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Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized clinical condition associated with features of metabolic syndrome and having insulin resistance as the underlying metabolic defect. Reduced insulin sensitivity favors the accumulation of free fatty acids and triglycerides within the hepatocytes, resulting in hepatocellular damage that may be self-maintaining and progressive. As the disease stems from excess calorie intake and/or low levels of physical activity, the correction of unhealthy lifestyles is the first line of approach to any prevention and treatment strategy. Patients are invited to modify their habits starting a restricted calorie dietary program associated with regular physical exercise, which should be maintained lifelong. Prescriptive diets are effective for short-term weight loss, but making patients increase and maintain their daily physical activity is hard to achieve. Only behavioral treatment can give patients the practical instruments to reach their eating and activity targets, incorporate them into their lifestyle, and maintain the results for long periods and possibly indefinitely. Very few studies have tested the effects of a behavioral approach in NAFLD patients, and adequate long-term trials having histology as an outcome measure have not been carried out so far. Future studies should test the potential of behavior treatment to restrict NAFLD progression to fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Given the difficulties of implementing lifestyle modifications in adults, healthy lifestyle habits should be promoted in children as part of prevention programs to reduce the future burden of liver disease of metabolic origin.

OBJECTIVE: To study the mechanism(s) linking insulin resistance (IR) to hepatic fibrosis and the role of the epithelial component in tissue repair and fibrosis in chronic hepatitis C (CHC). DESIGN: Prospective observational study. SETTING: Tertiary care academic centre. PATIENTS: 78 consecutive patients with CHC. MAIN OUTCOME MEASURES: IR, calculated by the oral glucose insulin sensitivity during oral glucose tolerance test; necroinflammatory activity and fibrosis, defined according to Ishak's score; steatosis, graded as 0 (66%). To evaluate the role of the epithelial component in tissue repair and fibrosis, the expansion of the ductular reaction (DR) was calculated by keratin-7 (CK7) morphometry. Nuclear expression of Snail, downregulation of E-cadherin and expression of fibroblast specific protein-1 (FSP1) and vimentin by CK7-positive cells were used as markers of epithelial-mesenchymal transition in DR elements. RESULTS: IR, the degree of necroinflammation and expansion of the DR (stratified as reactive ductular cells (RDCs), hepatic progenitor cells and intermediate hepatobiliary cells according to morphological criteria) were all associated with the stage of fibrosis. Nuclear Snail expression, E-cadherin downregulation and vimentin upregulation were observed in RDCs. By dual immunofluorescence for CK7 and FSP1, the number of RDCs undergoing epithelial-mesenchymal transition progressively increased together with the necroinflammatory score. By multivariate analysis, total inflammation and insulin resistance were the only factors significantly predicting the presence of advanced fibrosis (Ishak score ≥3) and the expansion of RDCs. CONCLUSION: This study indicates that IR is associated with the degree of necroinflammatory injury in CHC and contributes to hepatic fibrosis by stimulating the expansion of RDCs that express epithelial-mesenchymal transition markers.

Background & Aims: Increased visceral adiposity is considered the hallmark of the metabolic syndrome, whose hepatic manifestation is nonalcoholic fatty liver disease (NAFLD), although a subset of patients does not have visceral obesity. Our study aimed to compare metabolic alterations and liver damage in patients with NAFLD with and without visceral obesity. Methods: Four hundred and thirty one consecutive patients with liver biopsy-confirmed NAFLD were divided in three groups according to waist circumference, the simplest surrogate marker of visceral obesity. One hundred and thirty three patients (31%) had a waist circumference =2 were not associated with visceral adiposity. Alanine aminotransferase (ALT), ferritin, HOMA-IR >4, and severe steatosis were independently associated with NASH, whereas ferritin and impaired glucose tolerance were associated with fibrosis. Conclusions: Patients with normal waist circumference, despite milder metabolic alterations, may have NASH and are at risk of developing fibrosis, suggesting that once NAFLD is present, visceral obesity is not a major determinant of liver damage severity.

All over the world obesity represents a social and medical emergency. The obesity epidemic is particularly alarming in young age, as overweight or obese children and teen-agers are likely to become obese adults. Overweight and obesity in childhood and in adolescence can be ascribed to genetic factors as well as to socio-environmental factors peculiar to the principal contexts of life. All over the world, public institutions are taking action to break this vicious circle. Also in Italy, national, regional and local projects have been developed to favor healthy lifestyles in children, following a prevention model integrating ‘macro’ actions (of political and social nature) with educational interventions directed to the ‘micro’ environment of individual subjects. In this report, we revise the literature in the area of healthy life-style promotion in childhood, focusing on the results of a few Italian programs on the nutritional and physical habits of children. The main purpose was to demonstrate whether interventions aimed at increasing physical activity could produce significant changes in children’s behavior, as well as awareness about the needs of healthy choices in the family.

Viral infections and the metabolic syndrome may coexist in several individuals, due to the large prevalence of obesity and type 2 diabetes mellitus (T2DM). Antiviral therapy has changed the natural history of chronic viral hepatitis, but viral infection may remain undiagnosed in the absence of systematic screening. We determined the prevalence of HBV and/or HCV infection in an Italian cohort with T2DM (859 consecutive patients, 413 females) in three Italian centers: Turin, Bologna, and Naples. Screening for viral disease was coupled with the determination of parameters of metabolic syndrome. Fourteen patients were HBsAg-positive, 51 anti-HCV with a prevalence of genotype-1 infection in 58% of cases. Thirty cases had newly diagnosed viral markers, only one-third had already-diagnosed liver disease, 16 were being followed-up by a Liver Unit, and 9 cases had received antiviral treatment. Patients with viral markers had higher liver enzyme levels in comparison with virus-negative patients (P < 0.0001), whereas the prevalence of the metabolic syndrome was similar in the 2 groups. A positive correlation between BMI and alanine aminostransferase levels was only present in virus-negative cases, where the probability of enzyme levels above the upper limit of normal increased by 5% for unit of increase in BMI (OR: 1.05; 95% CI: 1.003–1.100, P = 0.037). In conclusion, the prevalence of HBV and HCV is non-negligible in patients with T2DM, but these cases may long remain undiagnosed. Elevated liver enzymes might be frequently disregarded in diabetes Units and ascribed to metabolic syndrome, thus excluding T2DM patients from specific disease-modifying antiviral treatment for hepatitis.

