NGHIEN CU'U TU" KHANG TH§ KHANG GLUTAMIC ACID DECARBOXYLASE 65 {GAD-65) VA KHANG INSULIN (lAA)
TREN BENH NHAN OAI THAO DU'dNG Thfi TRANG GAY
Phan Thi Minh Phuong Truang Bgi hgc YDugc Hui Tom tdt
Dat van de va muc tieu: Cac ty khang the khang Glutamic Acid Decarboxylase 65 (GAD-65) va khdng insulin (lAA) la cac chat chi diem huyet thanh d bfnh nhan dai thdo dudng the tu mien. Su hifn dien eua cac tu khang thS ndy d bfnh nhan ddi thao dudng ldn tudi gifip phan bift dupc dai thao dudng ty miSn tiera an d ngudi Ion (LADA) vdi dai thao dudng typ 2. Nhflng ngudi cd khang the tu miSn dupc xem la nhdm nguy ca cao va se tien trien thanh the dai thao dudng phy thupc insulin trong vdng 5 - 7 nam. DS tai nhdm muc tiSu: (1) Xdc djnh ti If duong tinh, nflng dp ty khang thi khang GAD-65,1 AA tren bfnh nhan dai thao dudng thi trgng gly. (2)Khdo sat moi lien quan gifla sy hifn difn cua ty khang the khang GAD-65, lAAvdi mpt so dgc diem ldm sdng vd cdn Idm sang d nhflng bfnh nhdn frSn. Dli tuang va phuong phdp: 86 benh nhan dupc chan doan DTD tlieo tieu chudn ADA 2015, vdi glucose mau d o ^ I26mg/dL (hoac > 7,0 mraol/L) va HbAjC> 6,5%i. Ky thugt ELISA gian tilp dupc thuc hien dk dinh lupng cac ty khang thi khang GAD-65 va lAA. Sinh phdm xSt nghiSm la AESKULISA GAD-65 cua hang AESKU -Dfic va sinh pham xet nghiem lAA ELISA cfia hdng DRG- Due. KSt qua: Ty le duong tinh vdi khdng the anti GAD-65 la 48.84%i va lAA la 30.23%.; ty IS duang tinh vdi mflt trong hai logi khang thS la 55,8 l%i; duang tinh vdi ca hai logi 23,26%. Nflng dp frung binh cua khang the khang GAD- 65 duong tinh la 51.08 ± 16,86 lU/raL; cua khang till lAA duong tinh la 1,46 ± 0,27 U/mL. VS moi lien quan gifla nflng dp khang GAD-65, lAA vdi dac dilm cdn ldm sang: co sy khac bift cd f ngliTa thong ke (p<0,05) gifla khang GAD-65 duong tinh vdi nflng dp insulin. Cd khac bift cd y nghTa thdng ke giua khang GAD-65 duang tinh vdi tang triglycerid mau gifla nhdra nghiSn cfiu vd nhdm chfing (p<0,05).
Tie khda: Tg khdng thi khdng glutamic acid decarboxylase (GAD), tie khdng thi khdng insulin, ddi thdo du&ng
Abstract
GLUTAMIC ACID DECARBOXYLASE 65 (GAD-6S) AUTOANTIBODY AND ANTI-INSULIN AUTOANTIBODY IN LEAN PATIENTS WITH DIABETES MELLTTUS
Phan Thi Minh Phuong Hue University of Medicine and Pharmacy Introduction and objectives: The Glutamic acid decarboxylase 65 (GAD-65) autoantibody and anti-insulin autoantibody (lAA) are serum markers of autoimmune diabetic patients. The presence of these autoantibodies in aging diabetic patients can differenciate the latent autoimmune diabetes in adults (LADA) from type 2 diabetes. Patients with these auto-antibodies were considered high risk group and will progress into insulin dependent in 5-7 years. This study was carried out with aims:(l) To define the positive rate, the concentration of GAD-65 autoantibody and lAA on lean patients with diabetes. (2) To indentify the correlation between the presence of GAD-65 autoantibody, lAA and several clinical and ',Y r Bia chi liin hp: Phan Thf Minh Phuang. email: [email protected] • ...•• - .._j, , •
~- -Ngdynhgnbdi: 19/1/2016 *Ngdy ddngy ddng: 25/2/2016 * Ngdy xudt ban: 7/3/2016 ' -"-'" "
Tgp chi Y Dugc hpc - Truft-ng Dai hpc Y Dupe Hui - Sl 31 137
laboratory characteristics of these patients. Objects and methods: 86 patients diagnosed of diabetes following the ADA 2015 criteria, fasting glucose > 126 mg/dL (or > 7.0 mmol/L) and H b A l O 6.5%.
