肥胖与高密度脂蛋白代谢异常研究进展

肥胖是代谢综合征发生发展的中心环节,其与代谢综合征的各个危险因素密切相关.高密度脂蛋白胆固醇水平降低是代谢综合征的特征性血脂代谢异常之一.有研究表明肥胖可通过多种途径影响体内高密度脂蛋白水平和功能,如高甘油三酯血症,脂肪细胞因子,炎症状态,载脂蛋白M异常等.而高密度脂蛋白胆固醇水平降低及功能异常是动脉粥样硬化进展的独立危险因素.本文就肥胖与高密度脂蛋白异常及其影响因素的研究进展作一综述.     

代谢综合征与冠状动脉狭窄程度及心血管危险评分的关系

目的 了解代谢综合征患者冠状动脉狭窄程度及心血管危险评分的特点,以探讨代谢综合征与后两者之间的关系.方法 连续收集胸部不适并行冠状动脉CT检查的136例患者,所有患者均检查血压、空腹血糖及血脂,包括甘油三酯、总胆固醇、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇.应用美国2001年NCEP-ATPⅢ代谢综合征诊断标准,将其分为代谢综合征组及非代谢综合征组.冠状动脉狭窄程度用多层螺旋CT测量,比较两组间冠状动脉狭窄程度的差异,并对心血管危险评分中各项指标的差异进行比较.结果 冠状动脉狭窄程度代谢综合征组均较非代谢综合征组为重,两组的高血压、糖尿病患者、血脂异常及心血管危险评分存在明显差异.结论 代谢综合征患者冠状动脉狭窄程度较重,且多数心血管危险评分较高.代谢综合征可作为冠心病的重要危险因素,早期全面干预其中的各个成分有助于冠心病的防治.     

深圳市坪山社区居民代谢综合征患病情况分析

目的 调查坪山街道社区居民代谢综合征及其各代谢异常组分患病情况,分析其患病特点,为制定社区家庭访视对代谢综合征生活质量及各代谢异常组分的研究提供依据.方法 调查深圳市坪山19个社区20～70岁常住人口1926例进行代谢综合征(MS)患病情况调查,新诊断或已确诊的代谢综合征患者398例,进行腰围、血脂、血压、血糖等的检测和分析.结果 代谢综合征、腰围偏大、血三酰甘油升高、高密度脂蛋白胆固醇降低、血压升高、空腹血糖升高的患病率分别为20.14%、25.9%、29.5%、17.2%、56.9%、20.0%;代谢综合征患病率随年龄增大而J,II'ai:代谢综合征组与非代谢综合征组血尿酸、丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、低密脂蛋白胆固醇的差异有统计学意义(P<0.01).结论 坪山社区居民人群代谢综舍征患病率较高,血压升高发生率最高,其他代谢异常组分的患病率也较高;代谢综合征常同时伴有多种组分检查指标的异常,综合防治工作不容忽视.     

核受体FXR与代谢综合征

法尼基衍生物X受体(FXR)是一种胆汁酸受体,属核受体超家族成员,在胆汁酸及胆固醇代谢中具重要作用.近年来的研究发现FXR能够降低血三酰甘油及血糖,从而与代谢综合征密切相关,并可能成为治疗代谢综合征的新靶点.     

脑梗死合并代谢综合征患者的临床特征

目的 旨在分析脑梗死合并代谢综合征患者的临床特征及与脑血管病变程度的相关性.方法 脑梗死患者585例按NCEP-ATPⅢ诊断标准分为代谢综合征组和非代谢综合征组.回顾性地比较两组患者临床特征,分析代谢综合征与脑血管病变程度的相关性.结果 脑梗死患者585例中有290例(49.6%)合并代谢综合征.代谢综合征组的体质量指数、腰围、动脉血压、总胆固醇、三酰甘油、尿酸、空腹血糖、餐后2 h血糖、糖化血红蛋白均显著高于无代谢综合征组;而高密度脂蛋白胆固醇水平显著低于后者;前者结构性影像(CT)大灶梗死和多灶梗死发生率和重型神经功能缺损积分均显著高于后者.相关分析显示,脑血管病变程度与患者腰围、动脉血压、总胆固醇、三酰甘油、糖化血红蛋白、空腹血糖及餐后2 h血糖水平呈明显正相关(P＜0.05),与高密度脂蛋白胆固醇呈负相关(P＜0.01).结论 脑梗死合并代谢综合征患者使动脉粥样硬化危险因子更加聚集,脑血管病变程度更加严重,应进行全面脑血管危险因素防治,以改善预后.     

