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fenofibrate and diabetes

Boris Waldman, Jean-Claude Ansquer, David R Sullivan, Alicia J Jenkins, Neil McGill, Luke Buizen, Timothy M E Davis, James D Best, Liping Li, Michael D Feher, Christelle Foucher, Y Antero Kesaniemi, Jeffrey Flack, Michael C d'Emden, Russell S Scott, John Hedley, Val Gebski, Anthony C Keech
BACKGROUND: Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up...
February 26, 2018: Lancet Diabetes & Endocrinology
Michel P Hermans, Paul Valensi
PURPOSE OF REVIEW: The aim of this review is to describe in diabetic patients the determinants underlying atherogenic dyslipidemia, a complex dyslipidemia defined as the coexistence of fasting hypertriglyceridemia and low high-density lipoprotein cholesterol level. Atherogenic dyslipidemia is often comorbid with hyperglycemia in patients with the common form of type 2 diabetes mellitus (T2DM), namely that associated with obesity, insulin resistance, hyperinsulinemia and the metabolic syndrome phenotype...
April 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Charlotte Koopal, Frank L J Visseren, Jan Westerink, Yolanda van der Graaf, Henry N Ginsberg, Anthony C Keech
OBJECTIVE: In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patients who respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to estimate the expected treatment effect of fenofibrate for individual patients with T2DM. RESEARCH DESIGN AND METHODS: To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort...
February 22, 2018: Diabetes Care
Kausik K Ray, Lawrence A Leiter, Dirk Müller-Wieland, Bertrand Cariou, Helen M Colhoun, Robert R Henry, Francisco J Tinahones, Maja Bujas-Bobanovic, Catherine Domenger, Alexia Letierce, Rita Samuel, Stefano Del Prato
AIMS: Individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia represent a high-risk and difficult-to-treat population. ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) compared alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with T2DM and mixed dyslipidaemia not optimally managed by maximally-tolerated statins. MATERIALS AND METHODS: UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (Q2W; with increase to 150 mg Q2W at Week [W]12 if W8 non-high-density lipoprotein cholesterol [non-HDL-C] was ≥2...
February 13, 2018: Diabetes, Obesity & Metabolism
Habib Yaribeygi, Mohammad Taghi Mohammadi, Amirhossein Sahebkar
BACKGROUND: Diabetes-induced oxidative stress has an essential role in pancreatic cells dysfunction. The present study aimed to evaluate whether peroxisome proliferator activated receptor- alpha (PPAR-α) induction by fenofibrate counterbalances oxidative stress in pancreatic cells. METHODS: In this in vivo study, male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated groups (n=6 in each group). Diabetes was induced by a single intravenous injection of streptozotocin (45 mg/kg)...
February 12, 2018: Drug Research
Filip M Szymański, Anna E Płatek, Anna Ryś, Karolina Semczuk-Kaczmarek, Bartosz Krzowski, Katarzyna Wróbel, Krzysztof J Filipiak
BACKGROUND: Dyslipidemia, especially elevated low-density lipoprotein (LDL) cholesterol is one of the most important cardiovascular risk factors. Treatment of dyslipidemia and prevention of cardiovascular disease with lipid-lowering drugs is one of the key issues in reducing cardiovascular mortality. Nevertheless, underutilization of statins and lipid-lowering drugs is still a problem globally. AIM: The present study aimed to describe the utilization of lipid-lowering drugs in groups of patients with indications for statin treatment and elevated LDL cholesterol...
January 9, 2018: Kardiologia Polska
Srilakshmi Srinivasan, Prathibha Hande, Jyoti Shetty, Sindhu Murali
PURPOSE: The purpose of this study is to study the benefit of addition of oral fenofibrate to the current regimen of diabetic macular edema (DME) management and quantify its effect on macular thickness and visual function in DME. METHODS: Fifty-three eyes of 50 patients were randomized into treatment (Group A) (oral fenofibrate 160 mg/day) and control groups (Group B). Both groups underwent treatment of DME as per the standard treatment protocol of our hospital including intravitreal injections (anti-vascular endothelial growth factor/steroid) and grid laser...
January 2018: Indian Journal of Ophthalmology
G Shyam Prasad, P Govardhan, G Deepika, V Vakdevi, R B Sashidhar
Fenofibrate, an anti-hyperlipidemic drug and its phase-I biotransformed metabolite fenofibric acid, was studied for COX-1 (PDB ID: 3N8Y) and COX-2 (PDB ID: 1PXX) inhibition potentials in silico and in vitro for their effects on human recombinant COX-2 enzyme isolated from a Baculovirus expression system in sf21 cells (EC using a conventional spectrophotometric assay. Furthermore, the compounds were also screened for their anti-inflammatory potentials in vivo using carrageenan-induced paw oedema method in Wistar rats...
December 13, 2017: Inflammopharmacology
Ana Lúcia B Zeni, Tatianne D Moreira, Ana Paula Dalmagro, Anderson Camargo, Larissa A Bini, Edésio L Simionatto, Dilamara R Scharf
Morus nigra L. (Moraceae) is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN) showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively), as well as antioxidant activity (83.85%) than decoction or hydromethanolic extracts...
December 7, 2017: Anais da Academia Brasileira de Ciências
Marijana Sekulic-Jablanovic, Vesna Petkovic, Matthew B Wright, Krystsina Kucharava, Nathan Huerzeler, Soledad Levano, Yves Brand, Katharina Leitmeyer, Andrea Glutz, Alexander Bausch, Daniel Bodmer
Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants...
2017: PloS One
Giorgia Pierelli, Rosita Stanzione, Maurizio Forte, Serena Migliarino, Marika Perelli, Massimo Volpe, Speranza Rubattu
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension...
