim kh nng s dng glucose ( cc c quan) [2]. 1.1.5.Tiu chun chn on i tho ng c chn on khi tha mn mt trong bn iu kin sau:-Glucose mu lc i (t nht sau 8h khng n) 126 mg/dL (7 mmol/L) -Glucosemubtk200mg/dL(11,1mmol/L)kmcctriuchnglm sng nh i nhiu, ung nhiu, st cn -Glucose mu 2 gi sau nghim php dung np glucose (ung nhanh trong 5 pht 75 g glucose ha 200 mL nc) 200 mg/dL (11,1 mmol/L) -HbA1c 6,5% [11], [23], [27], [34]. Chn on ch c xc nh khi xt nghim ln 2 c kt qu tha mn mt trong cc tiu ch trn (khng bt buc phi ng vi xt nghim ln u), tr tiu chun 2 (glucose mu bt k) ch cn mt ln xt nghim [11]. Vo nm 2009, mt hi ngh ton cu ca cc chuyn gia v T gm ADA (HiphiithongHoaK),IDF(LinonithongQuct)v EASD ( Hip hi nghin cu i tho ng chu u) khuyn co rng bnh nhn c chn on T nu HbA1c 6,5% v nn tin hnh xt nghim li HbA1c 6 c chn on xc nh tr khi bnh nhn c nhng triu chng r rt trn lm sng v glucose mu > 200 mg/dL (> 11,1 mmol/l) [43]. Tiu ch ny cng c T chc Y t Th gii (WHO) thng qua vo nm 2011 [41]. 1.1.6.Cc bin chng thng gp Bin chng cp tnh CcbinchngcptnhcabnhTthnglhuqucachnon mun, iu tr khng thch hp hoc do bnh gian ph hoc nhim khun cp tnh [2]. Hn m nhim toan ceton L tnh trng trm trng ca ri lon chuyn ha glucid do thiu insulin nng gy tng glucose mu, tng phn hy lipid, tng sinh th ceton gy toan ha t chc v hu qu l mt nc v in gii trong v ngoi t bo [17]. y l mt bin chng nng thng xy ra typ 1 nhng bnh cng c th gp mi typ T khi c iu kin thun li nh nhim trng, stress [11]. H glucose mu H glucose mu l hu qu ca tnh trng mt cn bng gia hai qu trnh cung cp glucose v tiu th glucose trong vng tun hon. Triu chng h glucose mu thng xy ra khi lng glucose mu ch cn mc 2,7 3,3 mmol/l, ty theo mc glucosemuscnhngbiuhinlmsngtngng[1].Nguynnhngyh glucose mu c th l: qu liu Insulin, h glucose mu do Sulfonylure, gim khu phn n hay gi n mun hn thng ngy, gng sc,[17]Hn m nhim toan acid lactic Nhim toan acid lactic l mt ri lon chuyn ha nng thng gp khi c ri lon cung cp oxy t chc, acid lactic c sn xut tng ln cc t chc nh c, xng v tt c cc t chc khi b thiu oxy trm trng [17]. Bnh thng xy ra trn ngi T ln tui do hai tc ng: thiu oxy do suy tim hoc suy h hp, lm dng Metformin [11]. Cc bnh nhim trng cp Ngi mc T d b nhim trng v kh cha, bn cnh dng khng sinh phi kim sot glucose mu tht tt. Mt s nhim trng hay gp l nhim trng da, 7 lao phi, vim ng tai ngoi cp tnh, vim rng li, vim ty xng, vim ti mt sinh hi, nhim nm Mucor, vim hoi t m t bo,[20]. Bin chng mn tnh Cc bin chng mn tnh ca T rt hay gp, thm ch cc bin chng ny c ngay ti thi im bnh c pht hin [2]. Bin chng mch mu ln Bnh tim mch T l mt qu trnh xy ra lu di v lin tc gia hai yu t x va mch v tng huyt p. Chng va l nguyn nhn va l hu qu ca nhau,thcynhaucngphttrin.Binchngmchmulncphnthnh: bnh mch vnh, bnh mch no, bnh mch mu ngoi vi [1]. Bin chng mch mu nh Bnhlbnchnlmtbinchngthnggp,gynnchyubihai nguyn nhn c nh hng tng h nhau: bnh thn kinh v bnh mch mu. Cc chn thng ng vai tr nh yu t thun li cho lot xut hin. Nhim trng lm trm trng thm lot, y l yu t nguy c cao cho ct ct chi di v thm ch t vong do nhim trng huyt [17]. Bin chng mt ngi T c phn ra cc nhm bao gm: bnh l vng mc, c thy tinh th v glaucoma. a s cc nguyn nhn gy m l do tn thng vng mc [14]. Bin chng thn: Bnh nhn mc bnh T thng c tn thng cu thn. TnthngsmnhtcuthncangiTliraproteinvith (microalbumin niu) [20]. Ngi mc bnh T typ 2 sau 20 nm c t l mc bnh thn l 5 10% [14]. Bin chng thn kinhngoi vi l mt bin chng mn tnh quan trng. Tn thng m bnh hc l mt bao myelin ca si thn kinh ln v nh, tng sinh ca m lin kt trong khi cc vi mch c s dy ln ca mng c c bn gy hp khu knh mao mch [14]. 8 1.1.7.iu tr 1.1.7.1. Mc tiu iu tr Mctiuiutrnhmlmgimnguycxuthinccbinchngmch mu nh v mch mu ln, ci thin cc triu chng, gim thiu nguy c t vong v ci thin cht lng cuc sng ca ngi bnh [11], [30]. Theo Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, mc tiu iu tr l cn phi nhanh chng a lng glucose mu v mc qun l tt nht, a HbA1c v khong 6,5% n 7,0% trong vng 3 thng [6].Bng 1.1: Mc tiu iu tr T typ 2 theo B Y t nm 2011 [6] Ch sn vTtChp nhnKm Glucose mu -Lc i -Sau n mmol/l 4,4 6,1 4,4 7,8 6,2 7,0 >7,8 n 10,0 > 7,0 > 10,0 HbA1c% 6,5> 6,5 n 7,5> 7,5 Huyt pmmHg 130/80130/80 140/90> 140/90 BMIkg/m218,5 2318,5 23 23 Cholesterol TPmmol/l< 4,54,5 - 5,2 5,3 HDL Cmmol/l>1,1 0,9< 0,9 Triglyceridmmol/l1,51,5 - 2,2> 2,2 LDL Cmmol/l< 2,52,5 3,4 3,4 Non HDLmmol/l3,43,4 4,1> 4,1 Bng 1.2: Mc tiu iu tr T typ 2 theo Hip hi T Hoa K nm 2014 [23] Ch tiuKhuyn co HbA1c< 7,0 % Glucose muGlucose mu mao mch lc i: 3,9 7,2 mmol/L (70 130mg/dL) nh glucose mu mao mch sau n (1 2 gi sau n): < 10,0 mmol/L (180 mg/dL) Huyt p< 140/80 mmHg Lipid muLDL C < 2,6 mmol/L 9 1.1.7.2. Phng php iu tr Khi thit lp mc tiu iu tr (mc tiu cn t c i vi HbA1c) th cn kt hp gia bin php iu tr khng dng thuc v bin php iu tr dng thuc t c mc tiu ny [39]. iu tr khng dng thuc Ch n Chnkhemnhlmtphnquantrngtrongchmscbnhnhn T, em li nhng li chtch cci vi vic kim sot cn nng, chuyn ha trong c th v th trng chung ca bnh nhn [40]. Hip hi i tho ng Hoa K (ADA2014)khuyncolngcalochomtngybaogm:4565%didng carbonhydrat, 25 35% di dng cht bo (trong cht bo bo ha t hn 7%) v 10 35% dng protein [38]. Tuy nhin, ch n ny phi c xy dng ph hp vi nhu cu, thi quen, ca tng bnh nhn [39].Vn ng th lc Nhn chung vic vn ng th lc em li nhiu li ch cho bnh nhn T. Tpthdcgpphncithintnhtrngkhnginsulin,kimsotglucosemu phn ln cc bnh nhn v gim nguy c cc bnh tim mch, gip gim hoc duy tr cn nng, ci thin tnh trng chung ca bnh nhn [30]. Bnh nhn nn vn ng th lc 30 - 45 pht trong vng 3 - 5 ngy/tun hoc 150 pht/tun vi cng tp trung bnh, t nht 3 ngy/tun [23], [40]. iu tr bng thucTi thi im chn on, Metformin c khuyn co l la chn u tay i vi bnh nhn T typ 2 tr khi Metformin b chng ch nh [23], [27], [34], [39]. Vi nhng bnh nhn T typ 2 mi c chn on c nng glucose mu tng cao r rt hay HbA1c cao v/hoc km theo cc triu chng r rt th cn nhc iu tr bng Insulin, c hoc khng km theo cc thuc h glucose mu khc. Nu n tr liu bng cc thuc iu tr dng ung vi liu ti a m khng t c hoc duy tr c mc tiu HbA1c sau hn 3 thng th b sung thm mt thuc khc, cht ng vn th th GLP - 1 hoc Insulin [23]. 10 Theo Hng dn chn on viu tr T typ 2 ca B Y t nm 2011 vic la chn ban u ca ch n tr liu nn da vo ch s khi c th (BMI), nu BMI < 23 nn chn thuc nhm Sulfonylure, nu BMI > 23 nn chn Metformin. ccbciutructhphihpviccthucthucnhmcch glucosidase. Hng dn ny cng ch r mt s trng hp nn dng thuc phi hp sm nh sau: -Nu HbA1c > 9,0% m mc glucose mu lc i trn 13,0 mmol/L c th ch nh 2 loi thuc vin h glucose mu phi hp -Nu HbA1c > 9,0% m mc glucose mu lc i trn 15,0 mmol/L c th ch nh dng ngay insulin [6]. Cc phc iu tr ca B Y t, Hip hi i tho ng Hoa K (ADA 2014) v Lin on i tho ng Quc t (IDF 2012) c trnh by Ph lc 1. 1.2. CC THUC IU TR I THO NG TYP 2 1.2.1.Insulin C ch tc dng: Insulin l mt hormon polypeptid do t bo ca o Langerhans tuyn ty tit ra. Nng glucose trong mu l yu t chnh iu ha tit insulin. ngi bnh thng, insulin tit khng u, nhiu nht sau ba n. Tc dng chnh ca insulin ln s n nh nng glucose mu xy ra sau khi insulin gn vi cc th th c hiu trn b mt t bo ca cc m nhy cm vi insulin, c bit l gan, c vn v m m. Insulin c ch to glucose gan, tng s dng glucose ngoi vi v do lm gim nng glucose trong mu. N cn c ch s phn gii m v do ngn s to thnh cc th ceton. Ngoi ra, insulin cn c tc dng ng ha do nh hng ln chuyn ha glucid, lipid v protid. Insulin b phn hy cc m gan, c v thn [9]. 11 Phn loi:Bng 1.3: Mt s dng insulin [16] Dng insulinBit dc c s ng k lu hnh ti Vit Nam Nng Thi gian khi pht tc dng Thi gian duy tr tc dng Cht tng t Insulin tc dng rt nhanh ApidraDung dch tim 100 IU/ml 10 20 pht 2 5 gi Insulin tc dng nhanh Actrapid HM Dung dch tim 100 IU/ml 15 30 pht 4 8 giInsulin bn chm (insulin trung bnh hoc NPH) Insulactard Flexpen, Insulactard HM Dung dch tim 100 IU/ml 1 2 gi10 16 gi Cht tng t Insulin tc dng chm (insulin glargin hay insulin determir) Lantus, Lantus SoloStar Hn dch tim 100 IU/ml 1,5 gi22 24 gi Hn hp Insulin bn chm/cht tng t Insulin NovoMix 30 Flexpen Hn dch tim 100 IU/ml 15 pht12 gi Hn hp Insulin bn chm/insulin nhanh Mixtard 30, Mixtard 30 FlexPen Hn dch tim 100 IU/ml 30 pht12 gi

