the unrelated mutant alleles. Thirty - two mutations were associated with a severe phenotype and 15 mutations with an attenuated one. Plasma and urine KS concentrations in MPS IVA patients were higher than those in age - matched normal controls. Plasma KS levels in MPS IVA patients with the severe phenotype were 1.4 times higher than in the patients with a milder form. Urine KS levels of MPS IVA patients with severe phenotype were 4.6 times higher than in the patients with a milder form. The percentage of KS in total urine GAG was 2.2% and 3.9% for attenuated and severe phenotype of patients, respectively. Normal controls had only 0.5% KS. Conclusions: This study provides evidence for extensive allelic heterogeneity of MPS IVA. Accumulation of mutations with clinical description and KS concentration has led us to predict clinical severity more precisely and w i l l be used for evaluation of responses to the possible treatments.
Keywords: Mucopolysaccharidosis IVA, Morquio A disease, GALNS gene
/v"
GIA TR| CUA HOMA, QUICKI TRONG CHAN DOAN KHANG INSULIN 6 BENH NHAN DAI THAO DU^NG TYP 2 ,(.
CAO TUOI CO HOI CHL/NG CHUYEN HOA
Ho Thj Kim Thanh, Pham Thing, D6 Thj Khanh Hy Benh vien Lao Khoa Trung uang
Phuang phap chinh xae nhat hay "tieu chuan vang" de danh gia khang insulin la phuang phap kep Hyperinsulinemic - Euglycemic Clamp. Tuy nhien de ap dung rdng rai tren lam sang va nghien cUu cdng dong ngudi ta da dUa ra rat nhieu phuang phap gian tiep, it xam nhap han. Chinh vi vay chiing tdi tien hanh nghien cdu nay nham: Muc tieu: danh gia mdi tuang quan giUa HOMA, QUICKI vdi ehl sd khang insulin bSng nghiem phap kep Hyperinsulinemic - Euglycemic Clamp d benh nhan dai thao dudng (DTD) typ 2 cao tudi cd hdi chdng chuyen hda (HCCH). Doi taang va phaang phap nghien ciiu: 52 benh nhan DTD typ 2 cao tudi cd HCCH. Dinh luang dudrig mau, insulin mau luc ddi, tinh HOMA, QUICKI. Tien hanh nghiem phap kep Hyperinsulinemic - Euglycemic Clamp (40mU/nr/phut), tinh tdc do truyen glucose trung binh trong 30 phiit cudi cua nghiem phap (M mg/kg/phut). So sanh tUang quan giUa HOMA, Log HOMA va QUICKI vdi M. Ket qua: HOMA tuang quan nghich chat che vdi M (mg/kg/ph) (r = - 0,558; p < 0,0001) va Log HOMA tuang quan nghich chat che M (mg/kg/ph) (r = - 0,577; p < 0,0001). QUICKI khdng tuang quan vdi M(r= 0,233; p = 0,081). Ket luan: HOMA va Log HOMA cd gia tri tdt danh gia mUc do khang insulin d benh nhan DTD typ 2 cao tudi cd HCCH.
Tir khoa: homa, quicki, khang insulin, dai dudng typ 2, hoi chiJng chuyen hoa
,^ nong dd insulin khong du de vUdt qua tinh trang
I. D A T V A N D E UU I .. . 1
Khang insulin d mo ngoai vi se gay tang glucose Khang insulin la mot cP che benh sinh quan mau man tfnh va benh DTD thUc sU se xuat hien.
trpng cua DTD. Nhidu nghien cdd da chdng minh Hon nUa khang insulin cung la yeu t d nguy co cua tinh trang khang insulin thddng di trddc sU xuat hien tim mach. Phat hien sdm tinh trang khang insulin cac trieu chUng lam sang cua benh DTD typ 2. Khi va cai thien dUOc dp nhay cua insulin cd the lam
cham cung nhu giam nguy cd D T D . De danh gia khang insulin ed rat nhieu phddng phap va chi sd danh gia. PhUdng phap dUdc coi la chinh xae nhat hay "tieu chuan vang" la phUdng phap kep Hyperinsulinemic - Euglycemic Clamp [6]. Tuy nhien de ap dung rpng rai tren lam sang va nghien cdu cpng dong ngUdi ta da dda ra rat nhieu phddng phap gian tiep, it xam nhap hdn.
