Clara Pirri

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).

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.

Western Dietary Pattern and Sedentary Life: Independent Effects of Diet and Physical Exercise Intensity on NAFLD

Western Dietary Pattern and Sedentary Life: Independent Effects of Diet and Physical Exercise Intensity on NAFLD

Coffee, nutritional status, and renal artery resistive index.

Background: The relationship between nutrition and atherosclerosis is known, even dissociated from protein malnutrition. Cardiovascular impact of several nutrients is known; among them the action of coffee is still debated and cardiovascular effect of caffeine has been investigated without definite results. Objective: The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. Methods: This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided. Results: By multiple linear regression, fat-free mass (FFM), HOMA (positive relationship), and number of cups of coffee/day (negative relationship) account for 17.2% of the variance to RRI. By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ≥ 3.0), and renal insufficiency (GFR ≤ 90); coffee, assessed by number of cups/day, reduces risk. Conclusion: Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI.

Lifestyle Interventions, Insulin Resistance, and Renal Artery Stiffness in Essential Hypertension

The study investigates lifestyle and effective anti-hypertensive intervention in overweight-obese patients can influence insulin-resistance (HOMA-IR) and US Renal-Resistive-Index (RRI). After a 1-year interventional program (including a personalized Mediterranean diet, physical activity increase, smoking withdrawal counseling), 156 Essential Hypertension (EH) patients still have abnormal HOMA-IR, significantly higher in comparison to 159 control group patients. Body mass index (BMI) and cholesterol-high-density-lipoprotein improvement are the best predictors of a HOMA-IR decrease; RRI improves in EH according to lifestyle interventions, but no predictor to RRI is identified. Persistence of IR can be tentatively assumed as a steady sign, persistent also after extended lifestyle intervention in EH, further warranting more intensive dietary interventions.

Relationship of MTHFR gene polymorphisms with renal and cardiac disease.

AIM To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.

Echocardiography and NAFLD (non-alcoholic fatty liver disease)

UNLABELLED Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. PATIENTS AND METHODS 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. RESULTS LVMM/m(2) is significantly greater in NAFLD, 101.62±34.48 vs. 88.22±25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42±5.49 vs. 24.87±3.81; p<0.0001) and HOMA (2.90±1.70 vs. 1.85±1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear-Regression, NAFLD and unhealthy dietary profile are associated also in lean non-diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. CONCLUSION NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function.

ADV36 adipogenic adenovirus in human liver disease.

Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.