Indirect ELISA technique was performed to measure anti GAD-65 autoantibody and lAA. Kits used m the study were AESKULISA GAD-65 from AESKU Company- Germany and lAA ELISA from DRG Company- Germany Results: the positive rate with anti GAD-65 and L ^ was 48.84% and 30.23%.
respectively. The positive rate with one of the two antibodies was 55.81%.; the positive rate with both antibodies was 23.26%.. Mean concentration of GAD-65 positive was 51.08 ± 16.86 lU/raL; The average concentration of lAA positive was 1.46 ± 0.27 U/mL. Regarding the correlation between the concentration of GAD-65.
lAAand laboratory data: there is a statistically significant difference (p<0.05) between positive GAD-65 antibody and insulin concentration. A statistically significant difference between GAD-65 antibody and hyperfriclycerideraia in the studied and confrol group (p<0.05) is also observed.
Key words: glutamic acid decarboxylase (GAD) autoantibody, insulin autoantibody, diabetes mellitus
L DATVANDE
Dai thao dudng Id bfnh rdi loan chuySn hda carbohydrat khi hormone insulin ciia tyy bj thilu hay gidm tdc dung, bieu hien bdng muc glucose trong mau cao. Benh khdng lay nhung tdc dp phdt trien rat nhanh va cd nhflng bien chfing nguy hiem. Theo dy bdo cua WHO thi den nam 2025 fren thS gidi cd khodng 300 trieu ngudi bj ddi thdo dudng t^p 2 chiSra 85 -90%.
tdng sd benh nhan mac bfnh dai thdo duong.
tgp trung d dp tudi 45 - 64 [I], Cac ty khdng ths khang Glutamic Acid Decarboxylase (GAD- 65) va khang insulin (lAA) la cac chat chi diem huyet thanh d bfnh nhdn ddi thdo dudng the tu miSn. Sy hifn dien cfia chung d benh nhdn ddi thdo dudng Idn tudi giup phdn biet dupc ddi thao dudng ty raien tiem an d ngudi ldn (LADA) vdi ddi thdo dudng typ 2 [15]. Ty khdng thS khdng GAD-65 vd lAA cdn la cdc thdng so quan trpng de phat hifn ddi thdo dudng typ I hoac ddi thdo dudng ty mien tiSm an d ngudi ldn tuoi. Vifc phat hien ty khang the khang GAD-65 d nhflng bfnh nhdn dai thao dudng tiln triln la hit sue can thiSt vi nd la yeu to quan trpng nhdt ddi vdi viec tiSn doan su dyng lifu phdp insulin trong vdng 3 nam d nhflng bfnh nhdn ddi thao dudng trudng thanh tre tuli khflng dupc xip vdo dai thdo dudng typ 1 trSn lam sdng. Khi dai thao duoTig cd pha huy tuyin tyy thi day la chi tieu chdn doan sdm, chinh xac ddi thao dudng phy thupc insulin [15].
NhiSu bfnh nhan duoc chdn dodn ddi thdo dudng typ 2 cd nong dp insulin mau thdp va
cd xu hudng cgn kift insulin. Bfnh nhan dfing thudc ha glucose mau nhu metformin hogc ket hpp vdi sulphonylurea khflng hifu qua ma phai nhd dSn insulin ngogi sinh de gidm nflng dp glucose mdu. Han nfla. frong thyc te cd nhflng bfnh nhdn dupc chan dodn ddi thdo dudng typ 2 nhung ngay tfi dau da dupc chi djnh dung insulin ngogi sinh. Theo nghiSn cuu cfia cac tdc gid LS Van Don vd Trucmg Ngpc Duong ty If cdc tu khdng thS nhu khdng GAD va lAA duong tinh tdp trung d nhflng bfnh nhan dai thdo dudng co chi sfl BMI thap. nhung benh nhdn ndy eung cd bilu hien can kift ngudn insulin ndi sinh va phdi dilu fri insulin ngogi sinh dl can bang glucose mdu [2], [3].
Theo tong kSt cfia chuang frinh phdng chdng bien chfing va kiera sodt ddi thdo dudng, nhflng ngudi khdng thupc dai thdo dudng tfp I nhung cd tu khang till khdng GAD-65, lAA tiii 61% frircmg hpp cd nguy co phdt friSn thanh dai thdo dudng typ 1 sau 5 ndm vd 50%. trudng hpp cdn Igi co nguy CO sau 10 ndm [6]. Vi vgy, nhdm gdp them CO sd khoa hpc giup cho cdc nha lam sang phdn typ dai thao dudng chinh xae ban va chi djnh sdm viec su dyng insulin cho bfnh nhan. chung tdi thuc hien dl tai ndy vdi 2 myc tiSu:
/. Xdc dinh ti Ip duang tinh. ndng dp tu khdng thi khdng GAD-65, lAA trin bpnh nhdn ddi thdo du&ng the trgng gdy
2. Khdo sdt mdi lien quan giiea su hien dien cda tu khdng the khdng GAD-65. lAA v&i mgt sd dgc diim ldm sdng vd can ldm sdng a nhieng bpnh nhdn trin.