Chinh vi vay chung tei tien hanh nghien cdu nay n h l m muc tieu:
Danh gia mdi taang quan giUa HOMA, QUICKI vdi chi sd khang insulin bang nghiem phap kep Hyperinsulinemic - Euglycemic Clamp d benh nhan dai thao dUdng typ 2 cao tudi co hoi chdng chuyen hoa.
II. DOI TLiONG VA PHliONG
PHAPNGHIEN CL/U
1. Ddi tuong nghien cu'u
- 52 benh nhan dai thad dddng typ 2 cd hpi chdng chuyen hda tudi td 60 trd len tinh nguyen tham gia nghien cdu.
- Benh nhan ddpc chan doan dai thao dddng theo tieu chuan cua Td chdc Y te The gidi 2002 (WHO 2002).
- BN ddpc chan doan cd hdi chdng chuyen hda dua vao tieu chuan cua NCEP/ATP III da chinh sda ap dung cho ngddi Chau A bao gdm cae tieu ehl sau (chan doan khi cd > 3/5 tieu chi) [9]:
- Vdng eo > 90 cm d nam, hoae > 80 cm d nU.
- Ndng dp triglycerid mau luc ddi > 1 50mg/dL.
- Huyet ap > 1 30/85 m m H g .
- Ndng dp HDL - C < 40mg/dL d nam, hoae <
50mg/dL d nd.
- Ndng dp glucose mau luc ddi > 100 mg/dL.
2. Tieu chuan loai triif
•- Benh nhan khdng hpp tac nghien cud.
- Benh nhan dang mac cae benh cap tfnh.
3. Phu'ang phap nghien cilu
- Mo ta cat ngang.
- Hdi benh va kham benh toan dien theo mpt mau thdng nha't.
- Cac xet nghiem sinh hda (lam tai Khoa Sinh hda - Benh vien Lao Khoa Trung UOng).
- Lay mau tTnh mach vao budi sang sau 8h ^ 10h nhjn ddi. Djnh Idpng glucose mau (G), IdOng eae thanh phan lipid man, insulin mau tren may xet nghiem Architect Ci4100. Dinh lUdng ure, creatinin, GOT, GPT mau, tdng phan tich nddc tieu.
- Nghiem phap kep Hyperinsulinemic Euglycemic Clamp: theo phuong phap cua Ralph A. DeFronzo et al [3].
- Tinh chi sd HOMA - IR (Homeostatic model assessement method insulin resistance - HOMA IR) do Matthews va cpng sU de xuat lan d I u nam 1995.
HOMA - I R lo (|.iU/m ) L X Go (mmol/L )l 22,5
lo: Ndng do isulin mau luc ddi.
Go: Nong do glucse mau liic ddi.
Chi sd QUICKI: Quantitative Insulin Sensitiv- ity Check Index.
1
QUICKI = • logdo) + log(Go)
4. Xu: ly sd lieu
Cac sd lieu dUpe xd ly va phan tich bang ehUdng trinh p h I n mem thdng ke y hpc SPSS for W i n d o w 16.0.
I I I . K E T Q U A
Chi sd HOMA tUdng quan nghjch chat che vdi ndng dp glucose trung binh dUpc truyen (M ( m g / k g / p h ) ) t r o n g n g h i e m pha'p k e p H y p e r i n s u l i n e m i c - E u g l y c e m i c Clamp (r = - 0 , 5 5 8 , p < 0,0001).
