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Metformin in obesity

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https://www.readbyqxmd.com/read/29925691/pan-ampk-activator-o304-improves-glucose-homeostasis-and-microvascular-perfusion-in-mice-and-type-2-diabetes-patients
#1
Pär Steneberg, Emma Lindahl, Ulf Dahl, Emmelie Lidh, Jurate Straseviciene, Fredrik Backlund, Elisabet Kjellkvist, Eva Berggren, Ingela Lundberg, Ingela Bergqvist, Madelene Ericsson, Björn Eriksson, Kajsa Linde, Jacob Westman, Thomas Edlund, Helena Edlund
AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29923295/dapagliflozin-a-sglt2-inhibitor-slows-the-progression-of-renal-complications-through-the-suppression-of-renal-inflammation-er-stress-and-apoptosis-in-pre-diabetic-rats
#2
Krit Jaikumkao, Anchalee Pongchaidecha, Nuttawud Chueakula, La-Ongdao Thongnak, Keerati Wanchai, Varanuj Chatsudthipong, Nipon Chattipakorn, Anusorn Lungkaphin
BACKGROUND AND AIMS: The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin has been shown to exert both anti-diabetic and anti-obesity effects in metabolic syndrome. However, the effects of dapagliflozin on the renal complications associated with metabolic dysfunction in diet-induced obesity (DIO) are not fully understood. In this study, to work towards a resolution of these issues, we evaluated the renoprotective roles of dapagliflozin in pre-diabetic rats. METHODS: DIO was induced by feeding a high-fat diet (HF) to male Wistar rats for 16 weeks...
June 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29914872/metformin-and-jq1-synergistically-inhibit-obesity-activated-thyroid-cancer
#3
Sunmi Park, Mark Willingham, Jun Qi, Sheue-Yann Cheng
Compelling epidemiological evidence shows a strong positive correlation of obesity with thyroid cancer. In vivo studies have provided molecular evidence that high-fat-diet-induced obesity promotes thyroid cancer progression by aberrantly activating leptin-JAK2-STAT3 signaling in a mouse model of thyroid cancer (ThrbPV/PVPten+/- mice). The ThrbPV/PVPten+/- mouse expresses a dominantly negative thyroid hormone receptor β (denoted as PV) and a deletion of one single allele of the Pten gene. The ThrbPV/PVPten+/- mouse spontaneously develops follicular thyroid cancer, which allows its use as a preclinical mouse model to test potential therapeutics...
June 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29898754/metformin-inhibits-stromal-aromatase-expression-and-tumor-progression-in-a-rodent-model-of-postmenopausal-breast-cancer
#4
Erin D Giles, Sonali Jindal, Elizabeth A Wellberg, Troy Schedin, Steven M Anderson, Ann D Thor, Dean P Edwards, Paul S MacLean, Pepper Schedin
BACKGROUND: Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases...
June 14, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29892566/patient-factors-associated-with-metformin-steady-state-levels-in-type-2-diabetes-mellitus-with-therapeutic-dosage
#5
Vitarani D A Ningrum, Zullies Ikawati, Ahmad H Sadewa, Mohammad R Ikhsan
Aims: This prospective study aimed to analyze metformin steady-state concentration in repeated constant dosage and the influencing patient-factors as well as to correlate them with glycemic control. Methods: The validated HPLC-UV method was used to examine metformin steady-state concentration, while FBG and glycated albumin were used as the parameters of glycemic control during metformin administration. Results: A total of 82 type-2 diabetes patients were involved with 32...
June 2018: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/29889977/ovulation-induction-in-polycystic-ovary-syndrome
#6
Tom Tanbo, Jan Mellembakken, Sverre Bjercke, Eva Ring, Thomas Åbyholm, Peter Fedorcsak
The objective of this narrative review is to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight PCOS patients the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without side effects in the doses recommended, may be suggested. Additional first line medical alternatives include insulin sensitizers, selective estrogen receptor modulators and aromatase inhibitors...
June 11, 2018: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/29880175/the-effects-of-different-therapeutic-modalities-on-cardiovascular-risk-factors-in-women-with-polycyst%C3%A4-c-ovary-syndrome-a-random%C3%A4-zed-controlled-study
#7
Serkan Bodur, Ozgur Dundar, Mine Kanat-Pektas, Mehmet Ferdi Kinci, Levent Tutuncu
OBJECTIVE: This study was designed to evaluate the effects of 3 mg drospirenone/30 μg ethinyl estradiol (OC) alone or combined with 1700 mg metformin on metabolic risk factors. MATERIALS AND METHODS: In this randomized, prospective, controlled study, 87 non-obese (18-30 BMI) women of reproductive age (18-39) with polycystic ovary syndrome (PCOS) were assigned to control (n = 17), OC (n = 21), combination (n = 20) and metformin (n = 29) therapy groups...
