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Coracina, Anna (2009) Steatosi epatica non alcolica e diabete mellito tipo 2: studio dell'associazione tra grado di steatosi, fattori metabolici e alterazioni vascolari. [Tesi di dottorato]

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Abstract (inglese)

NAFLD (non alcoholic fatty liver disease) is defined by the presence of hepatic steatosis not associated with a significant alcohol intake nor to the assumption of specific drugs. It is frequently associated with diabetes, obesity and metabolic syndrome. Many authors support the concept that NAFLD is the hepatic manifestation of the metabolic syndrome, and that the insulin-resistance is the common soil in the pathogenesis. Although the natural history of this disease seems to be benign, an evolution toward steatohepatitis and cirrhosis, and a link between NAFLD and cardiovascular (clinical and subclinical) diseases, have been demonstrated. The objectives of this research were to evaluate prevalence and degree of steatosis in patients with type 2 diabetes and the metabolic syndrome (defined by ATP III criteria); to search for metabolic factors which are predictive for the degree of steatosis, and to evaluate the possible link between hepatic steatosis and anatomic vasculopathy (intima-media thickness – IMT and carotid plaques) and endothelial function (flow mediated dilation - FMD).
An observational study was performed among 60 type 2 diabetic patients (M/F 25/35) with metabolic syndrome afferent to our Diabetes Center. Steatosis was evaluated by means of semi-quantitative ecography (4 grades) as well as by an “objective quantitative” method based on the determination of liver/kidney ratio (6 grades). The presence of carotid plaques and the IMT measurement were evaluated by means of ecocolordoppler of the supra-aortic arteries. The endothelial function was evaluated by means of ecography as the vasodilatation induced by ischemia in the brachial artery (FMD). We measured anthropometric variables (body mass index, waist circumference), metabolic parameters (lipids, HbA1c, HOMA), inflammation markers
(hs-PCR, IL-6, TNFα), thrombogenic factors (fibrinogen) and an adipokine (leptin). We applied a statistical program (Ordered Probit) to evaluated the probability to predict the degree of steatosis by the combination of metabolic parameters. The prevalence of steatosis was 88% (33% mild steatosis, 33% moderate e 22% severe). IMT was 0.88 ± 0.23mm; 63% of patients had carotid plaques. FMD (calculated in 45 patients) was reduced with respect to normal values (5.02 ± 1.81%). We demonstrated a correlation between the degree of steatosis and BMI, waist, the number of metabolic syndrome’s factors, sex, diastolic pressure, insulinemia, HOMA, Hb1Ac, HDL-cholesterol (inverse), hs-PCR, fibrinogen, leptin. We didn’t demonstrate any correlation between steatosis, and medium and maximum IMT, the presence of carotid plaques and FMD. With multiple regression analysis HOMA and BMI levels were indipendent factors which predict hepatic steatosis (p 0.033). Using the combination of HbA1c, waist and insulinemia, a prediction of the exact grade of steatosis (± one steatosis grade) (evaluated by ecography) was obtained in 96.5% of cases. This study confirms that, in this population of diabetic patients with metabolic myndrome, NAFLD can be considered the hepatic manifestation of the syndrome since it correlates with HOMA and obesity. A high prevalence of increased IMT and of presence of carotid plaques, as well as a reduced FMD compared to general population, are also demonstrated, although they are not apparently linked with steatosis.

Abstract (italiano)