Bang 1. Cac chi sd gian tiep danh gia khang insulin d benh nhan DTD typ 2 co HCCH cao tudi
N (Benh nhan) Glucose mau luc ddi (mmol/l)
Insulin mau Idc ddi (mU/ml) lO/GO ((mU/ml)/(mmol/l))
HOMA
QUICKI 1,93
52 6,5 ± 1,5 10,7 ± 5 , 3 0,82 ± 0,67 3,08 ± 1,95
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Bieu do 1. Taang quan ciia HOMA vdi M (mg/kg/phut)
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LOGHOMA
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r = - 0 , 5 7 7 p < 0,0001
Bieu do 2. Taang quan cua log - HOMA vdi M (mg/kg/phut)
Chi sd Log HOMA tuang quan nghich chat che vdi nong do glucose trung binh duac truyen (M (mg/kgj ph)) trong nghiem phap kep Hyperinsulinemic - Euglycemic Clamp (r = - 0,577; p < 0,0001)
r = 0,233 p = 0,081
QUICKI
Bieu do 3. Taang quan cua QUICKI vdi M (mg/kg/phiit)
Chi sd QUICKI khdng tUang quan vdi ndng dd glucose trung binh dugc truyen (M (mg/kg/ph)) trong nghiem phap kep Hyperinsulinemic - Euglycemic Clamp (r = 0,233, p = 0,081).
nhan dai thao dUdng cd nhieu khoang dao dpng I V . B A N L U A N
Hien nay phUdng phap danh gia khang insulin dUa vao chi sd HOMA - Homeostatic Model Assessement, va chi sd QUICKI (Quantitative Insu- lin Sensitivity Check index) la hai ehl sd dUpe sd dung rong rai trong cac nghien cdu vT day la phuong phap don gian, dd thUe hien va kha chinh xae khi so sanh vdi phUOng phap "kep glucose".
Theo nghien cdu cua Sarafidis va cpng sU tren 78 benh nhan tang huyet ap, dai thao dUdng typ2 thay: chi sd HOMA - IR lien quan nghjch chat che vdi M (r = - 0,572- p < 0,001). 1/HOMA - IR va QUiCKI tuong quan thuan vdi M (r = 0,342;
p < 0,05 va r = 0,456; p < 0,01) Chi sd McAuley's (iSI) lien quan long leo vdi M (r = 0,317;
p < 0,05). Nhu vay, vdi benh nhan THA va DTD type 2 thi chi sd HOMA - IR, 1/HOMA - IR va QUICKi cd gia tri danh gia dp nhay insulin [8].
Nghien cdu cua Yokoyama (2004) tren benh
dddng mau cho thay QUICKI lien quan chat ehe vdi Clamp - IR (r = 0 , 6 9 1 ; p < 0,001). Log HOMA - IR eung lien quan chat vdi Clamp - IR (r = 0,685;
p < 0,001) 110].
Theo Rabasa va cpng sd (2003) nghien cdu 148 ddi tupng (17 - 70 tudi): QUICKI va log HOMA lien quan chat vdi clamp IR (r = 0,78 va r = - 0 , 7 8 ; p < 0,001).
Ngdpc lai, Ferrara va Goldberg nghien cdu tren nam gidi Idn tudi cd rdi loan dung nap glucose thay khdng cd lien quan giUa HOMA IR va ket qua euglycemic clamp. Katsuki et al cung khdng thay lien quan giUa HOMA IR va ket qua euglycemic clamp d benh nhan dai thao dUdng type 2 cao tudi Nhat Ban [4, 5, 7].
Cae nghien cdu khac nhau tren chdng td tuy thupc mdi ddi tddng nghien cdu ma ta nen Ida chon phdong phap gian tiep nao cho phu hdp va
cd gia trj de chan doan khang insulin.
