Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes

What is known and Objective: The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes. Methods: Two hundred and fifty‐four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360 mg or placebo for 1 year. We evaluated at baseline and after 3, 6, 9 and 12 months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG), post‐prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA‐IR), lipid profile, retinol‐binding protein‐4 (RBP‐4), resistin, visfatin and high‐sensitivity C‐reactive protein (Hs‐CRP). Results and Discussion: We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP‐4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA_1c, PPG, FPI, HOMA‐IR, resistin and Hs‐CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA‐IR) were RBP‐4 and resistin concentration in the orlistat group (r = ?0·53, P < 0·05, and r = ?0·59, P < 0·01, respectively). What is new and Conclusion: To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP‐4 and visfatin, effects not observed with placebo.     

抵抗素-420C/G基因多态性与中国东北地区汉族人群2型糖尿病大血管病变相关性分析

目的:研究中国东北地区汉族人群抵抗素(RETN)-420C/G基因单核苷酸多态性(SNPs)的等位基因、基因型频率分布及其与2型糖尿病(T2DM)大血管病变之间的关系.方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对180例样本[T2DM并发大血管病变组60例,单纯T2DM组60例,正常对照(ND...     

C反应蛋白对人单核细胞抵抗素表达的影响

目的:研究C-反应蛋白(CRP)对培养的人外周血单核细胞抵抗素mRNA和蛋白表达的影响。方法:分离培养人外周血单核细胞,分为浓度效应组和时间效应组,即不同浓度的CRP(0,5,10,25,50μg/ml)刺激24h以及25μg/ml CRP刺激不同的时间(0,3,6,12,24h),分别用实时定量PCR和ELISA方法检测抵抗素的表达。结果:CRP可呈剂量依赖性和时间依赖性地诱导人单核细胞抵抗素mRNA和蛋白表达。结论:CRP可诱导人单核细胞抵抗素mRNA和蛋白表达。     

光明盐四味汤散对大鼠动脉粥样硬化的机制研究

目的：研究光明盐四味汤散对动脉粥样硬化（atheroscle rosis,AS）的影响并探讨其可能的作用机制。方法：用高脂饲料喂养加一次大剂量维生素D3腹腔注射造Wistar大鼠动脉粥样硬化模型,12wk后采血上自动生化分析仪测血脂生化的改变。光镜下观察动脉病理改变,采用免疫组化法检测PKC的表达,采用ELISA法测定抵抗素。结果：模型组大鼠的TC、TG、LDL水平与空白组比较是明显升高,HDL水平是明显降低。与空白组比较,模型组大鼠PKC的表达明显升高,与模型组相比,各治疗组PKC的表达各有不同程度的降低。与空白组比较,模型组大鼠抵抗素的浓度明显升高。结论：高脂饮食加一次性大剂量维生素D3负荷共同作用可成功建立大鼠早期AS模型。光明盐四味汤散对大鼠动脉粥样硬化早期炎症损伤具有一定保护作用,并能降低血脂,抑制PKC的活性,降低抵抗素水平从而阻断炎症损伤的发展。     

抵抗素蛋白在子宫内膜异位症患者中的表达及意义

 目的检测抵抗素蛋白在子宫内膜异位症患者异位子宫内膜、在位子宫内膜和正常子宫内膜中的表达情况。方法采
用免疫组织化学SP法检测抵抗素蛋白在异位内膜、在位内膜及正常子宫内膜组织中的表达情况,并分析和比较其表达是否有
差异。结果抵抗素蛋白在异位内膜的表达率及强度均高于在位内膜,差异有统计学意义（ P< 0.05）。而在位内膜与正常内膜
的表达率及强度比较差异无统计学意义（ P> 0.05）。阳性表达定位于子宫内膜间质细胞的细胞质。结论抵抗素蛋白在子宫内
膜异位症的发病中可能起重要作用。     