138 Tgp chi Y Duyc hgc - Tru*ng Dgi hgc Y Duyc Hue - Sl 31
2. D 6 I TU'gfNG VA PHUONG PHAP NGHIEN ctru
2.1. Dli tuong nghien cuu
86 bfnh nhan gdm 47 nam va 39 nfl dupc chdn doan DTD theo tiSu chuin ADA 2015 [7]. Trong nghiSn cfiu ndy chfing tdi chpn glucose mdu ddi va HbA|C de chin dodn gflm: glucose mau> 126mg/dL (hogc > 7,0 mmol/L) vd HbA,C> 6,5%.
Chung tdi khdng dua vao nghiSn cfiu nhihig trudng hpp sau: phy nfl dang raang thai, bfnh nhan suy thgn. suy gan; viem tyy man, viSm tuy cap. Cac bfnh npi tiet khae dnh huong din chuyen boa glucose nhu hfli chfing Cushing, Basedow, to dau chi. Bfnh nhan dang sfi dyng cac thudc Iam thay ddi chuyen hoa glucose md khdng thi ngung dieu frj dupc frong thdi gian quy djnh dl tiSn hanh nghiSn curu nhu cac steroids kich thich hogc chpn p, thiazid.
Bfnh nhan DTD dupc chia thdnh 2 nhdm:
nhom nghien efiu gdm 43 bfnh nhdn DTD cd thS trang gly (tgi thdi diem lay mau) dya theo chi sfl BMI <18,5 vd nhdm chfing gim 43 bfnh nhan DTD CO the trang khdng gay (tgi thdi diSm lay
radu) dya theo chi sd BMI > 18,5.
2.2. Phuang phap nghien cihi
Cdc xSt nghifra djnh lupng HbAlc. glucose.
Cholesterol, HDL-Cholesterol, LDL-Cholesterol, Triglycerid, dupc thyc hifn theo phuang phdp so mau dfing enzym fren may Cobas 501. Nhan dinh kit qud: tang cholesterol khi >5.2mmol/l;
tang triglycerid khi >2.3mmol/I; giam HDL- Cholesterol khi <0.9mmol/l; tang LDL- Cholesterol khi >3,5mmol/l. Dinh lupng insulin bdng k^ thudt raiSn dich hda phat quang theo nguyen 1^ sandwich, fren may Cobas e601. Ket qua nong dp insulin gidm khi<2,6pIU/ml.
Khang thi khdng GAD, lAA trong huyet thanh dupc do bdng ky thugt ELISA gian tiep. Sinh phdm dupc cung d p bdi hang AESKU. DRG. Dfic.
Nhgn djnh kit qua: khang GAD-65 < 30IU/mL:
am tinh, > 30IU/mL: duong tinh [5]. IAA< 0,95 U/raL: dm tinh; > 1,05 U/mL: ducmg tinh; tir 0,95 - 1,05: nghi ngd, lara Iai ldn 2 [9]. Kf thuat duac thyc hifn tgi Bd mfln Mien dich-Sinh 1;^ bfnh.
Trudng Dgi hpc Y Dupc Hue. Xu ly so lieu tren phan mem Medcalc 11.3.1.0
3. K t T QUA
Bang 3.1. Ti If duong tmh cfia khdng GAD-65, lAA ChisS
khang GAD-65 (> 30 lU/mL)
lAA (> 1,05 U/mL) khang GAD-65 va
lAA dirong ti'nh khing GAD-65 ho5c
lAA duong tinh
Nhom nghien ctru (11=43) S6TH
21 13 10 24
Ty 11 % 48,84 30,23 23,26 55,81
Nhom chung (n=43) S5TH
s
9 06 11
T y l 6 % 18,60 20,93 13,95 25,58
P
<0,05
>0,05
>0,05
<0,05
X SD P
BSug 3.2. Nong dp trung binh khang GAD-65 va lAA Kh^ng GAD-65 dirong tinh
(> 30 lU/mL) Nhom NC
(n=21) 51,08 16,68
Nhom chihig (n=08) 50,62 19,15
>0.05
lAA diro-ng tinh (> 1,05 U/mL) Nhom NC
(n=13) 1,46 0,27
Nhom chung (n=09)
1,42 0,43
>0,05 Tap chi Y Duyc hpc - "n-udug Bgi hgc Y Dup-c Hui - s l 31
Bing 3.3 LiSn quan giira khang GAD-65 voi m$t so dSc didm lam sang Khang GAD-65 duong tinh
D&c diem l&m si^ng Tiiu nhi^u Sytcan Nhin mcr
Nhom nghien cuu n
21 21 11
T y l | % 52,50 52,50 57,89
Nhom chuns
D
8 8 5
Ty le % 26,67 32,00 29,41
P
>0,05
>0,05
>0,05 Bang 3.4. Lien quan gifla lAA vdi mpt sd dac diem lam sang Dac diem 13m
sang Tieu nhieu
Sutcan Nhin mcr
LVA duong Nhom nghien ciiru n
13 13 10
Ty If % 30,23 30,23 52,63
tinh
Nhom chihig n
09 08 04
Ty le % 30,00 32,00 23,53
P
>0,05
>0,05
>0,05 Bang 3.5. Lien quan gifla khang GAD duong tinh vdi Insulin Chis6
Insulin (<2,6 ^IU/mL)
Insulin fe2,6 nIU/mL)
P
Khang GAD duong tinh Nhom nghiSn cihi
n 11 10
<o.
