男性胆囊胆固醇结石患者血浆脂联素、性激素水平与体脂分布的关系

目的探讨男性胆囊胆固醇结石患者血浆脂联素、性激素水平与体脂分布的关系。方法对30名男性胆囊胆固醇结石患者与30名健康志愿者，分别测定其血浆脂联素、雌二醇（E2）、游离睾酮（FT）、总睾酮（TT）水平，同时监测血压、腰围（WC）、体重指数（BMI）、腰／臀比（WHR），并进行比较。结果（1）结石组血浆FT、TT、脂联素水平较对照组低（P〈0．05），控制BMI、WC、WHR后，结石组脂联素水平仍较对照组低（P〈0．05），而E2值差异无统计学意义（P〉0．05）。结石组WC、WHR、BMI较对照组高（P〈0．01），均具统计学意义。（2）男性胆囊胆固醇结石血浆脂联素水平与WC呈负相关，TT水平与BMI呈负相关，FT水平与BMI、WHR、WC呈负相关，（P〈0．05）。（3）多因素分析提示WHR、TT水平为男性胆囊胆固醇结石发病的危险因素。结论（1）男性胆囊胆固醇结石患者血浆脂联素、TT、FT水平同时降低，TT水平是男性胆囊胆网醇结石发病的危险因素。（2）男性胆囊胆固醇结石患者存在体脂分布异常，雄激素在男性胆囊胆固醇结石病人脂联素水平的降低中似乎未参与调节，脂联素、雄激素水平同时降低可能是由于体脂分布异常所致，体脂分布异常是男性胆囊胆固醇结石发病的危险因素。     

胆囊胆固醇结石症易感基因的研究进展

胆囊胆固醇结石症是常见的消化系统疾病之一,也是胆囊癌的一个重要危险因素。胆囊胆固醇结石的形成与遗传和环境等多种因素的作用有关,其中胆汁胆固醇过饱和、促成核蛋白及胰岛素抵抗与之密切相关。此文将从这三方面就胆囊胆固醇结石症发生相关的基因研究进展作一综述,以期进一步增进对其发病机制的了解。     

基因多态性参与胆固醇结石发病机制的研究进展

胆汁胆固醇过饱和及胆汁淤积是胆固醇结石的重要诱因。基因多态性通过影响胆固醇的转运及代谢,导致胆汁胆固醇过饱和、降低胆囊动力加重胆汁淤积,使个体对胆固醇结石的易感性增加。此文就近几年来对基因多态性在影响胆固醇结石发生方面的研究进展进行综述,以期进一步了解基因多态性在胆固醇结石发生中的作用,增进对胆固醇结石发病机制的了解,并为胆固醇结石的诊治提供新的思路。     

老年胆固醇结石患者载脂蛋白E基因多态性分析

目的 探讨载脂蛋白E(ApoE)基因多态性在老年胆固醇结石发病中的意义.方法 采用聚合酶链反应-限制性片段长度多态性分析方法(PCR-RFLP),检测92例老年胆囊胆固醇结石患者和98例健康老年人的ApoE基因多态性及等位基因频率,对两组基因表型及等位基因频率进行统计学分析.结果 老年胆囊胆固醇结石患者组ApoE基因型ε3/4的频率26.1%(24/92)明显高于健康老年人对照组6.1%(6/98)(P＜0.05),老年胆囊胆固醇结石患者组ε4等位基因频率为32.7%,明显高于健康老年人对照组的21.4%(P＜0.05).结论 ApoE基因多态性与老年人胆囊胆固醇结石的发病相关;等位基因ε4是老年胆囊胆固醇结石形成的危险因素.     

胆固醇结石的发病机制与治疗

胆囊结石是整个世界范围内的常见消化道疾病之一,一旦出现并发症,会产生重大的经济和社会负担。胆囊结石中大部分患者为胆固醇结石。该文分析胆固醇结石的西医发病机制以及中医病因病机,同时进一步总结了胆固醇结石的治疗方法,从现代医学和传统医学角度提供胆固醇结石的诊疗思路。     

