目的:比较罗格列酮钠片与二甲双胍片分别联合胰岛素治疗2型糖尿病的疗效和安全性。方法:40例单用胰岛素控制血糖不理想的2型糖尿病患者,随机分为A组,太罗组(罗格列酮钠片)(21例);B组,二甲双胍组(19例),进行为期16周的对照观察。结果:两组治疗后空腹及餐后2小时血糖及糖化血红蛋白(HbA1c)均呈有意义的下降(Plt;0.05),从下降幅度的百分率统计,太罗组下降幅度明显高于二甲双胍组。结论:太罗联合胰岛素治疗对于血糖的控制明显优于二甲双胍联合胰岛素治疗。
目的:观察二甲双胍对慢性暴露于高糖和高游离脂肪酸的大鼠离体胰岛细胞胰岛素分泌功能的影响。方法:将大鼠离体胰岛细胞培养于5.5~16.7 mmol/L葡萄糖或5.5 mmol/L软脂酸中48 h,再加入不同浓度二甲双胍(0~5 mg/L)培养24 h。收集各组胰岛细胞,加入5.5~16.7 mmol/L葡萄糖刺激培养1 h。收集培养液,用放免法测定其基础及葡萄糖刺激的胰岛素分泌(GSIS)水平。结果:低糖组(5.5 mmol/L葡萄糖)用不同浓度二甲双胍(0~5 mg/L)处理后的β细胞基础及葡萄糖刺激的胰岛素分泌无显著性差异(Pgt;0.05);高糖(16.7 mmol/L葡萄糖)及高脂(0.5 mmol/L棕榈酸)组β细胞基础胰岛素分泌较对照组明显增高(Plt;0.01),GSIS较对照组明显降低(Plt;0.01);用2.5~5 mg/L二甲双胍干预后,高糖及高脂组β细胞基础胰岛素分泌较未治疗组明显降低(Plt;0.01),GSIS较未治疗组明显增高(Plt;0.01)。结论:低糖环境下,二甲双胍对β细胞胰岛素分泌功能无明显影响;慢性高糖及高脂可致β细胞胰岛素分泌功能受损;而2.5~5 mg/L二甲双胍能改善糖脂毒性所致β细胞胰岛素分泌功能异常。提示二甲双胍降糖效果除了其外周作用外,可能对糖脂中毒的β细胞具有直接保护作用。
Objective To observe the effect of metformin (Met) on inflammatory bodies and focal death in human retinal microvascular endothelial cells (hRMEC) in diabetes mellitus (DM) microenvironment. MethodsExperimental research was divided into in vivo animal experiment and in vitro cell experiment. In vivo animal experiments: 9 healthy C57BL/6J male mice were randomly divided into DM group, normal control group, and DM+Met group, with 3 mice in each group. DM group and DM+Met group mice were induced by streptozotocin to establish DM model, and DM+Met group was given Met 400 mg/ (kg · d) intervention. Eight weeks after modeling, the expression of NLRP3, cleaved-membrane perforating protein D (GSDMD) and cleaved-Caspase-1 in the retina of mice in the normal control group, DM group and DM+Met group were observed by immunohistochemical staining. In vitro cell experiments: hRMEC was divided into conventional culture cell group (N group), advanced glycation end products (AGE) group, and AGE+Met group. Joining the AGE, AGE+Met groups cells were induced by 150 μg/ml of glycation end products, and 2.0 mmol/L Met was added to the AGE+Met group. Pyroptosis was detected by flow cytometry; 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe was used to detect the expression of reactive oxygen species (ROS) in cells of each group. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to detect the relative mRNA and protein expression levels of NLRP3, cleaved-GSDMD, cleaved-Caspase-1 in each group of cells. Single factor analysis of variance was used for comparison among the three groups. ResultsIn vivo animal experiments: compared with the DM group, the expression of NLRP3, cleaved-GSDMD, and cleaved-Caspase-1 in the retina of normal control group and DM+Met group mice was significantly reduced, with significant difference among the 3 groups (F=43.478, 36.643, 24.464; P＜0.01). In vitro cell experiment and flow cytometry showed that the pyroptosis rate of AGE group was significantly higher than that of N group and AGE+Met group (F=32.598, P＜0.01). The DCFH-DA detection results showed that the intracellular ROS levels in the N group and AGE+Met group were significantly lower than those in the AGE group, with the significant difference (F=47.267, P＜0.01). The mRNA (F=51.563, 32.192, 44.473; P＜0.01) and protein levels (F=63.372, 54.463, 48.412; P＜0.01) of NLRP3, cleaved-GSDMD, and cleaved-Caspase-1 in hRMEC of the AGE+Met group were significantly reduced compared to the N group. ConclusionMet can down regulate the expression of NLRP3 inflammatory body related factors in hRMEC and inhibit pyroptosis.