Hin nay, trn th trng c cc loi insulin hn hp, insulin ny nhn c, c sncchpchttrnsn,hoclinsulintcdngnhanhhoclinsulintcdng chm, pha vi insulin tc dng bn chm, gip d dng a c hai loi thuc bng mt mi tim (chch). Nu insulin ny t l 30/70ngha l cha 30% insulin tc dng nhanh v 70% insulin tc dng bn chm. Cn 50/50 l 50% mi loi. Ch nh: -C th ch nh insulin ngay t ln khm u tin nu mc HbA1c > 9,0% m mc glucose lc i trn 15,0 mmol/l 12 -Ngi bnh T nhng ang mc mt bnh cp tnh khc; v d nhim trng nng, nhi mu c tim, t qu, -Ngi bnh T suy thn c chng ch nh dng thuc vin h glucose mu, ngi bnh c tn thng gan, -Ngi bnh T mang thai hoc T thai k -Ngiiutrccthuchglucosemubngthucvinkhnghiuqu; ngi b d ng vi cc thuc vin h glucose mu, [6]. -Ngi ang chun b phu thut [27] Chng ch nh: D ng vi insulin b hoc ln hoc vi cc thnh phn khc ca ch phm (metacresol/protamin/ methyl-parahydroxybenzoat). Dng n thun insulin tc dng trung gian v tc dng ko di trong trng hp toan mu hoc hn m i tho ng [9]. Tc dng khng mong mun: H glucose mu: Triu chng bo hiu sm h glucose mu s nh v thm ch b che giu hon ton trong thi gian dng Insulin ngi. Phn ng ti ch: D ng ban , nga ch tim, pht trin m m (thng do tim thuc di da nhiu ln ti mt v tr) [9]. 1.2.2.Cc thuc iu tr i tho ng typ 2 dng ung Cc thuc iu tr T typ 2 dng ung c chia lm nhiu nhm:-Nhm thuc kch thch s bi tit insulin: Sulfonylure, Meglitinid -Nhm thuc lm tng s nhy cm ca t bo vi insulin: dn xut Biguanid (Metformin), Thiazolidindion -Nhm thuc nh hng n s hp thu glucose: c ch - glucosidase-Nhmthucctcdnggingincretinhockoditcdngcaincretin: Exanatid v cc thuc c ch DPP - 4 -Thuckhc:Pramlintidhglucosemubngcchcchglucagonvlm chm qu trnh lm rng d dy [38]. 13 1.2.2.1. Nhm BiguanidC nhiu cht thuc nhm Biguanid c tc dng h glucose mu, trong , c 3 cht tng cmttrn th trng l:Metformin,Phenformin v Butformin. Hai thuc Butformin v Phenformin hin nay khng cn c dng v thng gy ra nhim acid lactic [12].C ch tc dng: Nhm Biguanid thc cht khng phi l nhm thuc h glucose mu m l thuc chng tng glucose mu. C ch tc dng ca nhm thuc ny l ci thin lin kt ca insulin vi th th. C th l: tng cng s dng glucose trong t bo, kch thchtrctipsphnhyglucosetrongtbo,kchthchtrctipsphnhy glucose trong cc m v tng vn chuyn glucose t mu vo m; lm gim s tn to glucose gan; ngoi ra cc Biguanid phn no c nh hng tt trn chuyn ha lipoprotein,thngbrilonngibTkhngphthucinsulin[12]. Biguanid khng kch thch ty tit insulin nn khng gy h glucose mu [6] v khng gy tng cn, y l u im so vi Insulin v nhm Sulfonylure [36].Metformin c tc dng h glucose trong khong 60 80 mg/dL (tng ng vi khong 4-5 mmol/L) v gim HbA1c t 1,5 2% [30]. Ch nh: ithongtyp2nhtlvinhngbnhnhnthacnhocboph [10], [24], [25]. Chng ch nh:-T typ 1, nhim toan ceton -Thiu oxy t chc ngoi bin (suy tim, suy h hp) -Suy thn v ri lon chc nng thn, ri lon chc nng gan -C thai -Ch n t calo ( gim cn) -Ngay trc v sau phu thut hoc bnh nhn > 70 tui [48]. 14 Tc dng khng mong mun: Tc dng khng mong mun (TDKMM) thng gp nht ca Metformin l trn tiu ha (tiu chy, bun nn, nn, kh tiu,...) xy ra trn 5-50% bnh nhn v khong6%bnhnhnphingngdngthucdoTDKMMny[37].TDKMM nghim trng nht l gy nhim toan acid lactic, trong 50% trng hp dn n t vong [22]. 1.2.2.2. Nhm ThiazolidindionCcThiazolidindion(TZD)csdnggm:Troglitazon,Rosiglitazon, Pioglitazon;tuynhin,Troglitazonbrtrakhithtrngvgybinchng nhim c gan nng [25].C ch tc dng: Cc TZD lm gim glucose mu c lc i v c sau khi n bnh nhn b T typ 2, do lm tng s nhy cm ca t bo ch i vi insulin. Ging vi cc Biguanid v cht c ch glucosidase, cc TZD khng gy h glucose mu ngi khng b T thm ch khi dng liu cao, v vy cc TZD phi c gi l thuc chng tng glucose mu ng hn l thuc h glucose mu [12]. C ch tc dng ca nhm thuc ny cha r rng nhng cc tc dng quan st c l lm tng cht vn chuyn glucose (GLUT 1 v GLUT 4), lm gim cc acid bo t do (FFA), lm gim tn to glucose gan, lm tng bit ha cc tin acid bo thnh cc acid bo [20]. Ch nh: T typ 2 c tnh trng khng insulin c th iu tr kt hp vi Sulfonylure hoc Metformin [20]. Chng ch nh: Mn cm vi thuc v cc thnh phn ca thuc, c thai v cho con b, bnh gan (enzym ALT > 2,5 ln gii hn cao ca bnh thng), suy tim [20]. 15 Tc dng khng mong mun: Thng gy tng cn ch yu do lm tng tch tr m di da v mt phn do gi nc. V vy, cn thn trng khi dng TZD iu tr cho cc bnh nhn b suy tim hoc c bnh tim, vim gan hoc c men gan cao [10]. 1.2.2.3. Nhm Sulfonylure Sulfonylure c chia lm 2 nhm chnh: -Thh1:NhngthucnygmTolbutamid,Chlopropamid,Diabetol, thng ng vin 500 mg. Cc thuc thuc nhm ny hin nay t c s dng do c tnh cao vi thn (v thuc c trng lng phn t ln). -Thh2:NhngthucthucnhmnygmGlibenclamid,Gliclazid, Glipizid, Glyburid, nhng thuc ny c tc dng h glucose mu tt, t c hn nhng thuc th h 1 [2], [6]. C ch tc dng: SulfonyurekchthchsbititinsulindognvireceptorSURvchn knh K+-ATPase t bo o ty lm gim K+ gy kh cc mng, lm tng lng Ca2+ t ngoi bo i vo trong t bo qua knh Ca2+. Nng Ca2+ ni bo tng khin cchtkchthchtitinsulindichuynnbmttbovxutbogiiphng insulin [25], [30]. Sulfonylure lm gim glucose trung bnh 50 -60 mg/dL, gim HbA1c ti 2% [6]. Ch nh:Sulfonylure c ch nh cho nhng bnh nhn khng b tha cn v nhng bnh nhn chng ch nh hoc iu tr vi Metformin khng hiu qu [24], [25].Chng ch nh: -i tho ng typ 1 -Suy gan, suy thn -i tho ng nhim toan ceton -C thai hoc d ng vi Sulfonylure [10], [25]. 16 Tc dng khng mong mun:-H glucose mu -Bun nn, nn, vng da mt -Bt thng v huyt hc: mt bch cu ht, thiu mu bt sn, thiu mu tiu huyt -Phn ng tng nhy cm ton thn v ngoi da -Phn ng ging disufiram, c bit l Chloproramid khi dng cng ru (gp 10 15% bnh nhn) -H natri mu d gp vi Chloropamid (khong 5% bnh nhn) [12], [25]. 1.2.2.4. Nateglinid v Meglitinid C ch tc dng: Kch thch ty tit insulin bng cch chn knh K+- ATPase trong t bo o ty [25], [38]. Ch nh:n tr liu hoc kt hp vi Metformin, vi Insulin. Ngi ta cng c nhng s liu chng minh vic kt hp Repaglinid vi Insulin NPH trc khi i ng t kt qu tt trong iu tr h glucose mu ngi T typ 2 [6]. Tc dng khng mong mun Ri lon tiu ha, au bng, tiu chy, to bn, nn, bun nn. H glucose mu thng nh. au khp, phn ng qu mn v tng men gan c th xy ra [54]. 1.2.2.5. Nhm thuc nh hng n s hp thu glucose Hin nay c 2 thuc ang c s dng l Acarbose v Miglitol [38]. C ch tc dng: Ccthucnylmgimshpthuquarutcatinhbt,dextrinvcc disaccarid, do c ch tc dng ca glucosidase ra bn chi ca rut. S c ch ny lmchm s hp thu ca carbonhydrat, do s tng glucosemu sau khi n gim c ngi T v ngi bnh thng [12], [25]. Trong n tr liu, Acarbose lm gim nng trung bnh ca HbA1c vo khong 0,6 1 % [9]. 17 Ch nh: Tng nh glucose mu sau n. iu tr n tr liu kt hp vi ch n hoc thuc khc [10]. Chng ch nh: -Qu mn vi Acarbose -Vim nhim ng rut, c bit kt hp vi lot -Do thuc c kh nng to hi trong rut, khng nn dng cho nhng ngi d b bnh l do tng p lc bng (thot v) -Nhng trng hp suy gan, tng enzym gan -Ngi mang thai hoc ang cho con b -H glucose mu -i tho ng nhim toan th ceton [9]. Tc dng khng mong mun: Cc TDKMM thng gp ca nhm thuc ny l y hi, chng bng, tiu chy v au bng, c bit l khi bt u iu tr, mt s trng hp phi ngng dng thuc[22].Hglucosemucthxyrakhiphihpccthuccch glucosidase vi Insulin hoc cc thuc kch thch bi tit insulin [31]. 