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Metformin in obesity

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https://www.readbyqxmd.com/read/28334683/combined-metformin-and-insulin-treatment-reverses-metabolically-impaired-omental-adipogenesis-and-accumulation-of-4-hydroxynonenal-in-obese-diabetic-patients
#1
Morana Jaganjac, Shamma Almuraikhy, Fatima Al-Khelaifi, Mashael Al-Jaber, Moataz Bashah, Nayef A Mazloum, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Wael Kafienah, Mohamed A Elrayess
OBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery...
March 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28330386/the-effects-of-dual-therapy-intensification-with-insulin-or-dipeptidylpeptidase-4-inhibitor-on-cardiovascular-events-and-all-cause-mortality-in-patients-with-type-2-diabetes-a-retrospective-cohort-study
#2
Mamza Jil, Mehta Rajnikant, Donnelly Richard, Idris Iskandar
PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure. METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014)...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28323503/add-on-dpp-4-inhibitor-alogliptin-alone-or-in-combination-with-pioglitazone-improved-%C3%AE-cell-function-and-insulin-sensitivity-in-metformin-treated-pcos
#3
Mojca Jensterle, Katja Goricar, Andrej Janez
PURPOSE: Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR. MATERIALS AND METHODS: In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34...
March 21, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28317764/cucurbitane-glycosides-from-the-fruit-of-siraitia-grosvenori-and-their-effects-on-glucose-uptake-in-human-hepg2-cells-in-vitro
#4
Fu Li, Fumei Yang, Xin Liu, Lun Wang, Bin Chen, Lianhong Li, Mingkui Wang
The mogrosides in the fruit of Siraitia grosvenori can serve as a sugar substitute for diabetics due to their sweetness, low calorie and positive effects on blood glucose level control. The present study was to purify the mogrosides from the fruit of S. grosvenori and evaluate their enhancement of glucose uptake rate in HepG2 cells in vitro. As a result, eighteen mogrosides were isolated, including six new ones and a known but new naturally occurring compound. The chemical structures of the new compounds were identified by 1D, 2D-NMR and HR-ESI-MS techniques, together with chemical methods...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28290049/type-2-diabetes-and-hepatocellular-carcinoma-risk-factors-and-pathogenesis
#5
REVIEW
P Wainwright, E Scorletti, C D Byrne
PURPOSE OF REVIEW: This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms. RECENT FINDINGS: The presence of type 2 diabetes significantly increases the risk of developing hepatocellular carcinoma, and treatment with metformin may be associated with a lower risk. Treatment with insulin and sulphonylureas may be associated with increased risk...
April 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#6
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#7
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
February 13, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28250276/atractylenolide-iii-enhances-energy-metabolism-by-increasing-the-sirt-1-and-pgc1%C3%AE-expression-with-ampk-phosphorylation-in-c2c12-mouse-skeletal-muscle-cells
#8
Mi Young Song, Hyo Won Jung, Seok Yong Kang, Yong-Ki Park
Targeting energy expenditure provides a potential alternative strategy for achieving energy balance to combat obesity and the development of type 2 diabetes mellitus (T2DM). In the present study, we investigated whether atractylenolide III (AIII) regulates energy metabolism in skeletal muscle cells. Differentiated C2C12 myotubes were treated with AIII (10, 20, or 50 µM) or metformin (2.5 mM) for indicated times. The levels of glucose uptake, the expressions of key mitochondrial biogenesis-related factors and their target genes were measured in C2C12 myotubes...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28208582/nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
Raniah Q Gabr, Ahmed A El-Sherbeni, Mohamed Ben-Eltriki, Ayman O 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 (i.v.). 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
#16
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
#17
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
#18
RANDOMIZED CONTROLLED TRIAL
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...
March 1, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28155616/crosstalk-between-oxidative-and-nitrosative-stress-and-arterial-stiffness
#19
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
#20
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan M Edgerton, Ann D Thor, Pepper Schedin, Steven M Anderson, Paul S MacLean
Several epidemiologic studies have associated metformin treatment with a reduction in breast cancer incidence in prediabetic 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. Epidemiologic reports consistently link western-style high fat diets (HFD), which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
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