氟他胺和二甲双胍在难治性多囊卵巢综合征中的临床应用

目的:探讨氟他胺和二甲双胍在难治性多囊卵巢综合征(PCOS)中的临床应用。方法:30例难治性PCOS的不孕患者,观察口服氟他胺和二甲双胍12周前后的临床症状及检测指标,比较生殖内分泌指标及糖代谢指标的变化。结果:治疗前后体重指数(BMI)、臀围比值(WHR)、多毛评分(F-G评分)、黄体生成素(LH)、黄体生成素/卵泡刺激素(LH/FSH)、总睾酮(T)、游离睾酮(FT)、雄烯二酮(A2)、硫酸脱氢表雄酮(DHEAS),空腹胰岛素(FINS)较治疗前明显下降,差异均有显著性(P<0.01～0.05),性激素结合球蛋白(SHBG)较治疗前明显升高(P<0.05),其余指标治疗前后无明显差异。用药后有21例(70%)患者恢复排卵性月经。结论:①氟他胺、二甲双胍治疗使大部分患者排卵异常得到很大改善,同时多毛、肥胖也得到一定控制。②氟他胺、二甲双胍能使难治性PCOS患者的卵巢-垂体生殖轴激素水平得到有效的改善。③对无生育要求的PCOS患者提供一种新的治疗手段;对有生育要求的患者,由于胎儿安全性问题不明,尚须做进一步深入研究。     

Fast liquid chromatographic-tandem mass spectrometric (LC-MS-MS) determination of metformin in plasma samples

Liquid chromatographic–tandem mass spectrometric (LC–MS–MS) methods for the determination of metformin in plasma from different species are presented. The first method employed a YMC cyano 2 mm×50 mm, 3 μm analytical column. For minimum sample preparation direct injection of samples after protein precipitation was performed. The polar column used with highly organic mobile phases provided a normal phase retention mechanism. The elution conditions were optimized to obtain reproducible peak areas and good peak shape. A step gradient from 100% acetonitrile to acetonitrile–water 80:20 (v/v) containing 10 mM ammonium acetate and 1% acetic acid was applied, leading to a sample-to-sample cycle time of 2 min. In a second method, a column-switching LC–MS–MS assay for on-line trapping was developed. The analyte and internal standard were trapped on a YMC cyano 2 mm×10 mm, 5 μm column using acetonitrile–methanol 95:5 (v/v). Elution was performed isocratically in back-flush mode on to the analytical column (YMC cyano 2 mm×50 mm, 3 μm) using 10 mM ammonium acetate in acetonitrile–water 80:20 (v/v) with 1% formic acid. With this approach, the signal-to-noise ratio was improved and the run time could be shortened to 1 min. Calibration samples were prepared in the matrix to be assayed in the range of 10–10,000 ng/ml. Quality control (QC) samples were prepared at 40, 400 and 4000 ng/ml and interspersed with the unknown study samples in the assays. Deviations for precision and accuracy were less than 20% for the lower limit of quantification (LLOQ) and low QC sample and less than 15% for other calibrators and QCs.     

二甲双胍改善多囊卵巢综合征患者的内皮功能及胰岛素抵抗

目的探讨二甲双胍对多囊卵巢综合征的患者的胰岛素抵抗及内皮功能的作用。方法40例多囊卵巢综合征患者分为肥胖组和非肥胖组,检测二甲双胍治疗前后患者的血脂谱、胰岛素抵抗指数(HO-MA-IR)、胰岛素敏感指数(ISI)及内皮依赖性舒张(EDV)功能的变化。结果肥胖组的血脂谱和HOMA-IR明显高于非肥胖组,肥胖组的ISI和EDV明显低于非肥胖组。经过16周二甲双胍的治疗后,肥胖组和非肥胖组的血脂谱和HOMA-IR明显下降,ISI和EDV明显上升。结论二甲双胍可以改善多囊卵巢综合征的患者的胰岛素抵抗及内皮功能。     

Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture

Objectives

One of the antidiabetic drugs, metformin, have shown that it prevented oxidative stress-induced death in several cell types through a mechanism involving the opening of the permeability transition pore and cytochrome c release. Thus, it is possible that the antioxidative effect of metformin can also serve as protection against gentamicin-induced cytotoxicity related to reactive oxygen species (ROS). The aim of this study was to examine the protective effect of metformin on gentamicin-induced vestibulotoxicity in primary cell culture derived from rat utricle.

Methods

For vestibular primary cell culture, rat utricles were dissected and incubated. Gentamicin-induced cytotoxicity was measured in both the auditory and vestibular cells. To examine the effects of metformin on gentamicin-induced cytotoxicity in the primary cell culture, the cells were pretreated with metformin at a concentration of 1 mM for 24 hours, and then exposed to 2.5 mM gentamicin for 48 hours. The intracellular ROS level was measured using a fluorescent dye, and also measured using a FACScan flow cytometer. Intracellular calcium levels in the vestibular cells were measured with calcium imaging using Fura-2 AM.

