Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome(MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance(IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease

AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.

Usefulness of the clip-flap method of endoscopic submucosal dissection: A randomized controlled trial

AIM To prospectively investigate the efficacy and safety of clipflap assisted endoscopic submucosal dissection(ESD) for gastric tumors.METHODS From May 2015 to October 2016, we enrolled 104 patients with gastric cancer or adenoma scheduled for ESD at Shiga University of Medical Science Hospital. We randomized patients into two subgroups using the minimization method based on location of the tumor(upper, middle or lower third of the stomach), tumor size(< 20 mm or > 20 mm) and ulcer status: ESD using an endoclip(the clip-flap group) and ESD without an endoclip(the conventional group). Therapeutic efficacy(procedure time) and safety(complication: Gastrointestinal bleeding and perforation) were assessed. RESULTS En bloc resection was performed in all patients. Four patients had delayed bleeding(3.8%) and two had perforation(1.9%). No significant differences in en bloc resection rate(conventional group: 100%, clip flap group: 100%), curative endoscopic resection rate(conventional group: 90.9%, clip flap group: 89.8%, P = 0.85), procedure time(conventional group: 70.8 ± 46.2 min, clip flap group: 74.7 ± 53.3 min, P = 0.69), area of resected specimen(conventional group: 884.6 ± 792.1 mm^2, clip flap group: 1006.4 ± 1004.8 mm^2, P = 0.49), delayed bleeding rate(conventional group: 5.5%, clip flap group: 2.0%, P = 0.49), or perforation rate(conventional group: 1.8%, clip flap group: 2.0%, P = 0.93) were found between the two groups. Lessexperienced endoscopists did not show any differences in procedure time between the two groups.CONCLUSION For patients with early-stage gastric tumors, the clipflap method has no advantage in efficacy or safety compared with the conventional method.

Continuous Subcutaneous Administration of Miso Extracts Attenuates Salt-Induced Hypertension in Dahl Salt-Sensitive Rats

Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) or a continuous subcutaneous infusion of a Miso extract attenuates hypertension in Dahl S rats. Materials and Methods: We investigated the effects of a bolus, i.p. injection of 50 mg Miso extract in 0.5 mL on hypertension in Dahl S rats, and examined whether a long-term subcutaneous infusion of the Miso extract (50 mg Miso/day), using an osmotic mini-pump working for 14 days, attenuates hypertension in Dahl S rats. Results: A bolus, i.p. injection of 50 mg Miso extract decreased SBP in 2 hrs. The reduction was significant at 4 hrs, and SBP returned to the baseline at 24 hrs. The SBP reduction at 4 hrs after the injection was increasingly greater each day during the 4 days. The SBP reduction by the Miso extract was dose-dependent and the antihy-pertensive activity occurs in a <5 kDa fraction of the extract. The subcutaneous infusion of 50 mg Miso extract/day for 14 days significantly attenuated hypertension in Dahl S rats. The SBP reduction was associated with significant decreases in the heart and kidney weights. Urinary protein excretion significantly decreased in the Miso group. The SBP reduction was not associated with increases in either urinary sodium excretion or fractional excretion of sodium. Conclusions: SBP reduction by very low-dose of the Miso extract may be mediated partly by mechanisms other than renal sodium handling.

Design of the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS): A Multidisciplinary Observational Epidemiological Study

Background: In the past few decades, the incidence of cardiometabolic diseases and disorders of the liver, kidney, pancreas, heart, and lung, have been increasing in Western and Asian countries, including Japan. Numerous factors, including abnormal body weight (obesity, overweight, or underweight), infrequent exercise, and other unfavorable lifestyle factors (e.g., smoking and heavy alcohol drinking) have been proposed as risk factors for the development and the progression of diseases, such as type 2 diabetes, hypertension, and dyslipidemia, which ultimately lead to impaired organ function and possibly death. However, the mechanisms that link these risk factors with diseases are still poorly understood, and the potential treatments, including pharmacotherapy and diet, have not been fully evaluated. Methods: In 2011, we established a new collaborative research program, the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS). This multidisciplinary observational epidemiological research study was designed to cover several high-profile diseases and some traditional fields of internal medicine, as well as apparently unrelated fields and particular lifestyle factors, such as unhealthy eating behaviors. In a series of studies, apparently healthy subjects who underwent a regular medical checkup were retrospectively identified based on the results of their medical checkups. In this way, the incidence, prevalence, causality, and clinical relevance of specific conditions and diseases have been investigated in cross-sectional analyses of 100,000 - 200,000 adults, and in longitudinal studies of several thousand subjects who underwent medical checkups multiple times. Discussion: This article describes the background, rationale, purpose, and methods of the SCDOIS. Using data obtained from annual medical checkups, our goals are to 1) establish criteria or identify clinical features that would enable clinicians to detect the presence of abnormal conditions associated with cardiometabolic diseases and/or organ impairment much earlier in the disease course;and 2) determine the potential mechanisms and therapies for these conditions.