抵抗素、miRNA-26b在婴幼儿毛细支气管炎中的表达

目的 探讨婴幼儿毛细支气管炎中miRNA-26b、抵抗素的变化.方法 收集毛细支气管炎患儿的血液,以正常儿童为对照,通过酶联免疫吸附(ELISA)法测定血清中白介素(IL)-8、抵抗素浓度,并利用实时定量PCR技术测定血液淋巴细胞中miRNA-26b、抵抗素mRNA表达,利用miRNA-26b mimics干预人肺上皮细胞A549,通过实时定量PCR技术测定miRNA-26b、抵抗素mRNA及细胞上清液中IL-8蛋白浓度变化.结果 毛细支气管炎患儿外周血清中IL-8、抵抗素浓度均升高,血液淋巴细胞中miRNA-26b、抵抗素mRNA表达增加;经过干预的A549细胞miRNA-26b、抵抗素mRNA及细胞上清液中IL-8蛋白浓度均有增加.结论 miRNA-26b、抵抗素在毛细支气管炎患儿血液淋巴细胞中存在差异表达,而这可能参与了炎症反应的发生.     

Higher circulating resistin protein and PBMCs resistin mRNA levels are associated with increased prevalence of small dense LDL particles in coronary artery disease patients

Recent in vitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low‐density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme‐linked immunosorbent assay; PBMC resistin mRNA was determined by real‐time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with proportion of sdLDL particles ≥ 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = ?0.254, P = 0.034) and total cholesterol (r = ?0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R² = 0.258; adjR² = 0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro‐atherogenic LDL particle phenotype.     

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HR_Q4vsQ1 = 0.95, 95% CI: 0.73–1.23; P_trend = .97; and HR_{per doubling of resistin concentration} = 1.00; 95% CI: 0.84–1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.     

肥胖儿童血清抵抗素变化及其临床意义

目的 探讨饮食控制和运动疗法对肥胖儿章血清抵抗素水平的影响及其临床意义。方法 测定36例肥胖儿童饮食控制和运动治疗前后血清抵抗素、胆固醇（CHO）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-C）、空腹和葡萄糖耐量试验（OGTT）2小时血糖、胰岛素,计算胰岛素抵抗指数（HOMA-IR）。结果 肥胖儿童血清抵抗素水平显著高于对照组（P〈0．05）,并与OGTT2小时血糖、胰岛素呈正相关（P〈0．05）;经饮食控制和运动治疗后肥胖儿童血清抵抗素、体重、BMI、血清CHO、TG、LDL-C、空腹和OGTT2小时胰岛素、HOMA-IR显著低于治疗前（P〈0．05）,治疗前后空腹和OGTT2小时血糖差异无显著性（P〉0．05）。结论 肥胖儿童血清抵抗素水平升高,并与OGTT2小时血糖、胰岛素呈正相关,推测将来有可能以检测血清抵抗素水平来了解肥胖儿童有否存在糖耐量受损;饮食控制和运动疗法可使肥胖儿童血清抵抗素降低,胰岛素抵抗减轻。     

脑血管病患者血浆抵抗素水平与胰岛素抵抗的相关性研究

目的　探讨脑血管病患者血浆抵抗素水平与胰岛素抵抗(IR)之间的关系。方法　采用酶联免疫方法(ELISA)测定50例动脉粥样硬化性血栓性脑梗死(ACI)、36例腔隙性脑梗死(LI)、36例脑出血(ICH)患者及46名健康对照者的空腹血浆抵抗素、胰岛素(INS)水平,同时检测空腹血糖、血脂、血压、身高和体质量,计算体质量指数(BMI)和INS敏感指数(QUICKI)。结果　ACI和ICH组空腹INS水平均明显高于对照组(P<0 .05,P< 0 .01 ),QUICKI值均显著低于对照组(P< 0 .05,P< 0. 01 );ICH组血浆抵抗素水平[ (7. 47±4. 60)ng/ml]与对照组[ (5. 32±2. 15)ng/ml]相比明显升高(P<0 .05 );ACI、LI组血浆抵抗素水平与对照组差异均无显著性(均P>0. 05)。血浆抵抗素水平与QUICKI呈负相关(r=-0 188,P<0 .05)。结论　脑血管病患者存在IR,血浆抵抗素水平可能与IR密切相关。