脂肪肝与胰岛素抵抗

采用病例对照研究,2型糖尿病伴有脂肪肝(DF)组33例,2型糖尿病不伴脂肪肝(NDF)组48例,脂肪肝(F)组13例,正常对照(C)组14例.检测4组患者的体脂参数、血脂、并行OGTT以及胰岛素释放试验,采用稳态模型胰岛素抵抗指数(HOMA IR)评价胰岛素抵抗.结果DF组与NDF组、F组与C组比较,体重指数(BM1)、腰围(W1)、腰臀比(WHR)、胆固醇(TC)、甘油三脂(TG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、HOMA IR水平明显升高(P<0.05).F组的空腹血糖、餐后血糖、空腹胰岛素和餐后胰岛素水平高于C组(P<0.05).结论脂肪肝患者普遍存在胰岛素抵抗,提示胰岛素抵抗及糖脂代谢异常在脂肪肝的发病机制中具有十分重要的作用.     

清肝调脂饮对非酒精性脂肪性肝炎大鼠胰岛素抵抗的影响

目的探讨清肝调脂饮对非酒精性脂肪性肝炎（NASH）大鼠胰岛素抵抗的干预机制。方法建立高脂饲料诱导的Wistar大鼠NASH模型并随机分组,清肝调脂饮低、中、高剂量组和西利宾胺组分别灌胃相应剂量药物治疗。实验12周后,检测各组大鼠血清TG、TC、葡萄糖、瘦素、FFA、INS;肝组织行脂肪染色、糖原染色并作定量分析。结果与模型组比较,各用药组均能不同程度改善以上各指标（P〈0.05,P〈0.01）,其中,在降低TG、葡萄糖、INS、FFA方面,中药高剂量组均明显优于西药对照组（P〈0.05）。结论清肝调脂饮促进游离脂肪酸代谢与肝内TG分解;改善胰岛素抵抗（IR）及瘦素抵抗（LR）。与西利宾胺比较,清肝调脂饮在抑制NASH的IR方面具有明显的疗效优势。     

健脾调脂汤对高三酰甘油血症患者胰岛素抵抗的影响

目的 观察健脾调脂汤对高三酰甘油血症(TG)患者胰岛素抵抗的影响.方法 筛选50例高三酰甘油血症患者为HTG组,另选50名健康者为对照组.高TG组予健脾调脂汤治疗,治疗8周,观察治疗前后临床特征、胰岛素抵抗程度及血清游离脂肪酸(FFA)水平变化.结果 健脾调脂汤治疗8周后,其TG、空腹胰岛素及空腹血糖、胰岛素抵抗指数、FFA明显降低,与治疗前比较差异有统计学意义(P＜0.05).结论 高三酰甘油患者存在明显的胰岛素抵抗,健脾调脂汤治疗可以降低血三酰甘油,减轻胰岛素抵抗.     

脂肪肝胰岛素抵抗大鼠模型的建立

目的 建立脂肪肝胰岛素抵抗大鼠模型。方法 雄性Wistar大鼠14只，随机分为模型组和正常组，模型组喂养高脂饮食，正常组喂养普通饮食，两组脂肪分别占摄入能量的45％和19％，共饲养8周。胰岛素敏感性用正常血糖高胰岛素钳夹技术稳态时的葡萄糖输注率(GIR)来评价，生物化学法测定氨基转移酶、甘油三酯(TG)、游离脂肪酸(FFA)、丙二醛(MDA)、超氧化物歧化酶(SOD)和放射免疫法测定胰岛素，并用光镜和电镜进行组织学和超微结构检查。结果 模型组大鼠肝细胞均呈现弥漫性脂肪变性、肝小叶内炎症及线粒体异常，而正常组肝脏无异常。且模型组的氨基转移酶、TG、FFA和肝指数均显著高于正常组，血清胰岛素升高，GIR明显低于正常组，肝脏MDA升高、SOD降低。结论 通过8周高脂饮食成功地建立脂肪肝胰岛素抵抗大鼠模型，为脂肪肝发病机制和治疗研究提供了一个理想的实验工具。     