June 2018: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29862487/the-influence-of-metformin-and-presence-of-type-2-diabetes-mellitus-on-mortality-and-hospitalization-in-patients-with-heart-failure
#8
Arkadiusz Retwiński, Marcin Kosmalski, Marisa Crespo-Leiro, Aldo Maggioni, Grzegorz Opolski, Piotr Ponikowski, Lech Poloński, Ewa Jankowska, Jerzy Drzewoski, Jarosław Drożdż
BACKGROUND: Metformin (MET) is one of antihyperglycaemic substances that reduces risk of major cardiovascular events, including fatal ones. Although it is formally contraindicated in moderate and severe functional stages of heart failure (HF), it is commonly used in patients with concomitant type 2 diabetes mellitus (T2DM). AIM: Evaluation of the effect of MET and T2DM on total mortality and hospitalization rates in patients with HF. METHODS: 1030 adult patients (>18 years) with HF from the Polish section of HF Long-Term Registry were included in years 2011-2014 into this retrospective analysis...
June 4, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29860743/-the-effect-of-metformin-on-metabolic-parameters-and-hypothalamic-signaling-systems-in-rats-with-obesity-induced-by-a-high-carbohydrate-high-fat-diet
#9
K V Derkach, I B Sukhov, V M Bondareva, A O Shpakov
Metformin (MF), a first-line drug in the treatment of diabetes mellitus, has been used in the recent years to treat obesity. Its therapeutic effect is due not only to the influence on the peripheral tissues, but also on the hypothalamus, which controls food behavior and energy metabolism. The aim was to study the effect of MF therapy (200 mg/kg/day, 8 weeks) in rats with obesity caused by a high-carbohydrate/high-fat diet on the metabolic and hormonal parameters and functional state of the hypothalamic signaling systems...
2018: Advances in Gerontology, Uspekhi Gerontologii
https://www.readbyqxmd.com/read/29858905/a-novel-mutation-in-the-proopiomelanocortin-pomc-gene-of-a-hispanic-child-metformin-treatment-shows-a-beneficial-impact-on-the-body-mass-index
#10
Mark A Hilado, Ruvdeep S Randhawa
BACKGROUND: Proopiomelanocortin (POMC) is a complex polypeptide that produces a variety of biologically active substances via cleavage in a tissue-specific manner [Challis BG, Millington GW. Proopiomelanocortin deficiency. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 1993-2018], yielding several products including adrenocorticotrophic (ACTH) and melanocyte stimulating hormones (MSH). These peptides have roles in the regulation of food intake, energy homeostasis, adrenal steroidogenesis, melanocyte stimulation and immune modulation...
June 2, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29808777/protective-effect-of-metformin-against-thyroid-cancer-development-a-population-based-study-in-korea
#11
Yoon Young Cho, Min Jin Kang, Soo Kyoung Kim, Junghwa Jung, Jong Ryeal Hahm, Tae Hyuk Kim, Joo Young Nam, Byung-Wan Lee, Yong-Ho Lee, Jae Hoon Chung, Sun Ok Song, Sun Wook Kim
BACKGROUND: Metformin, the most widely used drug for type 2 diabetes has recently attracted attention with regard to its anti-tumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development despite its anti-tumor effect in preclinical studies. METHODS: This was a retrospective cohort study using the Korean National Health Insurance claims database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence...
