Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery

Aim:  Hepatic steatosis affects up to 30% of the population. After weight loss, monitoring of the change in hepatic steatosis is not routinely performed. This study aimed to define the closest associates of change in liver fat content in a population of obese females following laparoscopic gastric banding surgery.
Methods:  Before and 3 months after surgery, proton magnetic resonance spectroscopy and magnetic resonance imaging were used to estimate the amount of lipid contained within the liver and abdominal subcutaneous and visceral compartments of 29 obese [mean body mass index (BMI) 39 ± 5 kg/m²], non-diabetic women aged between 20 and 62 years. Liver enzymes, fasting plasma glucose and insulin were also measured as well as body weight, BMI and waist circumference. Insulin sensitivity was estimated using homeostasis model assessment insulin resistance index.
Results:  Significant reductions occurred in body weight (p < 0.001), abdominal fat volumes (p < 0.001) and liver fat (p = 0.037) 3 months after surgery. Change in liver fat content more closely associated with change in serum gamma-glutamyl transferase (GGT; r = 0.71, p < 0.001) than with changes in weight (r = 0.10, p = 0.612) and waist circumference (r = 0.15, p = 0.468).
Conclusions:  Our findings suggest that obese non-diabetic female patients who have undergone significant weight loss over 3 months can be better assessed for the regression of excess liver fat content by monitoring changes in serum GGT levels rather than changes in simple anthropometry.     

Value of Visceral Fat Area and Resting Energy Expenditure in Assessment of Metabolic Characteristics in Obese and Lean Nonalcoholic Fatty Liver Disease

Background: The high prevalence and incidence of non-alcoholic fatty liver disease (NAFLD) have become a global medical concern. Compared with obesity, metabolic abnormalities may be more critical. Currently, there is lack of relevant data for nutritional status and energy metabolic characteristics in patients with obese and lean NAFLD.Methods: All the enrolled NAFLD patients were divided into 2 groups: the obese group (205 patients with body mass index (BMI) ≥ 25 kg/m²) and the lean group (73 patients with BMI < 25 kg/m²). Using a body composition analyzer, we analyzed their nutritional status including skeletal muscle, body fat, protein content, and visceral fat area (VFA). Energy metabolic characteristics including resting energy expenditure (REE), respiratory quotient, and oxidation rate of 3 major nutrients (carbohydrate, CHO%, fat, FAT%, and protein, PRO%) were analyzed by metabolic cart.Results: The lean NAFLD patients’ LDL-c and UA even increased significantly than the obese patients (P = .001 and .006, respectively). Compared with the control group, VFA and REE were significantly higher in the lean NAFLD group (P = .008, P < .001 respectively). CHO%, FAT%, and PRO% in the lean NAFLD group were 29.31 ± 7.07%, 55.59 ± 12.09%, and 15.10 ± 4.07%, respectively, and there was no significant difference compared to the control. However, compared to the obese NAFLD group, their CHO% increased, whereas FAT% decreased (both P < .001).Conclusion: NAFLD patients suffer from nutritional imbalances and energy metabolic abnormalities, regardless of whether they are associated with obesity. LDL, UA, VFA, and REE can be used as good evaluation indicators.     

Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects

Aim:  Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL.
Methods:  Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) >25 kg/m²] were studied with blood sampling, measurement of IHL and IMCL by ¹H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic–hyperinsulinaemic clamp as an index of peripheral insulin sensitivity.
Results:  A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 ± 0.86 to 7.82 ± 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 ± 1.0 to 4.2 ± 0.9, not significant), it decreased IHL by 21% (from 15.9 ± 2.8 to 11.8 ± 2.2%, p < 0.05).
Conclusions:  A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.     

Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease

Background and Aim:  Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity.
Methods:  Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII).
Results:  The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 ± 0.70 vs 2.25 ± 0.75, P  = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation ( r  = −0.368, P  = 0.045) and stage of fibrosis ( r  = −0.380, P  = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups.
Conclusion:  These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients.     

