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A Kautzky-Willer, S Thurner, P Klimek
AIM: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. METHODS: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins...
October 21, 2016: Journal of Internal Medicine
Fabio Broglio, Edoardo Mannucci, Raffaele Napoli, Antonio Nicolucci, Francesco Purrello, Elena Nikonova, William Stager, Roberto Trevisan
AIMS: To evaluate long term efficacy and safety of lixisenatide, a short-acting, prandial GLP-1 RA (Glucagon-Like Peptide-1 Receptor Agonists) as add-on therapy in type 2 diabetes mellitus. METHODS: A meta-analysis of 76-week results of five placebo-controlled clinical trials from the GetGoal program was performed including 3,000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea ± metformin (GetGoal-S), basal insulin ± metformin (GetGoal-L) or pioglitazone ± metformin (GetGoal-P)...
October 20, 2016: Diabetes, Obesity & Metabolism
Connie M Rhee, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction...
October 20, 2016: Nephron
Haleh Vaez, Moslem Najafi, Maryam Rameshrad, Negisa Seyed Toutounchi, Mehraveh Garjani, Jaleh Barar, Alireza Garjani
Toll like receptors (TLRs) are key players in the innate immune responses. The energy sensing enzyme, AMPK, has been implicated in the modulation of immunity. The present study investigated whether AMPK activation by metformin could contribute to the regulation of immune responses in the isolated heart via suppression of TLR4 activity, independent of circulatory immunity. Isolated Wistar rat hearts were perfused with Krebs-Henseleit buffer in the absence or presence of lipopolysaccharide (LPS; 0.2μM), LPS+metformin (10mM), and LPS+metformin+compound C (10μM)...
October 14, 2016: International Immunopharmacology
Noof A Alenazi, Jeffrey M Manthorpe, Edward P C Lai
Bisphenol A (BPA) is an estrogen-mimicking chemical that can be selectively detected in water using a chemical sensor based on molecularly imprinted polymers (MIPs). However, the utility of BPA-MIPs in sensor applications is limited by the presence of non-specific binding sites. This study explored a dual approach to eliminating these sites: optimizing the molar ratio of the template (bisphenol A) to functional monomer (methacrylic acid) to cross-linker (ethylene glycol dimethacrylate), and esterifying the carboxylic acid residues outside of specific binding sites by treatment with diazomethane...
October 14, 2016: Sensors
Bianca Hemmingsen, David Peick Sonne, Maria-Inti Metzendorf, Bernd Richter
BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether insulin secretagogues (sulphonylureas and meglitinide analogues) are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the effects of insulin secretagogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these...
October 17, 2016: Cochrane Database of Systematic Reviews
Muyesser Sayki Arslan, Esra Tutal, Mustafa Sahin, Melia Karakose, Bekir Ucan, Gulfer Ozturk, Erman Cakal, Zeynep Biyikli Gencturk, Mustafa Ozbek, Tuncay Delibasi
Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study...
October 15, 2016: Endocrine
Luciano Galdieri, Himavanth Gatla, Ivana Vancurova, Ales Vancura
AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de-novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription...
October 12, 2016: Journal of Biological Chemistry
Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst
AIMS/HYPOTHESIS: GLP-1 receptor agonists and DPP-4 inhibitors both stimulate GLP-1 receptors. Our objective was to determine, whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. METHODS: 16 subjects with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥ 2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (a) sitagliptin (100 mg p...
October 6, 2016: Diabetes, Obesity & Metabolism
C Coyle, F H Cafferty, C Vale, R E Langley
BACKGROUND: Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. PATIENTS AND METHODS: We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer...
September 28, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Madhur Nayan, Erin M Macdonald, David N Juurlink, Peter C Austin, Antonio Finelli, Girish S Kulkarni, Robert J Hamilton
Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer...
September 24, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
D Isrow, A Kolozsvary, K Lapanowski, S L Brown, J H Kim
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Jingfang Zou, Liangli Hong, Chaohuan Luo, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Huier Yuan, Yaqiu Hu, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Jiexiong Huang, Jidong Cheng
Metformin is an oral biguanide commonly used for the treating type II diabetes and has recently been demonstrated to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Our study demonstrated a marked loss of AMP-activated protein kinase (AMPK) phosphorylation and nuclear FOXO1 protein in estrogen-dependent endometrial cancer (EC) tumors compared to normal control endometrium...
