TAP CHi Y HOC Vl|T MAM TAP 451 - T H A N G 2 - S 0 1 • 2017
^c6N<fTRlNH NfiHliM CO'U
NGHIEN CU'U MOI LIEN QUAN C O A C H I S 5 KHANG INSULIN V a i MOT s o DAC TiNH LAM SANG BENH NHAN
CO H 6 I CHTFNG CUSHING DO CORTICOID
T6MTAT
Myc dich: l^ao sat ma lien quan cua chi s5 khang Insulin, d5 nh?y Insulin va chu'e nang te bao be- ta vdi 1 s5 d3c ti'nh lam sang d b€nh nhSn hpi DiiJtig cushing do corticoid. Phddng phap: 1V^ ngu'di bao gom 85 benh nh§n hpi chtlrtig Cushing do corticoid Vci 29 ngufli khoe manh co dp tuoi tu'dng dUdng duWc Icham Icim s^ng. lam xet nghiem glucose va insulin mau Idc doi de tfnh chi so Ichang insulin, d6 nhay insulin v l chut nSng \M bao be-ta theo mo iiirih H0MA2 (Homeostasis Modei Assessment). Ket qua:
Chi so khing insulin cf benh nhan hgi chiinq Cushing CO mS Wdng quan thuan mufc dp yeu y6\ vong bung (r=0.24, p < 0.05) co siT tuUng quan thuan mu'c do VLta vdi t f s6 eo hong (HWR) (r = 0.32, p < 0.05), va khong co mot lien quan vd! tuoi, BMI va r^ loan lipid mau (p >0.05). Chi so chii'c nang te bao beta theo, HOMA -13 kh6ng co moi lien quan v6i tuoi, BMI, v6ng bung, ty so HWR va txii loan lipid mau. Chi so nhay insulin co moi lien quan nghich mii'c dp nhe vdi vong bung (r = 0.25, p < 0.05), co SLT tu'tJng quan nghjch mii'c d$ vCa vdi ty s5 em hong (HWR) (r = 0.32, p <
0.05), dong thcfi co mffi liSn quan vdi roi loan lipid mau (p < 0.05). Kit luan: 6 benh nhan hpi chiihg Cushing co vong bung, chi so eo hong cao va co rai loan [ipid mau thi se tang chi so khang insulin va gicim d3 nhay insulin.
Tie Idioa: Hfli chCmg Cushing do corticoid, chi s6 khcing insulin.
SUMMARY
CORRELATION OF H 0 M A 2 - I R A N D H 0 M A 2 - B W I T H CLINICAL MANIFESTATION AND SERUM L I P I D I N CUSHING'S SYNDROME
PATIENTS
Purpose: investigation of the relation between insulin resistance, index, insulin sensitivity, pancreatic beta cell function, clinical features and serum lipid in patients with corticoid induced Cushing's syndrame.
Methods. 114 people included 85 patients with corticoid induced Cushing's syndmme and 29 normal subjects served as controls with equivalent age v/ere
*HgcYiinQu§nY
Oiiu trach nhi?m chinh: Pham Thanh Binh Email: thanhbinh412ld@gmail.(X)m Ngay nhan bai: 3/11/2016 Ngay phan bi§n khoa hoc: 5/12/2016 Ngay duyet bai; 19/01/2017
Pham Thanh Binh* Nguyin Minh N6i*
clinically examined, fasting seium glucose and insulin lever were used to calculate insulin resistance Index, insulin sensitivity and beta ceil function in the H0MA2 model (Homeostasis Model Assessment). Resultsi.^
The Index of insulin resistance in patients with Cushing's syndrome has a weak positive conflation withwaist circumference (r = 0.24, p < 0.05), medium positive correlation with hip-waist ratio (HWR) ( r . = 0.32, p < 0.05), and no relationship with age, BMI and serum lipid disorders (p > 0.05). The index of beta cell function by HOMA-^ has no relationship with age, BMI, waist circumference, HWR, and blood lipid disordei3. Insulin sensitive index has an negative correlation with_ waist circumference (r = 0^25, p <
0.05), has an negative correlation with hip-waist ratio (HWR) (r = 0.32, p < 0.05), and also has a relationship with serum lipids disorders (p < 0.05).
