Analytical Method Capable of Quantifying Eight Nitrosamine Impurities from Five Different Commercially Available Metformin Formulations with Glipizide,Glibenclamide, Gliclazide,Evogliptin, and Glimepiride by Ultra High Performance Liquid Chromatography Tripple Quadrupole Mass Spectrometry

Metformin and its combinations are widely used to treat type 2 diabetes. The drugs commonly used in combination with Metformin are Glipizide, Glibenclamide, Gliclazide, Evogliptin, and Glimepiride. Combination therapy is preferred over monotherapy of Metformin in most diabetics. About eighteen pharmaceutical manufacturers have lately recalled metformin formulation batches from the U.S. market due to N-nitrosodimethylamine (NDMA) impurities based on the food and drug administration (USFDA) guideline “Control of Nitrosamine in Human Drugs.” European Medicines Agency (EMA) and Health Canada have also established guidelines for nitrosamine impurities. Nitrosamines are well-known mutagenic impurities and probable human carcinogens found in pharmaceutical formulations. Thus, global regulatory agencies require pharmaceutical and formulation manufacturers to complete risk assessments for nitrosamine impurities for patient safety. Therefore, drug manufacturers must develop analytical techniques for monitoring trace nitrosamine impurities. Quantifying nitrosamine impurities in formulations requires modern equipment like LC-MS/MS and great intellect. The present study intends to give a single pre-packaged LC-MS/MS method parameters, including liquid chromatography and triple quadrupole mass spectrometer configuration. This method could quantify eight nitrosamine impurities from five different Metformin combinations (Metformin with Glipizide, Glibenclamide, Gliclazide, Evogliptin, and Glimepiride). The atmospheric pressure chemical ionisation (APCI) was used as an ionisation source, and the mass spectrometer was set to multiple reaction monitoring (MRM) mode for all eight nitrosamine impurities. A unified pre-packaged analytical setup allows analytical chemists to develop a reliable, sensitive, robust, and precise method for quantifying eight nitrosamine impurities from five different Metformin formulations of varying manufacturers. This analytical method saves time, money, and the environment using fewer pharmaceutical chemicals.     

Mucosa-associated microbiota in the jejunum of patients with morbid obesity: alterations in states of insulin resistance and metformin treatment

BackgroundStool samples have been widely used to evaluate gut microbiota; however, little is known about the composition of human small intestinal microbiota and the alterations provoked by insulin resistance.ObjectiveTo describe the composition of jejunal microbiota in morbidly obese patients, as well as its link with insulin resistance and metformin treatment.SettingVirgen de la Victoria University Hospital and Regional University Hospital, Málaga, Spain.MethodsJejunal biopsies from 46 morbidly obese patients were analyzed by next-generation sequencing method. Patients were classified in the following 3 groups: low homeostasis model assessment of insulin resistance index (HOMA-IR) value, high HOMA-IR value, and metformin-treated type 2 diabetes patients (T2D-metf).ResultsRichness (q = .011) together with Proteobacteria (W = 2), Fusobacteria (W = 2), and Bacteroidetes (W = 1) phyla were significantly higher in high HOMA-IR compared with low HOMA-IR group. At family level, several differences were found between low HOMA-IR and T2D-metf group, being the most important the higher abundance of Halomonadacea in T2D-metf group (W = 22). PICRUSt analysis showed that predicted genes involved in trimethylamine-N-oxide biosynthesis pathway could be increased in jejunal microbiota of T2D-metf group compared with the low HOMA-IR group, while indole biosynthesis pathway could be increased in the low HOMA-IR group compared with the high HOMA-IR group.ConclusionAn increase in richness and an enrichment in Proteobacteria, Fusobacteria, and Bacteroidetes was observed in jejunal from morbidly obese patients with high insulin resistance. Halomonadaceae family was significantly increased in metformin-treated patients. Functional analysis of predicted metagenome suggests that trimethylamine-N-oxide biosynthesis pathway could be increased in the jejunal microbiota of T2D-meft group, while indole biosynthesis pathway could be increased in low HOMA-IR group. These results contribute to the increase in the scarce knowledge about the mucosal microbiota of the hardly accessible small intestine.     

补气养阴降糖饮联合二甲双胍治疗老年2型糖尿病的疗效观察

目的:观察补气养阴降糖饮加减联合二甲双胍治疗老年2型糖尿病(气阴两虚证)的效果。方法:选取2018年4月至2019年10月北京市和平里医院收治的老年2型糖尿病(气阴两虚证)患者84例作为研究对象,随机分为对照组和观察组,每组42例。2组均予以基础治疗,对照组予以二甲双胍口服,观察组予以补气养阴降糖饮加减联合二甲双胍治疗。比较2组治疗前后主症、次症及总评分、糖代谢水平、临床疗效、胰岛素抵抗指数水平及不良反应。结果:治疗后2组主症、次症及总评分,糖代谢水平、胰岛素抵抗指数水平均下降,且观察组较对照组降低的更为明显,差异均有统计学意义(P0.05);治疗后观察组总有效率高于对照组,差异有统计学意义(P0.05);观察组不良反应发生率与对照组比较,差异无统计学意义(P0.05),且不良反应均轻微。结论:对老年2型糖尿病气阴两虚证予以补气养阴降糖饮加减联合二甲双胍可有效控制症状,改善糖代谢,增强临床疗效,减轻胰岛素抵抗,且安全。     

二甲双胍对糖尿病合并食管癌患者放疗效果分析

目的通过观察二甲双胍对糖尿病合并食管癌患者放疗效果,为糖尿病合并食管癌患者的治疗提供依据。方法选取2016年-2018年在该院确诊的糖尿病合并食管癌并口服二甲双胍降糖治疗的患者51例为观察组,同期诊断糖尿病合并食管癌并皮下注射胰岛素治疗的患者50例为对照组,所有的患者均实施内镜切除联合局部放疗治疗。治疗结束后随访1个月,根据RECIST标准对治疗效果进行评价两组患者的近期疗效。结果观察组患者近期疗效明显优于对照组(P<0.05)。结论二甲双胍可以提高食管癌患者的放疗效果。     

参芪降糖颗粒联合二甲双胍对2型糖尿病患者降糖效果的分析

目的：探析2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗的降糖效果。方法：选取2016年1月至2019年10月马鞍山市中心医院收治的2型糖尿病患者66例作为研究对象，按照随机数字表法分为对照组与观察组，每组33例，对照组通过二甲双胍进行治疗，观察组通过二甲双胍联合参芪降糖颗粒进行治疗，比较2组患者治疗总有效率、血糖参数、不良反应发生率等指标。结果：对照组、观察组的治疗总有效分别为75.76%、93.94%，与对照组比较，观察组的治疗总有效率明显较高（P<0.05）；观察组的空腹血糖、餐后2 h血糖等血糖参数在治疗后明显低于对照组患者（P<0.05）；对照组、观察组的治疗不良反应发生率分别为21.21%、3.03%，观察组治疗不良反应发生率明显低于对照组（P<0.05）。结论：2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗能够获得较为理想的效果，可明显改善血糖指标，安全性较高，对改善患者的治疗预后有着促进的作用。     

Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study

Background

There is evidence linking metformin to improved prostate cancer–related outcomes.

Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.