Correlation of adipose tissue with liver histology in Asian Indian patients with nonalcoholic fatty liver disease (NAFLD)

Background. There is sparse literature on the association of adipose tissue with liver histology in patients with nonalcoholic fatty liver disease (NAFLD).Aim. To study the correlation of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) with liver histology in Indian patients with NAFLD.Material and methods. A single slice CT scan at the level of L4-L5 vertebrae was done to assess the abdominal VAT and SAT volumes in 21 patients with histological diagnosis of NAFLD. Adult treatment panel III criteria with modified abnormal waist were used to define metabolic syndrome (MS). Histological grading was done according to the NAFLD activity score (NAS).Results. Twenty-one patients with NAFLD [13 males, median age: 35 years, median BMI: 25.97 kg/m²] were included prospectively. Even though overweight/obese patients had severe liver disease, there was no difference in the volume of VAT adjusted for BMI between 6 (28.5%) lean and 15 (71.5%) overweight/obese patients. Patients with NASH and borderline NASH were older, obese with higher VAT and SAT volumes than no-NASH group. SAT volume (SATV) correlated significantly with hepatic steatosis but none of the adipose tissue volumes had any correlation with other histological variables. Both SATV and TAT volume (TATV) correlated significantly with severity of liver disease as determined by NAS score whereas presence of MS or insulin resistance had no correlation with histological severity.Conclusion. Both subcutaneous and total adipose tissue volume are related to the disease severity as determined by NAFLD activity score in Indian patients with NAFLD.     

Association of nonalcoholic fatty liver disease with insulin resistance

BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal weight. We tested the hypothesis that there is an association between nonalcoholic fatty liver disease and insulin resistance that is independent of diabetes and obesity. SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "bright liver" on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex. RESULTS: Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70], fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/ liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects did not change the results. CONCLUSION: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.     

Visceral adipose tissue visfatin in nonalcoholic fatty liver disease

Background. Visfatin is a novel adipocytokine predominantly expressed and secreted by visceral adipose tissue. It is realized for its multiple functions of central importance in NAD biosynthesis, innate immunity and inflammation. Its phosphoribosyl transferase activity regulates cellular energetics and NAD dependent enzymes such as SIRTUINS. Although its expression in various tissues and circulating levels are documented, visceral visfatin levels in Nonalcoholic fatty liver disease (NAFLD) patients have not been reported.Objective. The aim of the present study was to assess visceral adipose tissue visfatin levels in NAFLD.Materials and methods. A total of 115 patients undergoing diagnostic laparoscopy were recruited in the study and categorized into two groups based on standard criteria for NAFLD. Visceral adipose tissue TNF-α, IL-6 and visfatin levels were measured by ELISA. Blood glucose, lipids, liver enzymes and non esterified fatty acids (NEFA) were estimated using standard procedures. Formalin fixed, Hematoxylene Eosin stained liver biopsy specimens were examined for the presence of steatosis and the degree of steatosis was ascertained as per Brunt’s classification.Results. The visceral visfatin level declined significantly (P < 0.001) in all groups of NAFLD as compared to non NAFLD group, while plasma NEFA level increased with progressive steatosis (P < 0.02). Significant increase in TNF a was observed in all groups of NAFLD, while IL-6 increased in NASH only.Conclusion. A significant decline in visceral adipose tissue visfatin level was found to be associated with degree of steatosis in NAFLD patients.     

强肝胶囊对非酒精性脂肪性肝病患者胰岛素抵抗指数和肝纤维化评分的影响

目的观察强肝胶囊对非酒精性脂肪性肝病(NAFLD)患者肝纤维化评分和胰岛素抵抗指数的影响。方法选取2014年8月-2015年7月在上海市第八人民医院就诊的NAFLD患者85例,随机分为治疗组(n=45)和对照组(n=40)。治疗组给予强肝胶囊,对照组给予多烯磷脂酰胆碱胶囊,2组疗程均为24周。观察2组治疗前后血清转氨酶(AST、ALT)、稳态模型胰岛素抵抗指数(HOMA-IR)以及NAFLD肝纤维化评分(NAFLDFS)的变化。计量资料组间比较采用成组t检验,组内治疗前后比较采用配对t检验;计数资料组间比较采用χ2检验。结果 2组治疗后ALT、AST水平均较同组治疗前明显改善,差异均有统计学意义(P值均0.05);与治疗前比,治疗组HOMA-IR、NAFLDFS治疗后均明显下降,差异均有统计学意义(3.58±0.85 vs 2.48±0.78,t=6.40,P0.05;-1.78±1.24 vs-2.35±0.98,t=2.40,P0.05)。2组间治疗后比较,治疗组HOMA-IR、NAFLDFS较对照组显著下降,差异均有统计学意义(2.48±0.78 vs 3.09±0.89,t=3.36,P0.01;-2.35±0.98 vs-1.48±1.08,t=3.80,P0.01)。整个疗程未见明显不良反应。结论强肝胶囊不仅能降低血清转氨酶水平,还可改善胰岛素抵抗和减轻NAFLD患者肝纤维化程度。     