Conclusion: Patients with Cushing's syndrome have a high waist circumference, increased hip waist ratio and serum lipid disorders have Increased insulin resistance index and reduced insulin sensih"\rity.
Keywonis: OsMnq syndrome's. Insulin resistance.
I.OATVANBI
Hoi chutig Cushing la mot tlnh trang roi loan ngi tiet do nong dp glucocorticoid (GCs) tang cao man tfnh trong mau gay ra. H6i chu'ng cushing do nhieu nguyen nhan khac nhau nhuYig CO bieu hien lam sang giong nhau. Trong d o , nguyen nhan do su* dung qua lieu va keo dai Cortisol hoac cac steroid tdng hdp giong Cortisol la nguyen nhan thu'dng gap tren lam sang d n h i i u chuyen khoa khac nhau. Hpi chu'ng Cushing do corticoid la viec su* dung GCs lieu cao keo dai lam cho nong dd thuoc trong trong mau cao htJn nong dd sinh ly tiJf do gay ra cac lac dung phu tren nhieu cd quan trong cd the.
Oai thao dui&ng la mpt trong cac bien chulig pho bien cua hoi chutig Cushing, no chiem khoang 2 0 % [ 7 ] . Dai thao du'dng trong hoi chutig cushing xuat hien chCi yeu la do hau qua cua khang insulin va giam tiet insulin va giam do nhay cilia insulin cf cac cd quan tnDng cd the do GCs tang qua mu'c. Tuy nhien co nhieu dac diem lam sang va can lam sang khac cua cd the c6 the anh hu'dng den cd che tren. Va tren moi benh nhan hpi chutig Cushing, su* ton tai hay kh6ng tBn tai cua n h i i u yeu to co the anh hudng den
VIETIIAM MEDICAL JOURNAL M l - FEBRUARY - 2017
nguy cd mac benh dai thao duSng oia ca the do.
Do do nghien ciJu ve si/ lien quan giula cac dac dilm lam sang va can iam sang vdi chi so i<hang insulin, chiJc ning t§ bao beta va do nh?y insuiin dong vai tro quan trong. Tai Viet Nam 6a co mpt so nghien clJu ve hoi chulig Cushing, tuy nhien danh gia ve mSi iien quan giuS ithang insuiin vdi cac bieu hien iam sang, can iam sang d benh nhan hoi cliiing Cushing thi chuS du'dc nghien cilu day du nSn chung toi Hen hanh nghien cffu de tai nay nhSm muc Heu: Tim hl&i ma lien quan aia chi so khing Insulin (HOMA-lr), dd nhay Insulin va chilt nang tebao bS-ta (HOMA-p) vdi mot so dac tinh lam sang, can lam sang d benh nhSn hgl chiihg Cushing do corticoid.
II. fidi TUWQ VA PHUtmS PHAP NGHliN OjU 2.1. SSi ti/dng nghiin cihi:
Bao gom 114 dot tUHng duBc chia lam ^2 nhom: nhom nghien cilu gom 85 BN dffdc chan doan hoi chutig Cushing theo Aron 2001, vao dieu tr| tai Idioa ithdp va n5i tiet benh viSn Quan Y 103. Nhom chiing gom 29 ngffdi i<h6ng mac b$nh CO do tuoi tffdng duUng nhom nghien cffu
2.2. PliiAfng phap nghiSn dhi:
Tat ca 114 dS tffdng nghien cffu dffdc kham iSm sang, can iam sang. Danh gia i<hang insulin dff^ vao nong dp glucose mau luc doi va insulin mau luc ddi theo mo hinh H0MA2 vi tinh da dffdc cap nhat hoan chinh nam 2004, phien ban 2.2.2 nam 2007 chay tren giao dien excel, phan III. KET QUA
3.1. iOiang insulin, giam chih; nang te iiao iKta, giam do nh^y insuiin vdi tuoi:
Bang 3.1: MSiliSn quan giita Ichang insulin vdi tuSi
mem dffdc cung cap mien phi qua frang web http//www.dtu.ox.ac.uk/homa. Diing cac cap nong dp glucose-insulin liSc doi d l tfnhj±i so khang insulin, chffe nang te bao beta, dp nhay insulin, ket qua dffdc phien giai nhff sau:
-H0MA2-IR: (Homeostasis i^odel Assessment, 2of Insulin resistance) chi so khang Insulin tfnh theo cap nong d6 glucose-insulin luc doi. Khi chl::
so nay cao hdn tff phan vj tren cua nhom chffng thi dffdc coi la co khang insulin.
