胰岛素抵抗与冠心病及其危险因素的关系

目的探讨冠心病患者的胰岛素抵抗状态,并分析其与冠心病危险因素及冠状动脉狭窄的关系。方法选择临床疑诊冠心病患者488例,其中男性364例,女性124例。采用高度敏感和高度特异的单克隆抗体生物素-亲和素夹心放大酶联免疫分析法测定冠心病患者的真胰岛素水平,并计算HOMA指数来评价胰岛素抵抗状态。将观察对象按照HOMA指数的四分位间距分成4组,各组间一般临床资料的比较采用计量资料的方差分析和Kruskal-wallis检验及计数资料的~2检验,应用Spearman相关分析法和多因素逐步线性回归分析法研究HOMA指数与冠心病危险因素及Gensini积分的相关性。结果单因素方差分析和非参数检验中Kruskal-wallis检验显示,年龄、三酰甘油、载脂蛋白A、HDL-C、尿酸、体质指数和Gensini积分在4组间的分布差异有统计学意义(P<0.05)。经Spearman相关分析法研究发现,冠心病患者的HOMA指数与三酰甘油、载脂蛋白B、尿酸、体质指数及Gensini积分呈正相关(均为P<0.05),与HDL-C和载脂蛋白A呈负相关(均为P<0.05)。多因素逐步线性回归分析显示,体质指数与HOMA指数呈独立正相关,其偏相关系数为0.090(P<0.05)。结论冠心病患者存在胰岛素抵抗,且胰岛素抵抗与冠状动脉狭窄程度呈正相关,与体质指数呈独立正相关。     

Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.

Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutraminine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. Weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant.     

网膜素与肥胖及胰岛素抵抗的关系

网膜素是新近发现的一种脂肪细胞因子,特异性表达于内脏脂肪组织.目前研究表明,网膜素能促进皮下和网膜脂肪细胞胰岛素刺激的葡萄糖转运和蛋白激酶B磷酸化,且与肥胖相关,在调节糖代谢中具有一定作用.因此,对网膜素的表达、作用机制及生物学功能的深入研究,有助于进一步阐明肥胖、代谢综合征及糖尿病等的发病机制,从而为这些疾病的治疗提供新的方向.     

网膜素与肥胖及胰岛素抵抗的关系

网膜素是新近发现的一种脂肪细胞因子,特异性表达于内脏脂肪组织.目前研究表明,网膜素能促进皮下和网膜脂肪细胞胰岛素刺激的葡萄糖转运和蛋白激酶B磷酸化,且与肥胖相关,在调节糖代谢中具有一定作用.因此,对网膜素的表达、作用机制及生物学功能的深入研究,有助于进一步阐明肥胖、代谢综合征及糖尿病等的发病机制,从而为这些疾病的治疗提供新的方向.     

网膜素与肥胖及胰岛素抵抗的关系

网膜素是新近发现的一种脂肪细胞因子,特异性表达于内脏脂肪组织.目前研究表明,网膜素能促进皮下和网膜脂肪细胞胰岛素刺激的葡萄糖转运和蛋白激酶B磷酸化,且与肥胖相关,在调节糖代谢中具有一定作用.因此,对网膜素的表达、作用机制及生物学功能的深入研究,有助于进一步阐明肥胖、代谢综合征及糖尿病等的发病机制,从而为这些疾病的治疗提供新的方向.     

Relationship between insulin resistance and accumulation of coronary risk factors

