西格列汀联合二甲双胍治疗初诊2型糖尿病的疗效观察

目的 探讨西格列汀联合二甲双胍治疗初发、肥胖2型糖尿病的临床疗效.方法 选取2012年1月至2013年12月期间在我院治疗的180例初发、肥胖2型糖尿病患者为研究对象,将其随机分为治疗组和对照组,其中治疗组92例,对照组88例.对照组患者给予格列美脲＋二甲双胍治疗,治疗组给予二甲双胍＋西格列汀治疗.入组前常规进行肝肾功能、血糖血脂、糖化血红蛋白、胰岛细胞分泌功能、胰岛素抵抗等评估,治疗期24周.治疗结束后分析两组患者的在体重、空腹血糖、餐后2小时血糖、糖化血红蛋白、胰岛细胞分泌功能、胰岛素抵抗指数等方面的差异.结果 治疗组患者各项监测指标（空腹及餐后血糖、糖化血红蛋白、胰岛细胞分泌功能、胰岛素抵抗指数）明显好于对照组患者（P＜0.05）,且治疗组的总有效率92.40％ （85/92）和对照组患者72.73％ （64/88）相比占优势,两组患者比较差异具有统计学意义（P＜0.05）.两组患者在体重、低血糖发作方面无明显差异（P＞0.05）.结论 二甲双胍联合西格列汀治疗初发、肥胖2型糖尿病患者安全有效,值得借鉴.     

二甲双胍和α-硫辛酸合用治疗Ⅱ型糖尿病的疗效研究

目的：探讨二甲双胍和α-硫辛酸合用治疗Ⅱ型糖尿病的疗效。方法：将Ⅱ型糖尿病患者随机分为观察组和对照组。观察组使用二甲双胍和α-硫辛酸合用治疗;对照组单用二甲双胍治疗,比较两组患者疗效。结果：观察组与对照组比较：治疗15 d后各项指标无显著性差异（t=5.32,P＞0.05）;治疗30 d后观察组各项指标明显下降,与对照组比较差异明显（t=9.12,P＜0.05）;治疗60 d后差异显著（t=10.73,P＜0.05）。两组不良反应发生率比较无显著性差异。结论：二甲双胍与α-硫辛酸合用后的效果明显强于对照组。     

Long term use of metformin leading to vitamin B 12 deficiency

Metformin is a commonly used oral hypoglycaemic agent worldwide. Gastrointestinal side effects and lactic acidosis related to metformin usage are commonly recognized. However, the associated vitamin B12 deficiency is less well known. We present a case of long term metformin use resulting in vitamin B12 deficiency     

Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells

Objective

Metformin and glucagon like peptide-1 (GLP-1) prevent diabetic cardiovascular complications and atherosclerosis. However, the direct effects on hyperglycemia-induced oxidative stress in endothelial cells are not fully understood. Thus, we aimed to evaluate the effects of metformin and a GLP-1 analog, liraglutide on high glucose-induced oxidative stress.

Methods

Production of reactive oxygen species (ROS), activation of protein kinase C (PKC) and NAD(P)H oxidase, and changes in signaling molecules in response to high glucose exposure were evaluated in human aortic endothelial cells with and without treatment of metformin and liraglutide, alone or in combination. PKC-NAD(P)H oxidase pathway was assessed by translocation of GFP-fused PKCβ2 isoform and GFP-fused p47phox, a regulatory subunit of NAD(P)H oxidase, in addition to endogenous PKC phosphorylation and NAD(P)H oxidase activity.

Results

High glucose-induced ROS overproduction was blunted by metformin or liraglutide treatment, with a further decrease by a combination of these drugs. Exposure to high glucose caused PKCβ2 translocation and a time-dependent phosphorylation of endogenous PKC but failed to induce its translocation and phosphorylation in the cells treated with metformin and liraglutide. Furthermore, both drugs inhibited p47phox translocation and NAD(P)H oxidase activation, and prevented the high glucose-induced changes in intracellulalr diacylglycerol (DAG) level and phosphorylation of AMP-activated protein kinase (AMPK). A combination of these drugs further enhanced all of these effects.