-H6MA2-%B:(HomeostasIsModel Assessment 2of beta-cell funcHon) dii so chffe nang te bao beta H'nh Hieo c3p nong dp glucose-insulin. Khi chi so nay nho hdii gia tn trung binh ciia nhdm chffng-SD duOc coi la giam diffc nang te bao b^ta.
-HOMA2-%S:(Homeostasisl^odel Assessment 2of Insulin sensitivity) d6 nhay insulin_t(nh theo cap nong dp glucose-insulin. Khi chi so nay nho hdn gia Hi trung binh cffa nhdm chfftig-SD dffdc coi la giam dp nhay insulin.
Cic chi SP nay dffdc so sanh giiJa benh nhan h6i chung Cushing va nhom chiing theo thuat toan t-test cho hai sS trung binh quan sat. Sau do du^ tren ket qua phan loai lihang insulin, diffc nang te bao beta, do nhay insulin, chiing toi se phan Ioai thanh hai nhom theo cac chi tieu vS cac ySu to lien quan, tff do so sanh de tim hieu moi lien quan giiici cac yeu to do vdi khang insulin, giam chffe nang te bao beta va giam do nhay insulin.
^ - ^ ^ ^ ^ ^ Nh6m Chisd ^ ^ ^ ^ ^ ^
Khanq insulin theo H0MA2-IR Giam CNTB 3 theo H0MA2- P Giam dp nhay insulin Hieo HOMA-S
£ 49 tuoi ( n = l l ) SL
4 2 3
36.36 %
18.18 27.27
50-59 tuoi { n = 3 « SL
15 4 13
»/o
48.39 12.90 41.94
60-69 tuoi (n=2S) SL 16 2 16
°/o 64.00
8.00 64.00
> 70 tuoi (n=18) SL
6 4 6
33.33 %
22.22 33.33
P
>0.05
>0.05
>0.05 Nl^n xSt; Moi lien quan giu^ chi so khang insulin, giam chffe nang te bao beta, giam dp nhay insulin vdi tuoi khong c6 y nghTa thong ke.
3.2. Khang insulin, giam chiifc nang te bao beta, giam do nhay insuiin vdi BMI.
Bang 3.2: Moi liSn quan giita Idiang insuiin vdi BMI BMI
Chis
BMI < 23 tn =57i
So iiftfng Tyle BMI > 23 (n=28) So lu'dng Tyie Khang insulin theo H0MA2-IR
Giam CNTB g theo H0MA2 - 8 >0.05
Giam dp nhay insulin theo H0MA2-IS
Nhan xet: Moi lien quan giiis chi so khang insulin, giam chffe nang te bao beta, giam dp nh?y
ciia insulin vdi BMI khpng co y nghia thong ke (p > 0,05)
TAP c r i Y HOC V ^ MAM TAP 451-THAMG 2 - s o 1-2017
33.'nMng qiBn gni^ idtang insubv 03 nhay dia insufa vdi chi so vong bvng, va t^ SO WHR.
Bang3J. Tifdng quan giita cac chi'solioHAvtt vong bang vatj so eoliSng.
