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Pioglitazone AND bone

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https://www.readbyqxmd.com/read/28057658/pioglitazone-and-cardiovascular-outcomes-in-patients-with-insulin-resistance-pre-diabetes-and-type-2-diabetes-a-systematic-review-and-meta-analysis
#1
Hung-Wei Liao, Jeffrey L Saver, Yi-Ling Wu, Tso-Hsiao Chen, Meng Lee, Bruce Ovbiagele
OBJECTIVES: To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes. DESIGN AND SETTING: Systematic review and meta-analysis of randomised, controlled trials. DATA SOURCES: Literature searches were performed across PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials from 1966 to May 2016 to identify randomised, controlled trials with more than 1 year follow-up. OUTCOME MEASURES: Relative risk (RR) with 95% CI was used to evaluate the association between pioglitazone and the risk of major adverse cardiovascular events (MACE: composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and safety outcomes, after pooling data across trials in a fixed-effects model...
January 5, 2017: BMJ Open
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#2
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#3
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27935736/pioglitazone-and-risk-for-bone-fracture-safety-data-from-a-randomized-clinical-trial
#4
Catherine M Viscoli, Silvio E Inzucchi, Lawrence H Young, Karl L Insogna, Robin Conwit, Karen L Furie, Mark Gorman, Michael A Kelly, Anne M Lovejoy, Walter N Kernan
CONTEXT: Pioglitazone reduces cardiovascular risk in non-diabetic patients after an ischemic stroke or transient ischemic attack (TIA) but is associated with increased risk for bone fracture. OBJECTIVE: To characterize fractures associated with pioglitazone by location, mechanism, severity, timing, and sex. DESIGN, SETTING AND PATIENTS: Patients were 3876 non-diabetic participants in the Insulin Resistance Intervention after Stroke trial randomized to pioglitazone or placebo after an ischemic stroke or TIA and followed for a median of 4...
December 9, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27889689/osteoarthritis-and-type-2-diabetes-mellitus-what-are-the-links
#5
REVIEW
Alice Courties, Jérémie Sellam
Osteoarthritis (OA) is the most frequent joint disorder and one of the leading cause of disability. During a long time, it was considered as the consequence of aging and mechanical stress on cartilage. Recent advances in the knowledge of OA have highlighted that it is a whole joint disease with early modifications of synovium and subchondral bone but also that it is associated with obesity and metabolic syndrome through systemic mechanisms. In the past year, type 2 diabetes has been described in two meta-analyzes as an independent risk factor for OA...
December 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27631136/serum-endotrophin-identifies-optimal-responders-to-ppar%C3%AE-agonists-in-type-2-diabetes
#6
Morten A Karsdal, Kim Henriksen, Federica Genovese, Diana J Leeming, Mette J Nielsen, Bente J Riis, Claus Christiansen, Inger Byrjalsen, Detlef Schuppan
AIMS/HYPOTHESIS: The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of procollagen type VI (also called Pro-C6), is involved in both adipose tissue matrix remodelling and metabolic control. We established a serum assay for endotrophin to assess if this novel adipokine could identify type 2 diabetic patients who respond optimally to PPARγ agonists, improving the risk-to-benefit ratio...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27585671/pioglitazone-is-equally-effective-for-diabetes-prevention-in-older-versus-younger-adults-with-impaired-glucose-tolerance
#7
Sara E Espinoza, Chen-Pin Wang, Devjit Tripathy, Stephen C Clement, Dawn C Schwenke, Mary Ann Banerji, George A Bray, Thomas A Buchanan, Robert R Henry, Abbas E Kitabchi, Sunder Mudaliar, Frankie B Stentz, Peter D Reaven, Ralph A DeFronzo, Nicolas Musi
To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA...
December 2016: Age (2005-)
https://www.readbyqxmd.com/read/27430581/pioglitazone-affects-the-opg-rankl-rank-system-and-increase-osteoclastogenesis
#8
Fei Xu, Yonghui Dong, Xin Huang, Peng Chen, Fengjing Guo, Anmin Chen, Shilong Huang
Thiazolidinediones are traditional anti‑diabetic therapeutic agents that have been associated with bone loss and increased fracture risk. However, the underlying mechanisms of this side effect require further elucidation. The present study aimed to investigate the effect of pioglitazone (PIO), a thiazolidinedione, on osteoblastogenesis, osteoclastogenesis and the osteoprotegerin (OPG) / receptor activator of nuclear factor‑κB ligand (RANKL) / RANK system. The MC3T3‑E1 murine pre‑osteoblastic cell line was treated with PIO and processed for reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis of OPG, RANKL, peroxisome proliferator‑activated receptor γ (PPARγ), Runt‑related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN), and western blotting analysis of OPG and RANKL...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27405860/the-insulin-resistance-intervention-after-stroke-trial-a-perspective-on-future-practice-and-research
#9
Philip M Bath, Jason P Appleton, Nikola Sprigg
The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures...
