Relationship of Alanin Aminotransferase and Γ-glutamyltransferase
Transcript of Relationship of Alanin Aminotransferase and Γ-glutamyltransferase
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PROBLEME DE CERCETARE
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REZUMAT
Obiective. Scopul studiului a fost evaluarea asocierilor enzimelor hepatice, respectiv alaninaminotransferaza(ALT), aspartataminotransferaza (AST) i -glutamiltransferaza (GGT) cu sindromul metabolic (SM) i diferitelesale componente la pacieni cu DZ2 nou descoperit, precum i cu unii parametri ai insulinorezistenei i uneleadipocitokine.Material i metod. Am realizat un studiu cross-secional ce a inclus 227 de persoane (113 femei i 114brbai) cu diabet zaharat tip 2 (DZ2) nou descoperit. Am analizat parametrii antropometrici, clinici, biochimicii unele adipocitokine n funcie de prezena SM, de numrul de componente ale sindromului i dupstratificareape quartile de AST, respectiv GGT.Rezultate.86,6% din pacienii cu DZ2 nou descoperit au prezentat i SM. Valorile AST s-au corelat negativ cu
vrsta (p
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ol (p
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Datele despre stilul de via(fumatul, consumulde alcool), despre antecedentele heredo-colateralei personale patologice i despre tratamente medica-mentoase cronice au fost obinute prin anamnez.S-au determinat greutatea i nlimea, CA, indicelede mas corporal (IMC). Probele de snge s-au
recoltat dimineaa, dup8-10 ore de repaus alimen-tar. Glicemia jeun (mg/dl), hemoglobina glicat(HbA1c) (%), colesterolul total (mg/dl), colesterolulcu densitate mare (HDL-colesterolul; mg/dl), TG(mg/dl), creatinina (mg/dl), acidul uric (mg/dl), ALT(U/l), AST (U/l), GGT (U/l) au fost msurate utili-znd metode biochimice curente. Colesterolul cudensitate mic (LDL-colesterolul) a fost calculatfolosind formula Friedewald (16). Concentraiileserice ale insulinei, proinsulinei, peptidului C, lep-tinei, adiponectinei au fost determinate prin tehnica
ELISA, folosind kituri disponibile comercial (EIA-2935, EIA-1560, EIA-1293, EIA-2395 i EIA-4177;DRG Instruments, Germania), n conformitate curecomandrile productorului. Citirea absorbane-lor s-a realizat pe un cititor de plci Multiskan Ex-Thermo Electro Corporation (CV = 2,6%). Rezis-tena la insulin a fost apreciat prin calculareaHOMA-IR (Homeostasis Model Asessment for In-sulin Resistance): [glicemie (mmol/l) x insulinemie(U/ml)]: 22,5 (17).
Rezultatele pentru variabile continue sunt pre-zentate ca medie deviaie standard (DS) sau caprocente. Evaluarea diferenelor dintre subloturile
analizate a fost realizatfolosind Student t test pen-tru variabilele numerice i testul 2 pentru vari-abilele nominale sau ordinale. Pentru testarea dife-renei dintre mediile a mai multe grupe diferite s-afolosit analiza de varianunifactorial(One-wayANOVA). Metoda de corelaie bivariatPearson a
fost utilizatpentru a examina corelaiile dintre va-riabile. Semnificaia statistic a fost definit ca p
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n rndul brbailor), HDL-colesterol, leptin iadiponectin (p
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i n funcie de diferitele sale componente. Rezulta-tele obinute documenteazo prevalendestul demare a valorilor crescute ale AST i GGT la paci-enii cu DZ2 nou diagnosticat (18,06%, respectiv28,2%) precum i asocierea dintre acestea i com-ponentele SM. Dei valorile ALT nu au fost sem-
nificativ mai crescute la pacienii cu DZ2 i SM fa-de cei frSM, acestea s-au corelat cu numrulcriteriilor SM ndeplinite de ctre o persoan, ceeace subliniazasocierea cu tulburri metabolice maicomplexe. Nivelul ALT a fost mai mare la brbaifade femei i am descris o asociere negativ aALT cu vrsta, n concordancu alte date din lite-ratur(19,20). Valorile ALT s-au corelat pozitiv cuCA, element central al SM, excesul ponderal fiindraportat n alte studii ca factor de risc pentru cre-terea ALT (21). Persoanele din quartilele superioare
de ALT au avut valori semnificativ mai mari pentruTG i raport TG/HDL-colesterol i mai mici pentruHDL-colesterol, ceea ce aratlegtura dintre ALTi dislipidemia aterogen, precum i pentru insulin,proinsulini HOMA-IR. Rezultatele noastre suntn concordancu cele din literatur, care au artatc ALT a fost semnificativ asociat cu insulinore-zistena la persoanele cu SM (22) i la pacienii cuDZ2 nou descoperit (23).