La steatosi epatica non alcolica (NAFLD) si definisce come la presenza di steatosi epatica in soggetti con modesto o assente consumo di alcol e mancata assunzione/esposizione a determinati farmaci o sostanze; è frequentemente associata al diabete, all’obesità e alla sindrome metabolica, tanto da essere considerata da molti autori come la manifestazione epatica della sindrome metabolica, avendo come fattore patogenetico comune l’insulino-resistenza. La storia naturale della NAFLD sembra benigna anche se può evolvere in steatoepatite e in cirrosi ed è stata dimostrata una correlazione tra NAFLD e patologie cardiovascolari (cliniche e subcliniche). Lo scopo dello studio è stato di valutare la prevalenza ed il grado di steatosi epatica in un gruppo di pazienti affetti da diabete mellito tipo 2 e sindrome metabolica (definita in base ai criteri dell’ATP III), di ricercare i fattori metabolici predittivi del grado di steatosi e di valutare l’eventuale relazione esistente tra steatosi epatica e vasculopatia anatomica (spessore medio-intimale carotideo [IMT] e placche carotidee) e funzionale (dilatazione flusso mediata [FMD]).
E’ stato eseguito uno studio osservazionale su 60 pazienti (M/F 25/35) affetti da diabete mellito di tipo 2 e sindrome metabolica afferenti al nostro servizio di Diabetologia. La presenza di steatosi è stata valutata mediante ultrasonografia sia con metodica soggettiva semiquantitativa (4 gradi) sia con metodica oggettiva quantitativa mediante la determinazione del rapporto fegato/rene (6 gradi). La ricerca di placche aterosclerotiche carotidee e la misurazione dell’IMT sono stati eseguiti con ecocolordoppler dei tronchi sovraaortici; la funzione endoteliale è stata valutata mediante ultrasonografia con valutazione della vasodilatazione indotta dall’ischemia a
livello dell’arteria brachiale (FMD). Sono stati misurati i parametri antropometrici (indice di massa corporea e circonferenza addominale), metabolici (assetto lipidico, HbA1c, HOMA), citochine infiammatorie (hs-PCR, IL-6, TNFα), fattori trombogenici (fibrinogeno) e adipochine (leptina). E’ stato utilizzato inoltre un programma statistico (Ordered Probit) in cui associando alcuni parametri metabolici viene predetta la probabilità del soggetto di appartenere ad una determinata classe di steatosi. La prevalenza di steatosi è risultata dell’88% (33% steatosi lieve, 33% moderata e 22% grave); l’IMT medio pari a 0.88 ± 0.23 mm; il 63% dei pazienti presentavano placche carotidee; l’FMD (calcolato su 45 pazienti) è risultato ridotto e pari a 5.02 ± 1.81%. Dividendo i pazienti per classi di steatosi abbiamo evidenziato una correlazione tra steatosi e BMI, circonferenza addominale, numero dei fattori della sindrome metabolica, sesso, pressione diastolica, insulinemia, HOMA, HbA1c, colesterolo-HDL (inversa), hs-PCR, fibrinogeno e log leptinemia. Non abbiamo dimostrato invece alcuna correlazione tra grado di steatosi e IMT medio o massimo, presenza di placche aterosclerotiche e valore di FMD. Con il modello di regressione multipla HOMA e waist sono risultati fattori indipendenti che influenzano il grado di steatosi epatica (p 0.033). Associando HbA1c, waist, insulinemia il modello statistico Ordered Probit mi predice il grado esatto o con un errore di un grado di steatosi soggettiva (valutato all’ecografia) nel 96,5% dei casi.
Questo studio conferma che nei nostri pazienti diabetici con sindrome metabolica la NAFLD correla strettamente con obesità e insulino-resistenza, può essere quindi considerata la manifestazione epatica della sindrome metabolica. E’ stata dimostrata un’elevata prevalenza di aumentato IMT e di placche carotidee, così come di riduzione dell’FMD rispetto alla popolazione generale, sebbene non sembra esservi correlazione con la steatosi epatica.

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Tipo di EPrint:Tesi di dottorato
Relatore:Avogaro, Angelo
Dottorato (corsi e scuole):Ciclo 21 > Scuole per il 21simo ciclo > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE DIABETOLOGICHE
Data di deposito della tesi:01 Febbraio 2009
Anno di Pubblicazione:Gennaio 2009
Parole chiave (italiano / inglese):NAFLD - DIABETE MELLITO TIPO 2 - SINDROME METABOLICA - IMT - FMD - ORDERED PROBIT
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/09 Medicina interna
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Clinica e Sperimentale
Codice ID:1843
Depositato il:01 Feb 2009
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