No effect of resveratrol on VLDL‐TG kinetics and insulin sensitivity in obese men with nonalcoholic fatty liver disease

The present study (NCT01446276, ClinicalTrials.gov ) assessed long‐term effects of high‐dose Resveratrol (RSV) on basal and insulin‐mediated very low‐density lipoprotein triglyceride (VLDL‐TG), palmitate and glucose kinetics, and liver fat content in men with nonalcoholic fatty liver disease (NAFLD). Participants (n = 16) were non‐diabetic, upper‐body obese (BMI > 28 kg/m², WHR > 0.9) men with NAFLD who were randomized (1:1) in a double‐blinded, placebo‐controlled clinical trial to either RSV or placebo (500 mg 3 times daily) for 6 months. Magnetic resonance (MR) spectroscopy, dual‐X‐ray absorptiometry and MR imaging assessed liver fat content and body composition, respectively. ¹⁴C‐labeled VLDL‐TG and ³H‐labeled glucose and palmitate tracers, in combination with indirect calorimetry and breath samples, were used to assess kinetics and substrate oxidations during basal and hyperinsulinaemic euglycaemic clamp conditions. RSV did not improve either basal or insulin‐mediated VLDL‐TG secretion, oxidation or clearance rates, nor did it affect palmitate or glucose turnover. Likewise, no changes in body composition or liver fat content occurred following RSV compared with placebo treatment. Therefore, RSV cannot be recommended for treatment of metabolic abnormalities in NAFLD.     

Association between low thigh fat and non-alcoholic fatty liver disease

Background and Aim:  Some people have a fatty liver despite having low visceral fat and a low body mass index (BMI). We investigated whether fat distribution, especially thigh subcutaneous fat and thigh intramuscular fat, is associated with non-alcoholic fatty liver disease (NAFLD).
Methods:  The patients consisted of 408 men and women. NAFLD was defined by an ultrasound scan and excluded other liver diseases. Visceral, subcutaneous abdominal, intramuscular, and subcutaneous thigh adipose tissue was measured by computed tomography.
Results:  The frequency of NAFLD decreased over a quartile of thigh fat independently of BMI in the female patients. Additional adjustments for age and visceral fat area did not change the results. This finding was not observed in the male patients. To investigate the relationship between each fat distribution and NAFLD, we performed a logistic regression analysis. Fat distribution was divided into four groups: visceral fat, abdominal subcutaneous fat, thigh subcutaneous fat, and thigh intramuscular fat. All four fat components were chosen as variables for the regression model. Age, BMI, and the homeostasis model assessment (HOMA) index were then adjusted successively. A larger subcutaneous fat area was negatively associated with NAFLD after adjustment for visceral fat and abdominal subcutaneous fat areas in women, but not in men. It did not change even after age adjustment, BMI, and the HOMA index.
Conclusion:  Low femoral subcutaneous fat amounts were shown to be independently associated with fatty liver disease in women. These results show the importance of accurate measurements of other regional body compositions as well as visceral fat amounts when investigating NAFLD.     

运动处方应用于非酒精性脂肪性肝病患者治疗作用和安全性评价

目的 探索运动处方在非酒精性脂肪性肝病(NAFLD)患者治疗中的作用和安全性。 方法 纳入59例NAFLD患者,33例被分配到运动干预组,给予有氧运动和抗阻运动,26例为对照组,未进行特别的运动指导和监督。使用全套“健民4型国民体质测试”设备进行运动前后筛查。使用FibroTouch检测肝内脂肪含量和肝脏硬度。结果 在干预组,在干预三个月末,受试者体质量、体质指数、脂肪含量和腰围分别从(81.9±10.4) kg、(28.5±2.4)kg/m²、(25.4±4.9)kg和(92.2±6.5)cm下降至,肝脏脂肪受控衰减参数由(281.5±15.4)dB/m 下降至,而对照组各项指标无显著变化。结论 初步研究提示运用运动处方干预NAFLD患者,可收到显著的治疗效果,且安全。     

Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (body mass index [BMI]: 38.1 ± 4.6 kg/m(2)) with NAFLD were randomized to 16 weeks of exercise training (45%-55% VO(2peak) , 30-60 minutes × 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 (apoB-100) secretion rates. Exercise training resulted in a 10.3% ± 4.6% decrease in IHTG content (P < 0.05), but did not change total body weight (103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training) or percent body fat (38.9% ± 2.1% before and 39.2% ± 2.1% after training). Exercise training did not change the hepatic VLDL-TG secretion rate (17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training) or VLDL-apoB-100 secretion rate (1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training). CONCLUSION: Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD.     

