非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性分析

目的 研究非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性.方法 选取非酒精性脂肪肝106例,非酒精性脂肪肝合并代谢综合征58例,单纯肥胖32例,健康体检42例作为对照组.测定体重指数（BMI）和腰臀比（WHR）,检测空腹血糖（FBS）、丙氨酸氨基转移酶（ALT）、胆固醇（TC）、甘油三脂（TG）和高密度脂蛋自（HDL）等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素（FINS）水平,计算胰岛素抵抗指数（HOMA）.同时酶联免疫法测定血清脂联素水平,并用相关及多元回归分析脂联素与各参数的相关性.结果 非酒精性脂肪肝组BMI、ALT、TC、TG、FBS、FINS和HOMA均较正常对照组高,HDL和脂联素水平较正常对照组低;非酒精性脂肪肝合并代谢综合征组胰岛素抵抗程度较非酒精性脂肪肝组更严重,脂联素水平更低.单纯肥胖组ALT、TC高于对照组,脂联素水平有下降趋势.非酒精性脂肪肝ALT异常组与ALT正常组比较,脂联素水平下降.结论 非酒精性脂肪肝存在不同程度胰岛素抵抗,脂联素水平降低;合并代谢综合征者胰岛素抵抗更为严重,脂联素水平更低;合并ALT异常时脂联素水平下降     

老年代谢综合征患者血清游离脂肪酸与胰岛素抵抗的相关性研究

目的探讨老年代谢综合征（MS）患者中血清游离脂肪酸（FFA）水平与胰岛素抵抗（IR）的相关性。方法选取2009年1月至2010年6月上海交通大学附属第一人民医院老年科住院患者96例,年龄≥65岁。采用2005年国际糖尿病联盟提出的标准,分为MS组38例及非MS组58例,分别检测血清FFA、胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆同醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FBG）、空腹胰岛素（FINS）,用稳态模式（HOMAModel）公式计算HOMA—IR评估胰岛素抵抗。分别测各组体重、腰围、身高,计算体质指数（BMI）。结果1、MS组的身高、体重、腰围、BMI、FBG、FINS及HOMA—IR、TC、HDL—C、TG水平均高于非MS组（P〈0．01）,MS组的FFA水平高于非MS组（P〈0．01）;2、直线相关分析显示在MS组中FFA水平与FBG、FINS、HOMA-IR呈正相关（P〈0．05）;3、多元逐步回归分析结果显示FFA与HOMA—IR独立相关（P〈0．05）。结论老年MS患者FFA升高,FFA水平与m存在相关性,FFA是老年MS患者IR的独立危险因素。     

非酒精性脂肪肝:代谢综合征的另一个特征

目的　分析非酒精性脂肪肝 (NAFL)临床及生化特征 ,以探讨NAFL可否成为代谢综合征的一个组成部分。方法　对 85例NAFL患者测体重指数、腰臀比、空腹血糖、血脂、胰岛素、餐后 2h血糖和胰岛素抵抗指数。以 43例非脂肪肝的体检者为对照组。结果　 1.在NAFL患者中 ,中心性肥胖占 70 .5 9% ,高血压病占 3 1.77% ,高TG血症占 62 .3 5 % ,低HDL C占 3 6.47% ,均明显高于对照组 (P <0 .0 0 5～ 0 .0 1) ,而DM/IGT/IPG的患病率 ,两组相比无明显差异 ;2 .血清FINS水平和IR脂肪肝组也较对照组明显增加 (P <0 .0 1) ;3 .在 12 8例研究对象中 ,有 2 1例患者患有代谢综合征 ,其中脂肪肝者占 85 .71% ,中心性肥胖者占 90 .48% ,高血压者占 76.19% ,血脂紊乱者占 10 0 % ,DM/IGT/IPG者占 3 8.10 %。结论　NAFL患者存在明显的胰岛素抵抗 ,可作为代谢综合征的一个组成部分。     

Non-alcoholic fatty liver disease and the metabolic syndrome： An update

Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease （NAFLD）. NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis （NASH） will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.     