- Khang insulin theo chi sd HOMA - iR:
Ket qua nghien cdu d bang 1 cho tha'y: nhdm benh nhan dai thao dddng type 2 cd ehl sd khang insulin cao chi sd HOMA - IR trung binh la 3,08 + 1,95. Ket qua cua chdng tdi tha'p hdn ket qua cua Nguyin Ddc Ngo (2008): nghien cdu tinh trang khang insulin theo chi so' HOMA - IR d 188 benh nhan DTD typ 2 la 7,92 + 5,47 [2]. N g u y i n Kim Luong (2000): 6,69 + J ,45 [ I j . Ket qua nghien cdu eua chdng tdi tUOng tit vdi ket qua nghien cdu cua mpt sd tac gia trong va ngoai nddc nhd Tran Thj Thanh Hda (2007): HOMA - IR d 114 benh nhan DTD typ 2 khong ce gan nhiem md la 3,94 + 3,77. Yokoyama H (2003): HOMA - IR d 45 benh nhan DTD typ 2 la 2,83 ± 1,19. Annette M.
Chang, Maria j . Smith (2005): 185 ngUdi tU 60 tudi trd len, HOMA cua nhdm benh 3,15 ± 0,17 cao hdn han nhdm chdng 2,72 ± 0,1 3 (p < 0,001), so vdi nhdm tudi tre (27 ± 5 tudi) chi sd HOMA = 2,09 ± 0 , 1 4 .
Su khac biet nay la do ddi tUdng nghien cdu khac nhau, ddng thdi nd cung phan anh thUe trang la chi sd HOMA va QUICKI phu thupe vao ndng dp glucose va insulin mau luc ddi nen se bie'n dpng theo thdi gian d tdng benh nhan, cung nhu gida cac benh nhan.
Nghien cUu cua chdng tdi tha'y ehi sd HOMA tddng quan nghjch chat che vdi ndng dp glucese trung binh ddpc truyen (M (mg/kg/ph)) treng nghiem phap kep binh dddng tang insulin mau (r
= - 0,558, p < 0,0001) va Log HOMA tUOng quan nghjch chat che vdi ndng dp glucose trung binh dUOc truyen trong nghiem phap kep binh dudng tang insulin mau (r = - 0,577, p < 0,0001). NhU vay HOMA va Log HOMA ed the dddc dung lam ehl sd gian tiep danh gia khang insulin 5 benh nhan dai thao dddng typ 2 cao tudi cd hpi chdng chuyen hda tai Viet Nam. HOMA eang cao thi mde do khang insulin eang nang.
- Khang insulin theo chi sd QUICKI:
Ket qua nghien cdu cua chdng tdi cho tha'y:
Chi sd QUICKI trung binh d nhdm DTD typ 2 la 1,93 ± 0,44. So vdi cac nghien cdu tren benh nhan dai thao dddng typ 2, ket qua nay cao hon ket qua nghien cdu cua Huichen (2005): 0,304 ± 0,007; Yokoyama H (2004): 0,34 + 0,03; N g u y i n Ddc Hoan (2008): 0,78 + 0 , 1 1 ; N g u y i n Ddc Ngo (2008): 0,37 ± 0,06 cd the do cac phUOng phap djnh Idpng insulin khac nhau, do'i tUdng benh nhan khac nhau. Nghien cUu cua chung tdi khdng tha'y moi tddng quan gifla chi se' QUICKI va ndng dp glucose trung binh dUdc truyen (M (mg/kg/ph)) trong nghiem phap kep Hyperinsulinemic - Euglycemic Clamp (r = 0,233; p = 0,081).
V. KET LUAN
0 benh nhan dai thao dddng typ 2 cao tudi cd hpi chdng chuyen hda:
- HOMA va log HOMA tddng quan nghjch chat che vdi chi so' danh gia khang insulin bang nghiem phap kep Hyperinsulinemic - Euglycemic Clamp (r = - 0,558, p < 0,0001 va r = - 0,577;
p < 0,0001), cd gia trj de chan doan khang insulin.