T y l ? % 78,57 34,48 05
Nh6m chung n 03 05
Ty le % 60,00 13,16
>0,05
P
>0,05
>0,05
Bang 3.6. LiSn quan gifla lAA duong tinh vdi Insulin Chi so
Insulin (<2,6 nIU/mL)
Insulin (>2,6 uIU/mL)
P
L ^ duong tinh Nhom ng
n 06 07
bien cuu Ty li %
42,86 24,14
>0,05
Nhom chung n 04 05
Ty le % 80,00 13,16
>0,05
P
>0,05
>0,05
Bang 3.7. Lien quan gifl^ khdng GAD-65 vdi mdt sl dgc dilm cgn Idm sdng khac Chis6
HbAlc fe6,5%) Glucose (> 7,0 mmol/l)
Cholesterol (> 5,2 mmol/l)
Triglycerid (> 2,3 mmol/l) HDL-Cholesterol
(<0.9 mmol/l) LDL-Cholesterol
(> 3,5 mmol/l)
Khang GAD-65 duong tinh Nhom nghien cihi
n 21 21 08 12 06 07
Ty 11 % 48,84 48,84 44,44 60,00 60,00 50,00
Nhom chihig n 08 08 03 04 01 03
T y l e % 18,60 18,60 18,75 19,05 16,67 27,27
P
<0,05
<0,05
>0,05
<0,05
>0,05
>0,05
140 Tgp chl Y Dugc hpc - Trudng ©gi hpc Y Dugc Hue - So 31
Bang 3.8. Lien quan gifla lAA vdi mpt sd dge dilm can lam sang khac Chi so
HbAlc 66,5%) Glucose (> 7,0 mmol/l)
Cholesterol (> 5,2 mmol/l)
Triglycerid fe 2,3 mmol/l) HDL-Cholesterol
( <0.9 mmol/l) LDL-Cholesterol
fe3,5 mmol/l)
lAA duong tinh Nhom nghien cuu
n 13 13 06 09 03 05
Ty le % 30,23 30,23 33,33 45,00 30,00 35,71
Nhom chung n 09 09 03 05 01 03
Ty le % 20,93 20,93 18,75 23,81 16,67 27,27
P
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05 4.BANLU4J^
4.1. Ti If dirong ti'nh, nong d$ trung binh khang thi khang GAD-65, lAA d bfnh nhan dai thao dudng nghiSn cii'u
Tren lam sang, bfnh nhdn DTD t>^p 1 vd typ 2 dfli khi rit khd phan bift. Bfnh DTD t^p 1 Id bfnh ty mien, sy thilu hyt insulin Id do tl bao p bj phd hfiy. Bfnh DTD typ 2 ddc trung bdi sy thilu insulin tuang doi, khflng cd sy hifn difn cfia cdc ySu to ty mien, lfic dau do sy dl khang insulin va sau dd la do khiem khuylt tilt insulin. DTD ths LADA khdi phat mupn va cd sy hifn difn cfia cac ty khdng till nhu anti GAD-65 vd !AA [13],
Ket qua d nhdm nghien cfin cua chung tdi cd 21 tnrdng hpp khang GAD-65 ducmg tinh frong tflng sd 43 frudng hpp chllm t^ If 48,84% (Bdng 3.1).
Ndng dp trung binh khdng GAD-65 duang tinh cfia nhdm nghiSn cfiu Id 51,08 ± 16,86 lU/mL (Bdng 3.2). Cf nhdm chfing, cd 8 trudng hpp khdng GAD-65 duang tinh chiem tf If 18,6%.
Ndng dp trung binh khdng GAD-65 d nhdm chfing Id 50.62 ± 19,15 lU/mL. Tfi kit qua tren cho thdy ty If duang tinh vdi khdng GAD-65 d nhdm nghiSn cfiu (bfnh nhdn DTD the trgng gay: BMI <18,5) cao ban rat nhieu so vdi nhom chfing (the trgng khong gdy: BMI > 18,5). Sy khde bift nay cd y nghTa thing ke vdi p<0,05. Dieu nay dong nghia vdi vifc nhflng bfnh nhdn DTD thi trang gay cd nguy ca cao vdi thi ty miSn ban so
vdi nhflng bfnh nhan DTD the frgng khflng gay.
Nghien cfiu cua Shilpa Oak va cpng sy (2014) trSn 3 84 bfnh nhdn DTD ldn tuli thi co 171 frudng hpp c6 khang thi khdng GAD chiSm ty" If 44,53%.