反式脂肪酸与代谢综合征

反式脂肪酸高摄入与代谢综合征关系密切.反式脂肪酸不仅可造成脂质代谢异常、胰岛素抵抗、腹型肥胖、全身炎症等代谢功能紊乱,而且增加心血管风险的发生.因此,了解反式脂肪酸-代谢综合征-心血管疾病这样一个关系链,可能为预防代谢综合征及心血管事件的发生提供新的有效途径.     

Management of fatty liver disease with the metabolic syndrome

Non-alcoholic fatty liver disease (NAFLD) is the liver disease of this century, increasing in parallel with obesity, insulin resistance and the metabolic syndrome. NAFLD can be seen as a component of the metabolic syndrome, and as such, contributing as a risk factor for cardiovascular disease. In fact, these patients die more often from cardiovascular disease than from direct consequences of liver disease. In this review, we will summarize the data that link NAFLD as a central player in this dysmetabolism, as well as the evidence for appropriate therapy, in order to improve not only liver disease prognosis, but also the overall prognosis and risk of mortality, with particular focus on cardiovascular risk.     

非酒精性脂肪性肝病与代谢综合征

非酒精性脂肪性肝病(NAFLD)是一种包括从单纯的肝脂肪变性到非酒精性脂肪性肝炎,以致最终发展为肝硬化的一组肝脏慢性广谱性临床病理综合征。近年来大量研究表明,NAFLD与代谢综合征(MS)的各个组分密切伴随,甚至有学者将其作为MS的组分之一,并发现胰岛素抵抗在NAFLD发病机制中起关键作用。迄今对NAFLD的发病机制还了解甚少,目前广泛接受的一个理论是“二次打击”假说。脂肪酸和甘油三酯在肝脏沉积造成的“第一次打击”之后,肝细胞对氧化应激和炎症因子作用导致的“第二次打击”的敏感性增加而引起肝损害。本文主要目的是对NAFLD的临床病理特点、与胰岛素抵抗及MS的关系以及可能的分子机制进行综述,同时也介绍了目前预防和治疗NAFLD的策略。     

非酒精性脂肪性肝病与代谢综合征关系研究进展

非酒精性脂肪性肝病的发病与胰岛素抵抗及其表型有关。胰岛素抵抗和代偿性高胰岛素血症是代谢综合征的中心环节。非酒精性脂肪性肝病是代谢综合征的临床疾病谱之一。非酒精性脂肪性肝病与动脉粥样硬化性心血管疾病、2型糖尿病及代谢综合征临床症候群的关系密切,本文就非酒精性脂肪肝与代谢综合征的关系作一综述。     

代谢综合征不同组分患者血清脂联素与游离脂肪酸谱代谢参数的比较

目的研究代谢综合征（MS）患者血清脂联素水平、游离脂肪酸（FFA）谱特征及与其他糖脂代谢参数间的关系。方法用放射免疫分析法测定157例含MS不同组分的患者与43例正常对照（NC）组血清脂联素水平，同时用气相色谱/质谱（GC/MS）联用法测定其血清FFA成分。结果MS组分≥3项组患者血清脂联素水平低于MS组分两项组与NC组（P〈0.05～0.01）。同时，MS组分≥3项组患者平均血压（MBP）、BMI、WC、TG、不饱和脂肪酸（UFA）（C18：2;C20：4;C22：6;C20：3）、多不饱和脂肪酸（PUFA）、n6PUFA等高于MS组分两项组与NC组（P〈0.05～0.01），HDL-C低于MS组分两项组与NC组（P〈0.01）。在研究对象中，脂联素与BMI、WC、TG呈负相关（r=-0.204，-0.203，-0.238，P〈0.01），与HDL-C呈正相关（r=0.238，P〈0.01）。总FFA（TFFA）、PUFA均与BMI、MBP、FPG、TG呈正相关（r=0.163和0.211，0.201和0.288，0.184和0.276，0.274和0.155，P〈0.05～0.01）。结论脂联素与FFA均与MS多种组分相关。脂联素与FFA代谢紊乱、n6系PUFA升高可能在MS发病中起重要作用。     