1.2.2.6. Nhm cc thuc I ncretin Cc thuc ng vn th th GLP - 1 Gn y, ngi ta tm ra ra hai loi hormon c gii phng ra t nim mcrutctcdnglmtngskchthchtitinsulinkhiglucosemucaol glucose-dependentinsulinotropicpolypeptid(GIP)vglucagon-likepeptid(GLP- 1), c gi chung l incretin hormon. Hai loi hormon ny c c ch kch thch bi tit insulin khc nhau. GLP - 1 lm tng ng k s bi tit insulin so vi GIP v vy n khng ngng c pht trin iu tr T typ 2. GLP - 1 cng lm gim s bi bit glucagon, lm gim thi gian lm rng d dy v gim s thm n. V vy, GLP - 1 c tc dng lm gim glucosemusau n v gim cn. Tuy nhin, n c nhcimlthigiantcdngngndobbthotbiDipeptidylpeptidaseIV enzym (DPP - 4) (sau 1-2 pht) nn GLP - 1 phi dng ng tim lin tc. Do , 18 ngi ta nghin cu ra cc cht ng vn th th GLP - 1 duy tr tc dng ca incretinvkhnglitcdngcaDPP-4[25].Thuccsdnghinnayl Exanatid. Cctcdngphcathucgmc:bunnngp15-30%bnhnhn (thng t ht), h glucose mu mu c th xy ra khi dng cng thuc kch thch tit insulin [10], [20]. Thuc c ch DPP - 4 Cc thuc c ch DPP - 4 cho n nay c 2 th h: Cc thuc c ch hot ng ca DPP - 4 c kim chng ln u vo cui nhng nm 1990 ca th k 20, nhng khng c s dng vo lm sng. -Th h 1 pht trin hon thin v c p dng vo iu tr l cc thuc Sitagliptin (2007) -Th h 2 l Saxagliptin (2009). Ngoi ra l cc thuc nh Vidagliptin (2008) ph bin chu u [6].Thuc c tc dng c ch enzym phn hy GLP - 1 l DPP - 4 (dipeptidyl peptidase-4) nh lm tng nng v tc dng ca GLP - 1 ni sinh [20]. Vildagliptin hoc Sitagliptin c tc dng gim HbA1c trung bnh t 0,7% n 1% vi liu 100 mg/ngy [30].Cc tc dng ph ca thuc gm c: vim mi, vim hng, nhim khun h hp trn v au u [36]. 1.2.2.7. Thuc khc Pramlintid l mt dn xut tng hp ca Amylin mt hormon tuyn ty c vai tr trong iu ha glucose mu. Thuc c tc dng lm chm tc lm rng d dy, c ch tit glucagon sau n v gim s thm n [54]. Tc dng ph ca thuc: nn, bun nn, chn n, au u [20]. 1.2.3.Phi hp thuc trong iu tr i tho ng typ 2 1.2.3.1. Phi hp insulin v cc thuc iu tr i tho ng typ 2 dng ung KhisdngccthucTtyp2dngungmkhngkimsotc glucose mu th vic bt u iu tr bng Insulin l cn thit. Khong 30% bnh nhn 19 Ttyp2cnphisdngInsulin[31].TheoNghincutincuvitho ngcaAnh(UKPDS)thtrongvng6nm,chn50%bnhnhnbanu c la chn s dng Sulfonylure mt cch ngu nhin cn phi iu tr thm bng Insulin t cmc tiuiu tr [52]. C th c nhiu phng php phi hp Insulin vi cc thuc iu tr T typ 2 dng ung, sau y l mt s phng php phi hp thuc: -Insulin + Metformin: s kt hp gia Insulin v Metformin gip kim sot glucose mu tt hn [37]. S gim liu Insulin c th l cn thit do d s gip hn ch TDKMM l gy tng cn v h glucose mu ca Insulin [51], [53]. Thng phi hpgiaInsulintcdngkodidng1ln/ngytrckhiinghocInsulin isophan 2 ln/ngy vi Metformin dng vo ba n [40], [51]. -Insulin + TZD: s phi hp ny gip lm gim liu Insulin v ch s HbA1c tuy nhin li gy tngcn[53]. chu u, Thiazolidindion kt hp vi Insulin l mt chng ch nh do s kt hp ny lm gia tng nguy c suy tim [29], [56]. -Insulin+Acarbose:vinhngbnhnhnbophcchngchnhhoc khng dung np vi Metformin c th iu tr phi hp Metformin v Acarbose [56]. S phi hp ny s gp phn ci thin glucose mu sau n ca nhng bnh nhn c ch n giu carbonhydrat [26]. 1.2.3.2. Phi hp cc thuc iu tr i tho ngtyp 2 dng ung Trong iu tr T typ 2, thng gp s phi hp gia cc thuc dng ung: - Metformin + Sulfonylure:Khi iu tr bng Metformin khng t hiu qu iu tr th nn phi hp vi Sulfonylure [6], [34]. y l kiu phi hp ph bin nht gip tng cng kim sot glucose mu v h m mu [28]. Nhiu th nghim lm sng cho thy khi phi hp 2 thuc ny th khng c thm tc dng ph no xut hin so vi khi dng tng thuc n c [57].Bitdcphihp:Glucovance(MetforminvGlyburid);Metaglip (Metformin v Glipizid). -Metformin+TZD:SphihpnygiplmgimHbA1c.uimca phi hp nyl Metformin hn ch tc dng gy tng cn ca TZD, ng thi tc 20 dng hip ng lm gim Triglycerid, tng HDL-cholesterol. Phi hp Metformin v TZD ngy cng c s dng ph bin do Metformin c ch s tn to glucose ti gan v TZD ch yu lm tng s nhy cm ca Insulin c [28]. Bitdcphihp:Avandamet(Rosiglitazon+Metformin);ActoPlusMet (Pioglitazon + Metformin). -Metformin + Thuc c ch DPP - 4: thuc dng phi hp gia Vildagliptin v Metformin c ch nh dng cho nhng bnh nhn T typ 2 dng liu ti a ca Metformin nhng vn khng kim sot c glucose mu. S phi hp ny gp phn ci thin glucose mu v chc nng ca t bo [49].Bitdcphihp:Janumet(Sitagliptin+Metformin),Galvusmet (Vildagliptin + Metformin). -Metformin + Acarbose: Acarbose c th c phi hp vi Metformin [36]. So vi iu tr n c bng Acarbose, s phi hp ny mang li hiu qu h glucose mu tt hn, gip t c mc tiu HbA1c, lm gim cn bnh nhn T typ 2 m khng gy h glucose mu [58]. 21 CHNG II: I TNG V PHNG PHP NGHIN CU 2.1. I TNG NGHIN CU i tng nghin cul cc bnh nhn T typ 2 iu tr ngoi trti Khoa Khm bnhPhngNi tit v i tho ng Bnh vinBch Mai t 01/01/2014 n 15/04/2014. 2.1.1.Thi gian v a im nghin cu -Thi gian: t 01/01/2014 15/04/2014. -a im: Khoa Khm bnh Phng Ni tit v i tho ng Bnh vin Bch Mai. 2.1.2.Tiu chun la chn -Bnh nhn c chn on xc nh l ln u mc T typ 2 v c bc s ch nh iu tr ngoi tr bng thuc iu tr i tho ng. -Bnh nhn cha dng mt thuc iu tr T typ 2 no trc thi gian iu tr Khoa Khm bnh Phng Ni tit v i tho ng Bnh vin Bch Mai. 2.1.3.Tiu chun loi tr -Bnh nhn iu tr ni tr trong thi gian nghin cu. 2.2. PHNG PHP NGHIN CU 2.2.1.Thit k nghin cu Nghin cu m t tin cu khng can thip, thu thp kt qu da trn phiu kho st (Ph lc 2). 2.2.2.Mu nghin cu C mu C mu thun tin ph hp vi iu kin ca ti. K thut chn mu Chn mu thun tin, khng xc sut, thu thp tt c bnh nhn tha mn tiu ch la chn v loi tr. 22 Cc bc tin hnh thu thp s liu Trong thi gian nghin cu, cc bnh nhn c khm lm sng v lm cc xt nghim sinh ha theo trnh t sau:Hnh 2.1: Cc bc tin hnh thu thp s liu 2.3. CC NI DUNG NGHIN CU 2.3.1.Mt s c im ca bnh nhn trong nghin cu: -Tui v gii tnh; tin s gia nh -Th trng bnh nhn ti thi im bt u nghin cu Bnh nhn nghin cu Thi im bt u nghin cu T0 Thi im sau 1, 2, 3 thng iu tr (T1, T2, T3) - Tui, gii tnh, tin s gia nh, cnnng,huytp,bnhmc km. - Xt nghim sinh ho mu (Glucose mu lc i, HbA1c, Cholesterol ton phn, Triglycerid, HDL-cholesterol, LDL-cholesterol, ASAT, ALAT, Creatinin mu). - Cc thuc iu tr ti thi im T0. -Cn nng, huyt p. -Xt nghim sinh ho mu (Glucose mu lc i, HbA1c, Cholesterol ton phn, Triglycerid, HDL-cholesterol, LDL-cholesterol, ASAT, ALAT, Creatinin mu). - CcthuciutrtithiimT1, T2, T3. - Ghi nhn cc bin c bt li m bnh nhn gp trong qu trnh iu tr. 23 -Cc ch s lin quan ti thi im bt u nghin cu: Glucose mu lc i, HbA1c,Huytp,Cholesteroltonphn,Triglycerid,HDL-cholesterol(HDL-C), LDL- cholesterol (LDL-C), ASAT, ALAT, Creatinin mu - Bnh mc km. 2.3.2.Tnh hnh s dng thuc trong iu tr i tho ng typ 2 trn bnh nhn ngoi tr: -T l bnh nhn ti khm -Danh mc cc thuc iu tr i tho ng typ 2 gp trong nghin cu -Tnhphhpcaviclachnphciutrtithiimbanuvi Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, Hng dn iu tr ca Hip hi i tho ng Hoa K nm 2014 (ADA 2014), Hng dn s dng thuc dnh cho cn b y t ca EMC (EMC) -Danh mc cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu. 2.3.3.S thay i nng glucose mu lc i v tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr:S thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr: -S thay i nng glucose mu lc i sau tng thng iu tr -Mc kim sot glucose mu lc i sau tng thng iu tr Tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr: -Cc bin c bt li (AE) bnh nhn gp phi trong qu trnh iu tr -Tng tc thuc gp trong nghin cu gia cc thuc iu tr i tho ng typ 2 vi cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu. 24 2.4. CC TIU CHUN NH GI Ch tiu nh gi glucose mu lc i, HbA1c, lipid mu, huyt p theo tiu chun ca B y t nm 2011 [6] Bng 2.1: Ch tiu nh gi glucose mu lc i, HbA1c, lipid mu, huyt p Ch sn vTtChp nhnKm Glucose mu -Lc i -Sau n mmol/l 4,4 6,1 4,4 7,8 6,2 7,0 >7,8 n 10,0 >7,0 >10,0 HbA1c% 6,5>6,5 n 7,5>7,5 Huyt pmmHg 130/80130/80 140/90>140/90 Cholesterol TPmmol/l< 4,54,5 - 5,2 5,3 HDL Cmmol/l>1,1 0,9< 0,9 Triglyceridmmol/l1,51,5 - 2,2>2,2 LDL Cmmol/l< 2,52,5 3,4 3,4 Ch tiu nh gi ch s khi c th (BMI) Tiuchunchnonthacn,bophdavoBMIpdngchongi trng thnh khu vc chu (Theo IDF, 2005) [6]. Bng 2.2: Ch tiu nh gi ch s khi c th BMI Phn loiBMI (kg/m2) Gy < 18,5 Bnh thng18,5 -22,9 Bo + C nguy c + Bo 1 + Bo 2 23 23 24,9 25 29,9 30 Cng thc tnh thanh thi creatinine (Clcreatinin) Cng thc Corkroft-Gault: Clcreatinin (ml/pht)= (140) ()72 (/) (Nu l n nhn vi 0,85) 25 Tnh ph hp ca vic la chn phc iu tr ban u trn bnh nhn i tho ng typ 2 Chng ti tin hnh nh gi tnh ph hp ca vic la chn phc iu tr ban u (c th l tnh ph hp trong vic la