Tac gia Molo khl so sanh nhflng dgc diem lam sang d nhung ngudi bfnh DTB typ 2 co anti GAD- 65 dra tinh va ngudi ldn khdi phdt benh DTD typ 1 cho cdc dfli tuang thi LADA cd anti GAD-65 duong tinh. Ket qud glucose mau d benh nhan the LADA cdn tdi tf ban bfnh nhan DTD typ 2.
Cudi cung bfnh nhan the LADA nhanh chdng tien triSn den dieu fri insulin. Theo tdc gid vifc xac dinh anti GAD-65 cd thS hflu ieh cho vifc phdn logi Iam sang cfia bfnh DTD frong trudng hap khdng rd rang ve mat ldm sang[12].
VllAA.kltqudbang3.I cho thay cd 13 fruong hpp duong tinh vdi lAA chiem ty If 30,23%i; ndng dp trung binh cua lAA duang tinh Id 1,46 ± 0,27 U/mL. 0 nhdm chfing cd 9 trudng hap duong tinh chiira ty If 20,93%; ndng dp trung binh Id 1.42 ± 0.43 U/raL. Nhu vgy, ty IS duong tinh va ndng dp ty khang thi lAA d nhdra nghien cfiru cao ban so vdi nhora chung. Theo tac gia Le Vdn Don nghiSn cvra frSn 226 bfnh nhdn DTD thi cd 17 frudng hop duang ti'nh vdi khang thS lAA chiem ty le 5,75%.
Tuy nhien nhdra dupc chdn doan la DTD typ 1 tbi ty If duong tinh vdi lAA la 20% (10/50). Nhdm cdn lgi dupc chdn doan Id DTD t^p 2, cd ty If lAA duong tinh 3,97% [2]. Mdt kit qua kliac cua Yu
Tan chf Y Duffc hgc - Truing Dai hoc Y Duoc Hue - Sl 31 141
Lipping vd cpng sy (2013) nghiSn cfiu tren 47 tre em dupc chdn doan la tien DTD, ket qua rat bat ngd vi ty If duotig tinh vdi khdng the lAA Id rat cao 44 trudng h^qp chiSm ty If 93.6% trong khi dd ty If anti GAD-65 duong tinh chi chiSra 36,2% [17].
Tfi kit qud dd cho thdy lAA duang tinh d nhflng bfnh nhdn tiln DTD la rat cao. Do vgy. lAA xudt hifn frong mau cd thi la ddu hifu canh bao sdm cua bfnh DTD trong tuong lai. Trong nghien cfiu cfia chfing tdi, nhdm nghien curu la nhflng bfnh nhdn DTD cd the trgng gay cd ty If lAA duang tinh cao hon so vdi nhdm chfing. VI vgy, nhung bfnh nhdn DTD the trang gdy cd lAA duong ti'nh se la nhdm cd nguy co cao tien frien thdnh DTD the ty mien so vdi nhdm cdn lgi.
Nhu vgy, sy xudt hifn cfia cdc khdng the ty raien nhu khdng GAD-65, lAA rat cd gid frj frong chan dodn va phdn loai cac typ cua DTD cung nhu theo doi sy tien frien cua bfnh. Trong nghien cfiu cfia chfing tdi, sd trudng hpp duong tinh vdi it nhat mpt frong hai ty khdng the khdng GAD-65 va lAA la 24 trudng hpp chiem ty If 55,81%. Sy cd mgt cfia cdc ty khdng the khdng GAD-65 va lAA deu cd gia fri tien luang sy phy thupc insulin d bfnh nhan DTD. tuy nhien khdng tbS khdng GAD-65 dupc xera la ddu an mien djch chinh dS chdn dodn DTD tu raien tiSm an d ngudi truong thdnh.
4.2. Lien quan giiia nong dp khang thS anti GAD-6S, lAA vdi mot sl ddc diem lam sang
Dgc diSm lam sang d bfnh nhdn DTD tuong ddi da dang, cdc dgc dilm thuong gap Id tieu nhieu vd syt can... Sy thieu hut insulin hay de khang insulin se Iam tang ndng dp glucose frong mau gay nen hien tupng tieu nhilu do tdng dp lyc thdm thau (glucose la chat cd dp lyc thdra thau cao).
Chinh vi vgy da phan nhflng bfnh nhan mdc bfnh DTD dSu cd frifu chfing Iam sang ndy. Hon nfla, lupng glucose radu bj ddo thdi qua dudng nude tiiu khdng dupc tdi hSp thu, vi vdy co the bdt bupc phdi huy dpng phdn gidi md co, md md dS cung cap nang lupng nen ngudi bfnh bj syt cdn [3].