September 16, 2016: Cancer Science
Sreenithya Ravindran, Vinitha Kuruvilla, Kerry Wilbur, Shankar Munusamy
Metformin, a well-known anti-diabetic agent, is very effective in lowering blood glucose in patients with type 2 diabetes with minimal side-effects. Metformin is also being recommended in the treatment of obesity and polycystic ovary syndrome. Metformin elicits its therapeutic effects mainly via activation of AMP-activated kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and activation of pathologic pathways such as mammalian target of rapamycin (mTOR), endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), oxidative stress, and hypoxia...
September 14, 2016: Journal of Cellular Physiology
Jonathan Adam, Stefan Brandmaier, Jörn Leonhardt, Markus F Scheerer, Robert P Mohney, Tao Xu, Jie Bi, Markus Rotter, Martina Troll, Shen Chi, Margit Heier, Christian Herder, Wolfgang Rathmann, Guido Giani, Jerzy Adamski, Thomas Illig, Konstantin Strauch, Yixue Li, Christian Gieger, Annette Peters, Karsten Suhre, Donna Ankerst, Thomas Meitinger, Martin Hrabe de Angelis, Michael Roden, Susanne Neschen, Gabi Kastenmüller, Rui Wang-Sattler
Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim is to investigate metformin's pleiotropic effect using a non-targeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA F4 cohort. To compare T2D patients treated with metformin (mt-T2D, n=74) and those without antidiabetic medication (ndt-T2D, n=115), we used multivariable linear regression models in a cross-sectional study...
September 12, 2016: Diabetes
Xingrong Tan, Shengbing Li, Ying Chang, Chao Fang, Hua Liu, Xingping Zhang, Yi Wang
PURPOSE: Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome (PCOS) in pregnant women. A systemic review and meta-analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients. METHODS: The literature was fully searched using MEDLINE, EMBASE, SCOPUS, and COCHRANE for continued metformin use during pregnancy in women with PCOS. A systematic review and meta-analysis were performed to evaluate the comprehensive effects of continued metformin treatment on pregnancy-related outcomes in these women...
2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
Jarrett J Failing, Heidi D Finnes, Lisa A Kottschade, Jacob B Allred, Svetomir N Markovic
Ipilimumab can induce long-term survival in 20% of patients with metastatic melanoma. Concurrent chronic medications may impact the patient's immune system, possess antimelanoma properties, and potentially affect clinical outcomes. This retrospective study sought to describe the efficacy and toxicity effects of 12 classes of chronic medications in metastatic melanoma patients treated with ipilimumab. A total of 159 adults who received ipilimumab for metastatic melanoma at Mayo Clinic (Rochester, Minnesota, USA) from 1 March 2011 through 31 December 2014 were included...
September 3, 2016: Melanoma Research
Akira Nakayama, Itasu Ninomiya, Shinichi Harada, Tomoya Tsukada, Koichi Okamoto, Shinichi Nakanuma, Seisho Sakai, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Katsunobu Oyama, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Sachio Fushida, Tetsuo Ohta
Esophageal cancer is one of the most aggressive tumor types because of its invasiveness and metastatic potential. Several reports have described an association between increased invasiveness after ionizing radiation (IR) treatment and epithelial-to-mesenchymal transition (EMT). The biguanide metformin is reported to prevent transforming growth factor-β (TGF-β)-induced EMT and proliferation of cancer. This study examined whether IR induces EMT and promotes the invasive potential of TE-9 esophageal squamous cell carcinoma cells and the effect of metformin on IR-induced EMT...
August 31, 2016: International Journal of Oncology
Ivan Kruljac, Miroslav Ćaćić, Petra Ćaćić, Vedran Ostojić, Mario Štefanović, Aljoša Šikić, Milan Vrkljan
Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department...
September 3, 2016: Endocrine
Sarita Bajaj
During pregnancy, when glycaemic levels remain uncontrolled, despite lifestyle modification, pharmacotherapy is advised, usually insulin which has been the gold standard for treatment. Recent studies however suggest that certain oral anti diabetic agents (OADs) may be safe and acceptable alternatives. There may be potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and foetus...
September 2016: JPMA. the Journal of the Pakistan Medical Association
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