代谢综合征患病率及分布特点-青岛港健康研究

目的探讨和分析青岛港职工代谢综合征的患病率及分布特点.方法利用2000年青岛港健康研究调查的18～54岁11536名男女职工完整资料.代谢综合征诊断标准采用ATP Ⅲ(美国国家胆固醇教育项目专家组关于在成人中高血胆固醇的检出、评价和治疗的第三次报告)标准和修改腹部肥胖的标准(男性≥85 cm 、女性≥80 cm).结果按ATP Ⅲ标准,男女职工代谢综合征的患病率分别为6.3%和3.5%,但其中腹部肥胖率最低,男女分别为22.4%和 42.9%;按修改标准男女职工代谢综合征的患病率分别上升为17.7%和4.2%.结论代谢综合征在该人群中占有一定的比例,特别是男职工较为流行,对心血管病和糖尿病的防治有重要意义.我国需要有适合国人特点的代谢综合征的诊断标准.     

老年代谢综合征的基础指标和炎症因子的临床观察

目的探讨老年人患代谢综合征的表现与血炎症因子浓度。方法代谢综合征组和非代谢综合征组老年人各25例。测定其血高敏C反应蛋白(high sensitive C reactive protein,hs-CRP)、白介素6(interleukin-6,IL-6)和肿瘤坏死因子(tumor necrosis factorα,TNFα)等。结果代谢综合征组较非代谢综合征组体质量指数、腰围和腰臀比、收缩压、舒张压、脉压、空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、和脂蛋白(a)抗原,代谢综合征组均较非代谢综合征组升高(P<0.05),而代谢综合征组高密度脂蛋白胆固醇较非代谢综合征组降低。代谢综合征组hs-CRP、IL6、TNFα均高于非代谢综合征组(P<0.01)。结论患代谢综合征老年人与炎症关系密切,表现为血清炎症因子水平升高,故加强炎症状态的监测和干预,对防治代谢综合征具有重要意义。     

代谢综合征患者血清高敏C-反应蛋白的变化及临床意义

目的 观察代谢综合征患者血清高敏C-反应蛋白(hs-CRP)水平的变化,以评价hs-CRP与代谢综合征的临床相关性及意义.方法 用免疫比浊法测定加例代谢综合征患者和30例健康对照者的血清hs-CRP水平,并两两比较.观察hs-CRP与腰围、血压、空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)的相关性.结果与健康对照组比较,代谢综合征患者的hs-CRP水平显著升高(P=0.006),且hs-CRP水平与腰围、收缩压、舒张压、TG、TC、LDL-C、FBG成正相关(r分别为0.37、0.28、0.26、0.39、0.21、0.23、0.18,P＜0.05),与HDL-C成负相关(r=-0.31,p=0.004).结论 hs-CRP可作为临床诊断代谢综合征及评价代谢综合征患者心血管疾病危险性增加的一个简易指标.     