Cac d l i so HOHA-P HOMA-IS
Vonq bung 0.24 <0.05 0.04 >0.05 0.25 <0.05 TYSoeohSnaOVHR) 0J2 <0.05
0.06>0.05 0.32 <0.05 XSt dli so eo hong co moi tffidng quan thuan miit dp vu& vdi chi so khang insulin (r = 032, p'< 0.05) va tffdng quan nghich mffc dp vift vdi dp nhay insulin (r = - 0.32, p < 0.05). Vong bmg 00 ma tiTdng quan thuan mffc dp yeu vdi chi so khang insulin (r = 0.24, p < 0.05) va tiAAig quan nghjch mffc dp yeu vdi dp nhay insulin (r = - 0.25, p < 0.05). Sff tffdng quan giua chffe ning te bao beta vdi vong bung va ty so eo hong khong o6 y nghia tiiong ke (p > 0.05).
ZA. iOiang insulin, giam ciiii^c nang te biw i i ^ a , giam do niiay insulin vdi l U l P mau.
Bang 3^; HSi liSn guan giS^ Idiang Insulin vdi rm loan lipid mSu^
——-....JInhtrang l U l P Ouso^ — __, .
Khang insulin theo ; ,t H0MA2-IR rf GamCniBptheo
H0MA2-P 6am do nhay insidn tfteo
'H0MA2-IS
Khong RLiP mau (n=22)
So I I A A K ] f n l
7 3 6
T Y I # ( % )
31.82 13.64 27.27
Co RLLP mau (n=63) So iiAJng (n)
34 9 32
Ty ie (%) 53.97 14.29 50.79
P
>0.05
>0.05
<0.05 j f U ^ x a t moi Ben quan 0ia dv so khang insulin, diut nang te bao beta vdi roi loan lipid mau Uiong GO y nghra tnSng ke (p > 0.(6). M^ lien quan giu^ do nhay insulin ttieo HOMA-IS v*^ roi loan lipid mau co y nghra thong 1^ (p < 0.05)
IV. BAN LUAN
€>ai ttiao dv^irtg la mgt frong cac trien chthig cpian trong cua hpi diuftig Qishing. Cd die chuih la do su* t ^ kh^ng insulin, giam dii^c nang te bao beta va gisn do nhay msulin do su* tang GCs keo dai. Tuy vAvexx, ktiong dii co s^ tac dpng dJa GC^ cac yai to ve tun, ^ 1 ^ vong bLmg,t/soeo hong, ra kian %iA mau, HA dkig o6 the a A hu£ftig dai cac ctf die t r ^ . Tu" do se aih hudng den nguy od nrac €nD d benh nhan hgi d^tig Cushing.
cr nhom tsinh nhan hgi diufhg Cutting do corticoid diung toi chia 1 ^ nhieu nhom tuoi, dula vao k 3 qua nghien cudi (Bang 3.1), chung toi Idiong tim thay ma lien quan nao giu^ cac dii S0H0MA2 - IR, H0MA2 - p, va H0MA2 - IS v6i tun (p>0.05). EX) khang insulin, giam diuD: nang te bEK) bda va dp ntiay insulin phu thupc vao rat nhieu yeu to khac nQ^ nhu* b ^ \k\\, tang huyet
&p, fS lean m3 mau va cac t>enh man linh klm theo cua benh nhan. Ngoai ra dii so HOMA lai ttiay dS tuy ttieo tirtig chung tpc, do do can co nhieu n^ien dKli vdi c3 mau ldn hcfn va ptian diia thanh nhieu nhom tuoi va cac yeu to nguy od rieng biet kfiac
K^ qua nghien ojtU aJa ciiung toi (Bang 3.2) rtfiai tfi!^ ly le kfiang insulin is nhom co BMI >
23 theo H0MA2-IR la 53.57%, ty Ie giam do nhay insufin ttieo H0MA2-IS la «.43 % tutfng dutftig wS nhom BMI < 23 (p>0.05). €Meu nay gd! y cho diung ^ ' tiep tuc nghien cuU XKXX
nhutig o3 miu ldn hdn vS k3: qua chfnh xac hcfn trong tutfng lai.