成人非酒精性脂肪肝与代谢综合征相关性分析

目的分析成人非酒精性脂肪肝病（NAFLD）和代谢综合征（MS）的关系。方法对2007年6月～10月广元市北街社区3180例20岁以上居民进行体格检查及肝脏B超检查,并检测空腹血糖（FBG）、血脂和丙氨酸氨基转氨酶（ALT）。结果（1）NAFLD患病率为13．5％,MS患病率为16．5％,丽病共患率为9．5％。（2）MS、中心性肥胖、血压升高、FBG升高、高甘油三酯（TG）、高密度脂蛋白（HLD—C）降低,各组NAFLD患病风险是对照组的12．7～24．1倍。（3）以NAFLD取代诊断MS的5个组分中的任何一个后,与原诊断定义相比有较高的一致性。结论该社区中1／8以上人群患有NAFLD或MS,且NAFLD与MS密切相关,NAFLD可能是MS的重要组成成分。     

Clinical significance of fatty liver associated with metabolic syndrome

Aim: Metabolic syndrome (MS) has been recognized as a high-risk disorder that leads to life-threatening diseases, such as coronary vascular disease. The aim of the present study was to investigate the association of fatty liver (FL) with MS in order to establish an effective treatment for FL. Methods: One thousand two hundred and fifty-four individuals (694 males, 560 females) who visited the Department of General Medicine, International Medical Center of Japan for a human dry dock annual check-up from 2000 to 2004 were analyzed. Results: FL was diagnosed in 41.5% of the males and 10.7% of the females, with the prevalence rate increasing in postmenopausal females over 55 years old. High body mass index and waist circumference were observed in those with FL, whereas body mass index reduction was strongly correlated with a decrease in alanine aminotransferase level (R = 0.6,P < 0.01). MS complications were more common in subjects with FL and the most common initial events of MS were shown to be obesity, hyperlipidemia and FL, followed by glucose intolerance and hypertension. Subjects with FL showed a higher level of high-sensitivity C-reactive protein (hs-CRP) (normal: FL = 0.38: 0.73 mg/L, P < 0.05), which was strongly correlated with serum markers that indicated lipid and glucose metabolism in females with FL (R = 0.61-0.77, P < 0.05). Conclusions: FL could be a part of or, at least, a predictor of MS. Further, bodyweight reduction is an effective treatment for FL.     

Clinical implications of fatty pancreas： Correlations between fatty pancreas and metabolic syndrome

AIM： To investigate the clinical implications of lipid deposition in the pancreas （fatty pancreas）. METHODS： The subjects of this study were 293 patients who had undergone abdominal computed tomography （CT） and sonography. Fatty pancreas was diagnosed by sonographic findings and subdivided into mild, moderate, and severe fatty pancreas groups comparing to the retroperitoneal fat echogenicity. RESULTS： Fatty pancreas was associated with higher levels for visceral fat, waist circumference, aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, total cholesterol, triglyceride, high density lipoprotein, free fatty acid, γ-GTP, insulin, and the homeostasis model assessment of insulin resistance （HOMA-IR） than the control group （P 〈 0.05）. HOMA- IR, visceral fat, triglyceride, and ALT also tended to increase with the degree of fat deposition in the pancreas on sonography. In a multivariate logistic regression analysis, HOMA-IR, visceral fat, and ALT level were independently related to fatty pancreas after adjustment for age, body mass index, and lipid profile. The incidence of metabolic syndrome in the fatty pancreas group was significantly higher than in the control group, and the numbers of metabolic syndrome parameters were significantly higher in the fatty pancreas group （P 〈 0.05）. CONCLUSION： Sonographic fatty pancrease showed higher insulin resistance, visceral fat area, triglyceride, and ALT levels than normal pancreases. Fatty pancreas also showed a strong correlation with metabolic syndrome.     

