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Metformin in obesity

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https://www.readbyqxmd.com/read/28208582/nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users
#1
REVIEW
Fedra Luciano-Mateo, Anna Hernández-Aguilera, Noemi Cabre, Jordi Camps, Salvador Fernández-Arroyo, Jose Lopez-Miranda, Javier A Menendez, Jorge Joven
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan...
February 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#2
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28198702/epigenetic-clock-analysis-of-diet-exercise-education-and-lifestyle-factors
#3
Austin Quach, Morgan E Levine, Toshiko Tanaka, Ake T Lu, Brian H Chen, Luigi Ferrucci, Beate Ritz, Stefania Bandinelli, Marian L Neuhouser, Jeannette M Beasley, Linda Snetselaar, Robert B Wallace, Philip S Tsao, Devin Absher, Themistocles L Assimes, James D Stewart, Yun Li, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Steve Horvath
Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions, and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti...
February 14, 2017: Aging
https://www.readbyqxmd.com/read/28193233/tacrolimus-in-the-prevention-of-adverse-pregnancy-outcomes-and-diabetes-associated-embryopathies-in-obese-and-diabetic-mice
#4
Ahmad J H Albaghdadi, Melanie A Hewitt, Samantha M Putos, Michael Wells, Terence R S Ozolinš, Frederick W K Kan
BACKGROUND: T2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28181993/bariatric-surgery-prior-to-index-screening-colonoscopy-is-associated-with-a-decreased-rate-of-colorectal-adenomas-in-obese-individuals
#5
Dmitriy Kedrin, Shaan-Chirag Chandrahas Gandhi, Molly Wolf, Jatin Roper, Omer Yilmaz, Kathleen Corey, Hamed Khalili, Fatima Cody Stanford, Manish Gala
OBJECTIVES: Obesity is an important risk factor for the development of colorectal cancer (CRC). Although the impact of bariatric surgery on CRC is conflicting, its impact on precursor lesions is unknown. The aim of this study was to determine whether bariatric surgery before index screening colonoscopy is associated with decreased development of colorectal adenomas. METHODS: We performed a retrospective cohort study of bariatric surgery patients who had undergone index, screening colonoscopy at an academic center from 2001 to 2014...
February 9, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28178338/the-impact-of-obesity-and-adiponectin-signaling-in-patients-with-renal-cell-carcinoma-a-potential-mechanism-for-the-obesity-paradox
#6
Ryuichi Ito, Shintaro Narita, Mingguo Huang, Taketoshi Nara, Kazuyuki Numakura, Koichiro Takayama, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin...
2017: PloS One
https://www.readbyqxmd.com/read/28177686/pharmacokinetics-of-metformin-in-the-rat-assessment-of-the-effect-of-hyperlipidemia-and-evidence-for-its-metabolism-to-guanylurea
#7
Raniah Q Gabr, Ahmed A El-Sherbeni, Mohamed Ben-Eltriki, Ayman Os El-Kadi, Dion R Brocks
Metformin pharmacokinetics are highly dependent upon organic cationic transporters. There is evidence of a change in its renal clearance in hyperlipidemic obese patients, and no information on its metabolic fate. To study some of these aspects, the influence of poloxamer 407 (P407)-induced hyperlipidemia on metformin pharmacokinetics was assessed. Control and P407 treated adult male rats were administered 30 mg/kg metformin intravenously (iv). The pharmacokinetic assessments were performed at 2 time points, 36 and 108 h, following the intraperitoneal dose of P407 (1 g/kg)...
December 15, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28167482/beneficial-effects-of-sitagliptin-and-metformin-in-non-diabetic-hypertensive-and-dyslipidemic-patients
#8
Mazhar Hussain, Moazzam Ali Atif, Muhammad Bilal Ghafoor
Obesity, dyslipidemia and hypertension are major risk factors for cardiovascular disease and its associated complications. To evaluate the beneficial effects of sitagliptin and metformin in non-diabetic dyslipidemic and hypertensive patients. A prospective randomized clinical trial was conducted on 70 newly diagnosed dyslipidemic patients with BMI > 25 and blood pressure > 130/80 at outpatient clinic of medical unit-1 of Sheikh Medical College/Hospital, Rahim Yar Khan. They were divided in to three groups each containing 35 patients; First group served as a healthy control while second and third study groups were given tablet sitagliptin 50mg and tab metformin 850mg respectively twice a day for twelve weeks...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28161303/comparison-of-exenatide-and-acarbose-on-intra-abdominal-fat-content-in-patients-with-obesity-and-type-2-diabetes-a-randomized-controlled-trial
#9
Li Shi, Jing Zhu, Ping Yang, Xiaoqiang Tang, Wenlong Yu, Changjie Pan, Moyu Shen, Dalong Zhu, Jinluo Cheng, Xinhua Ye
OBJECTIVE: To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. METHODS: This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months...
February 1, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28157691/the-effect-of-alfacalcidiol-and-metformin-on-metabolic-disturbances-in-women-with-polycystic-ovary-syndrome
#10
Jana Figurová, Ingrid Dravecká, Jana Petríková, Martin Javorský, Ivica Lazúrová
BACKGROUND: The aim of this randomized clinical trial (RCT) was to evaluate the effect of vitamin D supplementation in obese, insulin-resistant (IR) and vitamin D-deficient polycystic ovary syndrome (PCOS) women on metabolic abnormalities in comparison to the effect of metformin or combined metformin plus vitamin D therapy. MATERIAL AND METHODS: Thirty-nine PCOS women who fulfilled the inclusion criteria were randomized into three groups and treated with alfacalcidiol, combined alfacalcidiol and metformin therapy and metformin for 6 months...