We examined correlations between the frequency of insulin resistance and the accumulation of coronary risk factors in residents of rural comities in Japanese, using simple criteria for determination of insulin resistance based on evaluation by the euglycaemic-hyperinsulinaemic glucose clamp (GC) method. The subjects were 376 men and 589 women living in two rural communities in Japan. We measured body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), HDL cholesterol (HDL), and homeostasis model assessment (HOMA-R). Correlations between HOMA-R and those parameters were examined. To assess the existence of insulin resistance in these subjects, we used a practical index based on the GC method. The subjects with value of HOMA-R ≥ 1.73 have insulin resistance. In addition, the HOMA-R was divided into five quantiles based on the frequency distribution (0.60 or below, from 0.61 to 0.82, from 0.83 to 1.18, from 1.19 to 1.69, and 1.70 or higher), to examine the concentration of risk factors in each group. In total, 74 (19.6%) of the men and 119 (20.3%) of the women had insulin resistance (HOMA-R ≥ 1.73). It was found that the higher the HOMA-R, the higher was the number of coronary risk factors, such as hypertension, obesity, hypertriglyceridaemia and hypo HDL cholesterolaemia. The number of coronary risk factors was particular high in subjects with HOMA-R ≥ 1.70. HOMA-R in the case of no glucose loading is a useful and practical index for evaluation of insulin resistance and coronary risk factors in the epidemiological study.     

胰岛素抵抗与冠状动脉狭窄严重程度的关系

目的 探讨胰岛素抵抗（IR）与冠心病患冠状动脉狭窄程度及范围的关系。方法 纳入冠状动脉造影后的患97例,男、女各分一组,男63例,女34例,再将冠状动脉狭窄≥75％分为冠心病组,狭窄＜25％为对照组,所有患均抽血查胰岛素、糖耐量试验、胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A、载脂蛋白B水平,冠状动脉的狭窄程度用造影图像处理系统测量,再据病变损害的程度评分。用统计学方法分析控制其他易患因素影响后IR与冠心病的定性关系和IR与冠状动脉狭窄程度及范围的定量关系。结果 经偏相关分析发现,男、女冠心病患均与IR有关,IR独立于其他冠心病易患因素。多元回归分析发现,无论男、女IR均与冠状动脉狭窄的病变程度呈正相关（P＜0．005）。结论 IR可作为预测冠心病严重程度的参考指标之一。     

Relationship between insulin resistance, insulin secretion and insulin metabolism in simple obesity

The study was designed to evaluate whether the correlation occurring in simple obesity between insulin resistance and peripheral hyperinsulinemia corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the study investigated the relation existing in simple obesity between insulin resistance and insulin metabolism. For these purposes, we measured and correlated: (1) insulin sensitivity, estimated by glucose disappearance rate from plasma after intravenous insulin injection; (2) insulin secretion by the pancreas, estimated by fasting C-peptide levels in peripheral blood; (3) insulin metabolism, estimated by means of C-peptide: insulin molar ratio in peripheral blood. Twenty-five subjects (20 females, five males) aged 21 to 59 years were studied. All were obese and had a normal glucose tolerance. Glucose disappearance rate from plasma after i.v. insulin injection averaged 3.65 +/- 0.42 mg/dl/min (mean +/- s.e.m.). Fasting C-peptide was 0.90 +/- 0.09 nmol/l. Fasting C-peptide: insulin molar ratio averaged 5.94 +/- 0.48. Negative correlations were found between glucose disappearance rates after i.v. insulin injection, ie, insulin sensitivity, and fasting concentrations of both insulin (r = -0.806, P less than 0.001) and C-peptide (r = -0.525, P less than 0.01). A positive relationship was found between glucose disappearance rate from plasma after i.v. insulin injection and fasting C-peptide: insulin molar ratio, ie, insulin metabolism (r = 0.707, P less than 0.001). We conclude that in simple obesity insulin overproduction by the pancreas is negatively related to insulin resistance, and insulin resistance and impaired insulin metabolism are strictly related phenomena.     

Pathophysiological connections between gallstone disease,insulin resistance,and obesity

Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.     