高血压病合并脂肪肝发病的危险因素分析

目的探讨高血压病合并脂肪肝发病的危险因素。方法选择进行了肝脏B超检查的住院高血压病患者,根据超声影像的诊断结果分为高血压合并脂肪肝组(98例)和高血压未合并脂肪肝组(102例),分析体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、胰岛素抵抗指数(HO-MA-IR)、糖耐量试验各时段的血糖水平、胰岛素释放试验的胰岛素水平与脂肪肝之间的关系。结果(1)Logistic回归分析的结果表明空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症是高血压患者脂肪肝形成的独立危险因素;(2)高血压合并脂肪肝组的HOMA-IR、TG、空腹和糖负荷后2、3小时的血糖和胰岛素水平高于对照组(均P<0.05)。校正两组BMI后,上述差异仍然存在。结论(1)高血压病患者脂肪肝发病的独立危险因素是空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症,随着这些危险因素的聚集,脂肪肝的检出率增加。(2)脂肪肝是高血压病患者胰岛素抵抗的“重要标志”,脂肪肝是代谢综合征的一种表现。     

血清胆固醇及肝功能指标水平在鉴别胆结石类型中的价值

目的探讨血清胆固醇及肝功能指标水平在鉴别胆结石类型中的价值。方法回顾性分析在该院普外科接受手术治疗的158例胆结石患者的临床资料,按照术后结石中胆固醇的含量将患者分为胆固醇结石组和非胆固醇结石组。对比分析两组患者术前血清总胆固醇(TC)及肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总蛋白(TP)、球蛋白(G)、白蛋白(ALB)、总胆红素(TB)、直接胆红素(DB)和间接胆红素(IB)]的检测结果,筛选出鉴别胆结石类型的特异性指标;通过ROC曲线分析各指标诊断胆结石类型的特异度和灵敏度,并利用尤登指数计算诊断分界值。结果胆固醇结石组血清中的TC、AST水平高于非胆固醇结石组,DB水平低于非胆固醇结石组,且差异有统计学意义(P0.05);TC、AST和DB在胆固醇结石和非胆固醇结石患者之间的诊断界值分别为TC≥5.27 mmol/L,AST≥52.25 U/L,DB≤4.51μmol/L。结论 TC、AST和DB可以作为术前初步区分胆固醇结石与非胆固醇结石的参考指标。     

高血压合并脂肪肝与胰岛素抵抗的相关分析

目的：探讨高血压合并脂肪肝与胰岛素抵抗（IR）的相关性。方法：根据超声影像学的诊断结果将住院治疗的高血压患者分为高血压合并脂肪肝组（98例）和高血压未合并脂肪肝组（104例），研究两组的体重指数（BMD、血压（BP）、血糖、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、肝酶和血浆胰岛索，胰岛素抵抗指数（IRI）水平。结果：高血压合并脂肪肝组较高血压未合并脂肪肝组的血糖、胰岛素水平、甘油三酯和胰岛素抵抗指数均明显增高（P〈0．05）。Logistic回归结果表明空腹血糖（FBG）、肥胖、丙氨酸氨基转氨酶（ALT）、葡萄糖负荷试验后3h胰岛素水平、甘油三醋（TG）是脂肪肝形成的独立危险因素（OR=1．980～3．245，P〈0．05）。结论：高血压和脂肪肝均是胰岛素抵抗的重要表现，高血压合并的脂肪肝其发病机制与胰岛素抵抗有关。     

2型糖尿病患者不同降糖方案转换前后临床指标的变化

目的比较2型糖尿病患者在不同降糖方案转换前后各项临床指标的变化。方法在基线随访采用胰岛素治疗,后改用口服降糖药(OAD)治疗的为胰岛素改为OAD组(n=40);在基线随访采用口服降糖药治疗,后加用胰岛素治疗的称为OAD加用胰岛素组(n=100)。所有患者至少有3次随访(基线随访,转换随访和末次随访),每次随访均检测体质量、空腹血糖(FPG)和餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、血脂及空腹C肽。结果 (1)胰岛素改为OAD组患者发病年龄较轻,糖尿病病程较短,HbA1c水平较高,与OAD加用胰岛素组患者相比差异均有统计学意义。(2)OAD加用胰岛素组中,患者转换随访与基线随访相比,FPG、2hPG、HbA1c差异无统计学意义;三酰甘油(TG)及高密度脂蛋白胆固醇(HDL-C)水平降低(P均<0.05);患者末次随访与转换随访相比,FPG、HbA1c、总胆固醇(TC)下降(P均<0.05)。2hPG较前下降,但差异无统计意义。(3)胰岛素改为OAD组中,患者转换随访与基线随访相比,FPG、2hPG差异无统计学意义;HbA1c、TC、低密度脂蛋白胆固醇(LDLC)降低(P均<0.05);患者末次随访与转换随访相比,体质量下降(P<0.05),FPG、2hPG、HbA1c、空腹C肽水平、TC、TG、HDL-C、LDL-C差异无统计学意义。结论发病年龄较轻且病程较短的2型糖尿病患者,使用胰岛素后改OAD治疗仍可有效控制血糖水平;发病年龄较大且病程较长的2型糖尿病患者,OAD治疗控制不佳时加用胰岛素治疗可有效控制血糖水平。     

