Effect of Body Mass Index and Intra-Abdominal Fat Measured by Computed Tomography on the Risk of Bowel Symptoms

Background

This study aims to investigate the association between body mass index (BMI) or intra-abdominal fat measured by computed tomography (CT) and bowel symptoms.

Method

A cohort of 958 Japanese adults who underwent colonoscopy and CT and completed questionnaires after excluding colorectal diseases was analyzed. Six symptoms (constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) using a 7-point Likert scale were evaluated between baseline and second questionnaire for test-retest reliability. Associations between BMI, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and symptom score were analyzed by a rank-ordered logistic model, adjusting for age, sex, smoking, and alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia.

Results

Some bowel symptom scores were significantly (p<0.05) different between the age groups, sexes, smoking, and alcohol consumption. In multivariate analysis, constipation was associated with low BMI (p<0.01), low VAT area (p = 0.01), and low SAT area (p<0.01). Moreover, hard stools was associated with low BMI (p<0.01) and low SAT area (p<0.01). The remaining symptoms were not significantly associated with BMI or intra-abdominal fat. Test-retest reliability of bowel symptom scores with a mean duration of 7.5 months was good (mean kappa, 0.672).

Conclusions

Both low BMI and low abdominal fat accumulation appears to be useful indicators of increased risk for constipation and hard stools. The long-term test-retest reliability of symptom score suggests that bowel symptoms relevant to BMI or visceral fat remain consistent over several months.     

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity

Rationale

Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention.

Objectives

To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences.

Methods

Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography.

Results

Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m² or visceral fat area ≥100 cm²), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R² = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent.

Conclusions

Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation.     

Association of Adiponectin Gene Polymorphism with Nonalcoholic Fatty Liver Disease in Taiwanese Patients with Type 2 Diabetes

Objective

Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease.

Methods

We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured.

Results

Only adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively).

Conclusions

In patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with hypoadiponectinemia. Low serum adiponectin level may precipitate liver steatosis in patients with type 2 diabetes.     

Nonalcoholic Hepatic Steatosis Is a Strong Predictor of High-Risk Coronary-Artery Plaques as Determined by Multidetector CT

Background

Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT).

Methods

This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification.

Results

Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm²; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94–9.07, p<0.01).

Conclusions

Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.     

Non-Alcoholic Fatty Liver Disease Is a Risk Factor for the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Background

Non-alcoholic fatty liver disease (NAFLD) is prevalent in individuals with type 2 diabetes mellitus (T2DM). Diabetic nephropathy (DN) is also associated with T2DM. However, little is known about the interaction between these conditions in patients with T2DM.

Objective

To examine the association between NAFLD and DN in patients with T2DM.

Methods

This retrospective study included patients seen between January 2006 and July 2014.T2DM patients were divided into two groups based on NAFLD status (with NAFLD = group A; without = group B). The cumulative incidence of DN and chronic kidney disease (CKD) staging were compared between the two groups. Liver fat content was examined in some patients. Associations among NAFLD, other factors,and DN were analyzed by the additive interaction method.

Results

Cumulative incidence of DN in patients from group A (58.58%) was higher than in group B (37.22%) (P = 0.005). In both groups, the number of DN patients with CKD stage 1 was greater than the number of patients with stages 2–5. Increased liver fat content was associated with increased occurrence of severe and mild albuminuria and decreased glomerular filtration rate (GFR). There were positive correlations between NAFLD and insulin resistance index (HOMA-IR), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), omentin-1, visceral fat area, homocysteine (HCY), and serum uric acid (UA).

Conclusion

NAFLD might be a risk factor for DN. Elevated liver fat content could be associated with higher DN burden.     

Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

Background

Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.

Objective

To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.

Methods

Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m²/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m²/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion.

Results

Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile – 3rd quartile)] between Control and BCAA in either the 40U ([199 (167–278) vs. 186 (94–308)] or 80 U ([491 (414–548) vs. 478 (409–857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P < 0.05) with no differences between Control and BCAA in either of the experiments (P > 0.05).

Conclusion

Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.     

Peripheral and Hepatic Vein Cytokine Levels in Correlation with Non-Alcoholic Fatty Liver Disease (NAFLD)-Related Metabolic,Histological, and Haemodynamic Features

Background

Haemodynamic impairment, inflammatory mediators and glucose metabolism disturbances have been implicated in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD).

Aim

To investigate the cytokine profile in NAFLD patients in peripheral (P) and hepatic venous (HV) blood and to compare with histology, haemodynamic and metabolic parameters.