chn thuc v khng nh gi tnh ph hp v liu dng, cch dng trn bnh nhn mi c chn on T typ 2) vi cc ti liu: -Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011 -HngdniutrTcaHiphiithongHoaKnm2014 (ADA 2014). Trong hng dn ca B y t cng ch r v vic la chn v phi hp thuc nn tham kho theo hng dn ca Hip hi i tho ng Hoa K (ADA) -Hng dn sdng thuc dnh cho cn bY tcaAnh (EMC: electronic Medicines Compendium: https://www.medicines.org.uk/emc/default.aspx). Ngoi ra chng ti cn tham kho thm hng dn iu tr ca Lin on i tho ng Quc t (IDF 2012) v Hng dn iu tr cc bnh Ni khoa bnh i tho ng ca Bnh vin Bch Mai. Xc nh tng tc thuc thuc trong qu trnh iu tr: -Xcnhnguyctngtcthucdatrnccnguntiliu: www.Drugs.com; Drugs Interaction Facts 2009; Stockleys Drug Interaction (Pocket companion 2009), Tng tc thuc v ch khi s dng (Ti liu ca B Y t). -Lc cc tng tc c ngha: nhng tng tc c mc nh theo tng thang c loi b, cc cp tng tc c ghi nhn t 3 ti liu tr ln c la chn. 2.5. PHNG PHP PHN TCH V X L S LIU -Thu thp v x l cc s liu theo phng php thng k y hc. -Phn tch x l cc s liu bng phn mm SPSS 20.0. Cc s liu c trnh bydidngTrungbnh SD nu bin s phn phi chun v di dng trung v (t trung v) nu bin s phn phi khng chun. 26 CHNG III: KT QU NGHIN CU 3.1. MT S C IM CA BNH NHN TRONG NGHIN CU 3.1.1.Mt s c im chung ca bnh nhn trong nghin cu Bng 3.1: c im chung ca bnh nhn ti thi im bt u nghin cu c im chung (n = 52)S BN (%) Tui a53,10 11,33 Gii tnhNam 24 (46,15%) N28 (53,85%) Tin s gia nhC 14 (26,92%) Khng38 (73,08%) Bnh mc kmTHA9 (17,31%) RLLP18 (34,62%) THA + RLLP12 (23,08%) Bnh l thn3 (5,77%) Bnh l gan6 (11,54%) Chun b phu thut3 (5,77%) BMI (kg/m2)a22,63 2,41 Gy2 (3,85%) Bnh thng25 (48,08%) Nguy c bo ph15 (28,85%) Bo ph 110 (19,22%) Bo ph 20 (0,00%) Glucose mu lc i (mmol/L)b10,1 (7,6 15,3) Tt1 (1,93%) Chp nhn4 (7,69%) Km47 (90,38%) HbA1c (%)b9,1 (7,2 11,6) Tt7 (13,46%) Chp nhn7 (13,46%) Km38 (73,08%) a: Trung bnh SD; b: Trung v (T phn v); THA: tng huyt p; RLLP: Ri lon lipid mu 27 Nhn xt:-C 52 bnh nhn tham gia vo nghin cu trong thi gian t ngy 1/1/2014 n ngy 15/1/2014. -Tui trung bnh l 53,10 11,33 tui. -T l bnh nhn n (chim 53,85%) mc T typ 2 tng ng vi bnh nhn nam (chim 46,15%). -Bnh nhn c phng vn v c xp l c tin s gia nh c ngi mc T typ 2 nu trong gia nh c b, m, hoc anh ch em rut b bnh T typ 2. Hn 1/4 bnh nhn (26,92%) c tin s gia nh c ngi mc T typ 2. -Tng huyt p (THA) v Ri lon lipid mu (RLLP) l nhng bnh thng mc km vi T. V vy trong phm vi ti ny, chng ti tin hnh kho st t l bnh nhn T typ 2 c mc km hai bnh ny. Khong 3/4 bnh nhn (chim 75,01%) c mc THA, RLLP hoc c hai. -C 3 bnh nhn c bnh l v thn (2 bnh nhn c mc km suy thn v 1 bnh nhn tng ghp thn); 6 bnh nhn c bnh l v gan (3 bnh nhn vim gan B v 3 bnh c men gan tng cao gp 2 -3 ln gi tr bnh thng). -Ch s BMI trung bnh ti thi im chn on l 22,63 2,41 kg/m2 mc bnh thng. Bnh nhn c th trng bnh thng (chim 48,08%) v c nguy c bo ph (chim 28,85%) chim phn ln. -Ch s glucose mu lc i ti thi im chn on l rt cao, c trung v l 10,1 (7,6 15,3) mmol/L, thm ch c bnh nhn glucose mu lc i ln ti 28,4 mmol/L. Ch s HbA1c cng rt cao, c trung v l 9,1 (7,2 11,6) %. S lng bnh nhn c glucosemulcivHbA1ctithiimchnoncnhgikmchim phn ln: glucose mu lc i vi t l 90,38% v HbA1c vi t l 73,08%. 28 3.1.2.Cc ch s cn lm sng khc ti thi im bt u nghin cu Bng 3.2: Cc ch s cn lm sng khc ti thi im bt u nghin cu Nhn xt:-Ccchslipidmubanucgitrtrungbnhmckimsotkml Cholesteroltonphn(5,791,76)mmol/LvTriglycerid(2,932,84)mmol/L. Ngay ti thi im chn on ban u, c nhiu bnh nhn c mc kim sot km cc ch s lipid: Cholesterol ton phn (chim 62,75%), Triglycerid (chim 48,00%), LDL C (chim 45,65%).-Ch s huyt p trung bnh mc chp nhn 130,19 18,94/ 79,42 10,18 mmHg. Phn ln bnh nhn c huyt p mc kim sot tt (chim 65,38%). Ch sn vTB SDPhn loiS BN (%) Cholesterol ton phn (n = 51) mmol/L5,79 1,76 TtChp nhn Km 10 (19,60%) 9 (17,65%) 32 (62,75%) Triglycerid(n = 50) mmol/L2,93 2,84TtChp nhn Km 16 (32,00%) 10 (20,00%) 24 (48,00%) HDL C (n = 45) mmol/L1,27 0,39 TtChp nhn Km 30 (66,67%) 7 (15,55%) 8 (17,78%) LDL C (n = 46) mmol/L3,39 0,94 TtChp nhn Km 9 (19,57%) 16 (34,78%) 21 (45,65%) Huyt p (n = 52) mmHg130,19 18,94/ 79,42 10,18 TtChp nhn Km 34 (65,38%) 7 (13,47%) 11 (21,15%) 29 3.2. TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR 3.2.1.T l bnh nhn ti khmNghin cu c thc hin l mt nghin cu tin cu khng can thip, cc bnh nhn c chn vo nghin cu bao gm bnh nhn bo him v khng c bo him ang c iu tr ngoi tr ti Khoa Khm bnh Phng Ni tit v i tho ngcaBnhvinBchMai.Slngbnhnhnmithiimcskhc nhau v mt s bnh nhn khng quay li ti khm vi nhiu l do nh bnh nhn xa nn iu kin i li kh khn, bnh nhn sau khi iu tr 1, 2 thng chuyn v iu tr ti a phng, bnh nhn do cng vic bn rn khng th sp xp i ti khm,. Do , cc ch tiu u c tnh t l theo s lng bnh nhn thi im tng ng. Biu 3.1: T l bnh nhn ti khm Nhn xt:T l bnh nhn ti khm gim dn sau 3 thng. Tnh n thng th 3 ch c 21,15% bnh nhn ti khm so vi thi im ban u. 524226110102030405060T0 T1 T2 T3S bnh nhn ti khm30 3.2.2.Danh mc cc thuc iu tr i tho ng typ 2 gp trong nghin cu Bng 3.3: Danh mc cc thuc iu tr T typ 2 gp trong nghin cu Nhm thucHot chtTng (%) Insulin Insulin42 (22,34%) BiguanidMetformin86 (45,74%) SulfonylureGliclazid23 (12,23%) Glimepirid21 (11,17%) c ch - glucosidaseAcarbose8 (4,26%) c ch DPP - 4Sitagliptin 3 (1,60%) Vildagliptin 5 (2,66%) Nhn xt:-Cc thuc iu tr T typ 2 gp trong mu nghin cu rt phong ph gm cc nhm Biguanid, Sulfonylure, c ch glucosidase, c ch DPP - 4. Tuy nhin, nhm TZD (Rosiglitazon, Pioglitazon) khng c s dng. -Metformin l thuc c s dng nhiu nht (chim 45,74%). Thuc iu tr dng ung c s dng nhiu tip theo l nhm Sulfonyure (chim 23,40%) gm: Gliclazid (chim 12,23%) v Glimepirid (chim 11,17%). -Insulincng c sdng tng i nhiu(chim 22,34%) gm cc nhm Insulintcdngnhanh(ActrapidHM),Insulinbnchm(InsulactardHM),Cht tng t Insulin tc dng chm (Lantus SoloStar) hoc Hn hp insulin (NovoMix 30, Mixtard 30).-ng ch l ngoi cc nhm thuc iu tr c in, cc thuc T typ 2 th hmicngcavosdngdidngvinnnphihpgia2nhm Metformin v c ch DPP - 4. Tuy nhin dng thuc ny ch c s dng t gm: Sitagliptin (chim 1,60%) v Vildagliptin (chim 2,66%). -Cc thuc nhm c ch glucosidase t c s dng (chim 4,26%). 31 3.2.3.Tnh ph hp ca vic la chn phc iu tr ti thi im ban u vi Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, Hng dn iu tr ca Hip hi i tho ng Hoa K nm 2014 (ADA 2104), Hng dn s dng thuc dnh cho cn b y t ca EMC (EMC) Bng 3.4: La chn phc iu tr ti thi im ban u Phc S PPh hp (%)Cha ph hp (%)n tr liu4030 (75,00%)10 (25,00%) Metformin14113 Sulfonylure211 Acarbose202 Insulin22184 a tr liu124 (33.33%)8 (66.67%) Met + Sulfo725 Sulfo + Acar110 Insulin + Met110 Met + Sulfo + C DPP - 4202 Met + sulfo + Acar101 Tng5234 (65.38%)18 (34.62%) *Met: Metformin; Sulfo: Sulfonylure; Acar: acarbose; C DPP - 4: c ch DPP - 4 Nhn xt:Phn ln phc n tr liu c s dng ph hp (chim 75,00%). Trong cc phc a tr liu c s dng trn bnh nhn i tho ng typ 2 c 8 phc (trn tng s 12 phc ) c nh gi l cha ph hp. Nhn chung, phn ln cc phc c la chn iu tr trn bnh nhn l ph hp. Insulin Trong nghin cu, phc iu tr n c bng Insulin l phc c s dng nhiu nht thi im ban u nn chng ti tin hnh phn tch vic s dng ny. 32 Bng 3.5: La chn phc c Insulin ti thi im ban u nh giL do ( n = 22)S BN (%) Ph hp HbA1c > 9,0% + Glucose mu > 15,0 mmol/l6 (27,27%) Phu thut m polyp t cung3 (13,64%) Men gan tng cao hoc vim gan 4 (18,18%) HbA1c > 9,0% + Glucose mu > 15,0 mmol/l v men gan tng cao 2 (9,09%) HbA1c > 9,0% + Glucose mu > 15,0 mmol/l v suy thn/tin s ghp thn 3 (13,64%) Cha ph hpS dng ngoi cc ch nh dng Insulin theo Hng dn ca B Y t 4 (18.18%) Nhn xt:Phn ln cc ch nh s dng Insulin (chim 81,82%) trn bnh nhn ti thi im ban u l ph hp. 3.2.4.Danh mc cc thuc iu tr bnhmc km Tng huyt p vRi lon lipid mu THA v RLLP l 2 bnh thng mc km vi T nn chng ti tin hnh kho st cc thuc iu tr 2 bnh ny. Bng 3.6: Danh mc cc thuc iu tr bnh mc km THA v RLLP Nhm thucHot cht iu tr THA c ch men chuynLisinopril Perindopril Chn th th ATILosartan Chn adrenergicBisoprolol Metoprolol Li tiu ThiazidIndapamid iu tr RLLP StatinSimvastatin Atorvastatin Rosuvastatin FibratFenofibrat 33 Nhn xt: Danh mc thuc iu tr THA v RLLP a dng. Thuc iu tr THA gm c 4 nhm thuc: c ch men chuyn, Chn th th AT1, Chn adrenergic, Li tiu Thiazid. Thuc iu tr RLLP gm 2 nhm thuc: Statin v Fibrat. 