高血压病患者非酒精性脂肪肝病与胰岛素抵抗关系探讨

探讨高血压病患者的非酒精性脂肪肝病（NAFLD）与胰岛素抵抗（IR）的关系。190例不伴有糖尿病的患者分为正常血压和高血压组;再根据B超诊断有无脂肪肝将高血压组分为伴NAFLD 48例（观察组）,高血压不伴NAFLD 50例（对照组）。对两组间及高血压组内的体重指数（BM I）、血压、血糖、血脂、血胰岛素、胰岛素抵抗指数（HOMA-IR）及转氨酶等指标进行比较分析,并对NAFLD与上述指标的关系进行多因素logistic回归分析。经相关分析显示：HMOA-IR与血压升高呈显著负相关;高血压伴NAFLD组的BM I、甘油三酯、空腹胰岛素、口服75g葡萄糖后2h胰岛素、ALT,AST及HOMA-IR较不伴NAFLD组显著增高（P〈0.05-0.01）,而且NAFLD与HOMA-IR及ALT呈独立相关（P〈0.05,0.01）。高血压病伴NAFLD患者有更显著的IR,而且在非糖尿病患者中,IR是高血压和NAFLD的独立危险因素。     

非酒精性脂肪性肝病中脂肪组织胰岛素抵抗与肝巨噬细胞的相互作用

【据《J Hepatol》2019年11月报道】题:非酒精性脂肪性肝病中脂肪组织胰岛素抵抗与肝巨噬细胞的相互作用(作者Rosso C等)非酒精性脂肪性肝病(NAFLD)和脂肪性肝炎(NASH)的发病机制可能是由于紊乱的代谢环境与肝脏炎症和纤维化的局部介质之间的相互作用。该研究旨在阐明巨噬细胞活化、靶器官/组织胰岛素抵抗(IR)与肝损伤之间的相互作用。     

非酒精性脂肪性肝病胰岛素抵抗程度与全血细胞计数的相关性

目的探讨伴或不伴2型糖尿病(T2DM)的非酒精性脂肪性肝病(NAFLD)胰岛素抵抗(IR)程度与全血细胞计数各参数的相关性。方法选取糖耐量正常并除外糖尿病史的单纯NAFLD患者102例,T2DM合并NAFLD患者104例,正常对照104例为研究对象,测定空腹血糖(FPG)、空腹胰岛素(FINS)和全血细胞计数,分析胰岛素抵抗指数(HOMA-IR)与全血细胞计数各参数的相关性。结果 T2DM合并NAFLD患者IR及全血细胞计数异常程度较单纯NAFLD患者更重;相关性研究表明男性HOMA-IR与WBC、NEU、LYM、RBC、HGB、HCT呈正相关,女性HOMA-IR与WBC、NEU、LYM、MID、RBC、HGB、HCT呈正相关。结论 NAFLD时白细胞参数和红细胞参数的变化与IR密切相关,T2DM的存在加重了IR对上述血细胞参数的影响。全血细胞计数可以作为反映NAFLD患者IR程度的一种简单实用的检验指标。     

非酒精性脂肪性肝病与代谢综合征指标变化的相关性分析

目的探讨中老年人群中非酒精性脂肪性肝病(NAFLD)与代谢综合征相关指标变化的关系。方法收集2010—2011年暨南大学附属第一医院40岁以上体检人群腹部B超检查的数据,用多因素Logistic回归分析体重指数(BMI)、空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、血尿酸(UA)的变化值与NAFLD变化的关系。结果 2年内男性组和女性组NAFLD检出率都在增加,男性新增NAFLD总检出率为13.7%,明显高于女性新增NAFLD检出率7.5%(P<0.05);男性和女性的NAFLD消减率都是5.5%,且峰值都在60岁年龄组;BMI变化值与新增NAFLD密切正相关,BMI变化值的OR=1.474(95%CI 1.184～1.811),而TG和FBG的变化值与新增NAFLD无相关性;TG和BMI的变化值与NAFLD的消减呈负相关,TG变化值的OR=0.653(95%CI 0.508～0.838),BMI变化值的OR=0.628(95%CI 0.460～0.857),而FBG变化值未发现与NAFLD消减有相关性。结论 BMI变化值与NAFLD发生有密切相关性,TG和BMI的变化值与NAFLD的消减呈负相关,是影响NAFLD变化的重要因素之一。     

Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease

AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m 2 ). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m 2 to 25.0 ± 3.3 kg/m 2 , WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient’s insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r s = 0.90) and liver histology (P = 0.03, r s = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.     

Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease

Insulin resistance is associated with nonalcoholic fatty liver disease (NAFLD) and is a major factor in the pathogenesis of type 2 diabetes. The development of hepatic insulin resistance has been ascribed to multiple causes, including inflammation, endoplasmic reticulum (ER) stress, and accumulation of hepatocellular lipids in animal models of NAFLD. However, it is unknown whether these same cellular mechanisms link insulin resistance to hepatic steatosis in humans. To examine the cellular mechanisms that link hepatic steatosis to insulin resistance, we comprehensively assessed each of these pathways by using flash-frozen liver biopsies obtained from 37 obese, nondiabetic individuals and correlating key hepatic and plasma markers of inflammation, ER stress, and lipids with the homeostatic model assessment of insulin resistance index. We found that hepatic diacylglycerol (DAG) content in cytoplasmic lipid droplets was the best predictor of insulin resistance (R = 0.80, P < 0.001), and it was responsible for 64% of the variability in insulin sensitivity. Hepatic DAG content was also strongly correlated with activation of hepatic PKCε (R = 0.67, P < 0.001), which impairs insulin signaling. In contrast, there was no significant association between insulin resistance and other putative lipid metabolites or plasma or hepatic markers of inflammation. ER stress markers were only partly correlated with insulin resistance. In conclusion, these data show that hepatic DAG content in lipid droplets is the best predictor of insulin resistance in humans, and they support the hypothesis that NAFLD-associated hepatic insulin resistance is caused by an increase in hepatic DAG content, which results in activation of PKCε.     

Prognostic implication of liver histology in patients with nonalcoholic fatty liver disease in diabetes

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist due to shared risk factors. Their rising prevalence parallels the growing epidemic of obesity and insulin resistance (IR). In patients with T2DM and biopsy-proven NAFLD, a significantly higher prevalence of nonalcoholic steatohepatitis (NASH) (63–87%), any fibrosis (22–60%), and advanced fibrosis (4–9%) is noted. Possible risk factors for more advanced liver disease include concomitant metabolic syndrome with three or more components, visceral obesity, older age, increased duration of diabetes, and family history of diabetes. Liver biopsy is strongly suggested in these patients. Cardiovascular disease (CVD) and malignancy are the leading causes of death in this population, but a growing body of evidence shows liver-related mortality as an important cause of death, including an increased rate of hepatocellular carcinoma (HCC) in diabetes. The presence of NAFLD in T2DM is also associated with increased overall mortality. We aim with this review to summarize the results from studies investigating NAFLD in T2DM and to outline the factors that predict more advanced liver histology as well as the impact of these hepatic changes on CVD, overall and liver-related mortality.     

