格列美脲与沙格列汀联合治疗对2型糖尿病患者血糖控制、胰岛素抵抗及血脂的影响

目的:探讨2型糖尿病(T2DM)患者经格列美脲联合沙格列汀治疗后的临床效果,并分析其对患者血糖控制、胰岛素抵抗及血脂的影响。方法:选取我院2017年4月~2019年4月期间接收的88例T2DM患者,按乱数表法将患者分为研究组(n=44,格列美脲联合沙格列汀治疗)、对照组(n=44,沙格列汀治疗)。比较两组患者临床疗效、血糖、胰岛素抵抗及血脂指标,记录两组患者不良反应情况。结果:研究组治疗3个月后临床总有效率较对照组升高(P<0.05)。两组患者治疗3个月后空腹血糖(FBG)、餐后两小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)均下降,且研究组低于对照组(P<0.05)。两组患者治疗3个月后高密度脂蛋白(HDL-C)、空腹胰岛素(FINS)升高,且研究组高于对照组(P<0.05)。两组不良反应总发生率比较无差异(P>0.05)。结论:T2DM患者采用格列美脲联合沙格列汀治疗效果确切,可改善机体血脂水平及胰岛素抵抗,控制血糖水平,且用药安全性较好。     

格列美脲联合艾塞那肽治疗肥胖2型糖尿病的疗效观察

目的:探讨格列美脲联合艾塞那肽治疗肥胖2型糖尿病患者的临床效果。方法:选择2016年1月到2019年1月我院收治的82例肥胖2型糖尿病患者作为本次研究的对象,并将其随机的分为研究组和对照组,每组41例。研究组患者给予格列美脲联合艾塞那肽进行治疗,对照组患者给予格列美脲治疗,观察和比较两组患者治疗前后空腹血糖、餐后2 h血糖、空腹和餐后2 h血清C肽、身体质量指数(body mass index, BMI)、总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)和糖化血红蛋白(glycosylated hemoglobin, HbAlC)水平的变化。结果:治疗后,两组患者空腹血糖、餐后2 h血糖水平均较治疗前明显降低,餐后2 h血清C肽水平均较治疗前明显升高,且研究组以上指标的改善程度较对照组更明显(P0.05)。两组患者治疗前后空腹血清C肽水平比较差异无统计学意义(P0.05);治疗后,两组患者BMI、TC、TG、LDL-C和HbAlC水平均较治疗前显著降低,HDL-C水平明显升高,而研究组BMI、TC、TG、LDL-C和HbAlC水平显著低于对照组(P0.05),HDL-C水平明显高于对照组(P0.05)。结论:格列美脲片联合艾塞那肽治疗肥胖2型糖尿病可有效的控制患者血糖,降低BMI,改善血脂水平。     

Determination of glimepiride in human plasma using semi-microbore high performance liquid chromatography with column-switching

A fully automated semi-microbore high performance liquid chromatographic (HPLC) method with column-switching using UV detection was developed for the determination of glimepiride from human plasma samples. Plasma sample (900 microl) was deproteinated and extracted with ethanol and acetonitrile. The extract (70 microl) was directly injected into a Capcell Pak MF Ph-1 pre-column where the primary separation occurred to remove proteins and retain drugs using a mixture of acetonitrile and 10mM phosphate buffer (pH 2.18) (20:80, v/v). The analytes were transferred from the pre-column to an intermediate column using a switching valve and then subsequently separated on an analytical column and monitored with UV detection at 228 nm. Glimepiride was eluted with retention time 34.9 min without interference of endogenous substance from plasma. The limit of quantification (LOQ) was 10 ng/ml for glimepiride. The calibration curves were linear over the concentration range of 10-400 ng/ml (r(2) = 0.9997). Moreover, inter- and intra-day precisions of the method were less than 15% and accuracies were higher than 99%. The developed method was successfully applied for the quantification of glimepiride in human plasma and was used to support a human pharmacokinetic study following a single oral administration of 2 mg glimepiride.     

Determination of glimepiride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry

A sensitive and specific high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS-MS) method has been developed at our center for the determination of glimepiride in human plasma. After the addition of the internal standard, plasma samples were extracted by liquid-liquid extraction technique using diethyl ether. The compounds were separated on a prepacked C18 column using a mixture of acetonitrile, methanol and ammonium acetate buffer as mobile phase. A Finnigan LCQDUO ion trap mass spectrometer connected to an Alliance Waters HPLC was used to develop and validate the method. The analytical method was validated according to the FDA bioanalytical method validation guidance. The results were within the accepted criteria as stated in the aforementioned guidance. The method was proved to be sensitive and specific by testing six different plasma batches. Linearity was established for the range of concentrations 5.0-500.0 ng/ml with a coefficient of determination (r2) of 0.9998. Accuracy for glimepiride ranged from 100.58 to 104.48% at low, mid and high levels. The intra-day precision was better than 12.24%. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 5.0 ng/ml with a precision of 7.96%. The proposed method enables the unambiguous identification and quantitation of glimepiride for pharmacokinetic, bioavailability or bioequivalence studies.     

Glimepiride activates eNOS with a mechanism Akt but not caveolin-1 dependent

Insulin stimulates caveolin-1 and eNOS phosphorylation. The sulfonylurea glimepiride mimics several insulin actions by mechanisms that are poorly understood. Glimepiride induces caveolin-1 phosphorylation and activates PI3K and Akt in rat adipocytes. In this paper, we investigated the effect of glimepiride on eNOS activation in human endothelial cells. We found that glimepiride induces caveolin-1 and eNOS phosphorylation. To better understand the role of caveolin-1 in glimepiride action, we downregulated caveolin-1 expression by specific siRNA transfection. Caveolin-1 silencing did not change eNOS and Akt phosphorylation induced by glimepiride. On the contrary, LY294002, a specific PI3K inhibitor, blocked eNOS serine 1177 phosphorylation. These findings suggest that glimepiride induces eNOS phosphorylation in endothelial cells through an Akt-dependent mechanism, not regulated by caveolin-1.     

甘精胰岛素联合不同降糖药稳定2 型糖尿病血糖水平的效果

目的:评价甘精胰岛素联合沙格列汀或格列美脲稳定2型糖尿病血糖水平的作用效果。方法:将我院2收治的228例2型糖尿病患者按照随机数字表法分为研究组和对照组,每组114人。研究组给予沙格列汀联合甘精胰岛素进行治疗,对照组给予格列美脲联合甘精胰岛素进行治疗。全部病例在治疗前4 d及治疗满16周时应用动态血糖监测仪实施72 h动态血糖监测。对比两组治疗前后血糖水平相关指标及血糖水平浮动相关指标的变化。结果:研究组治疗后体质指数显著低于对照组(P0.05)。两组治疗后空腹血糖均比本组治疗前显著下降(P0.05)。两组治疗后糖化血红蛋白均比本组治疗前显著下降(P0.05)。两组治疗后胰岛素用量无显著差异。两组平均血糖水平治疗前后无显著差异(P0.05)。研究组治疗后血糖标准差、日内血糖平均波动幅度、日内血糖波动次数、日间血糖平均绝对差改善幅度显著优于对照组。两组高血糖治疗后均比治疗前显著改善,改善幅度无显著差异(P0.05)。两组低血糖曲线下面积治疗前后无显著差异(P0.05)。结论:甘精胰岛素并用沙格列汀更能在显著控制2型糖尿病患者血糖的同时,还可使其血糖水平保持持久稳定,且不增加其低血糖的发生风险。