3.3. STHAYINNGGLUCOSEMULCIVTNHAN TON KHI S DNG THUC IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR 3.3.1.S thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr T cc ti liu v bnh T typ 2 v cc bin chng ca n, vic nh gi hiu qu iu tr khng nhng ch da vo cc ch s glucose mu m cn phi nh gi da vo ch s HbA1c. Tuy nhin, ch s HbA1c ca bnh nhn ch c o lng y thi im chn on banu v khng c o lng y cc thi im tip theo. Do , trong nghin cu ny chng ti ch bc u nh gi hiu qu iu tr trn bnh nhn T typ 2 iu tr ngoi tr thng qua s thay i nng glucose mu lc i sau 3 thng iu tr. S thay i nng glucose mu sau tng thng iu tr Bng 3.7: S thay i nng glucose mu sau tng thng iu tr Thi imTrung v (T phn v) T010,1 (7,6 15,3) T17,9 (6,8 9,3) T27,6 (6,8 8,3) T35,8 (6,3 7,4) Nhn xt:Nng glucose mu lc i gim dn qua tng thng iu tr trn bnh nhn T typ 2. Ti thi im chn on ban u, nng glucose mu rt cao, c trung v l 10,1 (7,6 15,3) mmol/L v sau 3 thng ch cn 5,8 (6,3 7,4) mmol/L. Mc gim thng u tin l ln nht. 34 Mc kim sot glucose mu sau tng thng iu tr Bng 3.8: Mc kim sot glucose mu sau tng thng iu tr Nhn xt: Sau 3 thng iu tr, t l bnh nhn c mc kim sot glucose mu tt tng dn v mc kim sot km gim so vi thi im ban u. 3.3.2.Tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr 3.3.2.1. Cc bin c bt li (AE) gp trong qu trnh nghin cu Chng ti ghi nhn tt c cc bin c bt li xut hin bnh nhn trong thi gian nghin cu khi bnh nhn ti khm thng qua vic bc s hi v bnh, khm lm sng cng nh cc triu chng bt thng trong qu trnh dng thuc ca bnh nhn. Sau thng th 1, ch c 46 bnh nhn quay li ti khm v y l kt qu chng ti ghi nhn c trn 46 bnh nhn ny. Bng 3.9: Cc AE gp trong qu trnh nghin cu Cc bin c bt li (n = 46)S BN (%) Chng bng, y hi4 (8,70%) Tiu chy1 (2,17%) D ng (mn nga, ban ngoi da)3 (6,52%) au u, chng mt4 (8,70%) Thi imTt S BN (%) Chp nhn S BN (%) Km S BN (%) T0 ( n = 52)1 (1,93%) 4 (7,69%)47 (90,38%) T1 (n = 42)3 (7,15%)13 (30,95%)26 (61,90%) T2 (n = 26)5 (19,23%)3 (11,54%)18 (69,23%) T3 (n = 11)3 (27,27%)5 (45,46%)3 (27,27%) 35 Nhn xt:Cc bin c bt li trn tiu ha chim t l cao (chng bng y hi chim 8,70% v tiu chy chim 2,17%). Cc bnh nhn cng hay gp phi au u chng mt (chim 8,70%). 3.3.2.2. Tngtcthuc gp trong mu nghin cu gia cc thuciu tr i tho ng typ 2 vi cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu Chng ti ghi nhn cc cp tng tc xut hin trong n iu tr ngoi tr bnh nhn. Kt qu c trnh by qua bng 3.10: Bng 3.10: Tng tc thuc gp trong nghin cu (n = 52) Cc phi hp thuc c tng tcS BN (%)Mc tng tc * Gliclazid + Fenofibrat3 (5,77%)Thn trng Glimepirid + Fenofibrat1 (1,93%)Thn trng Lisinopril + Glimepirid1 (1,93%)Thn trng Perindopril + Gliclazid1 (1,93%)Thn trng Gliclazid + Indapamid1 (1,93%)Cn nhc li ch/nguy c * Theo Tng tc thuc v ch khi ch nh ca B Y t Nhn xt: Kt qu cho thy khng gp trng hp no c tng tc mc chng ch nh hoc nghim trng. Phn ln l cc cp tng tc cn thn trng hoc cn nhc li ch/nguy c. T l bnh nhn gp tng tc thuc kh thp: 7,70% bnh nhn ccptngtcSulfonylure+Fenofibrat;3,86%bnhnhnccptngtc Sulfonylure +c ch men chuyn; 1,93% bnh nhn c cp tng tc Gliclazid + Indapamid. 36 CHNG IV: BN LUN 4.1. MT S C IM CA BNH NHN TRONG MU NGHIN CU Tui v gii tnh Tui trung bnh ca bnh nhn trong nghin cu l 53,10 11,33 tui. tui ny cng tng t nh tui trung bnh trong nghin cu ca Nguyn Khoa Diu Vn l 52,4 8,64 tui [21]. Trong nghin cu ca chng ti, s bnh nhn n (chim 46,15%) mc T typ 2 tng ng s bnh nhn nam (chim 53,85%). T l ny tng ng vi nghin cu ca Nguyn Khoa Diu Vn (n 51,2% v nam 48,8%) [21] v nghin cu ca inh Th Thu Ngn (n 54,7% v nam45,3%) [15]. C th thy, T typ 2 c th xut hin c nam v n. Tin s gia nh Yu t di truyn ng vai tr rt quan trng trong bnh T typ 2. Nhng i tng c mi lin quan huyt thng vi ngi bnh T nh c b, m, hoc anh ch em rut b bnh T thng c nguy c b bnh T cao gp 4 6 ln ngi bnh thng (trong gia nh khng c ai mc bnh T) [3]. Qua thng k, t l bnh nhn c ngi thn b T typ 2 l 26,92%. T l ny cao hn so vi nghin cu ca inh Th Thu Ngn vi 17% bnh nhn c tin s gia nh c ngi mc T typ 2 [15]. Tuy c s khc nhau nhng c th thy c s lin h gia tin s gia nh vi bnh T typ 2. Do , tin s gia nh l mt yu t nguy c ca T typ 2. Cc bnh mc kmTHA vRLLP l haibnh thngmc km cng vi T typ 2.Trong bnh sinh ca T typ 2, khi lng insulin khng , tng hp m s gim, ngc li tng thoi ha m, tng iu ng m t cc kho d tr hu qu s tng lipid mu. Bn cnh , tnh trng THA va l yu t nguy c va l hu qu ca bnh T typ 2. Trong nghin cu ca chng ti, s bnh nhn mc km RLLP chim 34,62 %, mc km THA l 17,31% v ng thi c 2 bnh l 23,08%. iu ny cho thy, ti thi im chn on c mt t l ln bnh nhn mc km THA v/hoc RLLP. Do , 37 mc tiu iu tr khng ch dng li vic kim sot glucose mu m cn phi kim sot c cc ch s lipid mu v huyt p. Ngoi ra, trong 52 bnh nhn c 3 bnh nhn c bnh l v thn (2 bnh nhn suy thn v 1 bnh nhn c tin s ghp thn); 6 bnh nhn c bnh l v gan (3 bnh nhn vim gan B v 3 bnh c men gan tng cao gp 2 -3 ln gi tr bnh thng); c 3 bnh nhn n chun b phu thut m polyp t cung. y u l nhng i tng c bit nn vic la chn thuc trn cc bnh nhn ny cn phi thn trng. Th trng bnh nhn khi bt u nghin cu ChsBMItrungbnhcabnhnhntrongnghincutithiimbtu nghin cu l 22,63 2,41 kg/m2 trong phn ln bnh nhn c th trng mc bnh thng t 18,5 22,9 kg/m2 (chim 48,08%). Kt qu ny tng ng vi nghin cu ca Nguyn Khoa Diu Vn c BMI trung bnh ca bnh nhn l 22,92 2,66 kg/m2 [21]. Theo nghin cu v tnh hnh chm sc bnh nhn T Vit Nam v cc khu vc chu , BMItrung bnh ca bnh nhn T typ 2 Vit Nam l 21,9 3,6 kg/m2, trong khi bnh nhn T typ 2 trn th gii thng c th trng bo vi BMI > 25 kg/m2 [4]. y chnh l s khc bit gia bnh nhn b T typ 2 Vit Nam vi cc nc khc. Nguyn nhn c th do th trng ngi Vit Nam thng nh cn hn v c t l khi m thp hn ngi chu u. Glucose mu lc i v ch s HbA1c Ti thi im bt u nghin cu, nng glucose mu lc i ca bnh nhn rt cao c trung v l 10,0 (7,7 15,2) mmol/L. Kt qu ny tng ng vi nghin cu ca Nguyn Khoa Diu Vn c Glucose mu trung bnh l 10,73 3,20 mmol/L cng c tin hnh trn bnh nhn T typ 2 iu tr ngoi tr ti Bnh vin Bch Mai.Trongnghincucachngti,phnlnbnhnhnikhmkhixuthin nhng triu chng lm sng rm r (gy st, ung nhiu, tiu nhiu,) hoc tnh c ikhmvbnhlkhcvcphthinmcTtyp2.ngthichs HbA1c thi im ny cng rt cao 9,1 (7,2 11,6) % m HbA1c l gi tr phn nh glucose mu trung bnh ca bnh nhn trong 8 12 tun trc [41]. iu ny cho thy, phn ln bnh nhn trong nghin cu c pht hin mc T typ 2 mun. 38 Cc ch s lipid mu v huyt p ban u Ngay ti thi im ban u, c 2 ch s lipid mu mc kim sot km, l Cholesterol ton phn (5,79 1,76) mmol/L v Triglycerid (2,93 2,84) mmol/L. T l bnh nhn kim sot km cc ch s lipid u cao c bit l Cholesterol ton phn (chim 62,75%), Triglycerid (chim 48,00%).C th thy RLLP thng i km vi T typ 2 v ngay c nhng bnh nhn T typ 2 mi pht hin cng bt u c RLLP. Ch s huyt p ti thi im ban u mc chp nhn (130,19 18,94/ 79,42 10,18 mmHg). S bnh nhn c mc huyt p mc tt v chp nhn chim t l lnl 78,85% tuy nhin vn c 21,15% bnh nhn c mc kim sot huyt p km. Nh vy, ngoi RLLP, nhng bnh nhn T typ 2 cn hay mc km thm THA. 4.2. TNH HNH S DNG THUC TRONG IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR 4.2.1. T l bnh nhn ti khmNghin cu c thc hin l mt nghin cu tin cu khng can thip, cc bnh nhn c chn vo nghin cu bao gm c bnh nhn bo him v khng c bohimangciutrngoitr.Slngbnhnhnmithiimkhc nhau v c mt s bnh nhn khng quay li ti khm vi nhiu l do: bnh nhn xa nn iu kin i li kh khn; bnh nhn sau khi iu tr 1, 2 thng chuyn v iu tr ti a phng; bnh nhn do cng vic bn rn khng th sp xp i ti khm;T l bnh nhn ti khm tng thi im ngy cng gim so vi thi im ban u: thng th nht c 42/52 