非酒精性脂肪性肝病患者血清preptin水平与胰岛素抵抗的相关性分析

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清preptin水平的变化及其与胰岛素抵抗(IR)的相关性。方法选取2014年4-8月在上海中医药大学附属普陀医院、同济大学附属东方医院门诊、住院的72例NAFLD患者(NAFLD组),53例年龄、性别匹配的正常对照者(正常对照组)为研究对象。所有受试者进行B超检查,根据B超检查结果将NAFLD组患者分为轻度组(n=20)、中度组(n=30)和重度组(n=22)3个亚组。分别测量身高、体质量、收缩压、舒张压、腰围、臀围、肝功能、血脂、高敏C反应蛋白、空腹血糖、空腹胰岛素(FINS)、糖化血红蛋白、血清preptin水平,并计算BMI、腰臀比及稳态模型胰岛素抵抗指数(HOMAIR)。计量资料两组间均数比较采用两独立样本t检验,多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验;相关性分析采用Pearson相关系数法;采用多元线性回归分析各变量与preptin之间的关系,采用logistic回归分析各变量与NAFLD之间的关系。结果 NAFLD组preptin水平(385.54±72.78)pg/ml较正常组(303.85±57.54)pg/ml显著升高(t=-6.76,P0.001);轻度、中度和重度NAFLD组preptin水平逐渐升高,分别为(328.58±53.51)pg/ml﹑(376.71±57.77)pg/ml﹑(449.35±56.95)pg/ml,3组间比较差异有统计学意义(F=3.08,P0.001)。Pearson相关分析显示血清preptin水平与BMI(r=0.475,P0.001)、HOMA-IR(r=0.671,P0.001),FINS(r=0.763,P0.001)成正相关。多元线性回归分析显示FINS和HOMA-IR是影响血清preptin水平的独立相关因素,logistic回归分析显示preptin与NAFLD密切相关。结论 Preptin与NAFLD的发生密切相关,可能通过影响IR而参与NAFLD的发生发展。     

利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用*

目的研究利拉鲁肽对非酒精性脂肪性肝病（NAFLD）大鼠胰岛素抵抗（IR）的改善作用。方法取SD大鼠50只,采用高脂饲料喂养法建立NAFLD大鼠模型,将造模成功的32只大鼠随机分为4组,即模型组(A组,n=8）,其余3组为不同剂量利拉鲁肽处理组,包括B组【0.9 mg·kg-1·d-1,n=8】、C组【（1.8 mg·kg-1·d-1）,n=8】和D组【（3.6 mg·kg-1·d-1,n=8】。在药物干预4 w后,取血和肝脏,制备肝组织匀浆,分别测定大鼠体质量、肝质量、肝指数、血糖、胰岛素（FINS）、血脂（TG、TC）、转氨酶（ALT、AST）、血清丙二醛（MDA）、谷胱甘肽氧化酶（GSH-Px）、肝组织超氧化歧化酶（SOD）、肿瘤坏死因子α（TNF-α）水平。结果与模型组比,药物干预后大鼠体质量、肝指数、血ALT、FINS、FPG、HOMA-IR、MDA和肝组织TG、TC、MDA水平均显著下降（P<0.05）,大剂量组上述指标下降显著高于中小剂量组（P<0.05）;与模型组比,药物干预后大鼠肝组织GSH-Px和SOD水平均显著升高（P<0.05）,且大剂量组升高明显高于中小剂量组（P<0.05）;各组间TNF-α变化无明显差异（P>0.05）。结论利拉鲁肽能显著降低NAFLD大鼠血脂和血糖水平,改善IR,治疗作用呈明显的剂量相关性。     

非酒精性脂肪肝与血清脂联素及胰岛素抵抗的关系

NAFLD通常与超重或肥胖、2型糖尿病、高血压和高脂血症等代谢紊乱有关,胰岛素抵抗可能在脂肪肝形成过程中起重要作用。而脂联素作为一种新发现的由脂肪细胞分泌的激素,具有降低血脂、降低血糖、改善胰岛素敏感性以及拮抗动脉粥样硬化的作用,能拮抗胰岛素低抗。但是目前这     

非酒精性脂肪肝与胰岛素抵抗

目的探讨非酒精性脂肪性肝病（NAFLD）与胰岛素抵抗（IR）的关系。方法NAFLD组52例,非NAFLD组50例,比较两组间BMI、WHR、TC、TG、CRP、HDL-C、LDL-C、ALT、Cr、FBG、FINS和HOMA-IR的差异,并进行Logistic回归分析。结果NAFLD组与非NAFLD组在BMI（26.7±2.3与22.4±2.5,P〈0.01）、WHR（0.94±0.06与0.83±0.05,P〈0.01）、TG（2.4±0.6与1.8±0.6,P〈0.01）、ALT（37.3±8.3与28.1±7.2,P〈0.05）、FBG（6.2±1.4与5.2±0.7,P〈0.01）、FINS（23.6±13.6与8.6±3.5,P〈0.01）、HOMA-IR（6.7±4.7与2.0±1.6,P〈0.01）的差异有统计学意义,Logistic回归分析显示BMI（P〈0.01）、WHR（P〈0.01）、TG（P〈0.01）、ALT（P〈0.05）、HOMA-IR（P〈0.01）是NAFLD的独立影响因素。结论BMI、WHR、TG、ALT、HOMA-IR是NAFLD的独立影响因素。