围绝经期女性冠心病影响因素分析

目的分析围绝经期女性冠状动脉粥样硬化性心脏病(冠心病)发病的影响因素。方法入选2011年3月~2013年4月期间开滦总医院心内科收治的围绝经期女性疑似冠心病患者140例,年龄43~55岁。将患有冠心病分为冠心病组(65例),其余无冠心病患者分为对照组(75例)。患者入院次日测量总胆固醇、三酰甘油、低密度脂蛋白胆固醇、空腹血糖、雌二醇、计算体质指数(BMI)等。结果冠心病组患者的体质指数、总胆固醇、低密度脂蛋白胆固醇、空腹胰岛素及胰岛素抵抗指数均高于对照组,吸烟和饮酒的比例也较对照组升高,而雌二醇水平较对照组降低,差异有统计学意义(P均0.05)。多因素分析体质指数(OR=12.37,95%CI:4.47~34.27)、总胆固醇(OR=1.55,95%CI:1.27~1.89)、低密度脂蛋白胆固醇(OR=6.45,95%CI:3.05~13.65)、空腹胰岛素(OR=9.72,95%CI:4.40~21.47)及胰岛素抵抗指数(OR=18.79,95%CI:8.59~41.09)、吸烟(OR=7.10,95%CI:2.93~17.14)、饮酒(OR=8.68,95%CI:5.56~13.54)是围绝经期女性冠心病发病的危险因素,雌二醇(OR=0.36,95%CI:0.24~0.53)属于保护因素。结论围绝经期女性冠心病的危险因素包括总胆固醇水平、低密度脂蛋白胆固醇水平、体质指数、吸烟、饮酒、空腹胰岛素及胰岛素抵抗指数,雌二醇为保护因素。临床医生应尽早干预可控因素,降低冠心病发病率。     

Insulin injections enhance cholesterol gallstone incidence by changing the biliary cholesterol saturation index and apo A-I concentration in hamsters fed a lithogenic diet.

BACKGROUND/AIMS: A link between insulin and cholesterol gallstone disease has often been suspected but never demonstrated. The aim was to evaluate the direct implication of insulin in the gallbladder cholesterol gallstone formation process. METHODS: Hamsters fed with a soft-inducing lithogenic diet, enriched with sucrose, were injected daily, for 1 week, either with long-acting insulin or saline (controls). RESULTS: Insulin injections doubled the cholesterol gallstone incidence. The cholesterol saturation index (CSI) of bile significantly increased (+19%) and biliary apolipoprotein A-I (apo A-I) decreased, both in concentration (-71%) and the proportion relative to the total biliary proteins (-25%). No modifications in the biliary bile acid composition were noticed. Hepatic HMGCoA reductase activity was higher (+341%), CYP7A1 activity was lower (-52%), whereas CYP27A1 and CYP7B1 were not affected. The hepatic low-density liprotein (LDL)-receptor and SR-BI masses did not vary. The hepatic total cholesterol content increased (+42%). Fasting plasma phospholipid and triglyceride concentrations significantly decreased (-15 and -60%, respectively), but the cholesterol concentration remained constant. CONCLUSIONS: These results suggest that insulin injections enhance cholesterol gallstone incidence by increasing the CSI of bile and decreasing the concentration and proportion of a biliary anti-nucleating protein, apo A-I. Insulin modulates the major enzymes of cholesterol and bile acid metabolisms in vivo.     

Macronutrients and insulin resistance in cholesterol gallstone disease

Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies.     