Large weight losses are rarely achieved through non-surgical procedures, but are also possible without professional help. A massive weight loss may be complicated by the development of an eating disorder psychopathology, followed by weight regain. We report the case of a male patient with super obesity (BMI, 86.2 kg/m(2)), who achieved a massive weight loss (170 kg in 2 years) largely without professional help and without surgery. The final body weight (∼ 100 kg; BMI, 32.6) has now been maintained for nearly 2 years. After weight loss, the patient had massive skin redundancy in several areas including the breasts, arms, abdomen, back, and thighs and a true body weight probably in the normal range. All laboratory tests were normal, with the exception of low free testosterone. Sonographic examination showed gall bladder microlithiasis. No eating disorders and other axis I and axis II psychiatric disorders were present. The case illustrates how much weight loss and weight-loss maintenance can be exceptionally achieved without surgery and without developing an eating disorder of clinical severity or other psychiatric disorders.

Aims/hypothesis: To estimate the prevalence and the direct cost of pharmacologically-treated diabetes in Italy. Methods: The ARNO observatory database, containing the 20-year medical prescriptions of over 10 million Italian people, was used. Ten-year longitudinal data were available in 22 Local Health Districts (LHD). Subjects were classified as having diabetes when prescribed glucose-lowering drugs (oral agents or insulin) (311,979 individuals in 2006). The direct cost was calculated as the sum of drug use, financial compensation by LHD for the inpatient (hospital DRG) and outpatient activities (consultations, laboratory tests, radiology, etc.), all regulated by government contracts. Individuals with diabetes were compared with pharmacologically-treated subjects without diabetes, pair-matched for age, sex and general practitioner. Results: In the 10-year period, the prevalence of pharmacologically-treated diabetes increased from 3.08% to 4.45% (P for trend

Gli incretino-mimetici (exenatide) e gli inibitori della dipeptidil-peptidasi (DDP-4) (sitagliptin e vildagliptin) sono nuovi farmaci, attualmente disponibili in Italia, sviluppati per il controllo della glicemia in pazienti con diabete tipo 2. Un sistema di monitoraggio è stato attivato dall’AIFA per valutare i reali vantaggi in termini di efficacia e di sicurezza di questi farmaci altamente innovativi. L’analisi dei dati raccolti dal monitoraggio ha sostanzialmente confermato ciò che è emerso dagli studi pre-registrativi. L’exenatide si è dimostrata in grado di migliorare il compenso metabolico e di indurre un calo ponderale in soggetti con diabete tipo 2. E’ risultato essere un farmaco sicuro con effetti collaterali di lieve entità principalmente a carico dell’apparato gatro-intestinale e tendenti a scomparire con il protrarsi della terapia. L’ipoglicemia è risultata un evento molto raro, osservato quando l’exenatide era usata in terapia di associazione con sulfaniluree. Gli inibitori della DDP-4 hanno dimostrato una riduzione significativa dell’Hb-glicata (lievemente inferiore rispetto all’exenatide) ed un effetto complessivamente neutro sul peso corporeo. Si sono dimostrati farmaci ben tollerati, anche in soggetti in età avanzata, con bassissimo rischio di ipoglicemia. Dato anche l’alto costo saranno necessari ulteriori approfondimenti per definire meglio la tipologia del paziente che può usufruire di questi farmaci e i possibili effetti di queste molecole sui fattori di rischio cardiovascolare e sulle complicanze micro- e macro-angiopatiche. Interessante sarà confermare in vivo le capacità rigenerative e proliferative di queste molecole sulla beta-cellula.

The most extensive and thoughtful description of the symptoms associated with underweight and dietary restrictions, traditionally called “starvation symptoms”, was given by Keys et al. in 1950 in their classic book The Biology of Human Starvation. The individual reactions to dietary restrictions and to weight loss were heterogeneous among the men participating in the study. However, in most cases the participants experienced dramatic effects, developing abnormal attitudes and behaviors related to food and eating and various psychosocial and physical changes. The most frequent starvation symptoms reported by underweight eating disorder patients are preoccupation with thoughts about food and eating, irritability, mood changes, sleep disturbances, social withdrawal, weakness, gastrointestinal discomfort, cold intolerance, impaired concentration, apathy, and heightened satiety. The interaction of eating disorder psychopathology with starvation symptoms seems to stimulate further dietary restriction by undermining the person’s sense of being in control over their eating, shape, weight, or themselves in general. In addition, some eating disorder individuals interpret their starvation symptoms as a positive sign of being in control and as evidence that they are working hard to achieve their goal of controlling eating, shape, and weight. The knowledge of starvation symptoms and how they interact with eating disorder psychopathology have important implications both for understanding and treating eating disorders.

La steatosi epatica non alcolica (Nonalcoholic fatty Liver Disease, NAFLD), manifestazione epatica della sindrome metabolica, strettamente associata ad obesità e diabete, è patologia epatica che riconosce come meccanismo patogenetico l’insulino-resistenza, sia a livello dell’intero organismo, sia più specificamente epatica. La steatosi, definita per un accumulo di trigliceridi nel fegato superiore al 5-10% del suo peso, è variamente associata a fibrosi e necroinfiammazione, realizzando il quadro della steatoepatite non-alcolica (Non-Alcoholic Steatohepatitis, NASH), la fibrosi e la cirrosi. Attraverso questa via metabolica una percentuale non irrilevanti di pazienti giunge all’insufficienza epatica terminale; circa il 10-15% dei soggetti in lista di trapianto di fegato nella varie strutture potrebbero essere giunti ad una insufficienza epatica terminale attraverso questo via. Il riconoscimento di questa patologia come problema importante di salute ha condotto a verificare la possibilità che, accanto agli effetti negativi dell’eccesso ponderale, la progressione della patologia potesse essere sostenuta da errati comportamenti alimentari e/o dalla sedentarietà. Per quanto riguarda l’apporto alimentare, i soggetti con NAFLD si caratterizzano per un eccessivo apporto di grassi saturi e sopratutto di carboidrati raffinati, che vengono convertiti a trigliceridi all’interno del fegato. Una serie di studi condotti da un gruppo di ricerca finlandese ha estesamente dimostrato l’esistenza di fattori genetici che possono condizionare gradi diversi di steatosi in presenza di simile eccesso ponderale, un effetto diretto di una dieta sperimentale ricca di grassi sul contenuto in trigliceridi del fegato, sul quadro di insulino-resistenza globale ed epatica, ed infine sul profilo biochimico.