Nivelul GGT a fost semnificativ mai mare la pa-cienii cu DZ2 nou diagnosticat i SM comparativcu cei frSM i s-a corelat cu numrul de criteriiale SM. Asocierea mai bun a GGT cu SM lapacienii studiai ar putea fiexplicatfie prin prismancrcrii grase a ficatului pe care GGT so reflecteprobabil cu o mai mare acuratee, fie prin prismaimplicrii GGT n catabolismul extracelular al glu-tationului (24). GGT este astfel legatde cretereastresului oxidativ, ca marker nespecific. Prin acestmecanism GGT ar putea fimai strns corelat cu in-sulinorezistena i SM, ntruct este cunoscutim-
plicarea stresului oxidativ ca mecanism patogenic
ce leaginsulinorezistena de disfuncia beta celu-lar(25). Relaia dintre valorile GGT, obezitate iapariia SM a fost puspe seama acestui mecanism(26). De altfel, am documentat corelaia dintre GGTi insulinorezisten (evaluat prin insulinemie iHOMA-IR). Pe lngparametrii dislipidemiei atero-
gene, GGT s-a corelat i cu LDL-colesterolul, ceeace ar putea sugera un factor suplimentar de riscpentru BCV. GGT s-a corelat negativ cu adiponec-tina, observaie concordantcu alte date din litera-tur(27).
CONCLUZII
Rezultatele noastre documenteazasocierea din-tre ALT i GGT componentele clasice ale SM (nspecial HDL-colesterol sczut i TG crescute), dari cu insulinorezistena la persoanele cu DZ2 noudescoperit. AST este corelat cu distribuia de tipcentral a excesului de esut adipos (evaluat prinCA). n plus GGT se coreleaznegativ cu adipo-nectina. Determinarea acestor enzime hepatice esterecomandatla pacienii cu DZ2, ncde la debut,ca marker pentru SM i pentru identificarea unuisubgrup de persoane cu tulburri metabolice maicomplexe ce ar putea semnifica un risc cardiovas-cular mai mare.
MULUMIRI
Aceast lucrare a fost susinutde un grant alAutoritii Naionale Romne pentru Cercetaretiinific, CNCS-UEFISCDI, PN-II-ID-PCE-2011-3-0429. Mulumim doamnelor Manuela Mitui Janeta Tudosoiu de la laboratorul de cercetare alInstitutului Naional de Diabet, Nutriie i BoliMetabolice N.C. Paulescu pentru excelenta asis-tenacordatpe parcursul studiului.
1. Grundy S. Metabolic Syndrome: A Multiplex Cardiovascular Risk
Factor. Clin Endocrinol Metab 2007; 92: 399-404
2. Grundy S.M. Metabolic syndrome: connecting and reconciling
cardiovascular and diabetes worlds. J Am Coll Cardiol 2006;
47:1093-1100
3. Alberti K.G., Zimmet P., Shaw J. The metabolic syndrome: a new
worldwide definition. Lancet 2005; 366:1059-1062
4. Hanley A.J.G., Williams K., Festa A. et al. Liver Markers and
Development of the Metabolic Syndrome. The Insulin Resistance
Atherosclerosis Study. Diabetes2005; 54: 3140-31475. Pladevall M., Singal B., Williams L. et al. A Single Factor underlies
the Metabolic Syndrome: a Confirmatory Factor Analysis. Diabetes
Care2006; 29:113-22
6. Franzini M., Fornaciari I., Rong J. et al. Metabolic and
cardiovascular risk markers are important correlates of GGT fractions,
in particular of b-GGT. Correlates and reference limits of plasma
gamma-glutamyltransferase fractions from the Framingham Heart
Study. Clinica Chimica Acta2013; 417:19-25
7. Liu X., Hamnvik O.P.R., Chamberland J.P. et al. Circulating
alanine transaminase (ALT) and -glutamyl transferase (GGT), but not
fetuin-A, are associated with metabolic risk factors, at baseline and at
two-year follow-up: The prospective Cyprus Metabolism Study.
