Guglielmo M. Trovato

Human obesity relationship with Ad36 adenovirus and insulin resistance.

Objectives:Infection with specific pathogens may lead to increased adiposity: a specific adiposity-promoting effect of Ad36 human adenovirus, without the involvement of neurological mechanisms, was reported. The aim of this study is to investigate whether non-diabetic patients with earlier Ad36 infection show greater degrees of overweight obesity, of Insulin Resistance (IR), assessed by homoeostasis-model assessment (HOMA), and/or of other related factors. Moreover, the relationship, if any, among these factors and an earlier Ad36 infection, and the hypothesis of a mechanism involving IR are investigated.Subjects:Ad36 seropositivity is assessed in 68 obese and 135 non-obese subjects, along with body composition, HOMA and laboratory investigations.Results:Age, body mass index (BMI), waist–hip ratio, blood pressure, insulin, HOMA and triglycerides are significantly greater in the Ad36 seropositive group. Ad36 seropositivity, along with HOMA and total cholesterol, explains BMI variance. No Ad36 seropositivity effect to HOMA could be envisaged by the same statistical model.Conclusion:A significant association of Ad36 seropositivity with obesity and with essential hypertension in human beings is suggested by our study; this association is mostly significant in women. Our results do not support that any Ad36 adipogenic adenovirus effect is operating in human obesity through an insulin-resistance-related mechanism. Ad36 seropositive status could also be a hallmark of a clinical-metabolic profile possibly preceding obesity and diabetes in non-obese patients.

Protective Role of Coffee in Non-alcoholic Fatty Liver Disease (NAFLD)

AimThe benefits of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma have been reported, but there is a lack of satisfactory explanation. Thus, this study aims to investigate if coffee use has any relationship with bright liver, measured by ultrasound bright liver score (BLS), in patients with non-alcoholic fatty liver disease (NAFLD), and which relationship, if any, is present with BMI and insulin resistance.MethodsThis study was performed on 245 patients, 137 with NAFLD and 108 controls. Coffee drinking was defined according to the absolute number of cups of coffee (only espresso coffee), and also graded as 1 (0 cups of coffee/day), 2 (1–2 cups of coffee/day) 3 (≥3 cups of coffee/day). Insulin resistance was assessed by homoeostasis model-insulin resistance index (HOMA).ResultsLess fatty liver involvement is present in coffee vs. non-coffee drinkers. Odds ratios show that obesity, higher insulin resistance, lower HDL cholesterol, older age and arterial hypertension are associated with a greater risk of more severe BLS; to the contrary, coffee drinking is associated with less severe BLS. In the multiple logistic regression (MLR) model, number of cups of coffee, HOMA and BMI account for 35.8% of the variance to BLS. Coffee use is inversely associated with the degree of bright liver, along with insulin resistance and obesity, which, to the contrary, are directly associated with greater likelihood and severity of bright liver appearance.ConclusionsA possible opposite, if not antagonistic, role of coffee with regard to overweightness and insulin resistance, similar to that reported in hepatocarcinoma and cirrhosis, is envisaged in the natural history of NAFLD.

Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease

Aims: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non‐alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR).

Behavior, nutrition and lifestyle in a comprehensive health and disease paradigm: skills and knowledge for a predictive, preventive and personalized medicine.

Health and disease of individuals and of populations are the result of three groups of risk factors: genetics, environment and behavior. Assessment, interventions and tailored changes are possible with integrated approaches more effective if respectful of individuals and different cultures. Assessment tools and integrated interventional strategies are available, but widespread knowledge, skills and competence of well trained individual Medical Doctors still lack. Mediterranean diet is an appropriate reference paradigm because encompasses consistent research background, affordable sustainability, widespread comprehensibility and attractiveness inside a cultural framework of competences and skills in which the Medical Doctors can personally manage the need of prediction (early diagnosis), prevention (intervention on healthy persons) and tailored therapy and follow-up for patients. This profile is flexible and adjustable according to specific needs and preferences due to different economic and ethno-cultural milieus. It can enhanced through on-site/e-learning Continuous Medical Education (CME), by training and using friendly and affordable equipments.

Mediterranean diet and non-alcoholic fatty liver disease The need of extended and comprehensive interventions

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is mostly related to increased BMI and sedentary life, even if it not directly attributable only to these or to single specific factors. Unhealthy lifestyle and obesity are the most probable causes, also in non-diabetic and without alcohol abuse patients, even if lean individuals can be involved. NAFLD treatment is currently warranted and driven by comprehensive lifestyle intervention, a valuable objective that is more often wished for than actually achieved. The aim is to re-assess the effectiveness of an intervention focused to increase the Adherence to Mediterranean Diet Score (AMDS) and the level of physical exercise, investigating the factors associated with failure and reporting the time that must elapse before such intervention becomes effective. METHODS The study included 90 (F 46, M 44) non-alcoholic non-diabetic patients, aged 50.13 ± 13.68 years, BMI 31.01 ± 5.18 with evidence of fatty liver by ultrasound. RESULTS A significant decrease of Bright Liver Score (BLS) was observed only after 6 months of intervention: differently, at the first and third month of monitoring fatty liver changes were still not significant. By a multiple linear regression model Adherence to Mediterranean Diet change (p:0.015) and body mass index changes (p:<0.0001) independently explain the variance of decrease of fatty liver involvement (R2 = 0.519; p < 0.0001). CONCLUSION Adherence to Mediterranean Diet is a significant predictor of changes in the fat content of the liver in overweight patients with NAFLD. The effect of the diet is gradual and favorable and it is independent of other lifestyle changes.

Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study

Background: Nonalcoholic fatty liver disease (NAFLD) because of its association with obesity, diabetes and insulin resistance (IR), is the hepatic expression of metabolic syndrome. Exercise and nutritional intervention can improve and prevent these inter‐related conditions; the relationships between the degree of IR and ultrasound (US) morphological post‐interventional changes are not defined.

Insulin resistance in postmenopausal women: concurrent effects of hormone replacement therapy and coffee

Background In postmenopausal women, an increase in insulin resistance is associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Hormone replacement therapy (HRT) can reduce insulin resistance and coffee use is reported to decrease the incidence of diabetes. The aim of our study was to assess possible concurrent effects of HRT and espresso coffee intake on insulin resistance and on interdependent nutritional and clinical features. Methods A total of 478 healthy postmenopausal, non-diabetic women (aged 54.5 ± 4.2 years) were studied: 360 had been on HRT for at least 2 years and 118 were not treated. Insulin resistance was assessed by a conventional homeostasis model (HOMA-IR). Results Insulin resistance is directly related to body mass index (p < 0.0001), and not with age and blood pressure; hypertensive menopausal women have a slightly higher body mass index but the same degree of insulin resistance as normotensive women. Women on HRT show lower insulin resistance, but not lower prevalence of arterial hypertension. Coffee use is associated with a decrease in insulin resistance in non-obese women receiving HRT, but not in other subsets. Conclusions The combination of coffee consumption and HRT could lower insulin resistance in postmenopausal women. In overweight women, greater insulin sensitivity is associated with intake of espresso coffee and not with HRT; in normal weight women, only HRT is associated with lower insulin resistance.

Portal vein pulsatility ratio and heart failure

Heart diseases can alter liver volume, morphology, and circulation. The Doppler pulsatility of the portal vein and its pulsatility ratio (PR) have been reported as being closely associated with the right atrial pressure and with the New York Heart Association (NYHA) class. We examined the relationships between measurements of liver and spleen dimensions and blood flow in portal and hepatic veins, assessed noninvasively by Doppler sonography, and compared them with echocardiographic data.

Obesity-independent association of human adenovirus Ad37 seropositivity with nonalcoholic fatty liver disease.

Objective: Adenoviruses Ad36 and Ad37 increase adiposity in animals and are associated with obesity in humans; effects on the liver have been reported. The association of Adenovirus Ad36 seropositivity (Ad36+) with obesity but not with the severity of nonalcoholic fatty liver disease (NAFLD) has been previously shown. We investigate whether nondiabetic Ad37+ patients show a different prevalence of NAFLD and ultrasound Bright Liver score. Patients: A total of 268 adult nondiabetic patients (146 men, 122 women) were included after lifestyle counseling including a personalized Mediterranean diet, increase in physical activity, and smoking withdrawal. After an Ad37+/Ad36+ assay, overweight obesity, insulin resistance, C-reactive protein, and bright liver prevalence and severity were compared according to Ad37+. Results: Sixty-five of 268 patients were Ad37+ and 82/268 patients were both Ad37 seronegative (Ad37−) and Ad36−. The prevalence of obesity, defined as body mass index≥30, was not significantly different in Ad37+ (11/65; 16.9%) vs. Ad37− (15/82; 18.2%) patients; Bright Liver was present in 22/65 (33.8%) Ad37+ patients vs. 13/82 (15.8%) Ad37− patients (P<0.019). By odds ratio (OR), a consistent risk for NAFLD was associated with Ad37+, greater insulin resistance, and C-reactive protein. By a predictive multiple linear regression model, 40.0% of variance toward NAFLD and 50.4% toward the severity of Bright Liver score was explained significantly and independently by Ad37+ and by body mass index. Conclusions: Ad37+ status in nondiabetic patients on an appropriate diet is significantly associated with NAFLD; because fatty liver improves even without weight loss by a “healthy” diet, and not only by lower food caloric intake, Ad37+ may be an adjunctive hallmark of an unfavorable clinical-metabolic profile, if not a causative factor of NAFLD.

4Ps medicine of the fatty liver: the research model of predictive, preventive, personalized and participatory medicine-recommendations for facing obesity, fatty liver and fibrosis epidemics.

Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin resistance are displayed along with recommendations and position points. Evidences and practice can get sustainable and cost-benefit valuable outcomes by participatory interventions. These recommendations can be enhanced by comprehensive research projects, addressed to societal issues and innovation, market appeal and industry development, cultural acceptance and sustainability. The basis of participatory medicine is a greater widespread awareness of a condition which is both a disease and an easy documented and inclusive clue for associated diseases and unhealthy lifestyle. This model is suitable for addressing prevention and useful for monitoring improvement, worsening and adherence with non-invasive imaging tools which allow targeted approaches. The latter include health psychology and nutritional and physical exercise prescription expertise disseminated by continuous medical education but, more important, by concrete curricula for training undergraduate and postgraduate students. It is possible and recommended to do it by early formal teaching of ultrasound imaging procedures and of practical lifestyle intervention strategies, including approaches aimed to healthier fashion suggestions. Guidelines and requirements of research project funding calls should be addressed also to NAFLD and allied conditions and should encompass the goal of training by research and the inclusion of participatory medicine topics. A deeper awareness of ethics of competences in health professionals and the articulation of knowledge, expertise and skills of medical doctors, dieticians, health psychologists and sport and physical exercise graduates are the necessary strategy for detectin a suboptimal health status and achieving realistically beneficial lifestyle changes. “The devil has put a penalty on all things we enjoy in life. Either we suffer in health or we suffer in soul or we get fat” (Albert Einstein); the task of medical research and intervention is to make possible to enjoy life also without things that make sufferance in health and souls and which excessively increase body fat.