- QUICKI khong tdong quan vdi chi sd danh gia khang insulin bang nghiem phap kep H y p e r i n s u l i n e m i c - E u g l y c e m i c C l a m p (r = 0,233; p = 0,081).
TAI LIEU THAM KHAO
1. Nguyin Kim LUOng (2000). "Nghien cdu tinh trang re'i loan chuyen hda Lipid d BN DTD typ 2, Tang huyet ap, DTD cd tang huyet ap";
Luan an tien sT y hpc.
2. Nguyin Dufc Ngo (2008). "Nghien culi mdi lien quan khang insulin vdi beo phi, rdi loan lipid mau d benh nhan DTD typ 2"; Luan an tien sT y hoc.
3. Defronzo, Ralph A., Jordan D.B., Reubin A.
(1979). "Clamp technique: a method for quantifying insulin secretion and resistance"; A m .
J. Physiol. 37(3), 2 1 4 - 2 2 3 .
4. Emoto M., Nishizawa Y., Maekaw K. et al (1999). "Homeostasis model assessment as a Clinical Index of linsulin Resistancein type 2 Diabetic Patients treated w i t h sulfonylureas";
Diabetes Care, 22, 8 1 8 - 8 2 2 .
5. Ferrara C M , Goldberg AP (2001). "Limited value of the homeostasis model assessment to predict insulin resistance in older men with impaired glucose tolerance"; Diabetes Care 24, 2 4 5 - 2 4 9 .
6. Helen Karakelides, Brian A. Irving, Kevin R.
Short et al (2010). "Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function"; Diabetes, Vol.59, 89 - 97.
7. Katsuki A et al (2002). "Neither Homeostasis model Assessment nor Quantitative insulin sensitivity check index can predict insulin resistance in elderly patients with poorly
controlled type 2 Diabetes Mellitus"; The journal of Clinical Endocrinology and Metabolism, Vol.
87, N o l l , 5 3 3 2 - 5 3 3 5 .
8. Sarafidis, P. A.,et al (2007). "Validity and reproducibility of HOMA - IR, 1/HOMA - IR, QUICKI and McAuley's indices in patients with hypertension and type 11 diabetes"; J Hum Hypertens, 21(9), 709 - 16.
9. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (AdultTreatment Panel III) Final Report (2002). Circulation; 106; 3143.
10. Yokoyama H et al (2004). "Quantitative Insulin Sensitivity Check Index and the reciprocal index of Homeostatic model assessment are useful indexes of insulin resistance in type 2 diabetic patients with range of fasting plasma glucose". The journal of Clinical Endocrinology and Metabolism, Vol. 89; N°3, 1481 - 1484.
Summary
ROLE OF HOMA OR QUICKI IN PREDICTION FOR INSULIN RESISTANCE IN ELDERLY DIABETIC PATIENTS WITH METABOLIC SYNDROME
Hyperinsulinemic - Euglycemic Clamp is the "gold standard" for diagnosing insulin resistance. Which simple indeces of insulin sensitivity and insulin secretion should be used in epidemiologic studies, especially for elderly diabetic patients? Objective: To clarify whether homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) may be indicators of insulin resistance in the elderly diabetic patients with metabolic syndrome (MS). Methods: 52 diabetic patients with MS older than 50 yrs. Evaluate fasting blood glucose and insulin level, calculate HOMA, QUICKi. M was assessed by Hyperinsulinemic - Euglycemic Clamp (40mU/m~/min), Compare relationship between HOMA, QUICKi with the glucose infusion rate (M). Results: HOMA and Log - transformed HOMA were significantly negative correlated with the clamp IR M (mg/kg/min) (r = - 0,558, and r = - 0,577;
p < 0,0001), QUICKi was not correlated significantly with M (r = 0.233, p = 0.081). Conclusion: HOMA and Log HOMA should be used as an index of insulin resistance in elderly diabetic patients with metabolic syndrome.
Keywords: Homa, Quicki, Hyperinsulinemic - Euglycemic Clamp, elderly diabetic patients