October 2016: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/27062545/pioglitazone-alleviates-inflammation-in-diabetic-mice-fed-a-high-fat-diet-via-inhibiting-advanced-glycation-end-product-induced-classical-macrophage-activation
#10
Xian Jin, Liang Liu, Zhong'e Zhou, Junhua Ge, Tongqing Yao, Chengxing Shen
Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner...
June 2016: FEBS Journal
https://www.readbyqxmd.com/read/26934829/pretreatment-of-bmscs-with-tzd-solution-decreases-the-proliferation-rate-of-mcf%C3%A2-7-cells-by-reducing-fgf4-protein-expression
#11
Boon-Yin Khoo, Kalpanah Nadarajan, Siang-Yian Shim, Noorizan Miswan, Chuan-Bing Zang, Kurt Possinger, Elena Elstner
The present study aimed to investigate the effects of bone marrow‑derived mesenchymal stem cells (BMSCs) that had been pretreated with pioglitazone and/or rosiglitazone on the growth and proliferation rate of MCF‑7 cells. The adhesive interaction between the BMSCs and the MCF‑7 cancer cells revealed that the pretreatment of BMSCs with a combination of two types of thiazolidinedione drug reduced the growth and proliferation rate of the MCF‑7 cells. The proliferation rate of the MCF‑7 cells could also be reduced by the non‑adhesive interaction of the cancer cells with BMSCs pretreated with pioglitazone and/or rosiglitazone...
April 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26898430/pioglitazone-up-regulates-long-non-coding-rna-meg3-to-protect-endothelial-progenitor-cells-via-increasing-hdac7-expression-in-metabolic-syndrome
#12
H Z Liu, Q Y Wang, Y Zhang, D T Qi, M W Li, W Q Guo, Y H Ma, L Y Wang, Y Chen, C Y Gao
Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is expressed in endothelial cells and involved in angiogenesis and vascular function. It was proposed that MEG3 participates in the process of endothelial progenitor cells (EPCs) functions in metabolic syndrome (MetS). In this study, the circulating EPCs number and function were decreased in MetS subjects. The MEG3 expression was expressed at a lower level and microRNA-140-5p (miR-140-5p) was expressed at a higher level in circulating EPCs of subjects with MetS...
March 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/26886418/pioglitazone-after-ischemic-stroke-or-transient-ischemic-attack
#13
RANDOMIZED CONTROLLED TRIAL
Walter N Kernan, Catherine M Viscoli, Karen L Furie, Lawrence H Young, Silvio E Inzucchi, Mark Gorman, Peter D Guarino, Anne M Lovejoy, Peter N Peduzzi, Robin Conwit, Lawrence M Brass, Gregory G Schwartz, Harold P Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A Ford, Dawn Kleindorfer, John R O'Leary, Mark W Parsons, Peter Ringleb, Souvik Sen, J David Spence, David Tanne, David Wang, Toni R Winder
BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo...
April 7, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/26868449/delayed-wound-healing-and-dysregulation-of-il6-stat3-signalling-in-mscs-derived-from-pre-diabetic-obese-mice
#14
M van de Vyver, C Niesler, K H Myburgh, W F Ferris
Metabolic dysfunction that occurs in obesity and Type 2 diabetes results in a low-level inflammatory state which impacts on mesenchymal stem cells (MSCs) capacity to promote wound healing. The ability of either recombinant Interleukin-6 (rIL6) or pioglitazone to modulate MSC migration, essential for wound healing, by targeting the inflammation-modulated IL6/STAT3 signalling pathway was therefore investigated in bone marrow-derived MSCs from control (C57BL/6J) and pre-diabetic obese mice (B6. Cg-Lepob/J). The population doubling time, in vitro wound closure and mRNA expression profile of 84 genes involved in the IL6/STAT3 signalling pathway were assessed...
May 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/26849824/in-vitro-effects-of-pioglitazone-on-the-expression-of-components-of-wnt-signaling-pathway-and-markers-of-bone-mineralization
#15
D Avtanski, Y Hirth, N Babushkin, V Sy, D Sharma, L Poretsky, D Seto-Young
Pioglitazone is an insulin-sensitizing thiazolidinedione (TZD) whose use is associated with bone loss. We examined the effects of pioglitazone on components of the Wnt signaling pathway (Wnt1, β-catenin) and markers of bone mineralization [osteoprotegerin (OPG), bone sialoprotein (BSP), fibroblast growth factor (FGF)23] as well as mineral content in human osteoblast hFOB 1.19 cells. hFOB 1.19 cells were cultured in K12/DMD medium with or without pioglitazone. PPARγ Wnt1, OPG, BSP, or FGF23 mRNA expression was measured using qRT-PCR; β-catenin, OPG, BSP, or FGF23 using ELISA; and calcium or phosphate content using colorimetry...