Testosterone stimulates extra-hepatic but not hepatic fat oxidation (Fox): comparison of oral and transdermal testosterone administration in hypopituitary men

Background  Fat mass is increased in hypogonadal men and the changes are reversed by testosterone replacement. Testosterone administration enhances whole body fat oxidation (Fox). Fat is oxidized in the liver and in extra-hepatic tissues.
Objective  To determine whether the stimulation of Fox by testosterone arises primarily from the liver or from extra-hepatic tissues.
Design/patients  This was an open-label cross-over study. Thirteen men with hypopituitarism (age 53·1 ± 4·1 years) with both growth hormone (GH) and testosterone deficiency were studied sequentially after 2 weeks of treatment with transdermal testosterone (5 mg), no treatment, and stepwise incremental doses of oral crystalline testosterone (10, 20, 40 and 80 mg) in the absence of GH replacement.
Measurements  Serum testosterone, IGF-I, metabolic effects [resting energy expenditure (REE) and Fox], SHBG, and thyroid binding globulin (TBG) as markers of excessive hepatic androgen exposure, were measured at the end of each treatment period.
Results  When compared to the no-treatment phase, mean blood testosterone levels rose into the physiological range after transdermal testosterone delivery but did not significantly change after 10, 20, 40 or 80 mg oral testosterone treatment. Blood SHBG and TBG fell significantly with 80 mg oral testosterone dose but were unaffected by any other testosterone treatment. Fox increased significantly with transdermal but not with any dose of oral testosterone. Mean plasma IGF-I and REE were unaffected by testosterone, regardless of the route or dose.
Conclusions  Short-term testosterone administration does not stimulate hepatic fat oxidation but enhances whole body fat oxidation by acting on extra-hepatic tissues.     

The metabolic syndrome as a link between smoking and cardiovascular disease

Objective:  Smoking is associated with a significant increase in the cardiovascular risk. The possible relationship of smoking with insulin resistance might further enhance the cardiovascular risk of the patients and is therefore of great clinical interest.
Design, Setting and Subjects:  We have retrospectively evaluated data of 3804 non-diabetic men attending a medical outdoor clinic. Clinical [body mass index (BMI), percentage of body fat, waist-to-hip ratio] and laboratory results were compared between smokers (n = 124) and non-smokers (n = 1915) without cardiovascular disease, as well as between smokers (n = 759) and non-smokers (n = 1006) with cardiovascular disease.
Results:  Smokers without clinically manifest cardiovascular disease revealed significantly higher fasting glucose (5.8 ± 0.6 mmol/l) and triglyceride levels (1.8 ± 0.9 mmol/l) than non-smokers (fasting glucose: 5.1 ± 0.7 mmol/l, p < 0.010; triglycerides: 1.5 ± 0.8 mmol/l, p < 0.030). The adverse metabolic profile of smokers was even more pronounced in patients with cardiovascular disease. An age-matched analysis of smokers could demonstrate that cardiovascular patients revealed higher BMI values (27.3 ± 2.4 kg/m²) and a higher percentage of body fat (25.5 ± 5.5%) than those without cardiovascular disease (BMI: 25.7 ± 2.2 kg/m², p < 0.010; percentage of body fat: 23.0 ± 5.5%, p < 0.030).
Conclusion:  In men with and without clinically manifest cardiovasular disease, smoking was associated with a metabolic profile indicating a higher degree of insulin resistance.     