February 3, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28155616/crosstalk-between-oxidative-and-nitrosative-stress-and-arterial-stiffness
#11
Ioana Mozos, Constantin Tudor Luca
Arterial stiffness, the expression of reduced arterial elasticity, is an effective predictor of cardiovascular disorders. Oxidative stress is an imbalance between exposure to toxic reactive oxygen species (ROS) and antioxidant systems. The increase in reactive nitrogen species (RNS) is termed nitrosative stress. We review the main mechanisms and products linking arterial stiffness with oxidative and nitrosative stress in several disorders, focusing on recent experimental and clinical data, and the mechanisms explaining benefits of antioxidant therapy...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#12
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan Edgerton, Ann D Thor, Pepper Schedin, Steven Anderson, Paul MacLean
Several epidemiological studies have associated metformin treatment with a reduction in breast cancer incidence in pre-diabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiological reports consistently link western-style high fat diets, which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28143456/short-term-effectiveness-of-low-dose-liraglutide-in-combination-with-metformin-versus-high-dose-liraglutide-alone-in-treatment-of-obese-pcos-randomized-trial
#13
RANDOMIZED CONTROLLED TRIAL
Mojca Jensterle, Nika Aleksandra Kravos, Katja Goričar, Andrej Janez
BACKGROUND: Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. METHODS: Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m(2)) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1...
January 31, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28135899/insulin-use-increases-risk-of-asthma-but-metformin-use-reduces-the-risk-in-patients-with-diabetes-in-a-taiwanese-population-cohort
#14
Chiung-Zuei Chen, Chih-Hui Hsu, Chung-Yi Li, Tzuen-Ren Hsiue
objective -Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma. methods -We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856)...
January 31, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28124822/liraglutide-effects-on-beta-cell-insulin-sensitivity-and-glucose-effectiveness-in-patients-with-stable-coronary-artery-disease-and-newly-diagnosed-type-2-diabetes
#15
Christian Anholm, Preman Kumarathurai, Lene Rørholm Pedersen, Olav Wendelboe Nielsen, Ole Peter Kristiansen, Mogens Fenger, Sten Madsbad, Ahmad Sajadieh, Steen Bendix Haugaard
AIMS: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Design: A randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM...
January 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28114814/transcriptomic-effects-of-metformin-in-skeletal-muscle-arteries-of-obese-insulin-resistant-rats
#16
Jaume Padilla, Pamela K Thorne, Jeffrey S Martin, R Scott Rector, Sadia Akter, J Wade Davis, M Harold Laughlin, Nathan T Jenkins
We examined the effects of metformin, a commonly used antidiabetic drug, on gene expression in multiple arteries. Specifically, transcriptional profiles of feed arteries and second branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles as well as aortic endothelial scrapes were examined from obese insulin-resistant Otsuka Long-Evans Tokushima Fatty rats treated with ( n = 9) or without ( n = 10) metformin from 20 to 32 weeks of age. Metformin-treated rats exhibited a reduction in body weight, adiposity, and HbA1c ( P < 0...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28114566/the-effects-of-metformin-on-obesity-induced-dysfunctional-retinas
#17
Andy Jeesu Kim, Janet Ya-An Chang, Liheng Shi, Richard Cheng-An Chang, Michael Lee Ko, Gladys Yi-Ping Ko
Purpose: The purpose of this study was to determine the effects of metformin on dysfunctional retinas in obesity-induced type 2 diabetic mice. Methods: A high-fat diet (HFD)-induced diabetic mouse model (C57BL/6J) was used in this study. After 2 months of the HFD regimen, HFD mice were given daily metformin through oral gavage. Body weights, glucose tolerance, and retinal light responses were monitored regularly. Fluorescein angiography (FA) was used to assess changes in retinal vasculature...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28106245/a-randomized-controlled-trial-of-mediterranean-diet-and-metformin-to-prevent-age-related-diseases-in-people-with-metabolic-syndrome
#18
Patrizia Pasanisi, Giuliana Gargano, Maria Gaetana Di Mauro, Mauro Cortellini, Alice Casagrande, Anna Villarini, Eleonora Bruno, Eliana Roveda, Gabriella Saibene, Elisabetta Venturelli, Franco Berrino
PURPOSE: Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD...
January 20, 2017: Tumori
https://www.readbyqxmd.com/read/28093873/diagnostic-and-management-challenges-from-childhood-puberty-through-to-transition-in-severe-insulin-resistance-due-to-insulin-receptor-mutations
#19
Christina Wei, Christine P Burren
Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) and heterozygous p.Pro1205Leu mutation in the INSR gene encoding the insulin receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled and discontinued aged 16 years, as she became normoglycaemic...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28092404/metformin-versus-myoinositol-which-is-better-in-obese-pcos-patients-a-randomized-controlled-crossover-study
#20
Valeria Tagliaferri, Daniela Romualdi, Valentina Immediata, Simona De Cicco, Christian Di Florio, Antonio Lanzone, Maurizio Guido
CONTEXT: due to the central role of metabolic abnormalities in the pathophysiology of PCOS, insulin sensitising agents have been proposed as a feasible treatment option. OBJECTIVE: to investigate which is the more effective between metformin and myoinositol on hormonal, clinical and metabolic parameters in obese patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: crossover randomized-controlled study. PATIENTS: Thirty-four PCOS obese women (age: 25...
January 16, 2017: Clinical Endocrinology
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