KSt qud nghiSn curu cua chfing tdi ghi nhdn dupc dac diSm lam sang tiiu nhieu va sut cdn ed ty If cao nhai la 93.02%. nhin md chiim ty If 44.19%
(khdng frinh bay frong kit qud). Khi khao sat vS mdi lien quan gifla anti GAD-65 vdi nhflng ddc
diSra Idm sdng h^n. kit qud bang 3.3. cho thay tf If tiiu nhilu, syt cdn, nhin md d nhdm nghien cfiu deu cao hon nhdra chfirng, tuy nhiSn sy khde bift nay khdng cd f nghia thdng kS (p>0,05). Vl rail lien quan gifla lAA ducmg tinh vdi cdc ddc dilm lam sang nhu tiiu nhilu. syt cdn vd nhin md (Bang 3.4) cung khdng thdy cd sy khac bift cd y nghTa thdng ke gifla hai nhdm.
4.3. LiSn quan giira khang the khang GAD- 65, lAAvdi Insulin
Nflng dd insulin la mpt chi tiSu de phdn bift DTD tfp I va typ 2. Tuy nhien, ndng dp insulin bj anh hudng bdi nhieu yeu td nhu kha ndng tilt cua tS bdo p, chuySn hoa glucose, cdc yeu td dfli khdng insulin... NghiSn cfiu cfia Yang Lin theo ddi trong vdng sau nam, kiera tra radi 6 thdng rapt lan vl chfic ndng tS bdo p d 2 nhdm bfnh nhdn DTD ty miSn tiSm dn d ngudi ldn, mdt nhdm cd anti GAD- 65 duang tinh vd mpt nhdra cd anti GAD-65 dm tinh, tuong ung nhu theo ddi DTD tfp 2. Ket qua cho thay nhflng benh nhdn dupc chan dodn DTD typ 2 cd anti GAD-65 duong tinh thi tS bdo p ddo tyy se sdm bj suy kiet ban so vdi bfnh nhan DTD typ 2 am tinh vdi tu khdng the nay [16], Theo tac gia Dores Jorge, bfnh DTD typ 2 ngay cang tang cfing vdi sy tien frien cua bfnh ma phai ket hpp nhiSu logi thuoc khac nhau. Insulin la mdt thufle cd hifu qua nhdt dl kiSm soat glucose mdu d benh nhan DTD, tuy nhlSn bfnh nhan DTD typ 2 thudng khflng dupc dieu frj insulin dfi lieu frinh.
Dieu nay ddn den vifc mat kilm sodt glucose mdu va tyy ngdy cdng hgn chS vifc sdn xuat insulin [8].
Trong nghien cfiu cfia chung tfli, mac du khdng thflng ke dupc cd bao nhiSu benh nhdn da tfing dieu frj vdi insulin hay chua nhung ty IS bfnh nhdn giam insulin mdu d nhdm nghiSn cuu (nhom bfnh nhdn the frgng gay) la tuong ddi cao (32.56%);
frong khi ty If nay d nhdm chfing (nhdm bfnh nhan till frgng khflng gay) chi la 11,63% (khflng frinh bdy frong phdn kSt qud). Xet vS mfli liSn quan giua sy hifn difn ty khdng till khang GAD- 65. lAA vdi gidm ning dp insulin radu, Bang 3.5, Bang 3.6 cho thdy tinh trgng gidm insulin mau ehilm ty If rdt cao d cd nhdm nghien cfiu vd nhdm chung (ldn lupt Id 78,57% 42.86%; 60% va 80%).
0 nhdm nghiSn ciiru cd mfli lien quan cd y nghia
142 Tgp chi Y Duyc hpc - Truing Dgi hgc Y Dugc Hue - Sl 31
tiiong kS ve sy hifn difn ciia khdng GAD-65 vdi giam ndng dp insulm trong mau (p<0,05). DiSu nay cho thay sy hifn difn cua cac tif khang thi trong bfnh DTD nhu khang GAD-65, lAA lam suy kift insulin mdu bat kl thi frgng bfnh nhan gay hay khdng g4y. Vi vgy, nhflng bfnh nhdn DTD CO anti GAD-65 duong tinh, lAA duong tinh nSn dupc dieu frj insulin sdm va dfi lifu frinh de franh tinh frgng suy kiet tl bdo p ddo tyy.
4.4. Lien quan giira khang thi khang GAD-65, lAA vdi Glucose va HbAlc
Trudc day, xet nghifm glucose mdu ludn la uu tien hdng dau d nhung bfnh nhdn DTD nhung kJ thudt ndy khflng cd tinh dgc hifu cao (glucose mau thudng thay doi theo chl dp dn va tuy tung thdi dilm xet nghifra frong ngdy). HbAlc la lien hpp gifla glucose va hemoglobin trong hdng cau.