Metabolism2014; 63:773-782
8. Hwang A.C., Lin Y.C., Liu P.T. et al. Synergistic effect of gamma
glutamyltransferase and obesity on metabolic syndrome, independentof hepatic steatosis.Annals of Epidemiology2012; 22: 876-880
9. Schindhelm R.K., Dekker J.M., Nijpels G. et al. Alanine
aminotransferase and the 6-year risk of the metabolic syndrome in
Caucasian men and women: the Hoorn Study. Diabet Med 2007;
24:430-435
BIBLIOGRAFIE
-
7/23/2019 Relationship of Alanin Aminotransferase and -glutamyltransferase
6/6
REVISTAMEDICALROMN VOLUMULLXI, NR. 3, An 2014 201
10. Goessling W., Massaro J.M., Vasan R.S. et al. Aminotransferase
levels and 20-year risk of metabolic syndrome, diabetes, and
cardiovascular disease. Gastroenterology 2008; 135:1935-1944
11. Sookoian S., Pirola C.J. Alanine and aspartate aminotransferase
and glutamine-cycling pathway: their roles in pathogenesis of
metabolic syndrome. World J Gastroenterol. 2012; 18:3775-81
12. Schindhelm R.K., Diamant M., Dekker J.M. et al. Alanine
aminotransferase as a marker of non-alcoholic fatty liver disease in
relation to type 2 diabetes mellitus and cardiovascular disease.Diabetes Metab Res Rev 2006; 22:437-443
13. Lee D.S., Evans J.C., Robins S.J. et al. Gamma Glutamyl
Transferase and Metabolic Syndrome, Cardiovascular Disease, and
Mortality Risk The Framingham Heart Study.Arterioscler Thromb Vasc
Biol2007;27:127-133
14. American Diabetes Association Standards of medical care in
diabetes 2014. Diabetes Care 2014;37(Suppl. 1):S14-S80
15. Alberti K.G.M.M., Eckel R.H., Grundy S.M. et al. Harmonizing the
Metabolic Syndrome. A Joint Interim Statement of the International
Diabetes Federation Task Force on Epidemiology and Prevention;
National Heart, Lung, and Blood Institute; American Heart Association;
World Heart Federation; International Atherosclerosis Society; and
International Association for the Study of Obesity. Circulation
2009;120:1640-1645
16. Friedewald W.T., Levy R.T., Fredrickson D.S. Estimation of the
concentration of low-density lipoprotein cholesterol in plasma, without
use of the preparative ultracentrifuge. Clin Chem1972;18:499-502
17. Matthews D.R., Hosker J.P., Rudenski A.S. et al. Homeostasis
model assessment: insulin resistance and b-cell function from fasting
plasma glucose and insulin concentrations in man. Diabetologia
1985;28:412-9
18. Prati D, Taioli E, Zanella A et al. Updated definitions of healthy
ranges for serum alanine aminotransferase levels.Ann Intern Med
2002;137:1-9
19. Dong M.H., Bettencourt R., Brenner D.A. et al. Serum Levels of
Alanine Aminotransferase Decrease With Age in Longitudinal
Analysis. Clin Gastroentero Hepatol2012;10:285-290
20. Kim J., Jo I. Relationship between body mass index and alanine
aminotransferase concentration in non-diabetic Korean adults. Eur J
Clin Nutr2010;64:169-175
21. Jacobs M., van Greevenbroek M.M.J., van der Kallen C.J.H. et al.
The association between the metabolic syndrome and alanine
amino transferase is mediated by insulin resistance via relatedmetabolic intermediates (the Cohort on Diabetes and Atherosclerosis
Maastricht [CODAM] study). Metabolism2011;60:969-975
22. Zhang Y., Lu X., Hong J. et al. Positive correlations of liver
enzymes with metabolic syndrome including insulin resistance in
newly diagnosed type 2 diabetes mellitus. Endocr2010;38:181-187
23. Turgut O., Yilmaz A., Yalta K. et al. Gamma-glutamyltransferase is
a promising biomarker for cardiovascular risk. Med Hypotheses
2006;67:1060-1064
24. Ceriello A., Motz E. Is oxidative stress the pathogenic mechanism
underlying insulin resistance, diabetes, and cardiovascular disease?
The common soil hypothesis revisited.Arterioscler Thromb Vasc Biol
2004;24:816-823
25. Furukawa S., Fujita T., Shimabukuro M. et al. Increased oxidative
stress in obesity and its impact on metabolic syndrome. J Clin Invest
2004;114:1752-61
26. Kawamoto R., Tabara Y., Kohara K. et al. -Glutamyl transferase
and high-molecular-weight adiponectin levels are synergistically
associated with metabolic syndrome and insulin resistance in
community-dwelling persons. Metab Syndr Relat Disord2012;
10:83-91