目的:罗格列酮(RGZ)联合二甲双胍治疗初诊2型糖尿病(T2DM)的临床疗效和安全性。方法:40例初诊2型糖尿病联用罗格列酮和二甲双胍进行12周的治疗,测定治疗前后空腹血糖(FBG)、餐后2小时血糖(PPG)、糖化血红蛋白(HbA1c)、胰岛素、C-肽、甘油三脂、体重指数(BMI),胰岛素抵抗指数(IR)、血常规、肝、肾功能等。 结果:治疗前后对照,空腹及餐后血糖、胰岛素、甘油三脂、IRI降低,具有显著差异性(Plt;0.001),体重指数变化不大(Pgt;0.05),未发生肝肾功能损害。结论:罗格列酮联合二甲双胍治疗2型糖尿病,明显改善胰岛素抵抗,降糖疗效确切。
【摘要】 目的 探讨二甲双胍致不良反应的一般规律和特点。 方法 检索1994年-2011年中国期刊全文数据库中二甲双胍所致不良反应个案报道的文献，得到符合条件的文献29篇共33例，进行统计分析。 结果 33例不良反应主要表现为内分泌系统（48.5%），皮肤及附件（18.2%），变态反应（15.2%），消化系统（9.1%），神经系统（6.1%）等。 结论 临床上应重视二甲双胍引起的不良反应，用药时应加强对患者的监护，以减少严重药物不良反应的发生。【Abstract】 Objective To investigate the characteristics and the general pattern of the adverse drug reactions (ADR) induced by metformin. Methods The ADR induced by metformin reported in domestic medical journals during 1994-2008 were retrieved by means of CNKI. A total of 29 related literatures involving 33 cases, and a related database was established for statistical analysis. Results The main clinical manifestation represented as endocrine system (48.5%), lesion of skin and its appendants (18.2%), allergic reactions (15.2%), digestive system (9.1%), nervous system (6.1%) and so on. Conclusion It is necessary to pay attention to ADR induced by metformin and strengthen observation during medication in order to reduce serious ADR.
Objective To formulate an evidence-based treatment plan for a patient with gestational diabetes mellitus. Methods Based on the clinical questions raised from a real-life patient of gestational diabetes mellitus, we searched ACP Journal Club (1991 to Dec. 2006), The Cochrane Library (Issue 4, 2006), MEDLINE (1966 to Dec. 2006) and Chinese Biological Medical Database (1980 to Dec. 2006) for systematic reviews, randomized controlled trials, cohort and case-control studies. We used the following keywords: gestational diabetes, metformin, and pregnancy complication. The quality of the included studies was assessed.Results One meta-analysis (from MEDLINE) and two randomized controlled trials (from the Cochrane Central Register of Controlled Trials) were included. These studies concluded that there was no clear evidence on the benefits of metformin for gestational diabetes. Based on the current evidence, integrated with clinical expertise and the patient’s values, metformin was not used for this patient. Instead, intensive dietary control, blood glucose control, and appropriate exercise were administered. After this individual treatment, the patient gave birth to a healthy baby in 39+4 Weeks. Conclusion The appropriate management for gestational diabetes mellitus has been formulated with the approach of evidence-based medicine. Large-scale, methodologically-sound trials are required.
ObjectiveTo explore the relationship between metformin use and the risk and prognosis of esophageal cancer in patients with diabetes.MethodsThe PubMed, Web of Science, EMbase, VIP, WanFang and CNKI databases were searched by computer to identify relevant studies from inception to August 21, 2021. Newcastle-Ottawa scale (NOS) was used to evaluate research quality. The STATA 12.0 software was used to conduct the statistical analysis.ResultsA total of 14 studies involving 5 605 218 participants were included finally. NOS of all researches were≥6 points. The pooled results indicated that metformin use could decrease the risk of esophageal cancer in diabetics (OR=0.84, 95%CI 0.71-1.00, P=0.045), and could also prolong the overall survival of diabetics with esophageal cancer (HR=0.89, 95%CI 0.80-0.99, P=0.025).ConclusionMetformin use can not only decrease the risk of esophageal cancer in patients with diabetes, but also improve the prognosis of diabetics with esophageal cancer significantly. However, more prospective high-quality studies are still needed to verify the conclusion.