Trong nghien diu cua Nguyen Thj Thu Thao (2012) [3] nhan thay, DTD typ 2 c6 b ^ bung thi khang insulin va giam do nhay insulin nhieu hdn DTD ty p 2 khong ra beo tiung (p<0.G5), NgutfC iai nh6m DTD typ 2 khong co b ^ bung thi giam ciiu'c nang te bao beta nhieu hcAi nhwn DTD co beo bung d ca hai cap insulin (p < 0.001) va C- pepttd (p < 0.001
TuT nghien dSu chung toi thu dutfc k^ qua:
ciii so ktiang insulin d benh nhan hgi chuVig Cushing theo HOMA - IR co mS tutfng quan thuan mu'c do nhe vS vong bung cua benh nhan (r = 0.24, p < 0.05) va oo moi t u ^ : ^ quan thuan mu'c do vij^ v6l ty so eo hong (HWR) (r = 0.32, p < 0.05) Chi so dp nhay insulin theo HOMA - K CO moi tutfng quan nghjch mu'c do nhe vdi vong bung cua benh nhan (r = 0.25, p <
0.05) va CO ma tu'dng quan nghich mu'c do vuS vdi t^ so eo hong (HWR) (r = 0.32, p < 6.05).
Khong co ma tutfng quan giO^ dii so danh gia chu'e nang te bao bete theo HOMA-p vdi vong bung va ty so eo hong cua benh nhan (p > 0.05).
Nhieu nghien culi ve ma lien quan glQ^ roi ban chuyen hoa lipkl va dndc nang te bao beta dio ket qua khac nhau:
Tran Thj Thanh Hda (2009) [4] d benh nhan
OTD typ 2 nhan thay cd moi Utfng quan khong
chat gifls Triglycerid vffl chi so QuiW (r=-0.2313,
p<0.00133), tryglycerid vdi HOMAl-IR
WETMAM MEDICAL JOURHAL N'l - FEBRUARY - 2017
(r=0.1993, p<0.0335), giijB HDL-C vdi insulin (r=-0.2237, p<0.00157), giife HDL-C vdi HOMA - p (r=-0.2648), p<0.0044).
Nghien cull cua Tran Thj Thu'dng [5]^ cung cho thay Miang insulin d benh nhan cd roi loan lipid mau cao hdn d benh nhan kh5ng cd roi loan lipid mau, do nhay cua insulin giam nhieu d benh nhan tien DTO cd RLLP mau so vdi benh nhan Idiong r a loan lipid mau.
Le Oinh Tuan (2015) [2] cho thay chi so HOI^A-IR cua nhdm benh nhan DTO cd roi loan lipid mau thap hdn nhdm binh thu'dng cd y nghTa thong ke (p<0.05), chi so HOMA-IR cua nhom benh nhan benh nhan co chi so HDL-C, LDL-C va tryglycerid binh thu'dng thap hdn nhdm bSnh nhan co roi loan cac thanh phan lipid mau tren CO y nghTa tiiong ke (p <0.05). Tuy nhien, nghien cifu cua Do Oinh Tijng [1] va Nguyen Thj Thu Thao [ 3 ] chu^a thay moi lien quan gii?a cac chi so HOMA-IR va HOMA- p, HOMA-IS vdi cac thanh phan lipid mau.
Nghien cdu cOa chung toi, ty ie khang insulin d benh nhan hgi chuhg Cushing cd RLLM theo H0I^A2-IR la 53.97% cao hdn nhom khong cd RLLP mau la 31.82% (p > 0.05), t^ le giam do nhay cua insulin theo H0MA2-IS la 50.79%, cao hdn nhom khong co RLLP mau ia 27.27% (p <
0.05). Nhu" vay khong co sy" lien quan giiJa cac chi sff khang insulin, giam c h i i t nang te bao beta, d benh nhan hgi chiihg Cushing vdi RLLM mau. K§t^qua nay doi hoi can phai cd sir nghien cull cd mau ldn hdn de cd ket qua chi'nh xac hdn trong tu'dng lai. Cd s y lien quan giu:a do nhay insulin vdi roi loan lipid mau.
V . K E T LUAN
- Khong cd moi lien quan gida tuoi, BMI vdi chi so H0MA2-IR, HOMA-p, H0MA2-IS.
