Assaf Buch

Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up

BACKGROUND & AIMS Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLDs epidemiology in prospective follow-up of individuals sampled from the general population. METHODS Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. RESULTS Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. CONCLUSIONS Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.

Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up

Non‐alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre‐DM in a 7‐year prospective follow‐up of healthy volunteers.

Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial

AIM To evaluate the effect of resistance training (RT) on non alcoholic liver disease (NAFLD) patients. METHODS A randomized clinical trial enrolling NAFLD patients without secondary liver disease (e.g., without hepatitis B virus, hepatitis C virus or excessive alcohol consumption). Patients were randomly allocated either to RT, three times weekly, for 3 mo or a control arm consisting of home stretching. The RT included leg press, chest press, seated rowing, latissimus pull down etc. with 8-12 repetitions, 3 sets for each exercise, for a total duration of 40 min. Hepatic ultrasound, fasting blood tests, anthropometrics and body composition by dual energy X-ray absorptiometry were assessed. At baseline and follow-up, patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake. Steatosis was quantified by the hepatorenal-ultrasound index (HRI) representing the ratio between the brightness level of the liver and the right kidney. The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy. RESULTS Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching. After dropout or exclusion from analysis because of protocol violation (weight change > 3 kg), thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol. All baseline characteristics were similar for the two treatment groups with respect to demographics, anthropometrics and body composition, blood tests and liver steatosis on imaging. HRI score was reduced significantly in the RT arm as compared to the stretching arm (-0.25 ± 0.37 vs -0.05 ± 0.28, P = 0.017). The RT arm had a significantly higher reduction in total, trunk and android fat with increase in lean body mass. There was no correlation between the reduction in HRI in the RT arm and weight change during the study, but it was positively correlated with the change in trunk fat (r = 0.37, P = 0.048). The RT arm had a significant reduction in serum ferritin and total cholesterol. There was no significant difference between arms in dietary changes and these did not correlate with HRI change. CONCLUSION Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin. RT may serve as a complement to treatment of NAFLD.

Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age--An overview.

BACKGROUND AND AIM In western countries, the proportion of people over age 60 is increasing faster than any other group. This is linked to higher rates of obesity. Older age, co-morbidities and obesity are all associated with frailty syndrome. In the core of both frailty and sarcopenia there are dysfunction and deterioration of the muscle and the fat tissues. This overview interlinks the phenotypes presented in older adults such as sarcopenia and frailty-alone and with relation to obesity, muscle function and fat tissue accumulation. RECENT FINDINGS Observational studies have well described the loss of muscle mass and strength through the years of adult life, both components of frailty and sarcopenia. They have shown that these changes are associated with dysmetabolism and functional deterioration, independent of common explanatory variables. In the metabolic mechanism core of this link, insulin resistance and higher ectopic fat accumulation may play a role. Basic experiments have partially validated this hypothesis. Whether there is a synergistic effect of obesity and frailty phenotype on morbidity risk is still questionable and currently under investigation; however, few cohort studies have shown that the frail-obese or sarcopenic-obese group have higher probability for metabolic complications. SUMMARY Muscle mass loss and fat accumulation in the muscle in the elderly, with or without the presence of obesity, may explain some of the functional and metabolic defects shown in the frail, sarcopenic population.

Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults

BACKGROUND Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: β ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (β ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (β = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (β-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.

Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

AIM To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient’s disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients’ illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (β = 0.26; P = 0.002) and self-efficacy (β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (β = 0.55; P < 0.001), which was related with lower self-efficacy (β = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046). CONCLUSION Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

Protective role of soluble receptor for advanced glycation end-products in patients with non-alcoholic fatty liver disease

BACKGROUND Soluble receptor for advanced glycation end-products (sRAGE) exerts protective metabolic effects. AIMS To identify if sRAGE plays a protective role in NAFLD. METHODS sRAGE (n=55) and Nε-(Carboxymethyl) lysine (CML) (n=36) serum levels were measured in NAFLD patients. Liver steatosis and fibrosis were non-invasively quantified by the hepatorenal index and the NAFLD fibrosis score (NFS). RESULTS sRAGE levels were lower in NAFLD patients compared to controls (1207±439 vs. 1596±562ng/l, P<0.001) and were lower among subjects with moderate-severe steatosis compared with mild (1043±287 vs. 1378±506, P=0.005). Higher sRAGE was associated with lower steatosis with adjustment for age, gender, BMI and fasting insulin (OR=0.998, 0.996-0.999 95%CI, P=0.018). CML was not correlated with liver steatosis (r=0.07, P=0.683), but was positively correlated with AST (r=0.34, P=0.04), GGT (r=0.38, P=0.023) and HbA1C (r=0.37, P=0.027). sRAGE tended to be higher in subjects with NFS<-1.455 compared with NFS>-1.455 (1287±450 n=36 vs. 1051±364 n=13, P=0.08). While sRAGE was positively correlated with vegetables consumption (r=0.268, P=0.05), CML levels were not associated with sRAGE or dietary intake. sRAGE increased following a 3 month-lifestyle intervention (1194±446 vs. 1367±440 n=31, P<0.001) and change in sRAGE levels was negatively correlated with change in ALT levels (r=-0.37, P=0.041). CONCLUSION sRAGE plays a protective role in NAFLD and it is influenced by lifestyle.

Cognitive impairment and the association between frailty and functional deficits are linked to abdominal obesity in the elderly

OBJECTIVE To evaluate whether specific obesity phenotypes in community-dwelling elderly: (a) affect differently the relationship between frailty and functional impairment and (b) are related to cognitive impairment. STUDY DESIGN A post-hoc cross-sectional analysis of the last Israeli national health and nutrition survey of the elderly (≥ 65 yrs.; n = 1619). MAIN OUTCOME MEASURES We implemented a previously validated frailty model based on frailty-related variables that were obtained in the survey. Mild cognitive impairment was defined using the Mini-Mental State Examination (a score <24 and >17). The Katzs scale of activities of daily living was used for functional assessment. Data were clustered according to different obesity phenotypes using measured body mass index (BMI) and waist circumference (WC). RESULTS The link between frailty and disability was most prominent in subjects with abdominal obesity who were non-obese by BMI: compared with non-obese subjects as defined by WC and BMI, the odds ratio (OR) for functional limitations in this phenotype was 8.34 (95 % CI, 2.14-32.48) for pre-frail subjects and 69.26 (10.58-453.55) for frail subjects. The rate of cognitive impairment was 3.3 times higher (p = .023) in women who were obese by WC but not by BMI. CONCLUSIONS In elderly people with a large WC and BMI < 30 kg/m2, disability is more tightly linked to frailty than for any other form of obesity. Cognitive impairment was more prominent in women with central obesity and BMI < 30 kg/m2 than in the other anthropometric phenotypes. WC should be used for early detection of individuals at risk of progression of frailty to functional incapacity.