bnh nhn (chim 80,77%) quay li ti khm, thng th hai c26/52bnhnhn(chim50,00%)quaylitikhm,thngth3chcn11/52 bnh nhn (chim 21,15%) quay li ti khm. C th thy, mt s bnh nhn vn cha thc c mc nghim trng ca bnh nn khng ch trng vo vic iu tr u n. Nu tnh trng ny ko di th khng t bnh nhn s gp phi nhng bin chng ca T do khng c iu tr y t khi pht hin mc bnh.39 4.2.2. Danh mc cc thuc iu tr i tho ng typ 2 gp trong mu nghin cu Trong iu tr T typ 2, vic la chn cc thuc cho bnh nhn ph thuc rt ln vo c im ca tng c th. V vy, mt danh mc thuc a dng s gp phn to iu kin cho bc s ti u ha vic la chn thuc ph hp trn tng bnh nhn. Thng k t cc n thuc ngoi tr ca 52 bnh nhn trong mu nghin cu nhn thy cc thuc c s dng ti Khoa Khm bnh Phng Nt tit v i tho ng ca Bnh vin Bch Mai a dng vi 7 hot cht thuc cc nhm: thuc iu tr dng tim l insulin gm insulin tc dng nhanh, insulin bn chm, cht tng t insulintcdngchm,hnhpinsulin;ccthuciutrdngung:Biguanid, Sulfonylure, c ch glucosidase, c ch DPP 4. Khng ch phong ph v mt hot cht m cc dng bo ch trong danh mc thuc ny cng rt a dng: vin nn; vin nn tc dng ko di; vin nn phng thch c kim sot; insulin dng hn dch hay dung dch tim.MetforminlthuciutrTtyp2cnhiuuimnh:gimchs glucose mu hiu qu, khng gy tng cn, khng gy h glucose mu, c tc ng tt n cc ch s lipid mu [27], [29]. Ngoi ra thuc cn c gi thnh hp l, thp hn so vi cc thuc T typ 2 th h mi rt nhiu. C th do c nhiu u im nh vy nn Metformin l thuc c t l bnh nhn s dng cao nht vi 45,74%.Sulfonylure cng c s dng nhiu vi t l 23,40%. Trong nhm ny c 2 thuc c dng l Gliclazid (chim 12,23%) v Glimepirid (chim 11,17%), Trong nhm Sulfonylure, Glimepirid l thuc c liu dng thp nht, c tc dng ko di v ch cn s dng 1 ln/ngy. Gliclazid l thuc c tc dng trung bnh nhng hin nay c bo ch di dng phng thch c kim sot [38] do thng c dng 1 ln/ngy rt thun tin cho bnh nhn s dng (Diamicron MR 30 mg). Tt c bnh nhn trong nghin cu ny u c s dng Gliclazid dng vin nn phng thch c kim sot. Ngoi nhng thuc iu tr dng ung, Insulin cngc s dngvi t l kh ln (chim 22,34%), c bit c s dng nhiu nht trong thng u tin. Vic s dng ny s c chng ti bn lun k hn phn sau. 40 im c bit trong danh mc cc thuc c s dng l s c mt ca nhm thuccchDPP4cavosdngdidngvinnnphihpvi Metformin: Sitagliptin (chim 1,60%) v Vildagliptin (chim 2,66%). y l nhng thuc th h mi c tc dng kim sot glucose mu tt nhng gi thnh tng i cao so vi cc thuc T c in khc. Ngoi ra, thuc cng nm ngoi danh mc thuc c trong bo him ca bnh vin. Do vy, nhng thuc ny ch c s dng vi mt t l thp. Cc thuc nhm c ch - glucosidase (Acarbose) cng c s dng trong nghin cu ca chng ti nhng vi t l thp (chim 4,29%). Theo hng dn iu tr ca Bnh vin Bch Mai, thuc ny c dng khi bnh nhn c tng nh glucose mu sau n, iu tr n tr liu kt hp vi ch n hoc thuc khc [10]. Nhm TZD (Rosiglitazon, Pioglitazon) khng c s dng trong nghin cu ny. Ti Vit Nam, nm 2011, B Y t c cng vn v vic Ngng tip nhn v xem xt h s nhp khu i vi Rosiglitazon do lo ngi v nhng nguy c trn tim mch ca thuc ny [7]. Cng trong nm 2011, B Y t a ra Hng dn chn on v iu tr T typ 2, trong hng dn ny th Pioglitazon vn c s dng. Tuy nhin n nm 2012, Pioglitazon cng b tm ngng cp s ng k ln u v ng k li do lo ngi v nguy c gy ung th bng quang ca thuc ny [5]. Trong phc iu tr ca ADA 2014, nhm TZD vn c s dng nhng cn phi gim st cht ch trn bnh nhn c nguy c tim mch cao v gy xng [23]. Nh vy, vic khng s dng cc thuc nhm TZD ca bc s l ph hp vi Hng dn ca B Y t. 4.2.3.Tnh ph hp ca vic la chn phc iu ti thi im ban u theo Hng dn chn on v iu tr i tho ng typ 2 ca B Y t, Hng dn iu tr ca Hip hi i tho ng Hoa K (ADA 2014), Hng dn s dng thuc dnh cho cn b y t ca EMC (EMC)i vi T typ 2, vic iu tr nn c c th ha cho tng bnh nhn v vic la chn phc iu tr cho bnh nhn ti thi im ban u l rt quan trng. 41 n tr liu: -Metformin: Metformin c khuyn co l la chn u tay tr trng hp chng ch nh [23]. Theo EMC, chng ch nh dng Metformin khi bnh nhn c thanh thi Creatinin < 60 ml/pht. Trong 14 bnh nhn c s dng Metformin, c3bnhnhncthanhthiCreatininlnltl52ml/pht,48ml/pht,39 ml/pht (< 60 ml/pht). Nh vy, vic s dng Metformin trn nhng bnh nhn ny l cha ph hp. Hn na, 3 bnh nhn u l nhng bnh nhn cao tui (> 65 tui). C th bc s cha tnh thanh thi creatinin m ch da vo ch s creatinine mu ca bnh nhn khi kn ng thi cng cha ch nvic sdng thuc trn bnh nhn cao tui. -Sulfonylure: Theo ADA 2014, Sulfonylure khng phi l thuc c khuyn co la chn u tin khi bt u iu tr [23]. Theo IDF 2012, c th s dng thay thMetforminbngSulfonylurekhibnhnhncchngchnhviMetformin [34]. Theo Hng dn ca B Y t, nu bnh nhn c BMI < 23 kg/m2 th nn la chn nhm Sulfonylure [6]. Trong 2 bnh nhn c 1 bnh nhn c BMI = 22,2 kg/m2 nn vic dng Sulfonylure l ph hp.Bnh nhn cn li c BMI = 25,7 kg/m2(bo ph 1) m tc dng ph ca Sulfonylure l gy tng cn, bnh nhn cng khng c chng ch nh vi Metformin. Nh vy, s dng Sulfonylure trn bnh nhn ny l cha ph hp vi Hng dn ca B Y t v ADA 2014. C th bc s khng ch n BMI ca bnh nhn khi k n thuc. -Acarbose:TheoADA2014,Acarbosekhngckhuyncollachn u tay [23]. Hng dn ca B Y t cng ch ra rng Acarbose cn c s dng phi hp vi mt loi thuc h glucose mu khc [6]. V vy, bt u iu tr n c bng Acarbose l cha ph hp vi 2 hng dn ny. Tuy nhin, c 2 bnh nhn c s dng Acarbose u c thanh thi Creatinin l 52 ml/pht (< 60 ml/pht) nn khng th s dng Metformin [48]. Theo EMC, Acarbose khng c s dng khi bnh nhn c thanh thi creatinin < 25 ml/pht/1,73 m2 [47]. Hai bnh nhn ny u c thanh thi creatinin tnh theo din tch b mt da ln lt l 63 ml/pht/1,73 m2 v 58ml/pht/1,73 m2 nn vn c th s dng Acarbose. Hn na, theo hng 42 dn ca Bnh vin Bch Mai, c th la chn bt u iu tr bng Acarbose vi bnh nhn RLLP. C 2 bnh nhn u c mc km RLLP. Ngoi ra, Glucose mu lc i v HbA1c ca 2 bnh nhn ny ln lt l 7,5 mmol/L v 5,8%; 7,4 mmol/L v 6,4 %. C th thy c 2 bnh nhn u c mc Glucose mu khng qu cao v HbA1c < 6,5% (mc tiu chun chn on mc T) nn vic la chn mt thuc nhm c ch glucosidase c th xut pht t kinh nghim iu tr ca bc s. -Insulin: Cn c vo cc trng hp c ch nh dng insulin trong Hng dn ca B Y t th 18 trng hp c s dng ph hp v 4 trng hp cha ph hp. C 4 bnh nhn c s dng Insulin cha ph hp u khng nm trong cc trng hp cn ch nh dng Insulin. Tuy nhin, glucose mu lc i v HbA1c ca 4 bnh nhn u kh cao (Glucose mu lc i > 10,0 mmol/L v HbA1c > 8,0%). C th vic la chn dng Insulin ca bc s trn nhng bnh nhn ny l da trn kinh nghim. a tr liu: -Metformin + Sulfonylure: Theo B Y t khi c Glucose mu lc i > 13,0 mmol/L v HbA1c > 9,0 % th cn phi hp 2 thuc [6]. Trong 7 bnh nhn s dng phc ny ch c 2 bnh nhn c mc glucose mu lc i v HbA1c t ngng nh trn cn li 5 bnh nhn th cha c glucose mu lc i v HbA1c cao nh vy. C th bc s la chn phc ny da trn kinh nghim v Metformin phi hp vi Sulfonylure l kiu phi hp ph bin nht, em li nhiu li ch gip tng cng s kim sot glucose mu v h lipd mu [28].-Sulfonylure + Acarbose: Bnh nhn c dng phc ny c BMI = 21,6 kg/m2 (< 23 kg/m2), nh vy vic s dng Sulfonylure l ph hp theo Hng dn ca B Y t. Cng theo B Y t th nhm thuc c ch glucosidase u c th c phi hp vi cc thuc khc trong tt c cc bc iu tr [6]. Nh vy, vic s dng phc ny l ph hp. Vic bc s thm Acarbose c th do bc s nghi ng bnh nhn c tng glucose mu sau n nn thm thuc tng cng hiu qu kim sot glucose mu. 43 -Insulin + Metformin: Bnh nhn c s dng phc ny c Glucose mu lc i (20,5 mmol/L) v HbA1c (14,5%) u rt cao. Theo ADA 2014, vi nhng bnh nhn T typ 2 mi c chn on c nng glucose mu tng cao r rt hay HbA1c cao v/hoc km theo cc triu chng r rt th cn nhc iu tr bng Insulin, c hoc khng km theo cc thuc h glucose mu khc. V vy vic s dng ny l ph hp vi Hng dn ca B Y t v ADA 2014. -Metformin+Sulfonylure+Acarbose/cchDPP-4:Vicphihp3 thuc ngay t thi im chn on ban u l cha ph hp vi Hng dn ca B Y t v ADA 2014. Tuy nhin, c 3 bnh nhn u c mc glucose mu rt cao (> 15,0 mmol/L). Trong mt s trng hp c th phi hp 3 thuc nhng s phi hp c hiu qu kinh t thp hn so vi dng Insulin ng thi c mt t l ln bnh nhn khng t c mc tiu iu tr v gp cc TDKMM [32]. Vic s dng phc ny c th xut pht t kinh nghim iu tr ca bc s v c th do bnh nhn khng mun s dng thuc tim nn bc s la chn phi hp 3 thuc thay cho vic s dng Insulin. 