Results

Vestibular cells were more sensitive to gentamicin-induced cytotoxicity than auditory hair cells. Metformin protects against gentamicin-induced cytotoxicity in vestibular cells. Metformin significantly reduced a gentamicin-induced increase in ROS, and also reduced an increase in intracellular calcium concentrations in gentamicin-induced cytotoxicity.

Conclusion

Metformin significantly reduced a gentamicin-induced increase in ROS, stabilized the intracellular calcium concentration, and inhibited gentamicin-induced apoptosis. Thus, Metformin showed protective effect on gentamicin-induced cytotoxicity in vestibular primary cell culture.     

Specific interpretation of hair concentrations in 2 fatal metformin intoxication cases

Hair analysis is very useful for toxicological investigations since, by providing a wider detection window, it gives the possibility to perform a retrospective study on the historical consumption of a substance. Unfortunately, there are no data available for hair concentrations in metformin-related deaths. In this study, the authors present 2 cases of fatal metformin intoxication in which, for the first time, hair analysis was performed using a specific GC–MS/MS method. Metformin was tested positive in femoral blood (112.3 mg/L and 64.7 mg/L respectively) and cardiac blood (226.9 and 203.2 mg/L) of the two subjects. For case 1, other samples were also tested positive, including vitreous humor (31.1 mg/L) and gastric contents (773.5 mg/L). In case 2, metformin was measured at 844.9 mg/L in urine. Metformin hair concentrations were 28.3–44.8 and 22.5 ng/mg for both cases, respectively. The concentrations found in the 2 fatal cases are clearly higher than those obtained in a previous study with subjects under treatment (0.3–3.8 ng/mg) or those found in 3 post-mortem cases where metformin death was excluded (0.6–1.4 ng/mg). Excessive sweating during the agonal phase due to fatal hypoglycemia could explain these elevated concentrations as sweat can have contaminated the hair.     

艾塞那肽治疗初诊2型糖尿病的疗效观察

目的 观察艾塞那肽治疗初诊2型糖尿病的疗效.方法 将初诊肥胖2型糖尿病患者86例完全随机分为艾塞那肽组(42例)和二甲双胍组(44例).艾塞那肽组给予艾塞那肽治疗(5 ～0 μg,2次/d),二甲双胍组使用二甲双胍治疗(500 mg/次,3次/d).比较治疗前和治疗16周后2组患者空腹血糖(FBG)、餐后2h血糖(2 h PG)、糖化血红蛋白(HbA1c)、BMI、空腹C肽(FPC-P)、餐后2hC肽(2 h PPC-P),以及低血糖发生次数及不良反应.结果 治疗16周后,2组的FBG、2 hPG、HbA1c、BMI、TC、TG均下降[艾塞那肽组:(6.6 ±1.3)mmol/L比(7.6±2.1)mmol/L,(9.1±1.9) mmol/L比(16.6±1.4) mmol/L,(6.2±0.9)％比(8.2±1.7)％,(24.4±1.4) kg/m2比(28.0±2.3)kg/m2,(5.2±1.4) mmol/L比(6.6 ±2.1)mmol/L,(1.4±1.2) mmol/L比(2.6±1.6) mmol/L;二甲双胍组:(6.8±1.3)mmol/L比(7.6±2.1)mmol/L,(9.0±2.1) mmol/L比(16.9±1.6)mmol/L,(6.6±1.8)％比(8.4±1.9)％,(25.4±1.8) kg/m2比(27.9±2.5)kg/m2,(6.0±1.6) mmol/L比(6.7±2.4) mmol/L,(2.2±1.5) mmol/L比(2.8±1.6) mmol/L],差异均有统计学意义(P＜0.05或P＜0.01).与二甲双胍组比较,艾塞那肽组的BMI、TG、TC下降更明显,差异有统计学意义(P＜0.05).2组均无低血糖及严重不良反应发生.结论 艾塞那肽可有效控制初诊2型糖尿病患者血糖,并且能明显降低BMI、TC、TG等代谢指标,改善胰腺功能.     