Conclusions

Metformin and liraglutide ameliorate high glucose-induced oxidative stress by inhibiting PKC-NAD(P)H oxidase pathway. A combination of these two drugs provides augmented protective effects, suggesting the clinical usefulness in prevention of diabetic vascular complications.     

Stent thrombosis is not increased following percutaneous coronary intervention in patients with non-insulin dependent diabetes mellitus taking metformin

Objective

Recent studies have suggested that metformin may inhibit endothelialization following limus-eluting stent (LES) placement and may increase the risk of stent thrombosis. Therefore, we assessed the impact of metformin on stent thrombosis and major adverse cardiovascular events (MACE) in non-insulin-dependent diabetes mellitus (NIDDM) patients who receive drug-eluting stents (DES).

Methods

We assessed the impact of metformin and stent type on stent thrombosis, MACE, and death in NIDDM patients following DES placement. Of the 1201 patients included, 74.8% received LES, 25.2% received paclitaxel-eluting stents (PES), and 55% were taking metformin.

Results

There was no difference in stent thrombosis, regardless of stent type or metformin use. While Kaplan–Meier curves demonstrated reduced MACE (p = 0.007) and death (p = 0.006) with metformin use, multivariate analysis demonstrated that stent type and metformin use were not associated with outcome.

Conclusion

In NIDDM patients, metformin use or stent type following DES placement did not increase stent thrombosis and MACE rates.     

二甲双胍治疗青春期多囊卵巢综合征患者的效果分析

目的探讨二甲双胍治疗青春期多囊卵巢综合征患者的临床疗效。方法回顾性分析我院2011～2013年妇科收治的80例青春期多囊卵巢综合征患者的资料,随机分为观察组及对照组,各40例,两组均采用达英-35治疗,观察组患者加用二甲双胍片,连续治疗3个月,比较两组患者治疗前后血浆性激素、空腹血糖及空腹胰岛素变化情况。结果两组患者血浆性激素FSH、LH、LH／FSH、T指标均下降,观察组患者下降更为明显,比较差异有统计学意义（P〈0．05）;两组患者FBS、FIN及HOMA—IR均有改善,观察组患者改善更明显,比较差异有统计学意义（P〈0．05）。结论二甲双胍联合达英-35治疗青春期多囊卵巢综合征,能改善患者临床症状、卵巢功能及胰岛素抵抗,有效降低雄激素水平,疗效满意。     

二甲双胍对人胆管癌RBE细胞的作用及其机制

目的：探讨二甲双胍对人肝胆管癌细胞的增殖、凋亡和细胞周期的影响及机制。 方法：将人肝胆管癌RBE细胞分别用二甲双胍、Compound C（AMPK抑制剂）、二甲双胍+ Compound C处理,以未处理的RBE细胞作为空白对照,分别用MTT法检测细胞增殖、流式细胞仪检测细胞凋亡和细胞周期、Western blot检测细胞AMPK/mTOR通路蛋白的表达。 结果：与空白对照组比较,二甲双胍作用后的RBE细胞存活率降低;细胞凋亡率升高;G0/G1期比例增加,而S期比例减少;磷酸化AMPK（p-AMPK）蛋白表达上调,而磷酸化mTOR（p-mTOR）蛋白表达明显下调,差异均有统计学意义（均P<0.05）。二甲双胍与Compound C联合作用RBE细胞后,二甲双胍的上述作用均被取消,各项指标与空白对照组差异均无统计学意义（均P>0.05）。单独的Compound C作用RBE细胞后,各项指标未见明显改变,与空白对照组差异均无统计学意义（均P>0.05）。 结论：二甲双胍能抑制人胆管癌RBE细胞的增殖、促进凋亡和细胞周期阻滞,该作用可能其与激活AMPK从而抑制mTOR下游效应分子有关。

     

Low and high linear energy transfer radiation sensitization of HCC cells by metformin