代谢综合征与缺血性卒中或短暂性脑缺血发作的关系

代谢综合征是指多种心血病危险因素的组合。美国国家胆固醇教育计划成人治疗指南（NCEP／ATPⅢ）对临床应用中的代谢综合征进行了定义，应至少包括下列3项内容：空腹血糖升高、高血压、高密度脂蛋白胆固醇降低、三酰甘油增高和腹部肥胖。前瞻性研究已证实，代谢综合征能显著增加心血管病的发病率和病死率。     

冠心病合并代谢综合征患者脂联素水平与炎症因子及冠状动脉病变的关系

目的:探讨冠心病合并代谢综合征(metabolic syndrome,MS)患者脂联素水平与炎症因子及冠状动脉病变的关系.方法:将102例患者分为2组,冠心病合并代谢综合征57例(代谢综合征组);冠心病不合并代谢综合征45例(非代谢综合征组).检测血清脂联素、肿瘤坏死因子-白细胞介素－6、超敏C反应蛋白,并以冠状动脉病变积分评价其病变程度.结果:代谢综合征组和非代谢综合征组年龄、性别、总胆固醇、低密度脂蛋白－胆固醇、空腹胰岛素水平差异无统计学意义(P>0.05);代谢综合征组脂联素水平显著低于非代谢综合征组(P<0.05),肿瘤坏死因子-a、白细胞介素6、超敏C反应蛋白浓度显著高于非代谢综合征组(P<0.05～0.01),冠状动脉三支病变发生率和病变总积分显著高于非代谢综合征组(P<0.05).脂联素与肿瘤坏死因子－白细胞介素6、超敏C反应蛋白及冠状动脉病变程度呈负相关(P<0.05).结论:冠心病患者合并代谢综合征较为普遍,且脂联素水平降低,炎症因子水平升高,冠状动脉病变程度严重.     

Management of gallstones and its related complications

The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.     

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.     

Coordinate regulation of gallbladder motor function in the gut-liver axis

Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation.     

From lipid secretion to cholesterol crystallization in bile. Relevance in cholesterol gallstone disease

Failure of cholesterol homeostasis in the body can lead to cholesterol gallstone disease, the most common and costly gastrointestinal disease. The primum movens in cholesterol gallstone formation is the hypersecretion of hepatic cholesterol; this condition leads to bile chronically supersaturated with cholesterol which is prone to rapid precipitation as cholesterol crystals in the gallbladder. Essential topics reviewed here deal with pathways of biliary lipid secretion, cholesterol solubilization and crystallization in bile, according to recent advances. Main in vivo events in cholesterol gallstone disease are also described.     

Is the FXR the fix for cholesterol gallstone disease?

Cholesterol gallstone disease is characterized by several events, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we describe the same phenotype in mice lacking the bile acid receptor, FXR. Furthermore, in susceptible wild-type mice that recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR agonist prevented sequelae of the disease. These effects were mediated by FXR-dependent increases in biliary bile salt and phospholipid concentrations, which restored cholesterol solubility and thereby prevented gallstone formation. Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease.     

Epidemiology of gallbladder disease: cholelithiasis and cancer

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps.     

Gallstones and Plasma Lipids in a Danish Population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40,50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low-density-lipoprotein cholesterol and total cholesterol was seen.     

Gallstones and plasma lipids in a Danish population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low-density-lipoprotein cholesterol and total cholesterol was seen.     

Effects of colectomy on bile composition, cholesterol saturation and cholesterol crystal formation in humans

Total or subtotal colectomy is the surgical treatment of choice for patients with ulcerative colitis. Recently it has been reported that colectomy may lead to increased lithogenicity of bile, short nucleation time, cholesterol crystal formation, and gallstone disease. We examined whether colectomy in patients with ulcerative colitis leads to changes in bile composition that predisposes to cholesterol crystal formation and cholesterol gallstone disease. Ten consecutive patients who had previously undergone ileostomy and colectomy because of ulcerative colitis were admitted for ileal pouch surgery. At operation bile was obtained by puncture of the gallbladder. Controls were 35 patients undergoing cholecystectomy (23 for cholesterol gallstone disease and 12 for reasons other than gallstone disease). The gallbladder bile was analyzed for cholesterol crystals, bile acid, and biliary lipid composition, cholesterol saturation, and nucleation time. The colectomized patients had normal biliary lipid composition, normal cholesterol saturation, and normal nucleation time, in contrast to gallstone patients who displayed highly supersaturated bile with a short nucleation time. Thus patients with ileostomy after colectomy because of ulcerative colitis have normal cholesterol saturation and nucleation time of bile.