Methods

40 obese patients with an indication for a transjugular liver biopsy were enrolled. Besides an extended liver and metabolic work-up, interleukin (IL) 1B, IL4, IL6, IL10, IL23, tumour necrosis factor (TNF) α and interferon (INF) γ were measured in plasma obtained from P and HV blood by means of multiplex immunoassay. The T helper (Th)1/Th2, the macrophage M1/M2 and the IL10/IL17a ratios were calculated.

Results

A decrease of the P-IL10/IL17-ratio and an increase of the P-M1/M2-ratio (p<0.05) were observed in NASH versus no-NASH patients. A P-M1/M2-ratio increase was detected also in patients with portal hypertension in comparison with patients without it (p<0.05). Moreover diabetic patients showed an increase of the P-Th1/Th2-ratio in comparison with non-diabetic ones (p<0.05). The P-M1/M2 ratio positively correlated with steatosis grade (r = 0.39, p = 0.02) and insulin (r = 0.47, p = 0.003). The HV-M1/M2 ratio positively correlated with fasting insulin and Hepatic Venous Pressure Gradient (r = 0.47, p = 0.003). IL6 correlated with the visceral fat amount (r = 0.36, p = 0.02). The P- and HV-IL10/IL17 ratios negatively correlated with fasting insulin (respectively r = -0.4, p = 0.005 and r = 0.4, p = 0.01).

Conclusions

A proinflammatory cytokine state is associated with more disturbed metabolic, histological, and haemodynamic features in NAFLD obese patients. An increase of the M1/M2 ratio and a decrease of the IL10/IL17 ratio play a key role in this process.     

Liver Fat Content Is Associated with Elevated Serum Uric Acid in the Chinese Middle-Aged and Elderly Populations: Shanghai Changfeng Study

Background and Aims

Although many studies have indicated a relationship between nonalcoholic fatty liver disease (NAFLD) and hyperuricemia, a few studies specifically examining the effects of the severity of liver fat content (LFC) on serum uric acid (SUA) and the presence of hyperuricemia because of the limitation of the examination methods for NAFLD. In this study, we investigate the relationship between the NAFLD and SUA levels in the Chinese population using standardized quantitative ultrasound.

Methods

A community-based study was conducted from May 2010 to December 2012. A total of 4,305 people aged 45 years and above without excessive drinking were enrolled. A standard interview and anthropometric and laboratory blood parameters were collected for each person. The standardized ultrasound hepatic/renal ratio and hepatic attenuation rate was used to quantify LFC.

Results

The prevalence of NAFLD and hyperuricemia was 33.1% and 17.1%, respectively. A total of 23.5% of the NAFLD subjects had hyperuricemia, and their SUA was higher than that of non-NAFLD subjects (327.2±76.8 vs 301.9±77.4 μmol/L, P<0.001). The LFC was positively correlated with SUA (r = 0.130, P<0.001) and an independent factor for SUA (standardized β = 0.054, P<0.001). The OR for the presence of hypreuricemia was 1.175 (95% CI 1.048–1.318; P<0.001) with a 1 SD increase in the log LFC. LFC greater than 10% was related to elevated SUA and an increased presence of hyperuricemia.

Conclusions

LFC accumulation was associated with an increase in the prevalence of hyperuricemia and elevated SUA in our community-based population. LFC greater than 10% is related to the risk for hyperuricemia.     

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

Background

Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans.

Methods

We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD.

Results

The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values.

Conclusions

High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.     

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study

Background and Aims

Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD.

Methods

We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals.

Results

We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III.

Conclusions

This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.     

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

Background

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

Hypothesis

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

Methods and Results

We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.

Conclusion

Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression.     

Fatty Liver Index Associates with Relative Sarcopenia and GH/ IGF- 1 Status in Obese Subjects

Introduction

Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status.

Methods

427 subjects [age: 45.65±13.94 years, BMI: 36.92±6.43 kg/m²] were enrolled. Participants were divided into three groups: fatty liver index (FLI) <20, 20≥FLI<60, and FLI≥60. Body composition was assessed by DXA. The truncal fat mass (TrFM) to appendicular skeletal muscle (ASM) ratio was used as an indicator of sarcopenic obesity. ISI-Matsuda index was used.