小檗碱对非酒精性脂肪肝胰岛素抵抗及血清脂联素的影响

目的观察小檗碱对非酒精性脂肪肝（nonalcoholic fatty liver disease,NAFLD）胰岛素抵抗及血清脂联素（adiponectin,APN）的影响。方法选取我院门诊就诊的NAFLD患者68例,分为对照组（30例）和治疗组（38例）;健康体检者30例为健康组。治疗前分别测定NAFLD组及健康组的APN、血糖、血脂、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、胰岛素敏感性指数（HOMA-IAI）及肝功能水平的变化。治疗组予小檗碱0.5g/次,3次/d,连续3月;对照组予低脂饮食,治疗3月后测定上述各指标。结果 NAFLD患者空腹血糖（FPG）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、FINS、HOMA-IR及体质量指数（BMI）均明显升高,胰岛素敏感性降低,APN水平明显减少（P〈0.05）。口服小檗碱治疗后,治疗组FPG、TC、TG、LDL-C、FINS、HOMA-IR及BMI均明显下降,胰岛素敏感性,APN水平则明显升高（P〈0.05）,对照组各指标无变化（P〉0.05）。结论小檗碱治疗后,NAFLD患者血清APN水平明显升高,改善了胰岛素敏感性,降低了胰岛素抵抗。     

胰岛素抵抗与脂代谢紊乱

胰岛素抵抗(IR)是指机体靶组织对胰岛素敏感性/反应性降低,即一定量胰岛素产生的生物效应低于预计正常水平,胰岛素对靶组织作用减弱,加大胰岛素浓度可提高总效应.机体为克服IR常伴有代偿性的高胰岛素血症.     

胰岛素抵抗与脂肪肝

目前越来越多的研究提示胰岛素抵抗是代谢综合征的病理生理基础,而胰岛素抵抗又与血循环、肝细胞内的游离脂肪酸的蓄积、脂肪细胞中肿瘤坏死因子-α超表达以及铁的蓄积、瘦素等因素息息相关,从而影响脂肪肝和非酒精性脂肪性肝炎的发病,因此胰岛素抵抗可能并不是脂肪肝的继发改变,而可能是其原发始动因素.     

非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究

为了研究非酒精性脂肪肝(NAFL)患者的瘦素(Leptin)抵抗和胰岛素抵抗的状况，对40例NAFL患者和30例正常对照组的血清瘦素、胰岛素等水平进行了分析研究，现将结果报道如下。     

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。     

The Effect of Pioglitazone and Metformin on Liver Function Tests,Insulin Resistance,and Liver Fat Content in Nonalcoholic Fatty Liver Disease: A Randomized Double Blinded Clinical Trial

Background

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of insulin resistance (IR) syndrome. The effect of insulin sensitizers on liver function tests and metabolic indices in NAFLD patients is a matter of debate.

Objectives

The aim of study was to compare the effects of two different insulin sensitizers, pioglitazone, and metformin, on liver function tests (LFT), lipid profile, homeostasis model assessment-IR (HOMA-IR) index, and liver fat content (LFC) in NAFLD patients.

Materials and Methods

This double blind clinical trial was performed on patients who were referred to a gastroenterology clinic with evidence of fatty liver in ultrasonography. After excluding other causes, participants with persistent elevated alanine aminotransferase (ALT) levels and “NAFLD liver fat score” greater than -0.64 were presumed to have NAFLD and were enrolled. They were randomly assigned to take metformin (1 g/day) or pioglitazone (30 mg/day) for four months. Fasting serum glucose (FSG), ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, cholesterol (CHOL), high and low density lipoprotein (HDL, LDL), HOMA-IR, and LFC were checked at the baseline, two and four months post-treatment. LFC was measured by a validated formula.

Results

Eighty patients (68 males) with mean age of 35.27 (± 7.98) were included. After 2 months, LFT was improved significantly in the pioglitazone group and did not change in the metformin group. After four months, both medications significantly decreased serum levels of LFT, FSG, CHOL, LDL, HOMA-IR, and LFC, and increased serum level of HDL. No statistically significant differences were seen between the two treatment groups with regard to the changes of laboratory parameters and LFC from baseline to four months post-treatment.

Conclusions

During the four months, the use of metformin (1 g/day) and pioglitazone (30 mg/day) were safe and might have equally affected LFT, HOMA-IR, lipid profile, and LFC in NAFLD patients.     