HDL2-cholesterol/HDL3-cholesterol ratio was associated with insulin resistance,high-molecular-weight adiponectin,and components for metabolic syndrome in Japanese

AimsRecent data have suggested a relationship between the high-density lipoprotein (HDL) subclass ratio and metabolic syndrome (MetS). However, limited information is available regarding the relationships between the HDL subclass ratio and insulin resistance, associated adipocytokine levels, and MetS components. The associations of the high-density lipoprotein 2 cholesterol (HDL₂-C) to high-density lipoprotein 3 cholesterol (HDL₃-C) ratio with the homeostasis model assessment of insulin resistance (HOMA-IR) index, high-molecular-weight adiponectin (HMW-Ad) levels, and MetS components were examined.MethodsThe study included 1155 Japanese subjects who met our inclusion criteria and underwent an annual health examination that included an HDL subclass analysis.ResultsThe HDL₂-C/HDL₃-C ratio and the HMW-Ad level gradually decreased as the number of MetS components increased. In contrast, HOMA-IR gradually increased as the number of MetS components increased. The HDL₂-C/HDL₃-C ratio correlated inversely with HOMA-IR and positively with the HMW-Ad level. A strong positive correlation was observed between the HDL₂-C/HDL₃-C ratio and the HDL-C level. The HDL₂-C/HDL₃-C ratio exhibited moderate negative correlations with the body mass index, waist circumference, and triglyceride level. Weak negative correlations were observed for the HDL₂-C/HDL₃-C ratio with the systolic and diastolic blood pressure and fasting plasma glucose levels.ConclusionsOur data indicated that the HDL₂-C/HDL₃-C ratio was associated with insulin resistance, the HMW-Ad level, and MetS components, and it was useful for evaluating MetS in Japanese individuals.     

Non-alcoholic fatty liver disease: further expression of the metabolic syndrome

Non-alcoholic fatty liver disease has been associated with metabolic disorders, including central obesity, dyslipidemia, hypertension and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease refers to a wide spectrum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis, advanced fibrosis and cirrhosis.     

Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome

Aims/hypothesis The aim of this study was to investigate whether intrahepatic and intramyocellular fat are related to insulin resistance in these respective tissues or to the metabolic syndrome. Methods Hepatic (insulin 1.8 pmol kg⁻¹ min⁻¹ combined with [3-³H]glucose) and muscle (insulin 6.0 pmol kg⁻¹ min⁻¹) insulin sensitivity were measured on separate occasions in 45 non-diabetic men (age 42 ± 1 years, BMI 26.2 ± 0.6 kg/m²) using the euglycaemic–hyperinsulinaemic clamp. Liver fat and intramyocellular lipid (IMCL) were measured by proton magnetic resonance spectroscopy and body composition by magnetic resonance imaging. We also determined fasting serum insulin and adiponectin concentrations, components of the metabolic syndrome and maximal oxygen consumption. Results In participants with high [median 12.0% (interquartile range 5.7–18.5%)] vs low [2.0% (1.0–2.0%)] liver fat, fasting serum triacylglycerols (1.6 ± 0.2 vs 1.0 ± 0.1 mmol/l, p = 0.002) and fasting serum insulin (55 ± 4 vs 32 ± 2 pmol/l, p < 0.0001) were increased and serum HDL-cholesterol (1.26 ± 0.1 vs 1.48 ± 0.1 mmol/l, p = 0.02) and fasting serum adiponectin (9.5 ± 1.2 vs 12.2 ± 1.2 μg/ml, p = 0.05) decreased. In participants with high [19.5% (16.0–26.0%)] vs low [5.0% (2.3–7.5%)] IMCL, these parameters were comparable. Liver fat was higher in participants with [10.5% (3.0–18.0%)] than in those without [2.0% (1.5–6.0%), p = 0.010] the metabolic syndrome, even independently of obesity, while IMCL was comparable. Insulin suppression of glucose rate of appearance and serum NEFA was significantly impaired in the high liver fat group. Conclusions/interpretation Fat accumulation in the liver rather than in skeletal muscle is associated with features of the metabolic syndrome, i.e. increased fasting serum triacylglycerols and decreased fasting serum HDL-cholesterol, as well as with hyperinsulinaemia and low adiponectin.     