2017: Oxidative Medicine and Cellular Longevity
Cheng-Hsiu Lin, Yueh-Hsiung Kuo, Chun-Ching Shih
This study was designed to investigate the antidiabetic and antihyperlipidemic effects and mechanisms of eburicoic acid (TRR); one component of Antrodia camphorata in vitro and in an animal model for 14 weeks. Expression levels of membrane glucose transporter type 4 (GLUT4); phospho-5'-adenosine monophosphate-activated protein kinase (AMPK)/total AMPK; and phospho-Akt/total-Akt in insulin-resistant C2C12 myotube cells were significantly decreased by palmitate; and such decrease was prevented and restored by TRR at different concentrations...
November 2, 2017: International Journal of Molecular Sciences
Purvi Purohit, Daisy Khera, Praveen Sharma, Kuldeep Singh
Type V hypertriglyceridemia in children is a rare condition since it has often been associated with obesity, type II diabetes, metabolic syndrome and hormone therapy. We encountered a case of massive hypertriglyceridemia (1900 mg/dl) in a 6 years old boy with complains of acute pancreatitis but no physical manifestations. There was no family history of sudden cardiac death, father and younger male sibling were found to be normal. The mother however had hypertriglyceridemia. The child was managed by dietary changes, omega 3 capsules and low dose fenofibrate...
October 2017: Indian Journal of Clinical Biochemistry: IJCB
Tianshu Shi, Ke Lu, Siyu Shen, Qiaoli Tang, Kaijia Zhang, Xiaobo Zhu, Yong Shi, Xianglin Liu, Huajian Teng, Chaojun Li, Bin Xue, Qing Jiang
BACKGROUND: This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model. METHODS: T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot...
October 13, 2017: Lipids in Health and Disease
Guotao Deng, Elizabeth P Moran, Rui Cheng, Greg Matlock, Kelu Zhou, David Moran, Danyang Chen, Qiang Yu, Jian-Xing Ma
Purpose: Clinical studies have shown that peroxisome proliferator-activated receptor alpha (PPARα) agonist fenofibrate has therapeutic effects on diabetic retinopathy (DR). The purpose of this study was to identify a novel PPARα agonist and to evaluate its beneficial effects on DR. Methods: The transcriptional activity of PPARα was measured by a luciferase-based promoter assay. TUNEL was used to evaluate apoptosis in retinal precursor cells (R28). Diabetes was induced in rats by injection of streptozotocin...
October 1, 2017: Investigative Ophthalmology & Visual Science
Yundong Xie, Yanhong Xu, Zizhang Chen, Wenfang Lu, Na Li, Qiutang Wang, Lihua Shao, Yiping Li, Guangde Yang, Xiaoli Bian
Dyslipidemia, oxidative stress and inflammation are major risky factors involved in the pathophysiology of type 2 diabetes mellitus and atherosclerosis. Multifunctional intervene is more meaningful. The aim of this study was to evaluate the multifunctional effects of two new compounds, combination of fenofibric acid (FA) with tyrosol (T) or hydroxytyrosol (HT). Compared with fenofibrate (FF), FF-HT exhibited excellent antioxidant capacities in vitro and much improved hypolipidemia, reducing plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 76%, 54%, and 28%, while FF-T decreased the plasma parameters by 16%, 10%, and 20% in hyperlipidemic mice induced by Triton WR 1339...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shuang Zheng, Xingxing Ren, Tingting Han, Yawen Chen, Huiying Qiu, Wei Liu, Yaomin Hu
BACKGROUND: Fatty acid-induced lipotoxicity and macrophage migration inhibitory factor (MIF) affect pancreatic β-cell function, and may promote the development of diabetes mellitus. However, the association of lipotoxicity with MIF and the effect of Fenofibrate on β-cell function remain unknown. METHODS: LPL+/- mice and MIN6 cells stimulated with palmitic acid (PA) were utilized as models of lipid metabolism disorders. Factors associated with insulin secretion and apoptosis were assessed in the presence or absence of Fenofibrate...
December 2017: Metabolism: Clinical and Experimental
Xiao-Yan Li, Xiao-Hua Wang, Xiao-Qiang Huang, Ting-Ting Wu, Wen Xu, Shui-Sheng Wu
Peroxisome proliferators activated receptors (PPARs) are closely related to human chronic disease, such as diabetes mellitus and the other metabolic diseases. In this study, a cell-based PPARs (PPAR α/β/γ) model was developed for the screening of PPARs agonists from Alismatis Rhizoma (AR). Firstly, 293T cells were transfected with the reconstructed plasmid pBind-PPAR (α, β, or γ)-LBD and reporter gene pGL4.35, and the known PPARs agonists were used as the positive control (fenofibrate for PPARα, L165041 for PPARβ, and rosiglitazone for PPARγ)...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Ayumi Usui-Ouchi, Yasuo Ouchi, Nobuyuki Ebihara
A randomized clinical trial showed the beneficial effects of the selective peroxisome proliferator-activated receptor (PPAR)-α agonist, fenofibrate, in reducing the progression of diabetic retinopathy independent of serum lipid levels. All subtypes of PPAR (PPAR-α, PPAR-γ, and PPAR-β/δ) have been reported to play a key role in microvascular inflammation and angiogenesis. Therefore, the agonistic function of fenofibrate against the PPAR-α has been suggested to contribute to its medicinal effect. Furthermore, bezafibrate is a fibrate drug commonly used as a lipid-lowering agent to treat hyperlipidemia and acts as a pan-agonist of all PPARs subtypes...
November 2017: International Immunopharmacology
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
2017: Cellular Physiology and Biochemistry
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