HbAlc on djnh vdi thdi gian luu hanh cua hdng cdu frong mdu ngogi vi la II0-120 ngay va khdng bj dnh hudng bdi cac yeu to dinh dudng[ll]. Vi vdy hifn nay xet nghifm HbAlc thudng dupc ehi djnh dS chdn doan va theo ddi kha nang dap fing dieu frj cua bfnh DTD. Theo ADA 2015, mpt trong bon tieu chuan de chan doan DTD Id chi sfl HbAlc > 6,5% [7]. Mgc du chi so HbAlc cd lpi the so voi tiSu chuan glucose truyen thdng nhung no cung cd rapt so nhupc diem nhu cac bfnh vl hemoglobin, thilu mau, hong clu nhd, tuoi te bdo, nhilm d$c nifu, tang bllirunin mau va thilu sdt cd till lam tiiay doi kit qua HbAlc [11].
Theo tiSu chudn chpn mau nghiSn cuu cfia chung tfli. mdu dupc chon cd chi so glucose mau doi > 7.0 mmol/I vd HbAlc > 6,5%). KSt qua nghien cfiu cfia chfing tdi ghi nhgn dupc glucose CO ndng dp trung binh la 10.56 ± 3.43 mmol/l vd HbAlc trung binh la 9,06 ± 1.52%. (khdng trinh bay trong phan kit qua). Xet lien quan gifla khang GAD-65, lAA vdi HbAlC vd glucose mau Bang 3.7 vd 3.8 cho thay cd sy khde bift cd y nghia thing ke gifla nhdm nghiSn cuu vd nhdm chung.
Khi khdng GAD-65 vd lAA xuat hifn trong mau, khdng GAD-65 se pha hfiy protein mang tl bao tiiu dao p. ben canh dd lAA lam gidm tac dyng cfia insulin ddn den insulin ngdy cdng cgn kift, glucose trong mau tang cao va mat kilm soat tfi dd HbAlc cung se tang theo.
4.5. LiSn quan giiia khang thi khang GAD-6S, lAA vdi Lipid mau
Ddi thao dudng thudng dl kem vdi rfll logn nong d$ lipid va lipoprotein mdu cung nhu rdi logn vl chat lupng cdc lipoprotein, ddy cung la yeu to chinh gdy xo vfla dpng mgch. Dgc diem ndi bgt la tdng cholesterol todn phan, tang hdm lupng triglycerid. tang LDL-Cholesterol va gidm HDL- Chlesterol. Mfic dp cao cua cholesterol chu ySu Id LDL-Cholesterol cao da dupc chfing minh cd lien quan vdi sy phdt friSn xa viia. ddng mgch va bfnhtim[l]. [10], [14].Nongdp HDL-Cholesterol hg thap trong mdu la yeu to nguy co quan frgng cua biSn chfing mach radu Idn. Rii logn chuySn hoa lipid cd the cai thifn ro ret khl dudng huyet on djnh, bfnh nhan an uong va tgp luyfn dung each [4].
Kit qua nghien cfiu cua chfing tdi ghi nhgn tren 43 frudng hpp DTD cd 18 bfnh nhan (41,86%) tdng cholesterol vdi nong dp trung binb la 6,06 ± 0,54 mmol/I. frong sd nay cd 8 bfnh nhan khang GAD-65 duong ti'nh chiim ty If 44,44% (Bang 3.7). Cd 6*trudng hop lAA duang tinh trong sd 18 benh nhan tang cholesterol mdu chiem ty le 33,33%.
20 bfnh nhan (46,51%) tdng triglycerid vdi nong dp trung binh la 3.87 ± l.Il mmol/l, trong dd 12 bfnh nhdn duong tinh vdi khdng GAD-65 chiem ty If 60% va 9 bfnh nhan duong tinh vdi lAA chiem ty If 45%. 14 bfnh nhdn (32,56%) tang LDL-Cholesterol vdi nong dp trung binh la 4,19
± 0,48 mraol/1. frong dd cd 7 bfnh nhan khdng GAD-65 duong tinh chiim ty If 50%> va 5 benh nhdn lAA duong tinh chiem t^" If 35,71%. 10 bfnh nhan (23,26%) gidm HDL-Cholesterol vdi nflng dp trung binh la 0,78 ± 0,09 mmol/l, trong dd 6 bfnh nhan duong tinb vdi khang GAD-65 chiem 60% vd 3 bfnh nhdn duang tinh vdi lAA chiem 30%.
Nhu vgy, chfing tdi tim thdy ty If rdi logn lipid mdu d nhdm bfnh nhdn DTD thi frgng gay (nhdm nghiSn cfiu) cao han nhdm khflng gay (nhdra chfing) d ca trudng hop khang GAD duong tinh, lAA duang tinh. Ddc bift Id tdng friglycerid mau khac bift cd y nghia thong ke gifla hai nhdm vdi khang GAD-65 duang tinh (p<0,05).
Tgp chi Y Dug-c hpc - Trudng Dgi hgc Y Duyc Hue - So 31 143
5. K E T L U A N
Q u a k i t qua nghiSn cfiu tren 86 bfnh nhdn D T D till ty If d u o n g tinh v d i t y khdng t h i khdng G A D - 6 5 d bfnh nhdn ddi thao d u d n g t h i trgng g l y la 4 8 , 8 4 % ; l A A Id 3 0 , 2 3 % . Ty If d u o n g tfnh vdi It nhat mflt trong hai logi Id 5 5 . 8 1 % . T y If duong tinh vdi t y khang t h i khdng GAD-65 d n h d m nghiSn c u u cao h a n n h d m chfing (p<0,05).