We aimed to test the effects of a psychological support program on the psychological distress, mood, and quality of life of well-educated individuals with type 1 diabetes. A newly developed support program was offered to 60 patients with type 1 diabetes on intensive insulin treatment, previously enrolled in group-care educational programs. Thirty-three subjects participated (experimental group, in groups of 8–12 subjects); 22, who postponed their entry, were used as controls. The program consisted of 7 weekly work sessions of 2 hours chaired by a psychologist and covered aspects of daily living with diabetes using role-playing, metaplan, and problem solving. At baseline and approximately 6 months later, all participants completed a battery of questionnaires, and the differences between the experimental and the control group were analyzed by repeated-measurements ANOVA. In response to the psychological support program, subjects in the experimental group reduced their depressive mood (Beck Depression Inventory and depression scales of the Psychological Well-Being Index) and anxiety (Self-rating Anxiety Scale), improved disease-specific quality of life (Symptom and Well-Being scales of the Well-Being Enquiry for Diabetes), increased their internal and decreased their external locus of control. These changes were accompanied by a 0.3% decrease in glycosylated hemoglobin, whereas no significant changes were observed in the control group (ANOVA, P = 0.032). These results underline the importance of psychological aspects in individuals with type 1 diabetes; treating the psychological aspects related to the disease may be as important as medical control in order to improve living with diabetes.

Background/Aim: To test the short-term clinical usefulness of venesection associated with lifestyle counselling as against counselling alone on insulin resistance and liver enzymes in subjects with non-alcoholic fatty liver disease (NAFLD), using a propensity score approach. Methods: We carried out a 6- to 8-month observational analysis of 198 NAFLD patients in three Italian referral centres (79 venesection and 119 counselling alone). Insulin resistance was measured by the homeostasis model assessment (HOMA) method. Logistic regression was used to identify factors associated with normal HOMA and normal alanine aminotransferase (ALT) at the end of observation. The results were adjusted for the propensity score to be enrolled in the venesection programme, based on clinical and laboratory data, including common HFE polymorphisms and liver biopsy (available in 161 cases). Results: After adjustment for propensity and changes in BMI, venesection was significantly associated with normal HOMA [all cases: odds ratio (OR) 3.00; 95% confidence interval (CI) 1.51–5.97; cases with histology: OR 2.29; 95% CI 1.08–4.87] and ALT within normal limits (all cases: OR 2.56; 95% CI 1.29–5.10; cases with histology: OR 2.81; 95% CI 1.20–5.24). The results were confirmed in an analysis of 57 pairs matched for propensity, where venesection similarly increased the probability of normal HOMA (OR 3.27; 95% CI 1.16–7.84) and normal ALT (OR 5.60; 95% CI 2.09–15.00). Similar data were obtained in the subset of cases with normal basal ferritin (

Background and aim To investigate the hepatic expression of retinol-binding protein-4 (RBP4) in chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) patients, and its association with biochemical and histological patterns of liver damage. Materials and methods Sixty-six genotype 1 CHC and 32 NASH patients were tested for hepatic RBP4 expression. Liver expression at immunostaining was scored as 0 (slight), 1 (mild), 2 (moderate), and 3 (intense). In addition, the mRNA and the quantitative protein expressions of RBP4 were tested by PCR and by western blot, respectively, in 12 NASH and 28 CHC patients. Twelve subjects undergoing elective cholecystectomy served as controls. Results Ten (31%), 16 (50%) and 6 (19%) NASH patients, and 21 (32%), 31 (47%) and 14 (21%) CHC patients had scores of 1, 2 and 3, respectively. All control subjects scored 0. In both CHC and NASH liver RBP4 scores were directly related to western blot ( p = 0.001 and p = 0.03), not to mRNA expression ( p = 0.77 and p = 0.40). Older age (OR, 1.07; 95%CI, 1.01–1.13), RBP4 score (4.26; 1.27–14.21) and HOMA (2.26; 1.15–4.42) were independently associated with steatosis ≥10% in CHC patients. In NASH lobular inflammation (OR, 3.77; 95%CI, 1.01–24.22) and RBP4 score (4.87; 1.003–23.65) were the only risk factors for fibrosis ≥2 at logistic regression analysis. Conclusion Hepatic storage of RBP4, unrelated to its expression, could cause liver damage both in NASH and CHC.

The possibility that lifestyle changes may be shared by the family members of subjects with obesity attending cognitive-behavioral treatment (CBT) for weight loss has been scarcely evaluated. The purpose of this study was to measure the changes in body weight, lifestyle habits, and stage of change toward physical activity in the family members of 149 subjects with overweight/obesity enrolled into a weekly group CBT for weight management in the years 2007-2008. 230 adult (aged 18 years) family members (129 spouses, 72 children (43 female, 29 male), 29 with a different family relationship) completed a self-administered questionnaire at baseline and soon after the end of the completion of their relatives’ program (approximately 6 months later). The questionnaire consisted of qualitative information regarding food choices, estimation of energy and food intake, self-report of height and weight, and motivation toward physical activity. At baseline, self-reported body mass index was normal in 115 cases, in the range 25 to 29.9 in 80 and >=30 in 35. Following CBT of their relatives, the family members significantly reduced their average daily energy intake (-232 kcal/day; P

Physical activity plays a major role in the development and management of obesity. High levels of physical activity provide an advantage in maintaining energy balance at a healthy weight, but the amount of exercise needed to produce weight loss and weight loss maintenance may be difficult to achieve in obese subjects. Barriers to physical activity may hardly be overcome in individual cases, and group support may make the difference. The key role of cognitive processes in the failure/success of weight management suggests that new cognitive procedures and strategies should be included in the traditional behavioral treatment of obesity, in order to help patients build a mindset of long-term weight control. We reviewed the role of physical activity in the management of obesity, and the principal cognitive-behavioral strategies to increase adherence to exercise. Also in this area, we need to move from the traditional prescriptive approach towards a multidisciplinary intervention.

