G. Fabio Martines

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.

Regular coffee: a magic bullet or a naked gun? Regular coffee but not espresso drinking is protective against fibrosis in NAFLD.

Hong Deng Department of Infectious Disease, The Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong Univers ity, Xi’an, China Zongfang Li⇑ Departme nt of Hepatology and Surgery, The Second Affiliated Hospital, College of Medicin e, Xi’an Jiaotong University, Xi’an, China Address: Departm ent of Hepatology and Surgery, The Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong Universit y, 157 Xi Wu Road, Xi’an, Shaanx i 710004, China. Tel.: +86 29 87678006; fax: +86 29 876786 34 *Correspondi ng author . E-mai l address : Izf2568 @gmail.com Letters to the Editor

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.

Teens' obesity, noise and sleep deprivation: A perverse liaison. Let's move beyond “movida”

To the Editor: The experimental study by Chapman et al. (1) elegantly demonstrates how acute sleep loss increases food purchasing behavior in men. Sleep deprivation is associated with obesity (2,3) and with failure in obesity treatment (4). Few information on larger cohorts of patients are available. Another valuable advancement is the experimental study, on an animal model, which demonstrates that exposure to noise induces sleep-deprivation in obesity-resistant rats, determining also greater food intake and body weight compared to controls (5). Noise is a prominent feature of the environment including noise from transport, industry, and neighbors, which is enhanced by nightlife activities. The term movida refers to particular situations of animation, entertainment, and youngsters’ nightlife within historical centers of most European towns. This is allowing free access of teens in residential pedestrian precincts-car limited access areas, used often as a no-controls frank zone. The perceived social alarm is only a component of the more substantial health damage, not only to inhabitants living in such City centers but, conceivably, to teen visitors whose “moving” enhances loud noise from night lo early morning. We are studying in an Italian City with 300,000 inhabitants, relationship of perceived exposure to six different types of environmental noise with symptoms (tinnitus, headache, and sleep duration) and road accidents in 789 youngsters (15–30 years, 325 m,464 f; years 22.04 6 3.94) coming from other areas or towns to movida. The studied environmental noise were: at home, at work/school, during night leisure time (movida), musical events, sport activity, public buildings, distinguishing noise from machines, human voices, and music. Noise perception is assessed by 1–10 Likert’s scales, sleep duration and time of falling asleep are recorded on weekly, single days, and related to specific activity basis. Alcohol, coffee, cigarette smoking, illicit and stimulating drugs habits, work and school achievements are also considered. The main aim of this preliminary study is to assess internal relationship of these measures which are also challenged versus BMI, overweight (BMI> 25 30), obesity (BMI 30) and versus underweight (BMI 18). Individual perception of abnormal body weight is studied as well. Sleep deprivation is related to nightlife hours spent within “movida” and is greater and more prevalent in obese teens, in which BMI is 22.8 6 3.3 versus 21.8 6 3.1. Excluding from the subsequent analysis the 47 underweight subjects (BMI< 18.0), prevalence of obesity is 98/426 in subjects with sleep deprivation versus 52/316 subjects without sleep deprivation (P< 0.05). Greater perceived noise is associated with a greater prevalence of tinnitus, reported by 133/789 subjects. By multiple linear regression analysis, gender and age balanced, hours of sleep (inversely), and hours spent in nightlife explain significantly the greater levels of BMI. Our results confirm what is convincingly demonstrated in the animal model by Mavanji et al. (5). In youngsters, noise and sleep associated to nightlife and movida are significant independent determinants of obesity, seemingly undermining healthier nutrition and adequate physical exercise habits. Both should be addressed to as health risk factors with appropriate prevention and intervention strategies. O

Mala-movida: Late bed-timing and wake-up induce malnutrition and underweight in youngsters

malnutrition. Alcohol intake, coffee, cigarette smoking, illicit and stimulating drugs habits, work and school achievements are also considered. Average sleep duration (hours) is 7.26 ± 1.17 (2–11 hours), bed timing 2.00 a.m. ± 1.18 0 (0–6 hours), bed waking up 9.15 0 ± 1.29 0 am (5–16 hours), with an average daily time spent within movida of 3.15 0 ± 2.29 0 (0–14 hours). There is a reverse correlation of BMI with the nightlife time, p40.001, with the waking-up hour, p50.001, and with the sleep duration in hours, p40.0001. These effects were remarkably greater in the 49 youngsters (5.60%) who were frankly underweight (BMI518.0); since these effects resemble those of night shift workers, the term mala movida (bad nightlife) is becoming of current use.

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.

Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy.

Background: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. Methods: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m2), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. Results: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141–1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. Conclusions: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.

Comment on: Lin et al. Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection. Diabetes Care 2013;36:701–707

The innovative article by Lin et al. (1) raises the possibility that certain infections may modulate not only obesity but also diabetes risk. Obesity is currently regarded as an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Nonetheless, evidence is available that environmental infections, and notably adipogenic adenoviruses in humans, are associated with obesity, being causative factors of obesity in animals (1–3). How obesity relates to type 2 diabetes is still a mosaic of information and more comprehensive approaches may help advance effective and cost-effective interventions for both conditions, including more tailored therapy (4). The conjectural model that an improvement in …