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Metformin in obesity

Po-Jui Peng, Pei-Shen Ho, Chia-Kuang Tsai, San-Yuan Huang, Chih-Sung Liang
OBJECTIVES: A number of research studies support the weight loss effects of metformin and topiramate for obese people with schizophrenia. However, only a few studies have addressed the sustainability of the body weight reduction after discontinuation of these drugs. Moreover, head-to-head studies are still lacking. The study aims to evaluate and compare the efficacy of metformin and topiramate in weight reduction and weight maintenance after discontinuation of these drugs in obese people with schizophrenia...
October 18, 2016: Clinical Neuropharmacology
Ning Xia, Huige Li
Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators...
October 20, 2016: British Journal of Pharmacology
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
Mahalingam Balakumar, Durai Prabhu, Chandrakumar Sathishkumar, Paramasivam Prabu, Namita Rokana, Ramesh Kumar, Srividhya Raghavan, Avinash Soundarajan, Sunita Grover, Virender Kumar Batish, Viswanathan Mohan, Muthuswamy Balasubramanyam
PURPOSE: Diabetes and obesity are characterized by glucose intolerance, fat deposition, inflammation, and dyslipidemia. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects and modulating gut microbiota beneficially through specific probiotics could be a potential therapeutic option for type 2 diabetes/obesity. Therefore, we attempted to study the efficacy of probiotics of Indian gut origin (Lactobacillus plantarum MTCC5690 and Lactobacillus fermentum MTCC5689) along with a positive control, Lactobacillus rhamnosus (LGG) on glucose/lipid homeostasis in high-fat-diet-induced diabetic animal model...
October 18, 2016: European Journal of Nutrition
Rohit Kedia, Supriya Kulkarni, Meredith Ross, Vijay Shivaswamy
The dramatic rise in the prevalence of obesity and diabetes is associated with increased morbidity, mortality, and public health care costs worldwide. The need for new, effective, and long-lasting drugs is urgent. Recent research has focused on the role of the inhibitors of sodium- glucose co-transporter 2 (SGLT-2). Clinical trials have shown that SGLT-2 inhibitors have glycemic efficacy and weight-lowering potential. Dual drug therapy is a recommended therapy for patients with new-onset type 2 diabetes who need significant glycemic control...
2016: Patient Preference and Adherence
A Kargulewicz, M Szulińska, M Kujawska-Łuczak, E Swora-Cwynar, K Musialik, M Grzymisławska, M Kręgielska-Narożna, P Bogdański
OBJECTIVE: We compared the effects of three weight loss interventions on serum concentrations of adiponectin and leptin in obese premenopausal women. PATIENTS AND METHODS: 114 obese Caucasian women were randomized into three groups receiving a low-calorie diet (LC; n = 39), an isocaloric diet with 500 mg of metformin twice a day (IM; n = 38), and an isocaloric diet with 120 mg of orlistat three times a day (IO; n = 37), for three months. Serum concentrations of adiponectin and leptin were evaluated, along with anthropometric and body composition parameters, at baseline and after the study...
September 2016: European Review for Medical and Pharmacological Sciences
Bedowra Zabeen, Jebun Nahar, Samin Tayyeb, Fauzia Mohsin, Nazmun Nahar, Kishwar Azad
INTRODUCTION: Recent data show that the prevalence of diabetes among children and adolescents is increasing in some ethnic groups. The worldwide epidemic of childhood obesity has been accompanied by an increase in the incidence of type 2 diabetes (T2D) in youth. METHODS: The aim of this study was to describe the baseline characteristics of children and adolescents diagnosed ≤18 years who had features of T2D and presented at Changing Diabetes in Children, Paediatric Diabetes Clinic at Bangladesh Institute of Research and Rehabilitation of Diabetes, Endocrine, and Metabolic Disorders...
September 2016: Indian Journal of Endocrinology and Metabolism
Rosa Lauretta, Giulia Lanzolla, Patrizia Vici, Luciano Mariani, Costanzo Moretti, Marialuisa Appetecchia
Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth...