A paradox exists in the relationship between nutrition and cancer. Excessive dietary intake of nutrients and decreased physical activity represent two modifiable factors responsible for cancer development, namely for cancers of the gastrointestinal (GI) tract, and the present epidemics of obesity and diabetes is likely to increase the incidence of GI and metabolically-derived liver in the next few years. At the same time, in subjects diagnosed with cancer, malnutrition represents a risk factor of poor outcome following surgical resection, as well as of increased toxicity following chemo- and radiotherapy. Any effort should be made to modify the current trend of obesity for cancer prevention, as well as to provide enteral or parenteral nutritional support in cancer patients, to cope with nutritional needs and prevent cancer-related cachexia

Introduction: The diagnostic algorithm in children with head injury remains uncertain. The National Emergency X-Radiography Utilization Study II (NEXUS II) recently proposed a new decision aid. We analyzed the data prospectively recorded in a local database to evaluate the sensitivity and specificity of the variables proposed by NEXUS II, by comparing with an Italian proposal. Methods: The clinical data of 2,391 children with head injury (0–10 years old) were prospectively collected, for an 8-year period. Any posttraumatic intracranial lesion was selected as the main outcome. The predictive ability of the selected variables was tested by the area under the receiver operating characteristic (ROC) curve. Results: Eighteen of the 2,391 children (0.7%) showed the presence of intracranial lesions on computed tomography scan; neurosurgical intervention was needed in only one subject and an unfavorable outcome at 6-month follow-up occurred in only two subjects. The ability to correctly predict intracranial lesions was higher for the Italian proposal (ROC area, 0.896; 95% confidence interval, 0.887–0.904) than the NEXUS II (ROC area, 0.741; 95% confidence interval, 0.666–0.817; Fisher’s exact test; p< 0.001). The individual variables of the Italian proposal were both more sensitive (100% vs. 89%) and more specific (79% vs. 59%). No lesions remained undiagnosed by the variables considered in the Italian proposal, whereas two cases with lesions would have been missed by the NEXUS II rule. Conclusions: In our setting, the variables selected by the Italian proposal had higher discriminating capacity for intracranial lesions than those proposed by the NEXUS II rule, in children with head injury. These results should be considered in children with head injury attending an emergency department of a general hospital.

Background/aimsThe aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance.Patients and methods702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients.ResultsThe ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD.ConclusionsThe ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

Hepatologists have some primary tasks to accomplish with their patients: (1) to eradicate or halt viral infections; (2) to stop alcohol abuse; (3) to prevent and, later, treat common life-threatening complications (ascites, variceal bleeding, encephalopathy); (4) to support liver function and keep patients under surveillance for the risk of liver cancer; and (5) to decide on the timing for possible liver transplantation. All these tasks point to reduced liver-related mortality as the ultimate target. The nutritional status has long attracted attention as a factor generally associated with outcome; the majority of studies indicate a poor nutritional status (protein–calorie malnutrition) as potentially associated with mortality risk.1 This was mainly the case of skid-row patients with alcoholic liver disease (ALD), whereas a large observational Italian study in subjects with cirrhosis indicated that 29% of females and 18% of males were over-nourished.2 The precise aetiology of liver disease was not clearly defined at that time, but in the same years it became clear that obesity and other metabolic alterations were per se potential causes of liver disease, following the seminal observation linking fatty liver to ‘cryptogenic cirrhosis’, via non-alcoholic steatohepatitis. We now know that non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome,3 a …

Introduzione Il diabete mellito tipo 2 presenta un’alta prevalenza nella popolazione, non più solo limitata ai Paesi occidentali, ed in progressivo aumento in rapporto all’epidemia di obesità. In Italia vi è poi un’alta prevalenza di malattie epatiche, il rapporto ad una notevole diffusione del virus dell’epatite C ed a problemi alcol-correlati. Questo rende ragione della frequente associazione delle due patologie, semplicemente legata al caso. Tuttavia, un’analisi attenta del fenomeno documenta una prevalenza maggiore di quanto atteso, a significare un’associazione non soltanto legata al caso, ma con precise implicazioni patogenetiche. Il diabete si associa ad un ampio spettro di patologie epatiche che vedono in primo luogo la steatosi epatica non alcolica (Non-Alcoholic Fatty Liver Disease, NAFLD) nelle sue varie forme di progressione, dalla steatoepatite non alcolica (Non-Alcoholic Steato Hepatitis, NASH), alla cirrosi epatica criptogenetica, fino al carcinoma epatico. In questo caso, i fattori determinanti sono comuni e da ricondursi all’obesità, alla sedentarietà, e all’insulino-resistenza, sia generale, sia specificamente epatica. Questo meccanismo è alla base della sindrome metabolica (SM), un cluster di patologie che comprende l’obesità viscerale, il diabete tipo 2, l’ipertensione arteriosa, la dislipidemia, ed ha come manifestazione epatica la steatosi. Meccanismi in parte diversi sono invece alla base della steatosi presente nelle amlattie epatiche da virus, particolarmente da virus C, ove un meccanismo virale diretto si somma ai problemi metabolici. D’altra parte, il fegato ha un ruolo importante nel metabolismo dei carboidrati poiché regola il valore della glicemia plasmatica attraverso la gliconeogenesi e la glicogenolisi, favorendo così lo sviluppo di insulino-resistenza, di alterata glicemia a digiuno, e di diabete franco in ogni condizione di danno epatico, di qualunque eziologia (un tempo noto come “diabete epatogeno”), fino a problemi specifici in alcune condizioni nella quali fegato e cellule beta-pancreatiche possono essere contemporaneamente interessate (es. emocromatosi familiare). Infine, per la sua posizione a cavaliere tra la circolazione generale e la circolazione portale, per la sua azione di clearance dell’insulina, per il metabolismo epatico delle lipoproteine che consente al fegato di regolare i livelli plasmatici di colesterolo e trigliceridi, la malattia epatica finisce per produrre effetti sui livelli circolanti di insulina, sulla sensibilità insulinica e sulla regolazione generale del metabolismo dei carboidrati. Tutto questo comporta importanti riflessi terapeutici, anche per il fatto che molti farmaci, per il loro metabolismo epatico, trovano difficile impiego nelle patologie epatiche avanzate. Nella gestione del paziente diabetico tipo 2 con malattia epatica è quindi sempre necessario un non-facile compromesso tra il controllo ottimale dell’assetto glico-metabolico e la preservazione/miglioramento del quadro epatico.