Docosahexaenoic acid for the treatment of fatty liver: Randomised controlled trial in children

Background and aimNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children. We tested whether dietary supplementation with docosahexaenoic acid (DHA) can decrease liver fat content in children with NAFLD.Methods and resultsWe performed a randomized controlled trial of DHA supplementation (250 mg/day and 500 mg/day) vs. placebo in 60 children with NAFLD (20 children per group). The main outcome was the change in liver fat as detected by ultrasonography after 6, 12, 18 and 24 months of treatment. Secondary outcomes were changes in triglycerides, alanine transaminase (ALT), body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA). The odds of more severe versus less severe liver steatosis decreased to the same degree at 6 months in children treated with DHA 250 mg/day and DHA 500 mg/day vs. placebo and persisted virtually unmodified for 24 months (OR ≤ 0.02, p ≤ 0.05 for all time points). Triglycerides were lower in the DHA groups than in the placebo group at any time point and ALT was lower in these groups from month 12 onwards. HOMA was lower in the DHA 250 mg group vs. placebo at months 6 and 12.ConclusionDHA supplementation improves liver steatosis in children with NAFLD. Doses of 250 mg/day and 500 mg/day of DHA appear to be equally effective in reducing liver fat content.     

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.     

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.     

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally(100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis(macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor(TNF)-α in liver(156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P 0.05). Serum aspartate aminotransferase levels were also reduced(23.2 ± 6.9 and 12.1 ± 1.6 U/L for nontreated and treated obese mice, respectively; P 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α(106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P 0.05) and interleukin-6(340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P 0.05) levels; however, leptin(8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P 0.05) and plasminogen activator inhibitor-1(600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non-treated and treated lean mice, respectively; P 0.05) levels increased in lean adipose tissue. TNF-α level in the liver of lean mice also increased(29.6 ± 6.6 and 75.4 ± 12.6 pg/mL for non-treated and treated lean mice, respectively; P 0.05) while triglycerides presented a tendency to reduction.CONCLUSION: Pentoxifylline was beneficial in obese mice improving liver and adipose tissue inflammation. Unexpectedly, pentoxifylline increased pro-inflammatory markers in the liver and adipose tissue of lean mice.     

Non-alcoholic fatty liver disease and obesity: Biochemical,metabolic and clinical presentations

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m². However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m²) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.     

Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double-blind,randomized, placebo-controlled trial

Aim:  To assess the effect of sibutramine-assisted weight reduction program on insulin sensitivity and metabolic parameters in obese normal glucose tolerant individuals over a period of 24 weeks.
Research Design and Methods:  A double-blind, placebo-controlled, parallel, prospective clinical trial was carried out at our medical centre. Forty female normal glucose tolerant patients, body mass index: 34.3 ± 2.9 kg/m² and age: 41.1 ± 9.9 (range: 19–58 years), were randomized to placebo or sibutramine, 10 mg once daily.
Results:  Seventeen patients from sibutramine group and 14 placebo had completed the study protocol. Significant weight change was seen in sibutramine (p < 0.01) (−5.6 kg or −6.1% vs. +0.9 kg or +1.1% in placebo). Insulin sensitivity enhanced in sibutramine group ( K _itt: from 4.03 ± 1.97 to 5.09 ± 2.48%/min; p < 0.05). Homeostasis model assessment-IR (HOMA-IR) decreased from 7.8 ± 6.9 to 5.6 ± 4.5 (p < 0.05). HOMA-β also decreased from 508 ± 381 to 374 ± 256 (p < 0.05). No changes were observed in the placebo control group regarding insulin sensitivity or secretion. Concomitant reductions were observed in the sibutramine group in lipid parameters (triglycerides and high-density lipoprotein-cholesterol), uric acid and gamma-glutamyl transferase (p < 0.05).
Conclusions:  Sibutramine has demonstrated efficacy in reducing weight in non-diabetic women along with amelioration in insulin sensitivity and additional improvement in metabolic parameters.     

Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight,liver fat and liver function in obese patients with non‐alcoholic fatty liver disease: A pilot randomized trial

We compared the effects of weight loss induced by the glucagon‐like peptide 1‐agonist liraglutide with a structured lifestyle intervention in obese adults with non‐alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m², mean weight 96.0 ± 16.3 kg) non‐diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate‐intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had significant (P < .01) and similar reductions in weight (?3.5 ± 3.3 vs ?3.5 ± 2.1 kg, respectively, P = .72), LFF (?8.9 ± 13.4 vs ?7.2% ± 7.1%, P = .70), serum alanine aminotransferase (?42 ± 46 vs ?34 ± 27 U/L, P = .52) and aspartate aminotransferase (?23 ± 24 vs ?18 ± 15 U/L, P = .53). In this first randomized study comparing the 2 weight‐loss modalities for improving NAFLD, liraglutide was as effective as structured lifestyle modification.     