非对称性二甲基精氨酸和冠状动脉性心脏病及其危险因素的关系

目前有研究表明高血压、糖代谢异常等情况下,血浆非对称性二甲基精氨酸（asymmetric dimethyl-arginine,ADMA）浓度升高[1-2]。ADMA作为内源性一氧化氮合成酶（NOS）的抑制剂,通过抑制一氧化氮（NO）生成可加速动脉粥样硬化（AS）的进展,加重斑块的炎症反应,影响冠状动脉粥样硬化性心脏病（冠心病）患者的远期预后[3]。他汀类药物和冠状动脉支架置入术（PCI）作为冠心病治疗的主要药物和方法,     

非酒精性脂肪肝血浆抵抗素与肥胖和胰岛素抵抗关系的研究

目的探讨非酒精性脂肪肝(NAFLD)血浆抵抗素与肥胖和胰岛素抵抗的关系。方法对兰州大学第一医院2005年10月至2006年2月60例NAFLD患者和28名年龄、性别相匹配的正常对照者,采用ELISA方法测定空腹血浆抵抗素,同时检测其身高、体重、腰围、臀围、血压、血糖、血脂、肝功能及胰岛素水平,并计算体重指数、脂肪百分比、腰臀比和胰岛素抵抗指数。结果NAFLD组与正常对照组相比,其血浆抵抗素明显升高[(8.56±2.5)ng/mL对(6.39±2.81)ng/mL,P<0.01]。相关分析显示血浆抵抗素与空腹胰岛素、胰岛素抵抗指数呈显著正相关(分别为r=0.271,P=0.036;r=0.30,P=0.020);而与腰臀比、体重指数、脂肪百分比、收缩压、舒张压、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、血糖无相关性(P>0.05)。结论NAFLD患者血浆抵抗素明显升高,与胰岛素抵抗程度呈显著正相关,与肥胖无相关性。因而抵抗素可能主要与肝源性胰岛素抵抗有关,而与肥胖相关的胰岛素抵抗无关。     

Cross-sectional associations of resistin, coronary heart disease, and insulin resistance

CONTEXT: Recently, resistin was found to be present in atherosclerotic lesions in apoE(-/-) mice. Resistin may be associated with inflammation and atherosclerosis in humans; however, the role of resistin in human disease remains controversial. OBJECTIVE: This study assesses cross-sectional relationships of resistin with coronary heart disease (CHD). DESIGN, SETTING, AND PARTICIPANTS: Blood samples from the third examination of the Strong Heart Study (SHS)--the largest study of CHD in American Indians--were used. Cases who had suffered previous myocardial infarction (n = 100) were selected randomly from the three SHS sites and matched for study site and sex with controls who had no history of cardiovascular disease (CHD or stroke) (n = 100). MAIN OUTCOME MEASURE: Resistin levels by enzyme-linked immunosorbent assay method in cases and controls was the main outcome measure. RESULTS: Resistin levels were higher in cases than controls [median (interquartile range): 3.4 (2.5-4.7) vs. 2.8 (2.1-4.0) ng/ml; P = 0.003] and had univariate correlations with age (Spearman r = 0.21; P < 0.002), fasting insulin (r = 0.21; P = 0.003), insulin resistance by homeostasis model (r = 0.22; P = 0.04), albumin to creatinine ratio (r = 0.19; P = 0.01), and fibrinogen (r = 0.34; P < 0.0001). Cases were more likely to have diabetes (cases 67%; controls 41%; P < 0.0001) but had similar body mass index (cases 31.4 +/- 5.4; controls 30.7 +/- 6.3; P = 0.85). Resistin levels were higher in participants with established nephropathy (albumin to creatinine ratio >300 mg/g, n = 26) compared with those with normo- (n = 122) or microalbuminuria (n = 42). In multivariate analysis, nephropathy (P = 0.0013) but not previous myocardial infarction (P = 0.12) was significantly associated with resistin. CONCLUSIONS: Resistin is not independently associated with CHD. Resistin is elevated in survivors of myocardial infarction; however, this reflects a novel association of raised resistin with diabetic nephropathy.     