达英-35与二甲双胍联合治疗多囊卵巢综合征的疗效观察

目的探讨达英-35与二甲双胍联合治疗多囊卵巢综合征（PCOS）的临床疗效。方法PCOS患者84例,按随机数字表法分为治疗组和对照组各42例,对照组给予达英-35,治疗组给予达英-35＋二甲双胍片,在治疗3个疗程后比较两组患者生殖激素、内分泌及代谢指标的变化。结果与治疗前比较,治疗后两组卵泡刺激素、黄体生成素、睾酮、空腹胰岛素、空腹血糖、甘油三酯、低密度脂蛋白胆固醇均明显下降（P〈0．05）,且治疗组较对照组下降更为明显（P〈0．05）;治疗后两组卵巢体积和胰岛素抵抗指数均明显下降（P〈0．05）,但治疗组较对照组下降更为明显（P〈0．05）;治疗后治疗组体重指数较治疗前明显下降（P〈0．05）,而对照组无明显变化（P〉0．05）。结论达英-35联合二甲双胍能明显改善患者高雄性激素及胰岛素抵抗,是治疗PCOS较为理想的方法。。     

二肽基肽酶4抑制剂联合二甲双胍治疗2型糖尿病的临床疗效

目的观察并初步探讨二肽基肽酶4(Dipeptidyl peptidase 4,DPP4)抑制剂西格列汀联合二甲双胍治疗2型糖尿病的临床疗效。方法选择2014年1月至2015年2月来我院就诊的63例2型糖尿病患者作为研究对象,随机分为3组。对照组单一给药二甲双胍(A组)、西格列汀(Sitagliptin)(B组),观察组(C组)给予西格列汀联合二甲双胍治疗,治疗12周后检测并观察各组总体疗效及相关生化指标。结果 C组治疗后空腹血糖(FBG)、餐后2小时血糖(2h BG)分别为(7.4±1.7)、(8.2±1.9)mmol/L,与A组、B组相比显著降低,差异有统计学意义(P<0.05)。C组糖化血红蛋白(Hb A1c)、体重指数(BMI)及血尿酸(UA)均较A组、B组呈下降趋势,但差异无统计学意义(P>0.05)。结论 DPP4抑制剂西格列汀联合二甲双胍治疗2型糖尿病疗效显著,能够全面控制血糖,降低体重,降低血尿酸,不增加低血糖的发生,具有良好的安全耐受性,值得临床应用推广。     

卡托普利、双克联合二甲双胍治疗原发性高血压伴胰岛素抵抗的临床观察

目的观察卡托普利、双克联合二甲双胍对原发性高血压伴胰岛素抵抗(IR)患者相关参数的影响。方法90例原发性高血压伴IR患者,随机分为治疗组和对照组。治疗组给予卡托普利、双克加二甲双胍片,对照组单纯用卡托普利、双克,治疗前、后均作口服糖耐量试验、胰岛素释放试验及血压监测。结果两组收缩压与舒张压均下降,治疗组下降更显著。治疗组空腹胰岛素及餐后胰岛素均下降,与对照组相比有显著性差异(P<0.05)。结论卡托普利、双克联合二甲双胍可明显改善IR,更有效降低血压。     

沙格列汀与二甲双胍治疗2型糖尿病的临床对照研究

目的探讨沙格列汀与二甲双胍治疗2型糖尿病(T2DM)的临床疗效、安全性以及用药依从性。方法选择我院收治的2型糖尿病患者为研究对象,随机分为沙格列汀组和二甲双胍组,分别给予沙格列汀和二甲双胍控制血糖,观察并记录两组患者治疗前后空腹血糖(FBG)、餐后2 h血糖(PG2h)、糖化血红蛋白(HbA1c)、低血糖发生率、肝肾功能、体重变化情况,同时对两组患者用药的依从性进行对比分析。结果两组总有效率比较差异无统计学意义(P>0.05),但沙格列汀组显效率明显高于二甲双胍组,差异有统计学意义(P<0.05)。治疗12周后,沙格列汀组患者FBG、PG2h、HbA1c水平均较治疗前明显改善(P<0.01);二甲双胍组FBG、PG2h较治疗前明显改善(P<0.01),但HbA1c水平较治疗前改善不明显(P>0.05)。沙格列汀组治疗后FBG、PG2h、HbA1c改善程度均明显优于二甲双胍组,差异均有统计学意义(P<0.01)。两组患者治疗前后血谷丙转氨酶(ALT)、谷草转氨酶(AST)、血尿素氮(BUN)、血肌酐(Scr)等肝肾功能检查指标差异均无统计学意义(P>0.05),两组治疗12周后体重指数与治疗前比较差异无统计学意义(P>0.05)。两组患者用药期间不良反应发生率比较差异无统计学意义(P>0.05),且症状较轻微,均经对症处理后缓解。格列汀组患者用药依从性明显高于二甲双胍组,差异有统计学意义(P<0.05)。结论沙格列汀能有效控制2型糖尿病患者的血糖,降低糖化血红蛋白水平,同时对肝肾功能、体重等无明显影响,且不良反应少,但由于沙格列汀为新药,临床试验随访时间较短,其远期疗效、安全性以及患者的耐药性仍需进行长期的大样本研究加以证实。