Different predictors of steatosis and fibrosis severity among lean,overweight and obese patients with nonalcoholic fatty liver disease

BackgroundsNon-obese nonalcoholic fatty liver disease (NAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but worse prognosis relative to obese NAFLD.AimTo compare predictors of disease severity in NAFLD with different body mass index (BMI) categories.MethodsAll 1509 consecutive NAFLD patients were classified as lean (20.2%), overweight (23.1%) and obese (56.7%). Liver fat content (LFC) and fibrosis were estimated with magnetic resonance imaging-based proton density fat fraction and shear wave elastography respectively.ResultsLipid profiles and uric acid (UA) were significantly increased in parallel with BMI categories (pairwise comparison P < 0.001), but insulin resistance (IR) was significantly different between the non-obese and obese groups. For LFC ≥ 10%, increased waist circumference (WC) was an independent predictor in all groups, while UA elevation (P = 0.02) was predictive in the overweight patients, but BMI ≥ 28 kg/m² (P = 0.029) and IR (P = 0.026) were significant in the obese patients. For fibrosis, alanine aminotransferase (ALT) > 40 U/L (P = 0.031), increased WC (P = 0.012) and BMI ≥ 28 kg/m² (P < 0.001) plus ALT > 40 U/L (P = 0.007) were predictors in the lean, overweight and obese patients, respectively.ConclusionsWC was strongly predictive of disease severity in all NAFLD, while UA and BMI plus IR were additional predictors in the overweight and obese NAFLD respectively. Individualized screening strategies should be established for NAFLD according to different BMIs.     

The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease

Background and Aims:  We identified patients with nonalcoholic fatty liver disease (NAFLD) to determine the predictive value of serum markers to diagnose histological steatohepatitis (NASH).
Methods:  Demographic, serological, radiological and histological variables on 95 consecutive patients with NAFLD were recorded. The serum markers studied were CK18, Hyaluronic acid, TIMP 1 and YKL 40. The NAS score and the metavir score were the histological scoring systems used.
Results:  CK18 levels were higher in the NASH group compared to the simple steatosis group (394 ± 53 µ/L vs 194 ± 26 µ/L; P  < 0.05). In assessing clinical effectiveness, CK18 yielded an AUC of 0.8 for NASH (cut-off value 300 µ/L gives PPV 81% and NPV 85%).The fibrosis markers showed no differences between groups. We stratified the same cohort according to liver fibrosis (F0 vs F1–F4). Fibrosis was associated with advanced age, high body mass index and type 2 diabetes. The biomarkers performed relatively poorly at identifying liver fibrosis (F1–F4), with HA performing the best (AUC 0.73); performance improved for advanced fibrosis (F3/F4) - (HA: AUC 0.77). The NAS score performed the best overall at identifying liver fibrosis (AUC 0.79).
Discussion:  CK18 is the only biomarker studied that can identify NASH. Additionally, liver biopsy should be performed in all high risk patients to determine the standardised NAS score to identify patients at high risk of disease progression.     

Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population

Background: Non-alcoholic fatty liver disease(NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese population.Methods: Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver(normal or NAFLD), and body mass index(BMI) levels(non-obese if BMI 25 kg/m~2 or obese if BMI ≥ 25 kg/m~2).Results: There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver(group A), non-obese NAFLD(group B), obese normal liver(group C) and obese NAFLD(group D),respectively. The highest ratio of metabolic syndrome existed in the group B(26.9%), followed by group A(11.7%), group D(10.9%) and finally the group C(5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02) and glucose(OR = 1.02; 95% CI:1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases(adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals(OR = 2.81; 95% CI: 1.92–4.12).Conclusions: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.