2016: International Journal of Endocrinology
Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak
BACKGROUND: The risk of several types of cancer is increased in type 2 diabetes mellitus. The earliest possible diagnosis of cancer - difficult within regular outpatient diabetes care - is of utmost importance for patients' survival. The aim of this multicenter, retrospective (years 1998-2015), case-control study was to identify risk factors associated with malignancy in subjects with diabetes treated in a typical outpatient setting. METHODS: In the databases of 3 diabetic and 1 primary care clinics 203 patients (115 women) with type 2 diabetes mellitus who developed malignancy while treated for diabetes were identified...
October 10, 2016: BMC Cancer
Alessandro D Genazzani
Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols...
September 16, 2016: Reproductive Biomedicine Online
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
Rabia Farooq, Shajrul Amin, M Hayat Bhat, Rawoof Malik, Hilal Ahmad Wani, Sabhiya Majid
Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar...
October 5, 2016: Gynecological Endocrinology
Ulrich Rohde, Cecilie A Federspiel, Peter Vilmann, Ebbe Langholz, Steffen U Friis, Martin Krakauer, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. MATERIAL AND METHODS: Ten normal glucose tolerant (NGT) obese subjects and nine age, body weight and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and one (1w) and 26 weeks (26w) after implantation...
October 3, 2016: Diabetes, Obesity & Metabolism
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
Xingwei Liang, Qiyuan Yang, Lupei Zhang, Joseph W Maricelli, Buel D Rodgers, Mei-Jun Zhu, Min Du
Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates energy via heat generation, mitigating obesity and diabetes. The lactation stage is a manageable period for improving the health of offspring of obese mothers, but the impact of maternal HFD during lactation on offspring BAT function is unknown. To determine, female mice were fed either a control or HFD during lactation. At weaning, HFD offspring gained more body weight and had greater body fat mass compared to the control, and these differences maintained into adulthood, which correlated with glucose intolerance and insulin resistance in HFD offspring...
September 30, 2016: Scientific Reports
Henriikka Salomäki-Myftari, Laura H Vähätalo, Liisa Ailanen, Sami Pietilä, Asta Laiho, Arno Hänninen, Juha-Pekka Pursiheimo, Eveliina Munukka, Anniina Rintala, Eriika Savontaus, Ullamari Pesonen, Markku Koulu
BACKGROUND: Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known. METHODS: The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDβH)...
2016: PloS One
Manish M Wanjari, Sujata Mishra, Yadu Nandan Dey, Deepti Sharma, Sudesh N Gaidhani, Ankush D Jadhav
BACKGROUND: Chandraprabha vati is a classical Ayurvedic formulation, markedly used for mitigation of Prameha, which correlates in many ways with obesity, metabolic syndrome and diabetes mellitus. OBJECTIVE: The present study was aimed to investigate effect of Chandraprabha vati in experimentally-induced hyperglycemia and lipid profile alterations. MATERIALS AND METHODS: Antidiabetic effect of Chandraprabha vati was studied in fifty five Wistar rats...
July 2016: Journal of Ayurveda and Integrative Medicine
Assim A Alfadda, Madhawi M Al-Dhwayan, Abdulhameed A Alharbi, Basema K Al Khudhair, Omar M Al Nozha, Nawal M Al-Qahtani, Saad H Alzahrani, Wedad M Bardisi, Reem M Sallam, John J Riva, Jan L Brożek, Holger J Schünemann, Ainsley Moore
OBJECTIVE: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. METHODS: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence  RESULTS: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults...
October 2016: Saudi Medical Journal
Thozhukat Sathyapalan, Zeeshan Javed, Eric S Kilpatrick, Anne-Marie Coady, Stephen L Atkin
CONTEXT: Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk. OBJECTIVE: To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. DESIGN: Randomized, open-labelled parallel study...
September 21, 2016: Clinical Endocrinology
Qiyuan Yang, Xingwei Liang, Xiaofei Sun, Lupei Zhang, Xing Fu, Carl J Rogers, Anna Berim, Shuming Zhang, Songbo Wang, Bo Wang, Marc Foretz, Benoit Viollet, David R Gang, Buel D Rodgers, Mei-Jun Zhu, Min Du
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter...
October 11, 2016: Cell Metabolism
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