The purpose of this study was to investigate the efficacy of metformin as a radiosensitizer for use in combination therapy for human hepatocellular carcinoma (HCC). Three human HCC cell lines (Huh7, HepG2, Hep3B) and a normal human hepatocyte cell line were treated with metformin alone or with radiation followed by metformin. In vitro tests were evaluated by clonogenic survival assay, FACS analysis, western blotting, immunofluorescence and comet assay. Metformin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, metformin abrogated G2/M arrest and increased the cell population in the sub-G1 phase and the ROS level, ultimately increasing HCC cellular apoptosis. Metformin inhibits the repair of DNA damage caused by radiation. The radiosensitizing effects of metformin are much higher in neutron (high LET)-irradiated cell lines than in γ (low LET)-irradiated cell lines. Metformin only had a moderate effect in normal hepatocytes. Metformin enhances the radiosensitivity of HCC, suggesting it may have clinical utility in combination cancer treatment with high-LET radiation.     

二甲双胍联合达英-35治疗多囊卵巢综合征的疗效评价

目的探讨二甲双胍联合达英-35治疗多囊卵巢综合征的疗效。方法选择2012年1月～2013年10月在我院就诊的96例多囊卵巢综合征（PCOS）患者为研究对象,随机分为观察组和对照组,每组各48例。对照组患者给予达英-35治疗,观察组患者给予二甲双胍联合达英-35治疗。结果观察组总有效率（93．75％）高于对照组总有效率（79．17％）,差异有统计学意义（P〈0．05）。治疗后,两组患者LH,T,LH／FSH比值均出现明显下降,差异具有统计学意义（P〈0．01）,而且观察组下降更明显,组间比较差异有统计学意义（P〈0．01）。与治疗前相比,两组患者在治疗后HOMA—IR、BNI及卵巢体积均出现明显下降,差异具有统计学意义（P〈0．01）,而且观察组下降更明显,组间比较差异有统计学意义（P〈0．05）。结论对于多囊卵巢综合征患者采用二甲双胍联合达英-35具有比较好的治疗效果,能够有效降低LH、空腹胰岛素以及雄激素水平,并且能够增强多囊卵巢综合征患者对于促排卵的敏感性,对于提高患者的排卵率、妊娠率及恢复患者的生育功能有积极意义。     

Suppressive effects of metformin on colorectal adenoma incidence and malignant progression

BackgroundThe linear progression from normal colonic epithelium to adenoma initiation, carcinoma transformation and metastasis is considered the classical model of colorectal cancer (CRC) development. Although metformin has been extensively reported to be negatively related to cancer incidence, the effect of metformin on CRC development remains unclear. We aimed to evaluate the role of metformin in the entire CRC linear progression.MethodsSystematic searches and data extraction were performed in the PubMed, Embase, and Cochrane Library databases on Jan 31, 2019. The combined relative ratios (RRs) of colorectal tumor incidence and the hazard ratios (HRs) of overall survival (OS) and cancer-specific survival (CSS) were evaluated by a random-effects model. Then, the effects of metformin were further assessed through stratified analyses by population, medication duration and dosage, dose-response analysis and comparison with other antidiabetic agents.ResultsA total of 50 studies consisting of 238,540 cases of diabetes mellitus (DM) were included in this study. Metformin use was negatively associated with the incidence of colorectal adenoma (RR: 0.75, 95% CI: 0.65-0.86) and CRC (RR: 0.73, 95% CI: 0.58-0.90). Moreover, CRC patients benefited from metformin in terms of both OS (HR: 0.73, 95% Cl: 0.63-0.84) and CSS (HR: 0.60, 95% Cl: 0.50-0.73). Stratified analyses suggested that a long duration of high-dose metformin (RR: 0.52, 95% Cl: 0.36-0.83) was more effective than a short duration in Asian populations against colorectal adenoma (RR: 0.66, 95% Cl: 056-0.70) and CRC (RR: 0.45, 95% Cl: 0.29-0.70). Interestingly, metformin use decreased CRC risk in a dose-dependent manner (RR: 0.91, 95% CI: 0.87-0.95). In addition, the benefit of metformin on CRC was more significant than that of other antidiabetic agents, including insulin.ConclusionsThe use of metformin is associated with a lower incidence of adenoma and CRC and a better prognosis, especially in Asian populations.