Udgivelsesdato: 2010-Jan-21 AIM: To investigate the effect of transjugular intrahepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients. METHODS: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA). Glucose and insulin were measured for the calculation of the homeostasis model assessment insulin resistance (HOMA-IR); liver function was measured by the galactose elimination capacity (GEC); the severity of liver disease was graded by model for end-stage liver disease (MELD). RESULTS: Porto-systemic gradient decreased after TIPS (6.0 +/- 2.1 mmHg vs 15.8 +/- 4.8 mmHg, P < 0.001). Patients were divided in two groups according to initial body mass index. After TIPS, normal weight patients had an increase in dry lean mass (from 10.9 +/- 5.9 kg to 12.7 +/- 5.6 kg, P = 0.031) and TBW (from 34.5 +/- 7.6 L to 40.2 +/- 10.8 L, P = 0.007), as well as insulin (from 88.9 +/- 49.2 pmol/L to 164.7 +/- 107.0 pmol/L, P = 0.009) and HOMA-IR (from 3.36% +/- 2.18% to 6.18% +/- 4.82%, P = 0.023). In overweight patients only FFA increased significantly (from 0.59 +/- 0.24 mmol/L to 0.93 +/- 0.34 mmol/L, P = 0.023). CONCLUSION: TIPS procedure is effective in lowering portal pressure in patients with portal hypertension and improves body composition without significant changes in metabolic parameters.

We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda. The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2-3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection. Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out. Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy. Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease. Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis patients should undergo periodic evaluation of cardiovascular risk and of advancement of their liver disease; those with nonalcoholic steatohepatitis-cirrhosis should be evaluated for early diagnosis of hepatocellular carcinoma.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

A better knowledge of the biochemical mechanisms implicated in the development and progression of nonalcoholic fatty liver disease, linking fatty liver to insulin resistance and the metabolic syndrome, has shifted the goal of treatment from a mere clearing of fat from the liver to a systematic treatment of metabolic risk factors for fatty liver. Any attempt to modify the "unhealthy" habits responsible for fatty liver requires an integrated approach, based on the cognitive theory of behaviour by a multidisciplinary team including physicians, psychologists, dieticians and physical exercise experts, and recent data demonstrate that this is feasible and effective. Whenever this goal is not attained, a treatment based on insulin-sensitizers remains the best option, to simultaneously tackle all metabolic alterations of the metabolic syndrome. However, in individual patients, both raised blood pressure and dyslipidemia need to be controlled, in order to reduce cardiovascular risk. In these areas, any attempt should be made to use of drugs less likely to induce a deterioration of glucose control. It remains to be determined whether these treatments are able to modify the natural history of nonalcoholic fatty liver disease in the long term.

OBJECTIVE We describe a maturity-onset diabetes of the young (MODY) case with mutations involving both HNF4A and HNF1A genes. RESEARCH DESIGN AND METHODS A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both the parents (father at age 50 years, mother at age 54 years) and the sister (at age 32 years, during pregnancy). RESULTS The genetic screening showed a double heterozygosity for the mutation p.E508K in the HNF1A/MODY3 gene and the novel variant p.R80Q in the HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister, and her two children carried the MODY1 mutation. CONCLUSIONS MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation and early need of insulin therapy to control hyperglycemia).

Objective:The clinical significance of diagnosing the night eating syndrome (NES) in obese individuals has not been clearly demonstrated. We aimed to test the effect of NES on weight loss outcome in obesity. Method:In an observational case-control study, we measured weight loss outcome in obese individuals with NES (32 cases) and 68 non-NES matched participants entering a weight-loss program. The diagnosis of NES was generated by a twostage assessment, including the Night Eating Questionnaire (screening test) and the Night Eating Syndrome History and Inventory. The program included a 21-day inpatient treatment based on a low-calorie diet, exercise, and psycho-educational groups, followed by a 6-month outpatient follow-up. Body weight, metabolic parameters, and questionnaires of psychopathology were assessed at baseline, at the end of the inpatient period and at the end of follow-up. Results:NES participants were only characterized by significantly higher scores of the Beck Depression Inventory and the Night Eating Questionnaire. The time course of weight loss did not differ between groups throughout the study period. Only eight NES participants were still classified as NES at study end. Discussion:The presence of NES does not affect weight loss outcome of an obesity treatment based on lifestyle modification. V C 2010 by Wiley Periodicals, Inc.

Udgivelsesdato: 2010-Jun-14 BACKGROUND: Nonalcoholic fatty liver disease is associated with insulin resistance and low adiponectin levels. Adiponectin circulates as high-, medium- and low-molecular weight complexes, possibly exerting different insulin-sensitising effects. AIM: We investigated adiponectin isoforms in nonalcoholic fatty liver disease in relation to liver disease severity and insulin resistance. PATIENTS AND METHODS: Total adiponectin and isoform distribution were measured in 54 biopsy-proven, non-diabetic nonalcoholic fatty liver disease subjects, divided according to their fasting and 120-min glucose levels during an oral glucose tolerance test, as well as in 44 matched healthy controls. Insulin resistance/sensitivity was estimated in nonalcoholic fatty liver disease by the homeostasis model assessment and the oral glucose insulin sensitivity during oral glucose tolerance test. Total adiponectin and adiponectin isoforms were determined by in-house assays. RESULTS: Total adiponectin was reduced in nonalcoholic fatty liver disease (5.32+/-1.85mg/L vs. 9.11+/-3.46mg/L), with a relative abundance of high-molecular weight (34% vs. 47%) and low-molecular weight adiponectin (16% vs. 19%), coupled with dearth of medium-molecular weight adiponectin (50% vs. 34%) (P