July 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/26838084/repeated-intraportal-injection-of-mesenchymal-stem-cells-in-combination-with-pioglitazone-in-patients-with-compensated-cirrhosis-a-clinical-report-of-two-cases
#16
Massoud Vosough, Shirin Moossavi, Soura Mardpour, Shahram Akhlaghpoor, Vajiheh Azimian, Neda Jarughi, Seyedeh-Esmat Hosseini, Mandana Ashrafi, Sepideh Nikfam, Nasser Aghdami, Reza Malekzadeh, Mehdi Mohamadnejad, Hossein Baharvand
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) in combination with pioglitazone, an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), can reduce liver fibrosis in models of liver injury. In this study, we conducted a pilot study of intraportal infusion of autologous MSCs in combination with pioglitazone to assess safety, feasibility, and effectiveness in patients with compensated cirrhosis. METHODS: Two patients with compensated cirrhosis were enrolled in this study...
February 2016: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/26821947/pioglitazone-incorporated-nanoparticles-prevent-plaque-destabilization-and-rupture-by-regulating-monocyte-macrophage-differentiation-in-apoe-mice
#17
Soichi Nakashiro, Tetsuya Matoba, Ryuta Umezu, Jun-Ichiro Koga, Masaki Tokutome, Shunsuke Katsuki, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
OBJECTIVE: Inflammatory monocytes/macrophages produce various proteinases, including matrix metalloproteinases, and degradation of the extracellular matrix by these activated proteinases weakens the mechanical strength of atherosclerotic plaques, which results in a rupture of the plaque. Peroxisome proliferator-activated receptor-γ induces a polarity shift of monocytes/macrophages toward less inflammatory phenotypes and has the potential to prevent atherosclerotic plaque ruptures. Therefore, we hypothesized that nanoparticle-mediated targeted delivery of the peroxisome proliferator-activated receptor-γ agonist pioglitazone into circulating monocytes could effectively inhibit plaque ruptures in a mouse model...
March 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26478981/peroxisome-proliferator-activated-receptor-gamma-regulates-bone-remodeling-after-midpalatal-suture-expansion-in-mice
#18
Jing Wu, Nan Ru, Song Li
PURPOSE: The effectiveness of rapid maxillary expansion is adversely affected by failure and relapse. It is important to identify key factors that increase new bone formation and improve bone remodeling of midpalatal sutures to improve the stability and effectiveness of this commonly used orthodontic procedure. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in modulating osteogenesis and bone resorption in long bones. This study was designed to explore the function of PPARγ in bone remodeling and tissue engineering of midpalatal sutures...
November 2015: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/26305617/effects-of-tzd-use-and-discontinuation-on-fracture-rates-in-accord-bone-study
#19
RANDOMIZED CONTROLLED TRIAL
Ann V Schwartz, Haiying Chen, Walter T Ambrosius, Ajay Sood, Robert G Josse, Denise E Bonds, Adrian M Schnall, Eric Vittinghoff, Douglas C Bauer, Mary Ann Banerji, Robert M Cohen, Bruce P Hamilton, Tamara Isakova, Deborah E Sellmeyer, Debra L Simmons, Amal Shibli-Rahhal, Jeff D Williamson, Karen L Margolis
CONTEXT: In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown. OBJECTIVE: The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men. DESIGN: This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as time-varying covariates in proportional hazards models for occurrence of first non-spine fracture...
November 2015: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26249206/effect-of-exenatide-insulin-and-pioglitazone-on-bone-metabolism-in-patients-with-newly-diagnosed-type-2-diabetes
#20
RANDOMIZED CONTROLLED TRIAL
Renyuan Li, Wen Xu, Sihui Luo, Haixia Xu, Guoyu Tong, Longyi Zeng, Dalong Zhu, Jianping Weng
AIM: Preclinical studies suggested that insulin, incretin and thiazolidinediones had effect on regulation of bone metabolism. But clinical evidence is limited. We assessed the effects of these antihyperglycemic agents on bone metabolism in patients with newly diagnosed type 2 diabetes. METHODS: The present study was a two-center, randomized, parallel-group clinical trial. Sixty-two newly diagnosed and drug-naïve patients with type 2 diabetes were randomized to exenatide (EXE, n = 20), mixed protamine zinc recombinant human insulin lispro injection (25R; INS, n = 21) or pioglitazone (PIO, n = 21) group for a 24-week treatment...
December 2015: Acta Diabetologica
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