胆囊结石症的血清脂质、瘦素、胆囊收缩素和胆脂水平分析

目的 探讨胆囊胆固醇结石患者血清脂质、瘦素、胆囊收缩素(CCK)和胆脂水平变化与胆囊胆固醇结石形成的关系及临床意义.方法 按胆囊结石成分将患者分为胆固醇结石组(99例)和非胆固醇结石组(57例),测定该两组及正常对照组(52名)的血脂、脂蛋白、载脂蛋白(Apo)、瘦素、CCK水平和胆汁中胆固醇、磷脂和胆汁酸浓度,比较分析三组间血脂、胆脂、瘦素和CCK的水平差异.结果 胆固醇结石组血清三酰甘油、总胆固醇和载脂蛋白B(Apo-B)均高于正常对照组(P值分别为0.000、0.002和0.017),非胆固醇结石组血清三酰甘油、总胆固醇明显高于正常对照组(P值分别为0.000和0.001);两结石组患者的血清高密度脂蛋白与CCK均显著低于正常对照组(P值均为0.000).男性患者血清瘦素水平显著高于正常对照组(P=0.016).两组患者胆汁中的胆固醇饱和指数(CSI)均大于1.结论 血清CCK、三酰甘油、胆固醇、高密度脂蛋白、Apo-B和瘦素水平变化可能与胆囊结石的形成有关.     

Hepatic cholesterol metabolism in patients with gallstones.

Relative rates of cholesterol and bile acid synthesis were estimated in patients with cholesterol gallstones and biliary obstruction by determining the hepatic activities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, the respective rate-determining enzymes for cholesterol and bile acid synthesis. As compared with eight control studies, 3-hydroxy-3-methylglutaryl-CoA reductase activity was 27% higher in 12 gallstone subjects, but 75% lower in 5 subjects with biliary obstruction. Cholesterol 7 alpha-hydroxylase activity was reduced in the gallstone (47% lower) and biliary obstruction (78% lower) subjects. Liver cholesterol concentrations were 56% higher in the gallstone and 53% higher in the biliary obstruction subjects than the control group. These findings suggest that the pathogenesis of gallstones is related to both increased cholesterol synthesis and decreased bile acid formation, whereas cholesterol accumulates in biliary obstruction because of defective removal since cholesterol production is low.     

Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet

BACKGROUND & AIMS: Because apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets. METHODS: Bile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals. RESULTS: A high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice. CONCLUSIONS: These results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.     

Association between insulin, insulin resistance, and gallstone disease in Korean general population]

BACKGROUND/AIMS: Diabetes is one of the risk factors of gallstone diseases. Many studies found a positive association between insulin and gallstones in individuals with diabetes. However, this association is unclear in non-diabetes. So we conducted a case-control study for the evaluation of the association between gallstone diseases and fasting serum insulin level, insulin resistance in non-diabetic Korean general population. METHODS: This study was a prospective case-control study on 118 Korean subjects which included clinical examination, abdominal ultrasound, and blood chemistries. Serum fasting insulin level were determined by radioimmunoassay and concentrations of cholesterol, glucose, and triglycerides by standard enzymatic colorimetric methods. Insulin resistance was determined by the homeostasis model assessment (HOMA-IR). Body mass index (BMI), percentage of body fat, and waist hip ratio were also measured. RESULTS: We studied 118 subjects with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels, and BMI. In t-test and chi-square test for variables, the association between gallstone disease and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple logistic regression analysis, gallstone disease risk increased with the level of serum insulin (p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006). CONCLUSIONS: We suggest that hyperinsulinemia and insulin resistance could be associated with gallstone formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum glucose level.     