Chung tfli e h u a ghi nhdn d u p c m o i liSn q u a n
TAI L i f u 1. Tg van Binh (2007). Nhung nguyin ly nin tdng binh ddi thdo du&ng tdng gluocse mdu, NXB Y hpc. HdNfi, trang 23-76.
2. LS v a n Don (2010), Nghien cuu mgt s6 yiu id tg miin djch a binh nhdn ddi thdo du&ng de tien lugng vd dinh hudng diiu Iri, De tai Nghien cfiu khoa hoc, Vifn 108, Hd Nfi, frang 3-47.
3. Truong Ngpc Duong (2009), Nghien ciht ndng dp C-peptid. insulin, lu khdng Ihi khdng insulin, mpt sd chi so oxy hda/ chdng oxy hda a binh nhdn ddi thdo dudng typ 1, Luan dn l l l n sT Y hpc, Hpc vifn Qu§n y. Ha Npi, frang 7-14.
4. Nguyin Hai Thuy (2009). Bpnh tim mgch trong ddi thdo du&ng, NXB Dgi hpc Hue, frang 91-98.
5. AESKULISA (2014), Gad65 Instruction manual, Aesku, Germany, pp.l-9.
6 Achenbach Peter. Waracke Katharina, Reiter Ju'rgen et al (2004), "Sfratification of Type 1 Diabetes Risk on the Basis of Islet Autoantibody Characteristics", Diabetes, 53, 384-392.
7. ADA (2015), "Standards of Medical Care in Diabetes-2015 Abridged for Primary Care Providers", Diabetes Care, 33(2). 97-111.
8. Dores Jorge (2013), "Insulin therapy in type 2 diabetes", Rev Port Cardiol, 32(Supl.I), 25-31.
9. DRG (2015), DRG lAA Elisa, EIA-1593, USA, pp.l-9.
10. Fujihara Kazuya. Suzuki Hiroaki, Sato Akira et al (2012), "Carotid Artery Plaque and LDL-to-HDL Choleterol Ratio Predict Atherosclerotic Status in Coronary Arteries m Asymptomatic Pariends with Type 2 Diabetes Mellitus", J Alheroscler Thromb, 20(5). 452-464.
cd f nghTa t h i n g k e g i u a khdng G A D - 6 5 , l A A vdi mdt s l dgc d i l m ldm sdng n h u t i i u n h i l u , sut can. nhin md. C h u n g tdi tim thay sy khac bift cd y nghia t h i n g k e (p<0.05) gifla k h a n g G A D - 6 5 duong tinh v d i gidm n d n g dp insulin.
Trong nhflng t r u d n g h p p khdng G A D - 6 5 d u o n g tinh thi nhdra D T D t h i trgng gdy cd ty IS tdng glucose, H b A l C va friglycerid m a u c a o h a n n h d m khdng gdy (p<0.05).
T H A M K H A O
11. Herman William H. and Cohen Robert M. (2012),
"Racial and Ethnic Differences in the Relationship between HbAlc and Blood Glucose: Implications for the Diagnosis of Diabetes", J Clin Endocrinol Metab,91(4), 1067-1072.
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"Latent autoimmune diabetes (LADA) is perched between type 1 and type 2: evidence from adults in one region of Spain", Diabetes Metab Res Rev, 29(6),pp.446-51.
13. Sanchez-Quesada Jose Luis, Vinagre Irene.
De Juan-Francol Elena et al (2013). "Impact of the LDL subfraction phenotype on Lp- PLA2 distribution, LDL modification and HDL composition in type 2 diabetes". Cardiovascular Diabelology, 12(112), 1-8.
14. Stensfrom Gunnar. Gottsater Anders. Bakhtadze Ekaterine et al (2005). "Latent Autoimmune Diabetes in Aduhs Denfinition, Prevalence, p-Cell Function, and Treatment", Diabetes, 54(2), S68-72.
15. Winter William E. and Schatz Desmond A. (2011).
"Autoimmune Markers in Diabetes", Clinical Chemistry, 51(2), I6i-\15.
16. Yang Lin, Zhou Zhi-Guang, Huang Gan et al (2005), "Six-year follow-up of pancreatic P cell function in adults with latent autoimmune diabetes". Word Journal of Gastroenterology,
11(19), 2900-2905.
17. Yu Lipping, Dong Fran, Miao Dong Mei et al (2013),
"Proinsul in/Insulin Autoantibodies Measured With Electrocbemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet Autoimmunity", Diabetes Care, 36.2266-2270.
Tap chf Y Dug-c hgc - Trvtmg Dgi hpc Y Dup'c Hue - s l 31