- Vong bung co tu'dng quan thuan, mii'c do nhe (r = 0.24, p < 0.05) vdi khang insulin; tutfng^
quan nghjch mii'c do nhe (r = - 0.25, p < 0.05)f vdi do nhay insulin.
- t y so eo hong (HWR) cd tu'dng quan thuan mu'c do vij^a (r = 0.32, p < 0.05) vdi khaiig Insulin, tu'dng quan nghich mii'c do viTa (r = - 0.32, p < 0.05) vdi do nhay insulin.
- Khong cd moi tu'tfng quan g\da vdng byng, ty so eo hdng vdi chii'c nang te bao beta.
- - . *f
T A I LIEU T H A M K H A O j 1. Do Dinh Tung ( 2 0 0 8 ) , "Nghien cuU chu'e ninfi,
te bao beta do nhay insulin qua mo hinh H0i4fiit d benh nhan DTD dian doan lan dau", Luan "hk Thac sy y hoc, Hoc Vien Quan Y.
z. Le Binh Tuan ( 2 0 1 5 ) , "Nghien cuV Hnh trsng khang insulin & hinh nhan dai tfiao du'dng typ 2' tai benh vien da Idioa tinh Thai Binh", Oe tai kHCN^2015, Dai hoc Y du'dc Thai Binh.
3. Nguyen Thj Thu Thao (2012), "Nghien cuU dSc diem iam sang va tinh trang l&iang insulin tren b^nii nhan dai thao du'dng typ 2 mdi du&e dian doan"
Luan an ti§n 3/ Y hoc, Hoc Vien C^an Y. r ^ 4. Tran Thj Thanh Ifoa (2009), "Nghien culiM
trang i^ang insuiin d benh nhan dai thao du&iim 2 CO gan nhiem md phat hlin lan daulaib&ihm Ngiti&", Luan an Ti&i ^ Y hoc, Dai hoc Y HN.
5. Tran Thj Thu'cfng, N g u y i n Vinh QuangI (2014), "Nghien ciru khang insulin va chu'e nang|l te bao beta d benh nhan tien dai thao duflng^f
Tap chi Y hoc Oiut hanh, tr. 1 3 8 - 1 4 1 . J i 6. Geloneze B., e t a l . (2009), " H O M A l - I R ^
H0r^A2-IR indexes in identifying insulin resistaff"
and metabolic syndrome: Brazilian l ^ e t a ^ Syndrome Study (BRAMS)", Arq Bras Endoc
Metaboi, 53(2), 281-7. ^^
7. Pivonello R., e a l . ( 2 0 1 0 ) , "PathophysislcM diabetes mellitus in Cushing's syndro^rt Neuroendocrinology, 92 Supp! 1, 77-81. '
HIEU QUA C O A PHU-aNG PHAP DO DIEN THE THAT SOM NHAM XAC DINH VI TRI DICH TRONG TRIET DOT NGOAI TAM THU THAT Ttr DU'O'NG RA T H X T PHAI
Phan Dinh Phong*, Tr4n Tu^n Vi?f*
'''' ,. ^VC Heu: NghlSn ciJu gia tri cua phirong p f i l S l?p ban do diSn hoc bSng do dien the that s4m (EATjl trang Wet dot ngoai tam thu thSt (NTTT) l<hcli phat t n duWng ra that phai. Doi tu'cfng va phu'dng p h a p i l Nghien CIHJ thtfc hien tren 73 benh nhan duHc chalil doan ngoai tam thu that ididi pliat tir duSlng'ra ttiM phai, duBc lam thu thuat triet dot bang nSng l u a H song CO tan so radio qua du'dng ong thong (dSt d l H l tai Vien Tim mach V i a Nam trong i<hoanq thdi oiaifOT 1/2015-11/2015. Qua trinh triet dot c6 sif dilOT
*Tn/dng Dal hoc YHi NSI
Oiiu trach nhiem chinh: Phan Dinh Phong.
Email: [email protected].
Ngay nh§n bai: 12/10/2016 Ngay phan blen l<hoa hoc: 15/11/2016 Ngay duyet bai: 5/01/2017