4.2.4. Cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipd mu iu tr cc bnh mc km T typ 2 l mt trong nhng mc tiu iu tr v ccbnhmckmviTtyp2nhTHA,RLLPucthlinquanntnh trng bnh, din bin bnh, s tin trin bnh v cc bin chng ca bnh.i vi THA, trong nghin cu ca chng ti c 4 nhm thuc c s dng l:cchmenchuyn(Lisinopril,Perindopril),chnththangiotensinII (Losartan), chn adrenergic (Bisoprolol, Metaprolol), li tiu thiazid. Theo khuyn co nm 2013 ca Hi tim mch chu u v Hi Tng huyt p Chu u (ESC/ESH) th tt c cc nhm thuc h huyt p thng thng u c th s dng bnh nhn T [33]. Cn theo IDF 2012 v ADA 2014, nhm thuc c ch men chuyn hoc nhm thuc chn th th anigiotensin II l hai nhm thuc c khuyn co trong iu tr THA trn bnh nhnmc T[23], [34]. Trong nghin cu, ngoi hai nhm thuc trn, bnh nhn cn c s dng thuc h huyt p nhm chn -adrenergic. Theo EMC, hai thuc (Bisoprolol v Metoprolol) c s dng 44 trong nghin cu u cn phi thn trng khi dng trn bnh nhn T typ 2 v chng c th lm che lp du hiu h glucose mu [45], [46]. Tuy nhin 2 bnh nhn c dng nhm thuc ny c iu tr T bng Metformin m Metformin li t gy h glucose mu. Ngoi ra, trong nghin cu ca chng ti c mt bnh nhn c s dngnhmcchmenchuynphihpvilitiuthiazid(Perindopril+ Indapamid). Theo hng dn iu tr T typ 2 ca Canada, th c th s dng thuc li tiu thiazid iu tr THA trn bnh nhn T typ 2 [27]. iviRLLP,bnhnhncsdnghainhmthuclnhmStatin (Simvastatin,Atorvastatin,Rosuvastatin)vnhmFibrat(Fenofibrat).TheoADA 2014, Statin l thuc c khuyn co hng u trong iu tr RLLP trn bnh nhn T [23]. Nhng bng chng lm sng gn y cho thy vic s dng Fibrat c th gip ci thin cc bin chng trn thn v vng mc bnh nhn T v nhng li ch ny c th khng phi c c t tc dng h lipid mu ca nhm thuc ny [27]. 4.3. S THAY I NNG GLUCOSE MU LC I V TNH AN TON KHI S DNG THUC IU TR I THO NG TYP 2 TRN BNH NHN NGOI TR 4.3.1. S thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr S thay i glucose mu lc i qua tng thng iu tr MctiuiutrhngutrongiutrTtyp2laglucosemuv mc bnh thng v n nh. Sau ba thng iu tr, nng glucose mu ca bnh nhn trong mu nghin cu gim t 10,1 (7,6 15,3) mmol/L xung cn 5,8 (6,3 7,4) mmol/L. Nh vy, nng glucose mu sau 3 thng mc kim sot tt. Tuy nhin s gim c khc nhauquatngthng.Thngthnhtnngglucosemut10,1(7,615,3) mmol/L gim xung cn 7,9 (6,8 9,3) mmol/L, thng th 2 nng glucose gim xung cn 7,6 (6,8 8,3) mmol/L thng th 3 gim cn 5,8 (6,3 7,4) mmol/L. Mc 45 gim glucose mu sau thng th nht l ln nht. iu ny cho thy hiu qu ca can thip iu tr bng thuc trong thng th nht. Mc kim sot glucose mu sau tng thng iu tr nh gi vic gim glucose mu hiu qu hay khng, ngoi vic nh gi mc gim glucose mu th vic nh gi mc kim sot glucose mu cng rt quan trng, cn nh gi t l s bnh nhn t c mc tiu kim sot cc mc tt, chp nhn v km theo tiu chun ca B Y t [6]. Qua s liu thng k cho thy, t l bnh nhn kim sot glucose mu tt v chp nhn tng dn, trong khi t l kim sot glucose mu km gim dn sau ba thng iu tr. Ti thi im chn on, ch c 1,93% bnh nhn c mc kim sot tt, t l ny tng ln 27,27% sau 3 thng iu tr. Trong khi , ti thi im ban u c 90,38%bnhnhncmckimsotkm,sau3thngiutr,tlnygim xung cn 27,27%.Mc d gi tr trung v ca glucose mu lc i sau 3 thng iu tr mc kim sot tt nhng thc t vn cn mt s bnh nhn c mc kim sot km. V vy vic a nng glucose mu v bnh thng v n nh trn nhng bnh nhn ny lnhimvhngunhmngncnqutrnhnnglncaT,ngthilm gim cc bin chng do T gy ra. 4.3.2. Tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr 4.3.2.1. Cc bin c bt li (AE) gp trong nghin cu Cc bin c bt li hay gp nht l cc bin c trn ng tiu ha (chng bng, y hi chim 8,70%; tiu chy chim 2,17%). Ngoi ra, cc bnh nhn trong nghincucnghaygpcctriuchngauuchngmt(chim8,70%).Cc bincbtlinycthxyradosdngccthuciutrTtyp2nh Metformin v Acarbose, cc thuc ny thng gy ra tc dng ph trn ng tiu ha (y bng, chng hi, tiu chy) hay Gliclazid v Insulin thng gy h glucose mu (biu hin au u, chng mt). Tuy nhin, khng loi tr kh nng bnh nhn 46 s dng cc thuc khc hay do bt thng trong ch n ung sinh hot hng ngy m gyra nhng binc bt li ny. Trong3 bnh nhn gp d ng th c 2 bnh nhn b mn nga ti v tr tim Insulin.Nhnchung,ccbincbtlinyaphnlthongquavbnhnhn thng t khi. 4.3.2.2. Tng tc thuc gp trong nghin cu gia cc thuc iu tr i tho ng typ 2 vi cc thuc iu tr bnh mc km Tng huyt p v Ri lon lipid mu Trn thc t, bnh nhn T thng mc km cc bnh THA v RLLP nn ngoi thuc iu tr T, bnh nhn thng c dng km vi cc thuc iu tr 2 bnh ny. Do , c th xy ra tng tc thuc trn nhng bnh nhn ny. Qua thng k trn cc n thuc ca bnh nhn, chng ti ghi nhn c c 7 bnh nhn trong n c xut hin tng tc thuc. Cc tng tc l: -Sulfonylure + Fenofibrat: Nguy c tng tc dng h glucose mu [35]. Na i ca thuc iu tr T c th tng (c nu vi Clorpropamid) v khng insulin c th gim [8]. -Sulfonylure + c ch men chuyn: Phi hp ny, trong trng hp c bit, c th dn n h glucose mu ngi T [8]. -Gliclazid+Indapamid:ThuclitiuThiazidlmtngglucosemukhi i v lm gim tc dng h glucose mu ca Sulfonylure. Tc dng ny xut hin cnghintnghnatrimusaukhiungthuclitiuthiazidvingynvi thng. C ch cc thuc li tiu Thiazid lm gim tnh nhy cm ca m vi insulin, lm gim tit insulin hoc lm tng o thi kali, gy tng glucose mu [8]. Tuy nhin tc dng ny ph thuc liu, t gp liu thp khi dng iu tr tng huyt p [35]. Kt qu cho thy, khng gp trng hp no c cc cp tng tc chng ch nh hay mc nghim trng. Phn ln l cc cp tng tc cn thn trng hoc cn nhc li ch nguy c, khng c nhiu ngha lm sng. i vi cp tng tc gia Indapamid + Gliclazid, liu Indapamid c s dng l liu thp (1,25 mg) do 47 tng tc ny t gp. Mc d vy, cc bc s iu tr vn cn phi ch trong vic k n nhm hn ch ti a cc tng tc thuc c th xy ra. 4.4. NGHA V HN CH CA NGHIN CU ngha: Nghin cu c thc hin l mt nghin cu m t tin cu vi mc ch kho sttnhhnhsdngthuciutrTtyp2vbcunhgisthayi glucose mu lc i v tnh an ton trn bnh nhn ngoi tr c s dng thuc iu tr T typ 2 ti Khoa Khm bnh Phng Ni tit v i tho ng Bnh vin Bch Mai. i vi T typ 2 th vic ra mc tiu iu tr cng nh la chn phc iu tr hp l vi tng bnh nhn l v cng quan trng. Nhng bnh nhn tham gia vo nghincu u l bnh nhn ln u c chn onmc T typ 2, do , nghin cu ca chng ti nh gi c s ph hp ca vic la chn thuc khi bt u iu tr vi Hng dn chn on v iu tr T typ 2 ca B Y t, ADA 2014 v EMC. y chnh l s khc bit vi mt s nghin cu trc y nh nghin cu ca L Th Huyn Trang kho st ng thi c bnh nhn mc bnh lu nm v bnh nhn mi pht hin [19] hay nghin cu ca H Thanh Lim tin hnh trn bnh nhn mc T [13] nn khng nh gi c tnh ph hp trong vic la chn thuc ti thi im ban u. Hn na, thit k m t tin cu cho php chng ti ghi nhn c nhng bin c bt li m bnh nhn gp phi trong qu trnh iu tr m nhng nghin cu hi cu khng th thc hin c, ng thi cng hn ch c cc sai s nh li thng gp trong nghin cu hi cu. Bn cnh , nghin cu cng phn nh c thc trng iu tr ca cc bnh nhn ngoi tr l thng khng iu tr u n v y trong thi gian di m ch iu tr 1, 2 thng u. iu th hin qua t l ti khm gim dn mi thi im trong vng 3 thng. Nu nh trong cc nghin cu trc y ch yu c tin hnh bnh vin tuyn tnh hoc tuyn huyn vi danh mc cc thuc iu tr hn hp th nghin cu ca chng ti Bnh vin Bch Mai bnh vin tuyn cui c mt danh mc cc thuc iu tr a dng hn. in hnh l ngoi nhng thuc iu tr c in, trong nghin 48 cu ca chng ti c s xut hin ca thuc T typ 2 th h mi (thuc c ch DPP - 4) cng vi nhiu loi thuc tim insulin khc nhau. Nghin cu ca chng ti cng cp n ccyu tnguyc timmch km theo bnh T typ 2 l bnh RLLP v bnh THA. Ngoi cc ch s glucose mu lc i v HbA1c, chng ti cp thm cc ch s lipid mu, huyt p, chc nng gan thn nh gi tnh trng ca bnh nhn ti thi im ban u. Hn ch: Nghin cu ny c tin hnh Bnh vin Bch Mai l mt bnh vin tuyn cui. S lng bnh nhn mi c pht hin mc T typ 2 ti thi im bt u nghincukhngnhiu,phnlnbnhnhnciutrbngthuciutr T typ 2 a phng. Trong vng 3 thng nghin cu lin tc, chng ti ch la chn c 52 bnh nhn ph hp tham gia vo nghin cu. S lng ny tng i t so vi cc nghin cu khc. Mt khc, y l mt nghin cu tin cu m t khng can thip, phn ln l bnh nhn khng c bo him v bnh