Low Salt Diet in Pregnant Mothers Is Associated with Enhanced Salt Appetite in Their Offspring of Dahl Salt-Sensitive Rats

Objectives: We investigated an influence of salt intake during gestation or lactation in salt preference of weaning Dahl salt sensitive (Dahl S) strain. Material and Methods: Nine-week-old female Dahl S rats, after mated with the male, were divided into 1) high-salt group fed a 4% NaCl diet (high-salt mother) or 2) low-salt group fed a 0.3% NaCl diet (low-salt mother) during gestation or lactation periods. Using 0.4%, 0.6% and 0.8% (w/v) saline solutions, we assessed salt preference in their offspring after weaning. Systolic blood pressure (SBP) was determined by tail cuff method. Results: Both the male and female offspring from low-salt mothers during gestation consumed equal amounts of any saline solution. However, the amount of each saline solution was higher in the offspring of low-salt mothers than those of high-salt mothers. This resulted in a significant increase of salt intake in both the male and female offspring of low-salt mothers compared with those of high-salt mothers. In contrast, both the male and female offspring from low-mothers during lactation rather preferred the lower concentration of saline solution, and this resulted in less salt intake in the offspring of low-salt mothers than those of high-salt mothers. Conclusions: We demonstrated that low salt diet in pregnant mothers increased salt intake of their offspring. The offspring of mothers fed a low salt diet during lactation had less salt than those of high-salt mothers. The influence of salt intake of mothers in their offspring varies along with the growth stage of their babies.

Nutritional Screening in a University Hospital:Comparison between Oncologic and Non-Oncologic Patients

Background & Aims: We compared the screening nutritional data of patients with malignant and non-malignant disease, and classified their nutritional risk according to the primary tumor’s site. Methods: Subjective Global Assessment was applied to 3008 patients within 48 h of admission to a public university. Subjects were divided into Oncologic Group (n = 576) or Non-Oncologic Group (n = 2432) according to the presence of neoplasms or other diseases respectively. These data were compared by the t-student test and classic chi-square test, with statistical significance set at p < 0.05. Results: The Oncologic Group presented a higher prevalence of weight loss (60.3% vs. 49.3%), quantitative (40.7% vs. 28.5%) and qualitative (16.4% vs. 7.6%) alterations in the food intake pattern, gastrointestinal symptoms and muscle waste (23.2% vs. 13.2%) as compared to the Non-Oncologic Group. Also, there was a higher prevalence of nutritional disturbances in the Oncologic Group, with 49.5% of the subjects moderately (or suspected to be malnourished) and 12.7% severely mal-nourished. Severe malnourishment was mainly observed in patients with head and neck (25%), upper digestive tract (21.9%) and soft tissue and bones (17.9%) tumors. Conclusion: When compared to other hospitalized patients, patients with neoplastic disease were in higher nutritional risk.

Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.

Alimentary regimen in non-alcoholic fatty liver disease:Mediterranean diet

Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide.The mechanisms of the underlying disease development and progression are awaiting clarification.Insulin resistance and obesity-related inflammation status,among other possible genetic,dietary,and lifestyle factors,are thought to play the key role.There is no consensus concerning the pharmacological treatment.However,the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy.On the basis of its components,the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases,including obesity and diabetes.New evidence supports the idea that the Mediterranean diet,associated with physical activity and cognitive behaviour therapy,may have an important role in the prevention and the treatment of NAFLD.

New obesity classification criteria as a tool for bariatricsurgery indication

Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy(‘‘sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described:(1) normal weight obese(NWO);(2) metabolically obese normal weight;(3) metabolically healthy obese; and(4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.

Fructose-Induced Cognitive Dysfunction Is Associated with Increased Oxidative Stress in the Rat Brains

High fructose consumption is a risk factor for diabetes. Type 2 diabetes is associated with cognitive and memory impairment. To determine if fructose intake might affect memory function independently of diabetes development, we investigated the effects of monosaccharides on memory in prediabetic state. We examined whether 2.5% apple juice solution could influence cognitive function in salt-sensitive Dahl rats using passive avoidance methods. Furthermore, we examined the role of monosaccharides intake in cognitive function and oxidative stress in the brain. Four-week consumption of either apple juice or 2.5% fructose did not affect the blood glucose concentrations;however, apple juice, but not fructose, significantly decreased cognitive function compared with that of control rats given water. Second, Wistar rats aged 4 weeks were assigned to four groups given water, or 1.25% glucose, or fructose, or galactose solutions for 11 weeks. The fructose group had only slightly higher blood glucose concentrations than the control group. However, memory function engraved at age of 7 weeks and evaluated for 8 weeks in a passive avoidance test, was significantly decreased in the fructose and galactose groups compared with those in the glucose group. Oxidative stress in the brain, assessed by the tissue malondialdehyde (MDA) content, was significantly increased in the fructose group compared with that in the control group, and the decrease in cognitive function significantly correlated with the MDA content. These findings suggest that long-term apple juice consumption decreases memory function, possibly through an increase in oxidative stress in the brain, in turn induced by fructose overloading. Fructose-induced cognitive dysfunction is likely mediated by mechanisms other than insulin resistance.

Vague relationship between alcohol consumption and metabolic syndrome in nonobese people

Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies have shown that compared with no or occasional alcohol intake, moderate alcohol consumption is associated with lower prevalence rates of hypertension and type 2 diabetes, and lower levels of circulating C-reactive protein, a valuable marker for MS and insulin resistance. Considering these findings, light to moderate alcohol consumption has theoretical benefits on fatty liver and MS. Fatty liver, including non-alcoholic fatty liver disease, may be more clinically important than MS, particularly in non-obese individuals, because fatty liver can develop before MS in several conditions, such as regular alcohol consumers. Furthermore, most of the currently used MS criteria are unable to detect "true MS" because of variations in multiple factors such as age, height, medications, and complications.

肥胖的预防研究:预防儿童期和青春期肥胖的PRESTO研究项目

The PRESTO project has been launched as a school-oriented pilot project. The aims were to influence nutrition, physical activity and health. The intervention was performed by a multiprofessional team and covered 11 nutrition and health-related sessions with 1 h perweek in each class. The initial poor knowledge was improved significantly to the control group with better results in grammar schools compared to comprehensive schools. BMI was not improved in overweight children. However, this project could serve as a successful model in Austria.