Objective: To explore the temporal trend of incidence, causes of injury and main characteristics of adolescent and adult subjects with mild head injury (MHI). Design: This study had a retrospective design. Setting: The study was conducted in a longitudinal database of an Italian Emergency Department (ED). Participants: The study comprised 19 124 consecutive subjects who visited and were managed within 24 h from the event, according to a predefined protocol for MHI from 1997 to 2008. Main outcome measures: Incidence, demography, cause of injury and characteristics of any posttraumatic intracranial lesion within 7 days from MHI. Results: The number of subjects with MHI decreased from 2019 per year (1997–1999) to 1232 per year (2006–2008; P for linear trend

The psychological effects of dieting and weight loss have been an area of controversy in obesity. As part of a large multicenter study involving 1944 obese subjects seeking treatment at Italian medical centers, we investigated the effects of weight loss on psychological distress and binge eating in 500 subjects remaining in continuous treatment at different centers with slightly different strategies (78.8% females; age: M = 46.2 years, SD = 10.8; BMI: M = 37.3 kg/m2, SD = 5.6). At baseline and after 12 months all subjects were evaluated by the Symptom CheckList-90 Global Severity Index (SCL-GSI) and by the Binge Eating Scale (BES). In both males and females, weight loss was associated with improved psychometric testing. Changes in SCL-GSI were associated with changes in BMI (ß = 0.13; t = 2.85; p < 0.005), after adjustment for age, gender, initial BMI and center variability. Similarly, BES changes were associated with BMI change (ß = 0.15; t = 3.21; p < 0.001). We conclude that in subjects compliant to follow-up a successful management of obesity, not directly addressing psychological distress, is associated with a significant improvement of both psychological distress and binge eating, linearly related to the amount of weight loss, independently of treatment procedures.

La terapia dell'obesità è un dilemma: a volte i risultati sono troppo facili, anche in assenza di qualsiasi razionale o professionalità. Qualsiasi individuo può perdere peso da solo e chiunque può mettersi a fare la professione, anche senza alcuna competenza. A volte, ed è quasi la regola, la situazione è talmente problematica che i pazienti obesi (e i loro medici) annoverano una tale successione di fallimenti da abbassare il livello dell'autoefficacia e quindi dell'autostima ("self-efficacy": processo cognitivo della percezione della propria competenza e abilità nel compiere una determinata azione). Si deve pertanto attivare un rapporto relazionale terapeutico a triangolo paziente-medico-malattia e ogni lato deve trovare la sua giusta dimensione e interazione. Risultati troppo facili generano eccessivi entusiasmi che non permettono alcuna riproduicibilità; il successo è destinato al fallimento per la ripresa del peso perduto. Le fortune commerciali della "diet industry" non hanno limite: in America si calcola che vengano spesi, ogni anno, 30 bilioni di dollari per il controllo del peso. Se i risultati sonmo problematici i pazienti sono obbligati a ricercare terapie aggressive, cruente e prescrittive e spesso si abbandonano alle frodi ed alle mistificazioni. Il risultato non è mai quello desiderato: ottenere, cioè, una migliore qualità della vita ed una migliore aspettativa per la riduzione del rischio di mortalità. La lezione della storia non è ancora definita. Pochi l'hanno imparata e poco viene insegnata dall'Accademia.

Lifestyle changes are considered first line treatment in type 2 diabetes, but very few data are available in the “real world” of diabetes units. We aimed to measure the effectiveness of moderate and high intensity interventions on weight loss, metabolic control and insulin use We report a prospective cohort study, carried out in 822 consecutive subjects with type 2 diabetes, first seen in a 4-year period in a diabetes unit of an academy hospital. Subjects were either treated with a sole prescriptive diet (Diet), or received an additional short-course Elementary Nutritional Education (4 group sessions - ENE) or an intensive Cognitive Behavioral Therapy (12-15 group sessions - CBT). The results were adjusted for the propensity score to be assigned different treatments, derived from logistic regression on the basis of age, gender, BMI, HbA1C, diabetes duration and insulin use at baseline. Main outcome measures were weight loss and weight loss maintenance, metabolic control, secondary failure to insulin use. Both structured programs produced a larger weight loss, and the adjusted probability of achieving the 7% weight loss target was increased. Similarly, both programs favoured metabolic control, irrespective of insulin use. After adjustment for propensity score, both ENE (hazard ratio, 0.48; 95% CI, 0.27-0.84) and CBT (hazard ratio, 0.36; 95% CI, 0.16-0.83) were associated with a reduced risk of de novo insulin treatment. We conclude that structured behavioural programs aimed at lifestyle changes are feasible and effective in the “real world” setting of a diabetes unit for the treatment of type 2 diabetes.

Nonalcoholic fatty liver disease has long been neglected by healthcare professionals unless cirrhosis develops; however, this disesae has now been shown to be a cause of poor health-related quality of life. The association of nonalcoholic fatty liver disease with chronic metabolic diseases and cardiovascular complications, however, makes it difficult to define a specific role for liver damage in the poor perceived health status of these patients.

La NAFLD è una malattia epatica di sempre più frequente rilievo in individui di tutte le età e di ogni razza, senza distinzione di sesso; rappresenta oggi la principale causa di malattia cronica epatica in molti Paesi. È generalmente associata ad obesità, diabete e dislipidemia, ma può presentarsi anche in soggetti magri e con normale tolleranza glucidica. Nella maggior parte dei casi è associata ad insulino-resistenza, che favorisce il deposito di lipidi anche al di fuori del tessuto adiposo. Alla sua patogenesi concorrono numerosi fattori: una possibile base genetica, stili di vita a rischio, lo stress ossidativo, la produzione di citochine. L’assenza di una franca sintomatologia porta alla diagnosi in modo occasionale per transaminasi alterate o fegato brillante all’ecografia, ma la conferma e la stadiazione della malattia si basano esclusivamente sulla biopsia epatica.