ObjectiveTo observe the effect of metformin on the polarization state and photoreceptor cell activity of microglia (BV2 cells) in a high glucose environment. MethodsAn experimental study. BV2 cells were divided into a control group, a high glucose group, and a metformin+high glucose group. The cells in the high glucose group were cultured with 75 mmol/L glucose in the medium; the cells in the metformin+high glucose group were pretreated with 2 mmol/L metformin for 12 h and then placed in 75 mmo/L glucose concentration medium. The relative expression of M1 marker inducible nitric oxide synthase (iNOS), CD86 and M2 markers arginase 1 (Arg-1), and CD206 protein were detected by Western blot. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-4 were detected by enzyme-linked immunosorbent assay (ELISA). BV2 cells were co-cultured with mouse retinal photoreceptor cells (661W cells) for 24 h. The proliferation rate of 661W cells in each group was measured by methyl thiazolyl tetrazolium (MTT) colorimetric assay; the apoptosis rate of 661W cells in each group was measured by flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). An independent sample t-test was used for comparison between groups. ResultsWestern blot assay showed that the relative expression of iNOS and CD86 protein was increased and the relative expression of Arg-1 and CD206 protein was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant (t=－16.783, －11.605, 4.325, 4.649; P＜0.05); compared with the high glucose group, the relative expression of iNOS and CD86 protein was decreased and the relative expression of Arg-1 and CD206 protein was increased in BV2 cells in the metformin + high glucose group compared with the high glucose group, and the differences were all statistically significant (t=7.231, 5.560, －8.035, －8.824; P＜0.01). ELISA results showed that compared with the control group, the BV2 cells in the high glucose group had increased IL-6, TNF-α content and IL-4 content was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant (t=－64.312, －127.147, 71.547; P＜0.001); compared with the high glucose group, IL-6 and TNF-α content was significantly decreased and IL-4 content was significantly increased in BV2 cells in the metformin+high glucose group, and the differences were all statistically significant (t=44.426, 83.232, －143.115; P＜0.001). After co-culture of BV2 cells with 661W cells for 24 h, the results of MTT colorimetric assay showed that compared with the control group, the activity of 661W cells in the high glucose group was significantly reduced, and the difference was statistically significant (t=7.456, P＜0.01); compared with the high glucose group, the activity of 661W cells in the metformin+high glucose group was increased (t=－3.076, P＜0.05). TUNEL method and flow cytometry showed that the apoptosis rate of 661W cells in the high glucose group was significantly higher compared with the control group, and the differences were both statistically significant (t=－22.248, －22.628; P＜0.001); compared with the high glucose group, the apoptosis rate of 661W cells in the metformin+high glucose group was significantly decreased, and the difference was statistically significant (t=11.767, 6.906; P＜0.001, 0.01). ConclusionIn the high glucose environment, metformin inhibited the inflammatory response and attenuated the apoptosis of photoreceptor cells by regulating the polarization of microglia toward the M2 type.
目的 采用液相色谱-串联质谱法测定人血浆中二甲双胍的浓度。 方法 血浆样品用乙腈（含0.1%甲酸）沉淀蛋白后用二氯甲烷反洗后进行分析。使用Agilent C8（75 mm×4.6 mm，3.5 μm）色谱柱。流动相：A泵：5 mmol/L醋酸铵（三乙胺调pH值至7.5），B泵：乙腈。线性梯度洗脱，流速0.4 mL/min。采用电喷雾离子源，多反应离子监测。用于定量分析的离子对二甲双胍为130.2/71.1，内标吗啉胍为172.2/60.2。 结果 线性范围为50～2 000 ng/mL，最低定量限为50 ng/mL，预处理回收率为81.7%～98.0%，二甲双胍的基质效应＜9.97%，日内和日间相对标准偏差均＜5.2%。 结论 液相色谱-串联质谱法快速、简便、灵敏度高，是一种适用于人血浆中药物浓度的测定及药物动力学和生物利用度研究的方法。