脂类对非酒精性脂肪性肝病发生的影响

作为代谢综合征重要组分之一的非酒精性脂肪性肝病（NAFLD）在肥胖、2型糖尿病和高脂血症人群中有着相当高的发病率．如不予及时干预,将给人类健康带来巨大威胁。脂质在肝脏异常异位蓄积是NAFLD发生的主要原因,其中起重要作用的脂类主要包括三酰甘油、胆固醇和脂肪酸。这些脂质来源各异,分别在NAFLD肝细胞脂肪变性的不同阶段发挥作用。本文就不同脂类在NAFLD发生中的作用作一综述。     

活血化瘀化痰利湿法对肥胖性脂肪肝大鼠胰岛素敏感指数和肿瘤坏死因子的影响

目的:探讨活血化瘀、化痰利湿法改善肥胖性脂肪肝大鼠胰岛素抵抗(IR)状态的机制,为临床中医辨证治疗脂肪肝提供实验依据。方法:32只健康雄性SD大鼠随机分为正常组、造模组、西药组、中药组。除正常组饲以普通饲料外,其余各组均饲以高脂饲料。造模4周后,上述4组分别以生理盐水、生理盐水、0.08％东宝肝泰混悬液、中药煎剂灌胃。实验第16周测定血清和脂肪组织中肿瘤坏死因子-α(TNF-α)及血糖、胰岛素等。并取肝组织标本病理切片。结果:①胰岛素敏感指数(ISI):治疗组较造模组显著提高(P<0.05);中药组与正常组相比无显著性差异(P>0.05),与西药组相比有明显差异性(P<0.05)。②血清和脂肪组织TNF-α:治疗组与造模组相比有显著性差异(P<0.01),治疗组与正常组相比无明显差异性(P>0.05),中药组与西药组相比无明显差异(P>0.05)。③肝脏病理切片:正常组大鼠肝脏无异常病变、模型组大鼠肝脏均出现不同程度的肝脂变。各治疗组大鼠肝脏脂变程度明显减轻。结论:活血化瘀、化痰利湿法能够降低脂肪细胞TNF-α的表达,提高肥胖性脂肪肝大鼠ISI,改善IR状态;改善肝细胞的病理损伤状况,从而达到抗脂肪肝的目的。     

脂肪肝与胰岛素抗性的关系

目的探讨脂肪肝与胰岛素抗性的关系。方法对30例诊断为脂肪肝患者的临床资料作回顾性分析。结果多数患者合并胰岛素抗性综合征(高血压、肥胖症、糖尿病、高脂血症),18例接受口服葡萄糖耐量试验(OGTT)患者中,1例确诊为2型糖尿病,17例患者中3例空腹血糖减损(IFG),1例糖耐量减退(IGT)及13例糖耐量正常(NGT)具有较正常人为高的血浆胰岛素(INS)浓度,胰岛素抗性指数为8.91±1.52%。结论脂肪肝与胰岛素抗性所致的代谢紊乱关系紧密,呈正相关关系。     

核因子-κB与非酒精性脂肪性肝病

KB是一类重要的转录调控因子．通过调节免疫和炎症相关因子的表达在炎症和免疫反应中起枢纽作用。NF-KB与NAFLD的关系密切，对NF-KB的研究可能为探讨NAFLD的发病机制和治疗方案提供新的线索。本文就NF-KB的生物学特性、功能及其在NAFLD发生、发展中的作用作一综述。     

非肥胖高血压病患者的非酒精性脂肪肝与胰岛素抵抗的相关性

目的探讨非肥胖的高血压病患者的非酒精性脂肪肝(NAFLD)与胰岛素抵抗(IR)的相关性。方法93例非肥胖的不伴有糖尿病的高血压病患者,根据B超诊断有无脂肪肝分为高血压伴NAFLD45例,高血压不伴NAFLD48例。对两组患者的体重指数(BMI)、血压、血糖、血脂、血胰岛素、胰岛素抵抗指数(HOMAIR)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的logistic回归分析。结果高血压伴NAFLD组的BMI(25.2±1.5vs24.1±1.9,P=0.002)、甘油三酯(2.3±1.0vs1.9±0.8,P=0.034)、空腹胰岛素(15.0±6.0vs10.9±5.3,P=0.001)、口服75g葡萄糖后2h胰岛素(50.5±22.4vs37.9±16.0,P=0.003)、丙氨酸氨基转移酶(ALT)(22.8±8.9vs16.7±6.7,P<0.001)、天门冬氨酸氨基转移酶(18.8±6.4vs16.2±5.1,P=0.030)及HOMAIR(1.2±0.5vs0.8±0.5,P=0.001)较不伴NAFLD组显著增高,而且NAFLD与HOMAIR(OR2.847,95%CI1.122～7.228;P=0.028)及ALT(OR1.075,95%CI1.013～1.140;P=0.016)呈独立相关。结论高血压病伴NAFLD患者有更显著的IR,而且在非肥胖的高血压病患者中,IR是NAFLD的独立危险因素。     

Effect of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease

Background:

Nonalcoholic fatty liver disease (NAFLD) has different prevalence rates in various parts of the world and is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis, cirrhosis, and liver failure.