代谢综合征合并冠心病患者血浆纤溶酶原激活物抑制剂-1水平与胰岛素抵抗的关系

目的 探讨代谢综合征（MS）及合并冠心病（CHD）患者血浆纤溶酶原激活物抑制剂-1（PAI-1）水平与胰岛素抵抗和MS其他指标的关系.方法 用液相蛋白芯片结合流式细胞仪测定单纯MS组（27例）、MS＋CHD组（40例）和健康对照组（30例）空腹血浆PAI-1水平,用酶联免疫吸附法（ELISA）测定空腹血浆真胰岛素水平,收集MS的其他有关数据如腰围、体重指数、空腹血糖和血脂,计算胰岛素敏感指数（ISI）.结果 PAI-1水平健康对照组为（167.1±44.8）ng/L,MS组为（413.9±107.5）ng/L,MS＋CHD组为（551.6±167.3）ng/L,三组间差异有统计学意义（P〈0.05）.PAI-1水平与ISI呈负相关,与空腹真胰岛素、体重指数、甘油三酯呈正相关;以PAI-1为应变量的多元逐步回归分析提示,ISI、空腹真胰岛素、体重指数、甘油三酯与PAI-1具有相关性.结论 MS患者的PAI-1水平增加,合并CHD的MS患者更为明显,并与胰岛素敏感性有关,可能在MS发展为CHD中起一定作用.     

脂联素与冠心病关系的研究进展

脂联素(APN)是脂肪组织分泌的一种细胞因子。具有增强胰岛素敏感性、调节糖脂代谢、抗动脉粥样硬化、抗炎症等诸多作用,与冠心病的发生发展密切相关。     

内脂素与冠心病

内脂素是一种新的脂肪因子,主要来源于内脏脂肪,具有类胰岛素样作用。近年来的许多研究发现,内脂素与缺氧、易损斑块、内皮功能紊乱、炎症、血管增生等冠心病,尤其动脉粥样硬化的发生和发展过程相关。此外,内脂素还能通过延长氧化应激状态下线粒体渗透转运孔（mPTP）的开放时间,发挥一定的心血管保护作用。     

冠心病与高尿酸血症关系的探讨

目的:研究冠心病与高尿酸血症之间的关系。方法:选择156例经冠状动脉造影证实冠心病患者和非冠心病患者的临床资料,冠心病组又分为单支病变组55例,双支病变组21例,3支病变组20例,分别测定血尿酸(SUA)水平,同时记录性别、年龄、血尿酸、血糖、血脂、血压、肌酐及冠状动脉造影结果,分析2组之间血尿酸水平,分析冠心病与高血尿酸血症的关系。结果:冠心病组血尿酸水平显著高于非冠心病组(P<0.05)。单支病变组、双支病变组及多支病变组血尿酸水平呈递增趋势,各组之间的差异有统计学意义。结论:冠心病与血尿酸水平密切相关。     

高尿酸血症与冠心病的关系

目的 探讨血清尿酸水平升高与冠心病发生、发展的关系.方法 选取疑诊冠心病患者455例,根据冠状动脉造影情况分为冠心病组268例（又分为单支病变组102例和多支病变组166例）和非冠心病组187例.在未行冠状动脉造影前,所有病例分别进行血清尿酸（UA）、血肌酐（Cr）、尿素氮（BUN）、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）水平测定.结果 冠心病组与非冠心病组比较血清UA、Cr、BUN差异有统计学意义（P均＜0.05）,冠心病单支病变、多支病变血清UA、Cr、TG、LDL-C水平比较有统计学差异（P均＜0.05）.结论 高尿酸血症与冠心病的发生、发展有关,冠脉病变程度增加,血清尿酸水平增高.     

Relationship between Chlamydia pneumoniae and classical risk factors of coronary heart disease

In order to elucidate relationship between Chlamydia pneumonia infection and established risk factors of coronary heart disease (hypercholesterolemia, hyperglycemia, hyperfibrinogenemia, smoking, age) chlamydial IgA and IgG antibodies were determined by solid phase enzyme immunoassay in 122 patients with ischemic heart disease and 40 healthy subjects. Elevated titers of IgA class antibodies were found to be associated with presence of ischemic heart disease as well as with hypercholesterolemia, hyperglycemia, hyperfibrinogenemia, and smoking.