May 29, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29808092/the-efficacy-and-safety-of-the-chinese-herbal-formula-jttz-for-the-treatment-of-type-2-diabetes-with-obesity-and-hyperlipidemia-a-multicenter-randomized-positive-controlled-open-label-clinical-trial
#12
Xiaotong Yu, Lipeng Xu, Qiang Zhou, Shengping Wu, Jiaxing Tian, Chunli Piao, Hailong Guo, Jun Zhang, Liping Li, Shentao Wu, Meizhen Guo, Yuzhi Hong, Weirong Pu, Xiyan Zhao, Yang Liu, Bing Pang, Zhiping Peng, Song Wang, Fengmei Lian, Xiaolin Tong
Background and Aim: Studies have shown an increasing number of type 2 diabetes (T2D) patients with concomitant obesity and hyperlipidemia syndromes, resulting from relevant metabolic disorders. However, there are few medications and therapies, which can thoroughly address these issues. Therefore, the current study evaluated the efficacy and safety of using JTTZ, a Chinese herbal formula, to treat T2D with obesity and hyperlipidemia. Methods: A total of 450 participants with T2D (HbA1c ≥ 7...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29802412/the-histamine-h-3-receptor-inverse-agonist-pitolisant-reduces-body-weight-in-obese-mice
#13
Magdalena Kotańska, Kamil J Kuder, Katarzyna Szczepańska, Jacek Sapa, Katarzyna Kieć-Kononowicz
The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. Therefore, we studied the influence of pitolisant on body weight, water and sucrose intake as well as metabolic disturbances in the high-fat and high-sugar diet-induced obesity model in mice. To induce obesity, male CD-1 mice were fed a high-fat diet consisting of 40% fat blend for 14 weeks, water and 30% sucrose solution available ad libitum...
May 25, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29789365/structural-alteration-of-gut-microbiota-during-the-amelioration-of-human-type-2-diabetes-with-hyperlipidemia-by-metformin-and-a-traditional-chinese-herbal-formula-a-multicenter-randomized-open-label-clinical-trial
#14
Xiaolin Tong, Jia Xu, Fengmei Lian, Xiaotong Yu, Yufeng Zhao, Lipeng Xu, Menghui Zhang, Xiyan Zhao, Jian Shen, Shengping Wu, Xiaoyan Pang, Jiaxing Tian, Chenhong Zhang, Qiang Zhou, Linhua Wang, Bing Pang, Feng Chen, Zhiping Peng, Jing Wang, Zhong Zhen, Chao Fang, Min Li, Limei Chen, Liping Zhao
Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement...
May 22, 2018: MBio
https://www.readbyqxmd.com/read/29788487/the-effects-of-metformin-and-weight-loss-on-biomarkers-associated-with-breast-cancer-outcomes
#15
Ruth E Patterson, Catherine R Marinac, Dorothy D Sears, Jacqueline Kerr, Sheri J Hartman, Lisa Cadmus-Bertram, Adriana Villaseñor, Shirley W Flatt, Suneeta Godbole, Hongying Li, Gail A Laughlin, Jesica Oratowski-Coleman, Barbara A Parker, Loki Natarajan
Background: This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG)...
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29788134/novel-insights-into-the-impact-of-lifestyle-based-weight-loss-and-metformin-on-obesity-associated-biomarkers-in-breast-cancer
#16
Ana Elisa Lohmann, Isabel Pimentel, Pamela J Goodwin
No abstract text is available yet for this article.
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29779196/retrospective-analysis-of-an-insulin-to-liraglutide-switch-in-patients-with-type-2-diabetes-mellitus
#17
Eveline Bruinstroop, Laura Meyer, Catherine B Brouwer, Diana E van Rooijen, P Sytze van Dam
INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015)...
June 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29770221/risperidone-induced-type-2-diabetes-presenting-with-diabetic-ketoacidosis
#18
Clarissa Ern Hui Fang, Mohammed Faraz Rafey, Aine Cunningham, Sean F Dinneen, Francis M Finucane
A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM). On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS) of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2 ). Dipstick urinalysis showed ketonuria and glycosuria...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29764225/initial-combination-therapy-with-vildagliptin-plus-metformin-in-drug-na%C3%A3-ve-patients-with-t2dm-a-24-week-real-life-study-from-asia
#19
Manoj Chawla, Tae Ho Kim, Roberto C Mirasol, Pathan Faruque, Kathryn Cooke, Peggy Hours-Zesiger, Abhijit Shete
AIMS: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). METHODS: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29760016/diabetes-induced-cardiomyocyte-passive-stiffening-is-caused-by-impaired-insulin-dependent-titin-modification-and-can-be-modulated-by-neuregulin-1
#20
Anna-Eliane Hopf, Christian Andresen, Sebastian Kötter, Malgorzata Isic, Kamila Ulrich, Senem Sahin, Sabine Bongardt, Wilhelm Roell, Felicitas Drove, Nina Scheerer, Leni Vandekerckhove, Gilles W De Keulenaer, Nazha Hamdani, Wolfgang A Linke, Martina Krüger
<u>Rationale:</u> Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. <u>Objective:</u> We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness...
May 14, 2018: Circulation Research
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