nhn n t cc tnh khc nhau nn vic i li tng i kh khn. y c th l nguyn nhn chnh khin bnhnhnkhngquaylitikhmynnchngtichanhgitondin c hiu qu iu tr trn tt c bnh nhn tham gia vo nghin cu. Mt hn ch khc trong nghin cu ca chng ti l cha nh gi c hiu qu iu tr thng qua ch s HbA1c v cc ch s lipid mu v khng phi thi im no cc bc s cng cho bnh nhn xt nghim y . c bit l vi ch s HbA1c, thng 2 hoc 3 thng bc s mi cho bnh nhn tin hnh o li ch s ny nh gi hiu qu iu tr. iu ny khin chng ti ch c th nh gi c s thay i glucose mu lc i ca bnh nhn.Vic tun th iu tr (s dng ht thuc v ung thuc ng gi) cng l mt yutquantrngcthtcmctiuiutr.Phnlnbnhnhntrong nghin cu ca chng ti n t cc tnh ngoi thnh ph H Ni, do chng ti khng th n tn nh kim tra vic s dng thuc ca bnh nhn. Mc tun th iu tr ca bnh nhn ch c ghi nhn qua phng vn v do tnh chnh xc khng cao v c th gp sai s nh li.49 KT LUN V KIN NGH KT LUN Qua nghin cu trn 52 bnh nhn mi c chn on i tho ng typ 2 ti Khoa Khm bnh Phng Ni tit v i tho ng Bnh vin Bch Mai, chng ti c nhng kt lun sau: 1. V c im ca bnh nhn trong mu nghin cu -TlmcbnhTtyp2n(chim46,15%)tngngvinam(chim 53,85%). -Bnh nhn mc km THA v/hoc RLLP chim t l cao (chim 75,01%). -Mt s bnh nhn c bnh l v gan (chim 11,54%) hoc bnh l v thn (chim 5,77%). -Ch s BMI trung bnh ti thi im nghin cu l 22,63 2,41 kg/m2. Bnh nhn cthtrngbnhthng(chim48,08%)vcnguycboph(chim28,85%) chim phn ln.-Ch s glucose mu lc i ca bnh nhn ti thi im chn on rt cao vi gi tr trung v l 10,1 (7,6 15,3) mmol/L, trong mc kim sot km chim 90,38%. Ch s HbA1c cng rt cao vi gi tr trung v l 9,1 (7,2 11,6) %, trong mc kim sot km chim 73,08%.-Ch s lipid mu ban u c gi tr trung bnh mc kim sot km l Cholesterol tonphn(5,791,76)mmol/L,trongmckimsotkmchim62,75%; Triglycerid (2,93 2,84) mmol/L trong mc kim sot km chim 48,00%. -Ch s huyt p trung bnh mc chp nhn 130,19 18,94/ 79,42 10,18 mmHg, phn ln bnh nhn c mc kim sot tt vi 65,38%. 2. V tnh hnh s dng thuc trong iu tr i tho ng typ 2 -T l bnh nhn ti khm gim dn sau 3 thng so vi thi im ban u. -Danh mc cc thuc iu tr T typ 2 trn bnh nhn ngoi tr gm Insulin dng tim v cc thuc dng ung (Metformin, Sulfonylure, c ch glucosidase, c chDPP4).TrongccthuccsdngnhiunhtlMetformin(chim 45,74%) v Insulin (chim 22,34%). 50 -Ti thi im ban u, phn ln cc phc c s dng ph hp vi Hng dn chn on v iu tr i tho ng typ 2 ca B Y t nm 2011, Hng dn iu tr ca Hip hi i tho ng Hoa K nm 2014, Hng dn s dng thuc dnh cho cn b y t ca EMC (chim 65,38%).-Danh mc cc thuc iu tr bnh mc km tng huyt p v ri lon lipid mu rt phong ph. 3. V s thay i nng glucose mu lc i v tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn iu tr ngoi tr V s thay i nng glucose mu lc i khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr -Sau 3 thng iutr, nng glucosemuthi im ban u gim t10,1 (7,6 15,3) mmol/L xung cn 5,8 (6,3 7,4) mmol/L. -Sau 3 thng iu tr, t l bnh nhn kim sot glucose mu tt tng t 1,93% n 27,27% ng thi mc kim sot km gim t 90,38% xung cn 27,27%. V tnh an ton khi s dng thuc iu tr i tho ng typ 2 trn bnh nhn ngoi tr -Trong qu trnh iu tr, c nhiu AE c ghi nhn. Cc bin c bt li trn ng tiu ha chim t l cao (chng bng y hi chim 8,70%, tiu chy chim 2,17%). au u, chng mt cng rt hay gp (chim 8,70%). -Khng c trng hp no c cp tng tc chng ch nh hay mc nghim trng. Phn ln l cccp tng tccn thn trng hoc cn nhc li ch nguy c khng c nhiu ngha trn lm sng. 51 KIN NGH Cn trin khai xt nghim HbA1c, cc ch s lipid mu (Cholesterol ton phn, Triglycerid, HDL-C, LDL C) y nhm pht hin kp thi cc bin chng ca T cng nh nh gi c hiu qu ca vic iu tr. Cnsmiuchnhliuvphcphhpvibnhnhnchatchs glucose mu mc tiu nhm ci thin t l bnh nhn c ch s glucose mu t mc kim sot tt, gim thiu cc bin chng. Cn c thm dc s lm sng phi hp cng bc s iu tr t vn s dng thuc hp l, theo di cc tc dng ph v tng tc thuc, ng thi phi nhn mnh tm quan trng ca vic iu tr u n bnh T typ 2, khuyn khch bnh nhn ti khm ng hn v y . Cn ch n thanh thi creatinin v ch s BMI ca bnh nhn khi la chn thuc iu tr. Cn nhc bnh nhn khi ti khm mang theo v thuc ung, iu ny gip cho vic nh gi mc tun th iu tr chnh xc hn. Do nghin cu ny mi ch tin hnh trong mt khong thi gian ngn (3 thng) nn cha th nh gi mt cch ton din vn s dng thuc v hiu qu iu tr. Trong tng lai, mong rng s tip tc c nhng nghin cu trong khong thi gian di hn. 52 TI LIU THAM KHO TI LIU TING VIT 1.TVnBnh(2007),Lmgphngchngbnhithongvbin chng, NXB Y hc, H Ni. 2.T Vn Bnh (2006), Bnh i tho ng - Tng glucose mu, NXB Y hc, H Ni. 3.T Vn Bnh (2003), Dch t hc bnh i tho ng Vit Nam cc phng php iu tr v bin php d phng, NXB Y hc, H Ni. 4.T Vn Bnh (2001), "Tnh hnh chm sc bnh nhn T ti Vit Nam v mt s quc gia chu ", Y hc thc hnh, (11), tr. 32 - 35. 5.B Y t (2012), Cng vn 13707/QLD-K ngy 13/09/2012 v vic ng k thuc cha thnh phn Pioglitazon do Cc Qun l dc ban hnh. 6.B Y t (2011), Hng dn chn on v iu tr bnh i tho ng typ 2. 7.B Y t (2011), Cng vn 3886/QLD-K ngy 22/03/2011 v vic ng k, sn xut, nhp khu, lu hnh, s dng thuc cha Rosiglitazon do Cc Qun l Dc ban hnh. 8.B Y t (2006), Tng tc thuc v ch khi ch nh, NXB Y hc, H Ni. 9.B Y t (2002), Dc th Quc gia Vit Nam, NXB Y hc, H Ni. 10.B Y t, Bnh vin Bch Mai (2011), Hng dn chn on v iu tr bnh ni khoa, NXB H Ni, H Ni, tr. 416 - 432. 11.TrnHuDng(2011),"ithong",Bnhnititchuynha,NXB Gio dc Vit Nam, H Ni, tr. 268 - 300. 12. 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PH LC 1: Mt s phc iu tr i tho ng typ 21.Hng dn chn on v iu tr T typ 2 ca B Y t 2.Hng dn iu tr ca Hip hi i tho ng Hoa K (ADA 2014)

3.Hng dn iu tr ca Lin on i tho ng Quc t (IDF 2012) PH LC 2: PHIU THEO DI BNH NHN M bnh nhn: M bnh n: Ngy ly dliu: H v tn bnh nhn:Gii tnh: Nam NTui: a ch:Ngh nghip:S in thoi lin lc: Xt nghim cn lm sng T0T1T2T3 Glucose mu lc i (mmol/L) HbA1c (%) Cholesterol ton phn (mmol/L) HDL-CLDL-C Triglycerid (mmol/L) SGOT (U/L) SGPT (U/L) Creatinin (mol/L) Tin s gia nh: C ngi mc bnh T C Khng Tin s bn thn -Bnh mc km:- Tng huyt p RLLP mu C hai Khm lm sng T0T1T2T3 Chiu cao (m) Cn nng (kg) Huyt p (mmHg) Mc tun th iu tr Dng thuc T u Khng u S dng ht thuc C Khng Thc hin ch n ung v luyn tp C Khng Thi im Ch s Thi im Ch s Cc thuc c s dng Thi im T0Thuc 1Thuc 2Thuc 3Thuc 4Thuc 5Thuc 6 Bit dc Hot cht, hm lng Liu dng, cch dng Thi im T1Thuc 1Thuc 2Thuc 3Thuc4Thuc 5Thuc 6 Bit dc Hot cht, hm lng Liu dng, cch dng Thi im T2Thuc 1Thuc 2Thuc 3Thuc4Thuc 5Thuc 6 Bit dc Hot cht, hm lng Liu dng, cch dng Thi im T3Thuc 1Thuc 2Thuc 3Thuc4Thuc 5Thuc 6 Bit dc Hot cht, hm lng Liu dng, cch dng Tc dng khng mong mun gp trong qu trnh iu tr (Ngy xut hin:..) Biu hinX tr (nu c)Tnh trng bnh nhn sau x tr 1.Chng bng y hi 2.D ng 3.Tiu chy 4.au u, chng mt 5.Khc: C Khng C Khng C Khng C Khng PH LC 3: DANH SCH BNH NHN STTM BNH TnTuiGiia ch 101Nguyn ThM.52NH Ni 202V VnhX.66NamThi Bnh 303Nguyn Duy T.40NamH Ni 404Nguyn VnC.50NamNam nh 505Phm nhB.61NamThi Bnh 606Phm ThH.60NNam nh 707Trn Vn H.41NamH Ni 808Bi Thy .64NPh Th 909Phm ThL.61NBc Giang 1010 Th H.61NH Ni 1111Phm ThP.68NThi Nguyeen 1212Phm ThH.43NHng Yn 1313Trn VnT.49NamH Ni 1414Phm ThL.62NH Nam 1515Lu ThS.61NHi Phng 1616Phm Vn L.41NamSn La 1717Chu Th ThyH.56NBc Ninh 1818Nguyn Ch C.34NamH Ni 1919Bi VnL.56NamH Ni 2020 ThT.49NHi Phng 2121V VnS.42NamBc Giang 2222Phm ThH.56NH Ni 2323Bi Th54NSn La 2424Trnh CngQ.50NamH Ni 2525Trn ThN.28NH Ni 2626Phan MnhH.29NamPh Th 2727V Th.74NH Ni 2828Nguyn ThH.44NH Ni 2929Trng VnT.38NamH Ni 3030Phm VnT.56NamHng Yn 3131on Hu H.45NamH Ni 3232Phm ThC.66NNinh Bnh STTM BNH TnTuiGiia ch 3333Nguyn VnT.46NamH Nam 3434V Vn .60NamNam nh 3535Nguyn ThP.30NHng Yn 3636Trn nhT.36NamH Ni 3737Nguyn XunS.37NamH Nam 3838Kiu Vn .55NamThi Nguyn 3939L ThB.67NH Ni 4040 Th T.66NH Ni 4141Khc ThM.68NHng Yn 4242Nguyn ThH.68NHi Phng 4343Nguyn ThN.58NH Ni 4444Trn VnB.51NamThi Bnh 4545ng ThP.61NVnh Phc 4646Nguyn c H.44NamH Ni 4747Trn ThT.38NPh Th 4848Trn TchD.54NamH Ni 4949Nguyn VnS.55NamNam nh 5050Hong ThL.67NH Ni 5151Nguyn ThL.62NH Ni 5252Phm Th HngV.59NH Ni