Serum and bile lipid levels in patients with and without gallstones

The aim of the present study was to investigate predisposing factors that lead to the formation of gallstones. In a group of 70 patients (51 with gallstones and 19 without, 20 possible risk factors were studied: percent of ideal body weight, the presence of superoxide dismutase in erythrocytes and in serum, lipid peroxide in serum, total serum cholesterol (Ch), high density lipoprotein (HDL)-cholesterol (Ch), low-density lipoprotein (LDL)-Ch, very low-density lipoprotein (VLDL)-Ch, serum triglyceride (TG), HDL-TG, LDL-TG, VLDL-TG, serum bile acids (lithocholic acid, deoxycholic acid, chenodeoxy cholic acid, ursodeoxycholic acid, and cholic acid) and serum apolipoproteins (apo A-1, apo B-100, and apo A-1/apo B-100). Levels of apo B-100 and serum insulin in patients with gallstone were strikingly higher, and superoxide dismutase in erythrocytes was significantly lower than in individuals with no gallstones. Apo A-1 and HDL-Ch were also higher and LDL-Ch was lower in the gallstone group, albeit non-significantly so (P>0.05) byt-test. However, Apo A-1, HDL-Ch, and LDL-Ch showed remarkably good discriminatory power in stepwise discriminant analysis of the 20 factors. Bile lipid composition was also measured and the cholesterol saturation index was calculated, but no significant differences were seen between the two groups. The results demonstrate that serum lipid patterns differ to some extent in patients with and without gallstones. Lipid derangement may contribute to the development of gallstone disease.     

Non-mucin proteins in the matrix of human cholesterol gallstones

Human cholesterol gallstones contain a pigmented organic matrix that may originate from biliary sludge. The cholesterol gallstone matrix contains mucin, bile pigments, and calcium salts. The goal of this study was to examine whether non-mucin proteins are present in the matrix of cholesterol gallstones. Matrix was prepared from cholesterol gallstones from 18 patients. Proteins were identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and by molecular sieve high-performance liquid chromatography (HPLC). Two proteins were present in each gallstone and migrated with or just adjacent to standards of bovine serum albumin on SDS-PAGE. Several additional lower molecular weight proteins were identified, but not in every gallstone. Protein fractions contained visible pigment after chloroform extraction, and pigment co-eluted with proteins on HPLC, suggesting binding of pigments to proteins in the matrix. We conclude that low molecular weight proteins are present in the cholesterol gallstone matrix. The major protein appears to be serum albumin, although definitive identification has not been established. The origin of these matrix proteins and their possible significance in the pathogenesis of cholesterol cholelithiasis is unknown.     

Physical activity, biliary lipids, and gallstones in obese subjects

OBJECTIVE: Gallstone disease is a major source of morbidity in the US. Reduced physical activity has been shown to be a risk factor for gallstone formation in recent studies; however, the mechanisms to explain how physical activity may protect against gallstone formation have not been well elucidated. We investigated the relationships between physical activity, biliary lipids, and gallstone disease. METHODS: Three types of habitual physical activity (work, sport, and leisure time), biliary lipids, and serum lipids were estimated or measured in 53 obese subjects undergoing gastric bypass surgery. These physical activities were defined as activity at work, sport activity during leisure time, and activity during leisure time excluding sports, respectively. RESULTS: We found that sport activity but not work and leisure time activities was inversely associated with gallstone disease. Lower levels of biliary bile salts and percent biliary bile salts (expressed in percentage of total biliary lipids) and higher levels of percent cholesterol were also found to be associated with gallstone disease. A lower level of sport activity appeared to be associated with higher levels of biliary cholesterol, percent biliary cholesterol, and serum triglycerides. CONCLUSION: Our findings demonstrate that low levels of physical activity are associated with gallstone formation. Our study also suggests that a possible mechanism for the protective effect of physical activity on gallstone formation is the lowering of biliary cholesterol levels, thus preventing cholesterol from precipitating in the bile. In addition, our data suggest that sport activity is a more effective form of physical activity than working and leisure activities in the prevention of gallstone disease.     

血浆脂蛋白在胆囊胆固醇结石形成中的作用研究

目的：探讨血浆脂蛋白在胆囊胆固醇结石形成中的作用。方法：用常规生化方法分别测定了56例胆囊胆固醇结石及24例非胆石对照患者血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）,低密度脂蛋白（LDL）的含量。结果：胆石组血清TC、HDL、LDL以及TG／TC比值均与对照组有显著性差异（P＜0．01或P＜0．05）。并且胆囊胆固醇结石组血清TG与TG／TC比值呈显著正相关关系。结论：本实验结果提示：血浆脂蛋白的变化,可能因影响体内的胆固醇及胆汗酸等代谢而与胆囊胆固醇结石的形成密切相关,TC、TG的测定及TG／TC比值可以作为间接反映胆囊胆固醇结石成核的参考指标。