Background Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance seems to improve insulin sensitivity. We aimed to evaluate the time course of IR in response to antiviral therapy in non-diabetic, non-cirrhotic G1 HCV patients and to assess the effect of metabolic factors on sustained virological response (SVR). Methods A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was >2.7. All cases had a liver biopsy scored for staging, grading and steatosis. Anthropometric parameters and HOMA were re-evaluated at the end of antiviral therapy and at follow-up. Results SVR was achieved in 46 (55.4%) patients. By logistic regression, female gender (odds ratio [OR] 0.132, 95% confidence interval [CI] 0.33–0.529), γ-glutamyltransferase >50 IU (OR 0.217, 95% CI 0.066–0.720) and presence of steatosis (OR 0.134, 95% CI 0.028–0.654) were independent negative predictors of SVR, whereas low-density lipoprotein cholesterol >107 IU (OR 6.671, 95% CI 1.164–11.577) was a positive predictor of SVR. The proportion of patients with IR significantly decreased ( P=0.02) during antiviral therapy and at follow-up in patients achieving SVR. A similar trend, even if not significant, was observed in relapsers and non-responders. Conclusions In non-diabetic G1 HCV patients undergoing antiviral therapy, IR improved in all patients, independently of virological outcome. HCV viral clearance was an additional factor in IR improvement. Female gender, hepatic steatosis and other metabolic parameters, but not IR, were identified as negative predictors of SVR in this study.

Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU . minute(-1) . kg(-1)) coupled with infusion of tracers ([6,6-H-2(2)] glucose, [2 H-5]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25% lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal endogenous glucose production (EGP) was 20% higher (P = 0.011) and its suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P < 0.05) and interleukin-18 (P < 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation. (HEPATOLOGY 2009;50:697-706.)

Indirect methods for predicting the presence of esophageal varices (EV) in cirrhotic patients are not sensitive enough to be used as a surrogate for endoscopy. We tested the effectiveness of liver stiffness measurement (LSM) by transient elastography (TE) and the presence of insulin resistance (IR), a marker associated with fibrosis progression, in the non-invasive prediction of portal hypertension. One hundred and four consecutive patients with newly diagnosed Child A HCV cirrhosis underwent upper GI endoscopy to search for EV. Clinical, anthropometric, biochemical, ultrasonographic and metabolic features, including IR by the homeostasis model assessment (HOMA), and LSM by TE, were recorded at the time of endoscopy. EV were detected in 63 of 104 patients (60%). In 10 patients (16%) the EV were medium-large (≥ F2). By multivariate analysis presence of EV was independently associated with a low platelet count/spleen diameter ratio (OR 0.998; 95% CI; 0.996-0.999) and with a high HOMA score (OR 1.296; 95%CI; 1.018-1.649) but not with LSM (OR 1.009; 95%CI; 0.951-1.070). It is noteworthy that 9/10 patients with medium-large EV had a platelet/spleen ratio of < 792 and/or a HOMA of > 3.5. The independent association between low platelet/spleen ratio (OR 0.998; 95%CI; 0.996-1.000), high HOMA score (OR 1.373; 95%CI; 1.014-1.859) and presence of EV was confirmed in the sub-group of 77 non-diabetic subjects. Conclusions: In patients with Child A HCV cirrhosis, a low platelet/spleen ratio and a high HOMA score, regardless of diabetes, are the strongest independent predictors of the presence of EV. In this specific setting LSM seems not contribute to the diagnosis of portal hypertension.

OBJECTIVES: Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and higher stages of fibrosis in patients with CHC resulting from genotype 1 HCV (G1-HCV). METHODS: Two hundred one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Nondiabetic patients were defined as insulin resistant if HOMA-IR was >2.7. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis. RESULTS: Ninety-six patients were noninsulin resistant (group 1), 76 were insulin resistant without diabetes (group 2), and 29 were diabetic (group 3). At multivariate analysis, fibrosis of >/=3 was independently associated with high necroinflammatory activity (odds ratio [OR] 2.994, 95% confidence interval [CI] 1.422-6.098), low platelets (OR 0.994, 95% CI 0.981-0.999), low cholesterol (OR 0.987, 95% CI 0.976-0.998), high ferritin (OR 1.002, 95% CI 1.001-1.004), and a high prevalence of IR (OR 2.692, 95% CI 1.463-4.954). Diabetic patients were twice as likely to have severe fibrosis (60%) than those with IR but no diabetes (30%) (P= 0.006). The degree of steatosis and that of fibrosis were weakly associated with each other (P= 0.42). CONCLUSIONS: In subjects with CHC resulting from G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis, regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.

Objective: Underweight patients with eating disorder not otherwise specified without the over-evaluation of shape and weight (EDNOS-W) represent a diagnostic challenge. We aimed to evaluate their clinical characteristics and treatment outcome, compared with anorexia nervosa (AN) cases. Method: Eighty-eight consecutive patients (81 females; age range 13–50 years, 71 AN, and 17 EDNOS-W) were studied. The differential diagnosis of AN and EDNOS-W was based on the eating disorder examination. Results: Compared with AN, EDNOS-W cases had a milder eating disorder psychopathology, but no differences in anthropometric and clinical data. The response to inpatient cognitive behavioral treatment was good and similar between groups, and no differences in the dropout rate or time-to-dropout were observed. The normalization of body weight in EDNOS-W cases was not associated with the appearance of the over-evaluation of shape and weight. Conclusion: The data gives preliminary support to the proposal to include EDNOS-W in the diagnosis of AN. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008

Objective: Obesity treatment is finalized to increase physical and psychological health, by reducing body weight, but management of therapy should consider the baseline conditions. We tested the psychological profile of morbid obese patients seeking medical treatment, as a basis for developing more specific therapeutic protocols. Patients and methods: 135 consecutive patients with a BMI > 40 mg/kg2 admitted to an outpatient program of cognitive-behavioral treatment (CBT) were investigated. At enrolment, the patients filled in a series of self-administered questionnaires on binge eating (Binge Eating Scale, BES), depression symptoms (Beck Depression Inventory, BDI), obesity-specific quality of life (Obesity-Related Well Being-97, Orwell-97), and generic health-related quality of life (HRQL) (Psychological General, Well-Being, PGWB), where psychological distress is clustered in six domains related to mood states. Results: 27% of cases had a BES score ≥ 17, indicative of possible binge eating, and 13% had a BES ≥ 27, largely indicative of binge eating, with a higher prevalence in females. The BDI score was above normal in 30% of males and 45% of females, and 13% of females were in the range of moderate-severe depression. BES and BDI were significantly correlated with each other (r= 0.722; P < 0.001). Orwell-97 was much higher in females, and similarly the generic PGWB was indicative of a poorer HRQL in females. PGWB was positively associated with age, without any effect of BMI. The association with age was maintained in female (r = 0.290; P < 0.05), not in males (r = 0.038). Both the Orwell-97 and the PGWB were associated with both BES and BDI in both genders. Conclusions: Psychological distress is common and largely variable in patients attending CBT for morbid obesity. This data should be considered for individual treatment protocols, and should be compared with similar series of patients enrolled for bariatric surgery.

Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and the metabolic syndrome, where behavior therapy remains the primary treatment, simultaneously addressing all the clinical and biochemical defects. However, very few studies have tested the effectiveness of intensive behavior therapy in NAFLD, aimed at lifestyle modifications to produce stable weight loss by reduced calorie intake and increased physical activity. Searching the literature for studies testing weight loss and lifestyle modifications for the treatment of NAFLD, only 14 reports were traced where the entry assessment satisfied well-defined criteria. The final effectiveness was based on hard histological outcomes in 5 cases. All but 1 were pilot, uncontrolled studies or limited case series, and in general the details of treatment were scanty. In only 3 cases treatment was carried out along the guidelines of behavior treatment to reduce excess nutrition and increase exercise; in these cases, a remarkable effect on weight loss and an improvement in liver histology were reported. The principles of behavior therapy are presented in detail, to help physicians change their prescriptive attitude into a more empowerment-based approach. A brief section is also included on the practical aspects and public policies to be implemented at societal level to obtain the maximum effects in lifestyle changes. There is a need for multidisciplinary teams including dietitians, psychologists, and physical activity supervisors caring for patients with NAFLD. Alternatively, general practitioners and physicians working in gastrointestinal units should limit their intervention to engage patients with NAFLD before referral to specialized teams set up for the treatment of diabetes and obesity. Copyright © 2008 by the American Association for the Study of Liver Diseases

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and gamma-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34- 1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17-1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.

Per molto tempo la malattia epatica ad origine metabolica è stata sottovalutata come condizione di scarsa rilevanza clinica. Solo oggi si sta prendendo coscienza dell’importanza della patologia, in termini epidemiologici e clinici, anche in rapporto all’epidemia di obesità e diabete del mondo occidentale. L’importanza della NAFLD rimane comunque sottovalutata, se si considera come la presenza di una patologia epatica complichi spesso anche le malattie epatiche di altra eziologia (virus B e C, emocromatosi, malattie autoimmuni ed alcoliche), peggiorandone significativamente la prognosi e riducendo le prospettive terapeutiche. Vi è l’esigenza di trasferire percorsi strutturati di terapia cognitivo-comportamentale, specifici per il diabete e l’obesità, verso il trattamento multidisciplinare dei soggetti NAFLD (68). Vi è l’esigenza di attivare protocolli di sorveglianza epatologica in soggetti con NAFLD evoluta a fibrosi avanzata, per ridurre il rischio di giungere troppo tardivamente alla diagnosi delle complicanze più severe della malattia.

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance. We tested serum levels of RB4 to assess its link with steatosis in patients with genotype 1 (G1) chronic hepatitis C (CHC) or non-alcoholic fatty liver disease (NAFLD). Non-diabetic patients with CHC (n=143) or NAFLD (n=37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including insulin resistance by the homeostasis model assessment (HOMA). Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild

Backgound and Aims: We evaluated whether hyperinsulinemia and/or insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in nondiabetic subjects. Methods and Results: A database of hyperinsulinemic euglycemic clamp carried out with standard technique (40 mU per min per square meter of body surface area) in nondiabetic Italian subjects has been recently established. In this database we evaluated the relationships existing between fasting plasma insulin (FPI), glucose metabolized during clamp (M) and plasma levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure (BP) in nondiabetic subjects with fasting plasma glucose

Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed in patients having undergone liver transplantation (LTx). These alterations are probably multifactorial in origin, and cluster to generate a metabolic syndrome (MS), increasing the risk of cardiovascular events. We assessed the prevalence of MS (National Cholesterol Education Program-Adult Treatment Panel III criteria) in 296 LTx patients in the course of regular follow-up, at least 6 months after transplantation (median, 38 months). Several pre-LTx and post-LTx data were collected to identify the factors associated with the presence of MS. In a subset of 99 patients, insulin resistance was measured by the homeostasis model assessment. High blood pressure was present in 53% of cases, hyperlipidemia in 51%, high glucose in 37%, and enlarged waist circumference in 32%. Overall, MS (defined as 3 or more of the above features) was present in 44.5% of cases. Insulin resistance (homeostasis model assessment > 2.7) was observed in 41% of cases. Hypertension and hyperlipidemia were more frequent in subjects on cyclosporine than in tacrolimus-treated cases, whereas the type of immunosuppressive drug had no effect on the prevalence of diabetes, enlarged waist, and MS. In a logistic regression analysis, only pre-LTx body mass index (odds ratio, 1.20), body mass index increase (odds ratio, 1.18), and pre-LTx diabetes (odds ratio, 2.36) predicted MS; age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were removed from the model. Disorders related to MS are frequent in LTx patients, and are related to both pre-LTx conditions and to weight gain. Weight control is mandatory in LTx patients to prevent risk factors of premature atherosclerosis.

Premature, unilateral interruption of inpatient treatment of eating disorders (ED) is a key factor limiting success. We evaluated the role of personality dimensions (temperament and character) in predicting drop-out in 145 consecutive ED patients (133 females) admitted to a cognitive behavior inpatient treatment. Baseline assessment included anthropometry, the Eating Disorder Examination, the Beck Depression Inventory, the State-Trait Anxiety Inventory, and the Temperament and Character Inventory (TCI). Treatment was based on the new transdiagnostic cognitive behavior theory of ED, adapted for inpatient setting; it was manual-based and lasted 20 weeks (13, inpatients; 7, residential day-hospital). Thirty-four patients (23.4%) discontinued treatment. Dropouts had a lower education, a higher prevalence of separation or divorce in the family, and lower scores at TCI Persistence scale. After correction for age, gender and BMI, Persistence maintained a significant effect on drop-out (odds ratio, 0.77; 95% confidence interval, 0.61 – 0.98; P = 0.033), and the association was confirmed by Kaplan-Meier analysis (Log-rank Mantel-Cox, P = 0.025). Eating disorder patients with low Persistence are significantly less likely to complete inpatient treatment. The results may be used to adapt treatment according to the temperament of individual patients.