Results

BMI, fat mass, and the TrFM/ASM ratio were higher in subjects with FLI≥60. GH, IGF-1 and ISI-Matsuda were lower in the high FLI group (all p<0.05). A significantly positive correlation between FLI and TrFM/ ASM ratio (r = 0.221, p<0.001) was found, whereas FLI levels were negatively correlated with ISI- Matsuda (r = -0.335, p<0.001), GH (r = -0.200, p = 0.006), and IGF- 1 levels (r = -0.157, p = 0.028). Stepwise linear regression analysis showed that GH levels were significantly negatively correlated with FLI, while the TrFM/ ASM ratio was positively associated with FLI, after adjustment for age, BMI, total fat mass, truncal fat mass, fat- free mass, and ISI- Matsuda.

Conclusions

Impairment of GH/IGF-1 axis seems to be associated to the risk of the development of sarcopenic obesity and ectopic fat deposition in the liver. Metabolic and hormonal derangements as determinants of ectopic fat deposition and body composition deserve to be evaluated in obese subjects.     

Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease

Objectives

A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.

Methods

A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.

Results

As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.

Conclusion

BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.

Trial Registration

ClinicalTrials.gov NCT00633282     

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

Background & Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.

Design

Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.

Results

We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r² = 0.64, p<0.05), fibrosis (r² = 0.66, p<0.05) and pathological angiogenesis (r² = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.

Conclusions

These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.     

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis

Background

Few studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.

Methods

CT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.

Results

Participants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.

Conclusion

The relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used.     

The Normal Limits,Subclinical Significance,Related Metabolic Derangements and Distinct Biological Effects of Body Site-Specific Adiposity in Relatively Healthy Population

Background

The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized.

Materials and Methods

In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines.

Results

TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05). Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05), serum insulin (ß-coef.:0.17, p<0.05) and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05). These relationships persisted after adjustment in multivariable models (all p<0.05). A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74–0.83) to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05).

Conclusion

In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and subclinical atherosclerosis in a relatively healthy population.     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Traditional but Not HIV-Related Factors Are Associated with Nonalcoholic Fatty Liver Disease in Asian Patients with HIV-1 Infection

Background

The prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) are largely unknown in HIV-1 monoinfected patients.

Methods

The present study elucidated the prevalence and factors associated with NAFLD among Asian patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Diagnosis of NAFLD was based on the liver to kidney contrast and diffusion in hepatic echogenicity. Uni- and multi-variate logistic regression analyses were applied to estimate factors associated with NAFLD.

Results

435 Asian patients free of chronic hepatitis B or C virus infection and without excessive alcohol intake were analyzed. NAFLD was diagnosed in 135 (31%) patients. Obesity (BMI >30 kg/m²) was evident in 18 (4.1%) patients, and BMI was >25 kg/m² in 103 (24%). Multivariate analysis identified higher BMI (per 1 kg/m² increment, adjusted OR = 1.198; 95% CI, 1.112–1.290; p<0.001), dyslipidemia (adjusted OR = 2.045; 95% CI, 1.183–3.538; p = 0.010), and higher ALT to AST ratio (per 1 increment, adjusted OR = 3.557; 95% CI, 2.129–5.941; p<0.001) as significant factors associated with NAFLD. No HIV-specific variables, including treatment with dideoxynucleoside analogues (didanosine, stavudine, and zalcitabine) and cumulative duration of antiretroviral therapy (ART), were associated with NAFLD.

Conclusions

The incidence of NALFD among Asian patients with HIV-1 infection is similar to that in Western countries. NAFLD was associated with high BMI, dyslipidemia, and high ALT/AST ratio, but not with HIV-related factors. The results highlight the importance of early recognition and management of NAFLD and traditional factors associated with NAFLD for Asian patients with HIV-1 infection.     

Effortless Attention as a Biomarker for Experienced Mindfulness Practitioners

Objective

The present study aimed at comparing frontal beta power between long-term (LTM) and first-time meditators (FTM), before, during and after a meditation session. We hypothesized that LTM would present lower beta power than FTM due to lower effort of attention and awareness.

Methods

Twenty one participants were recruited, eleven of whom were long-term meditators. The subjects were asked to rest for 4 minutes before and after open monitoring (OM) meditation (40 minutes).

Results

The two-way ANOVA revealed an interaction between the group and moment factors for the Fp1 (p<0.01), F7 (p = 0.01), F3 (p<0.01), Fz (p<0.01), F4 (p<0.01), F8 (p<0.01) electrodes.

Conclusion

We found low power frontal beta activity for LTM during the task and this may be associated with the fact that OM is related to bottom-up pathways that are not present in FTM.

Significance

We hypothesized that the frontal beta power pattern may be a biomarker for LTM. It may also be related to improving an attentive state and to the efficiency of cognitive functions, as well as to the long-term experience with meditation (i.e., life-time experience and frequency of practice).