代谢综合征患者阿司匹林抵抗的临床研究

目的探讨代谢综合征患者阿司匹林抵抗的发生率和临床特征。方法对2005年5月至6月北京首钢社区人群中221例病情稳定的代谢综合征患者,口服阿司匹林200mg/d共10d后,应用血小板聚集仪测定花生四烯酸(AA)诱导的血小板聚集率。以0.5g/LAA诱导的血小板平均聚集率≥20%为阿司匹林抵抗。结果阿司匹林抵抗发生率为17.6%(39/221)。阿司匹林抵抗(AS)组患者的纤维蛋白原水平显著高于阿司匹林敏感(AR)组的患者[(2.6±0.4)g/L对(2.4±0.4)g/L,P=0.017)]。两组患者的血压、年龄、空腹血糖、血脂以及体重指数等差异均无统计学意义;性别、吸烟、既往心梗或脑梗病史的分布也无统计学意义。进一步根据患者性别进行分层分析发现,在男性患者中心梗病史是阿司匹林抵抗的预测因素(50%对14.5%,P=0.020),在女性患者中舒张压高于85mmHg(1mmHg=0.133kPa)是阿司匹林抵抗的预测因素(34.0%对15.5%,P=0.043)。结论研究人群中阿司匹林抵抗的发生率为17.6%,高纤维蛋白原是阿司匹林抵抗的危险因素,心梗病史和较高的舒张压可能分别是男性和女性阿司匹林抵抗的预测因素。     

代谢综合征与自由脂肪酸的关系

目的探讨代谢综合征及其不同组分与自由脂肪酸（free fatty acid,FFA）的关系。方法1999年9月至10月,在北京市自然人群中采用分层随机抽样方法进行危险因素的横断面调查。分析了997名35～64岁男女两性的血浆FFA浓度与代谢综合征及其组分的关系。结果（1）代谢综合征的患病率随着FFA的升高而升高。（2）采用多因素logistic回归调整了年龄、性别、吸烟、饮酒、体重指数（BMI）和胰岛素抵抗后,FFA四分位分层的第二、三、四层的OR值分别为3．1、3．1和4．1,均有统计学意义（P 〈 0．01）。（3）在相关分析中,FFA与甘油三酯（TG）、血糖、收缩压、舒张压和腰围的相关均有统计学意义（P 〈 0．01）,其中与TG的相关性最强,与血糖的相关性其次。FFA与高密度脂蛋白胆固醇（HDL-C）的相关无统计学意义。（4）用多因素logistic分析调整了BMI和胰岛素抵抗等因素后,FFA仍与代谢综合征5个组分中的腹部肥胖、高TG血症、高血压、高血糖4个组分相关,与低HDL-C血症的关系无统计学意义。（5）调整了FFA和BMI等因素的作用后,胰岛素抵抗也与代谢综合征及其5个组分中的腹部肥胖、高TG血症、高血糖和低HDL-C血症相关,而与高血压的关系无统计学意义。结论FFA与代谢综合征和代谢综合征5个组分中的腹部肥胖、高TG血症、高血压、高血糖4个组分均相关,提示FFA是代谢综合征的发病基础或危险因素之一。FFA和胰岛素抵抗可能通过不同的机制共同导致代谢综合征。     

Adiponectin--a key adipokine in the metabolic syndrome

Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.