新诊断2型糖尿病患者采取沙格列汀联合二甲双胍治疗的疗效及安全性分析

目的：探究新诊断2型糖尿病患者开展沙格列汀联合二甲双胍治疗的临床疗效及安全性,并为这类患者最优化诊疗服务积累循证经验。方法选取该院内分泌科2012年2月—2014年1月收治的94例新诊断2型糖尿病患者,利用随机数字表法进行分组,分别设为观察组和对照组,每组各47例。其中对照组给予阿卡波糖联合二甲双胍治疗方案,观察组给予沙格列汀联合二甲双胍治疗方案。记录二组患者治疗前后空腹血糖（FBG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素、胰岛素抵抗指数（HOM A －IR）、体重及体质指数,同时比较二组服药依从性情况及不良反应发生率。结果二组治疗前FBG、2hPG及HbA1 c值差异无统计学意义（P＞0．05）;治疗后,观察组FBG、2hPG及 HbA1 c值均低于对照组,差异有统计学意义（P＜0．05）。二组治疗前空腹胰岛素水平及 HOMA －IR值差异无统计学意义（P＞0．05）;治疗后,观察组空腹胰岛素水平高于对照组（P＜0．05）,HOMA －IR值低于对照组（P＜0．05）。二组治疗期间低血糖发生率差异无统计学意义（P＞0．05）;观察组 HbA1 c达标率高于对照组,差异有统计学意义（P＜0．05）。二组治疗前后体重及体重指数差异无统计学意义（P＞0．05）。观察组药物漏服率及错服率均低于对照组,差异有统计学意义（P＜0．05）。结论二甲双胍配伍沙格列汀治疗2型糖尿病患者的临床疗效优于二甲双胍配伍阿卡波糖方案,且安全性尚佳,值得在临床上进一步推广。     

Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients

Micronucleus (MN) assay was performed on the exfoliated urothelial cells to detect the genotoxic effects of the anti-hyperglycemic drugs, metformin and glimepiride in T2DM patients and to use it as a biomarker for DNA damage by assessing the frequency of micronuclei in the exfoliated urothelial cells. A total of 201 subjects (147 T2DM patients & 54 Normal cases) were selected from diverse age groups (25–75 years) and the mean MN frequency was examined per 1000 cells in all the subjects. Relative to the control group (5.02 ± 1.01), an increased MN frequency was observed in females (26.15 ± 2.15) when compared to males (23.08 ± 2.09) in T2DM patients. Further analysis showed that there was a profound increase in the number of MN in the patients using metformin alone (23.02 ± 4.44), or combination of metformin & glimepiride (24.98 ± 2.87) than to the subjects using glimepiride alone (17.52 ± 3.28). It has been proven by this simple, reliable and non-invasive method that metformin has a potential role in causing genotoxicity and that the MN observed in exfoliated urothelial cells could be used as a reliable biomarker in monitoring the genotoxic risk of the anti-hyperglycemic drugs.     

糖耐量异常患者凝血功能变化及二甲双胍的干预效应

目的 探讨糖耐量异常患者凝血功能变化及二甲双胍的干预效应.方法 将100例糖耐量异常患者按照随机数字表法分为试验1组和试验2组,每组50例,另选择健康志愿者50例作为对照组.试验2组给予二甲双胍治疗,试验1组给予安慰剂治疗.治疗前后各组行口服葡萄糖耐量试验(OGTT),检测糖负荷后2h血糖(2 h PBG),并检测糖化血红蛋白以及凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib).结果 治疗前试验1组和试验2组2 h PBG、糖化血红蛋白、Fib均明显高于对照组,Am、PT明显低于对照组,差异有统计学意义(P＜0.05).治疗后试验2组2 h PBG、糖化血红蛋白、Fib明显低于试验1组[(6.6±2.5) mmol/L比(7.9±3.6)mmol/L、(5.2±1.3)％比(5.8±1.4)％、(3.0±1.0) g/L比(3.6±1.2) g/L],APTT、PT明显高于试验1组[(34.3±6.8)s比(31.6±6.5)s、(12.6±0.7)s比(12.3±0.7)s],差异有统计学意义(P＜0.05),且与对照组比较差异无统计学意义(P＞0.05).三组TT比较差异均无统计学意义(P＞0.05).Pearson直线相关分析结果显示,APTT、PT与2hPBG和糖化血红蛋白呈负相关(P＜0.01),Fib与2h PBG和糖化血红蛋白呈正相关(P＜0.01),TT与2hPBG和糖化血红蛋白无相关性(P＞0.05).结论 糖耐量异常患者已出现凝血功能异常,适当的干预治疗可降低心血管疾病的危险因素.     

当飞利肝宁胶囊联合二甲双胍治疗非酒精性脂肪性肝病的临床效果观察

目的：观察当飞利肝宁胶囊联合二甲双胍治疗非酒精性脂肪性肝病（ NAFLD）的临床疗效。方法选取2010年2月-2012年12月医院收治的 NAFLD 患者120例,接受当飞利肝宁胶囊联合二甲双胍治疗,观察患者治疗前后血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、三酰甘油（TG）、总胆固醇（CHO）、超敏 C 反应蛋白（hs-CRP）变化情况,超声图像变化及药物不良反应。结果治疗后临床症状较治疗前明显改善者109例,有效率90.83%;治疗后超声影像表现较治疗前明显好转;ALT、AST、TG、CHO、hs-CRP 较治疗前显著改善,差异有统计学意义（P ＜0.05）。所有患者治疗期间均未出现不良反应。结论当飞利肝宁联合二甲双胍治疗 NAFLD 患者,血脂、肝功能、肝纤维化、超声等指标均有明显改善,疗效显著。     

Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1

Aims/hypothesis The aim of this study was to determine the effect of several antidiabetic agents on insulin-stimulated glycogen synthesis, as well as on mRNA expression.Methods Cultured primary human skeletal myotubes obtained from six healthy subjects were treated for 4 or 8 days without or with glucose (25 mmol/l), insulin (400 pmol/l), rosiglitazone (10 mol/l), metformin (20 mol/l) or the AMP-activated kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) (200 mol/l). After this, insulin-stimulated glycogen synthesis was determined. mRNA levels of the glucose transporters GLUT1 and GLUT4, the peroxisomal proliferator activator receptor gamma (PPAR gamma) co-activator 1 (PGC1) and the myocyte-specific enhancer factors (MEF2), MEF2A, MEF2C and MEF2D were determined using real-time PCR analysis after 8 days exposure to the various antidiabetic agents.Results Insulin-stimulated glycogen synthesis was significantly increased in cultured human myotubes treated with insulin, rosiglitazone or metformin for 8 days, compared with non-treated cells. Furthermore, an 8-day exposure of myotubes to 25 mmol/l glucose impaired insulin-stimulated glycogen synthesis. In contrast, treatment with AICAR was without effect on insulin-mediated glycogen synthesis. Exposure to insulin, rosiglitazone or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25 mmol/l glucose treatment increased GLUT1 mRNA expression. Metformin also increased mRNA expression of the MEF2 isoforms.Conclusions/interpretation Enhanced insulin-stimulated glycogen synthesis in human skeletal muscle cell culture coincides with increased GLUT4 and PGC1 mRNA expression following treatment with various antidiabetic agents. These data show that chronic treatment of human myotubes with insulin, metformin or rosiglitazone has a direct positive effect on insulin action and mRNA expression.     

水飞蓟素联合二甲双胍治疗肥胖型非酒精性脂肪肝疗效分析

目的分析水飞蓟素联合二甲双胍对肥胖型非酒精性脂肪肝患者的治疗作用。方法符合诊断标准的肥胖型非酒精性脂肪肝患者48例分为两组，试验组24例联合水飞蓟素及二甲双胍治疗，对照组24例服用水飞蓟素及维生素C片治疗，疗程均为4～6月。治疗前后测定各组患者血清转氨酶水平（ALT、AST）、血脂水平（TG、TC、LDL-C及HDL-C）、血清TNFα水平、胰岛素抵抗指数（IRI）及肝／脾CT比值并作统计学处理，同时观察实验过程中出现的不良反应。结果治疗后两组患者血清ALT均明显降低，其中尤以试验组降低明显（P〈0．01）；试验组患者治疗后各项血脂水平均显著改善；试验组胰岛素抵抗指数于治疗后明显下降（P〈0．05），而对照组无明显改变（P〉0．05）；两组患者治疗后血清TNFα均明显下降，尤以试验组下降明显（P〈0．01）；同时试验组治疗后肝／脾CT比值显著升高（P〈0．01）。用药期间两组患者均未出现显著不良反应。结论水飞蓟素联合二甲双胍对肥胖型非酒精性脂肪肝有显著疗效且用药安全。     

Metformin enhances certain insulin actions in cultured rat hepatoma cells

Summary The effect of the oral antidiabetic agent metformin on insulin regulation of glycogen metabolism, tyrosine-aminotransferase activity, and [1-¹⁴C]aminoisobutyric acid uptake was studied in H4IIE cultured rat hepatoma cells. Metformin enhanced both basal (from 0.213±0.016 to 0.262±0.024 nmol/mg protein,p<0.01) and insulin stimulated [³H] glucose incorporation into glycogen in a time-dependent and dose-dependent manner. A small effect of metformin was seen at 1 μmol/l, and its greatest effects were obtained at 10 μmol/l. At the same concentrations, metformin did not influence basal tyrosine-aminotransferase activity but it potentiated insulin stimulated tyrosine-aminotransferase activity (+ 29.2±1.4%,p<0.01) and prevented the loss of tyrosine-aminotransferase responsiveness to insulin in H4IIE cells desensitised by a previous exposure to insulin. In contrast, metformin had no effect on basal or insulin-stimulated [1-¹⁴C]aminoisobutyric acid uptake. Over the concentrations of metformin that enhanced insulin action in H4IIE cells, the drug had no significant effect on insulin binding to its receptor. These studies suggest, therefore, that metformin may influence cellular metabolism by potentiating certain insulin actions through mechanisms that may be beyond insulin receptor binding.     

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients

Summary In this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL₂-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL₃-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.     

盐酸二甲双胍肠溶胶囊中二甲胺残留量的测定

目的:建立盐酸二甲双胍肠溶胶囊中二甲胺残留量的柱前衍生HPLC测定方法.方法:用十八烷基硅烷键合硅胶为填充剂,以1.0%甲酸溶液-乙腈为流动相,采用梯度洗脱程序,检测波长为265 nm.结果:在选定的色谱条件下,二甲胺在0.254~4.065μg·mL-1的浓度范围内线性关系良好(r>0.999);精密度试验的RSD为1.6%,稳定性试验的RSD为1.5%;回收率为100.3%(n=9,RSD<1.5%).二甲胺的检测限为0.0508μg·mL-1,在测定的3批样品中,3批均检出二甲胺分别为0.01%,0.04%,0.02%.结论:本方法专属性强,准确度高,重现性好,能控制盐酸二甲双胍肠溶胶囊中二甲胺残留量.