Objectives:

The current study aimed to investigate the effect of Aerobic Training (AT) and resistance training (RT) on hepatic fat content and liver enzyme levels in Iranian men.

Patients and Methods:

In a randomized clinical trial study, 30 men with clinically defined NAFLD were allocated into three groups (aerobic, resistance and control). An aerobic group program consisted of 45 minutes of aerobic exercise at 60% - 75% maximum heart rate intensity, a resistance group performed seven resistance exercises at intensity of 50% - 70% of 1 repetition maximum (1RM ) and the control group had no exercise training program during the study. Before and after training, anthropometry, insulin sensitivity, liver enzymes and hepatic fat were elevated.

Results:

After training, hepatic fat content was markedly reduced, to a similar extent, in both the aerobic and resistance exercise training groups (P ≤ 0.05). In the two exercise training groups, alanine amino transferase and aspartate amino transferase serum levels were significantly decreased compared to the control group (P = 0.002) and (P = 0.02), respectively. Moreover, body fat (%), fat mass (kg), homeostasis model assessment insulin resistance (HOMI-IR) were all improved in the AT and RT. These changes in the AT group were independent of weight loss.

Conclusions:

This study demonstrated that RT and AT are equally effective in reducing hepatic fat content and liver enzyme levels among patients with NAFLD. However, aerobic exercise specifically improves NAFLD independent of any change in body weight.     

他莫昔芬对肝细胞胰岛素敏感性的影响

背景: 胰岛素抵抗是非酒精性脂肪性肝病(NAFLD)发生的中心环节。他莫昔芬可诱发肝脏脂肪变性,但该作用是否与胰岛素抵抗有关尚不清楚。目的: 观察他莫昔芬对肝细胞胰岛素敏感性的影响并探讨其可能机制。方法: 体外培养人正常肝细胞株L02,予不同浓度他莫昔芬干预24h(联合或不联合抗氧化剂N-乙酰半胱氨酸),加入500ng/ml胰岛素和11.1 mmol/L葡萄糖,以葡萄糖氧化酶-过氧化物酶(GOD-POD)法检测各组葡萄糖吸收量,同时检测细胞内谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平。结果: 与空白对照组相比,1、3、5μmol/L他莫昔芬可显著抑制L02细胞对葡萄糖的吸收(P0.05),作用呈浓度依赖性,并显著减低细胞内GSH和SOD水平(P0.05)。N-乙酰半胱氨酸能改善他莫昔芬对L02细胞葡萄糖吸收的抑制作用(P0.05)。结论: 他莫昔芬能诱导肝细胞发生胰岛素抵抗,氧化应激可能参与其发生机制。     

The Effect of Helicobacter Pylori Eradication on Liver Fat Content in Subjects With Non-Alcoholic Fatty Liver Disease: A Randomized Open-Label Clinical Trial

Background

The role of Helicobacter pylori (HP) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is unclear.

Objectives

The aim of this study was to evaluate the effect of HP eradication on liver fat content (LFC), liver function tests (LFT), lipid profile, and homeostasis model assessment-IR (HOMA-IR) index in NAFLD.

Patients and Methods

Dyspeptic patients with increased serum aminotransferase levels were enrolled in the study. The exclusion criteria were factors affecting serum aminotransferase or HP treatment strategy. Participants with persistent elevated serum aminotransferase level and ultrasound criteria for identification of fatty liver were presumed to have NAFLD. “NAFLD liver fat score” was used to classify NAFLD. Those with “NAFLD liver fat score” greater than -0.64 and positive results for urea breath test (UBT), were included. Lifestyle modification was provided to all participants. HP eradication was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein (HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of eight weeks and twenty four weeks.

Results

One hundred (49 males) patients with the mean age of 43.46 (± 11.52) were studied. Repeated measure ANOVA showed a significant reduction in LFC, anthropometric measurements, and laboratory parameters (except for HDL) in the both groups during the study; however, no significant difference was observed between the groups.

Conclusions

It seems that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin resistance in dyspeptic NAFLD patients.     

肠道微生态失衡致非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病（NAFLD）已成为一种常见的慢性肝病。近年肠道微生态失衡致NAFLD发病的机制研究已成为一个新的热点。国内外文献已报道相关发病机制可能包括干扰代谢、促进胰岛素抵抗、产生毒性代谢产物、增加肠壁通透性、激活肠道免疫、加重肝脏脂质氧化和氧化应激、激活肝脏免疫炎症损伤和肝纤维化等。而NAFLD发展到一定阶段后又可反过来影响肠道微生态,形成恶性循环。本文就肠道微生态失衡致NAFLD发病机制的研究进展作一综述。