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fenofibrate in diabetic retinopathy

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https://www.readbyqxmd.com/read/27720395/fenofibrate-inhibits-cytochrome-p450-epoxygenase-2c-activity-to-suppress-pathological-ocular-angiogenesis
#1
Yan Gong, Zhuo Shao, Zhongjie Fu, Matthew L Edin, Ye Sun, Raffael G Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Samuel B Burnim, Steven S Meng, Fred B Lih, John Paul SanGiovanni, Darryl C Zeldin, Ann Hellström, Lois E H Smith
Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs)...
September 30, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27525681/fenofibrate-and-diabetic-retinopathy
#2
REVIEW
Jared E Knickelbein, Akshar B Abbott, Emily Y Chew
Diabetic retinopathy, a common and sight-threatening microvascular complication of diabetes mellitus, is a leading cause of blindness among working-aged adults. Medical therapies including intensive control of hyperglycemia and hypertension have been shown to reduce the incidence and progression of diabetic retinopathy. The association of dyslipidemia and treatment with statins with diabetic retinopathy is inconsistent in epidemiologic studies. However, two recent randomized clinical trials have demonstrated beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels...
October 2016: Current Diabetes Reports
https://www.readbyqxmd.com/read/27479624/vision-loss-in-older-adults
#3
Allen L Pelletier, Ledy Rojas-Roldan, Janis Coffin
Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts...
August 1, 2016: American Family Physician
https://www.readbyqxmd.com/read/27334889/therapeutic-targeting-of-diabetic-retinal-neuropathy-as-a-strategy-in-preventing-diabetic-retinopathy
#4
Gabriela de Moraes, Christopher J Layton
Diabetes causes a panretinal neurodegeneration herein termed diabetic retinal neuropathy, which manifests in the retina early and progresses throughout the disease. Clinical manifestations include changes in the ERG, perimetry, dark adaptation, contrast sensitivity and colour vision which correlate with laboratory findings of thinning of the retinal neuronal layers, increased apoptosis in neurons and activation of glial cells. Possible mechanisms include oxidative stress, neuronal AGE accumulation, altered balance of neurotrophic factors, and loss of mitohormesis...
June 23, 2016: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/27267786/effect-of-micronized-fenofibrate-on-microvascular-complications-of-type-2-diabetes-a-systematic-review
#5
Leszek Czupryniak, Shashank R Joshi, Jaideep A Gogtay, Meena Lopez
OBJECTIVE: Micronized fenofibrate prevents the progression of microvascular complications in type 2 diabetes, but no systematic review has summarized these effects. Therefore, we performed a systematic review to investigate the effects of micronized fenofibrate on type 2 diabetes-related microvascular complications. RESEARCH DESIGN AND METHODS: The PubMed database was systematically searched for trials in English language published between January 1990 and November 2015 that examined the effects of fenofibrate on microvascular complications in patients with type 2 diabetes...
August 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27073156/estimation-of-adjusted-rate-differences-using-additive-negative-binomial-regression
#6
Mark W Donoghoe, Ian C Marschner
Rate differences are an important effect measure in biostatistics and provide an alternative perspective to rate ratios. When the data are event counts observed during an exposure period, adjusted rate differences may be estimated using an identity-link Poisson generalised linear model, also known as additive Poisson regression. A problem with this approach is that the assumption of equality of mean and variance rarely holds in real data, which often show overdispersion. An additive negative binomial model is the natural alternative to account for this; however, standard model-fitting methods are often unable to cope with the constrained parameter space arising from the non-negativity restrictions of the additive model...
August 15, 2016: Statistics in Medicine
https://www.readbyqxmd.com/read/26676667/biomarkers-in-diabetic-retinopathy
#7
REVIEW
Alicia J Jenkins, Mugdha V Joglekar, Anandwardhan A Hardikar, Anthony C Keech, David N O'Neal, Andrzej S Januszewski
There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients...
April 2015: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/26676661/risk-factors-and-comorbidities-in-diabetic-neuropathy-an-update-2015
#8
Nikolaos Papanas, Dan Ziegler
Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes...
April 2015: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/26297615/beneficial-effects-of-fenofibric-acid-on-overexpression-of-extracellular-matrix-components-cox-2-and-impairment-of-endothelial-permeability-associated-with-diabetic-retinopathy
#9
Sumon Roy, Dongjoon Kim, Cristina Hernández, Rafael Simó, Sayon Roy
In the Fenofibric Acid (FA) Intervention and Event Lowering in Diabetes (FIELD) study, FA, a lipid-lowering drug, has been shown to significantly reduce macular edema in diabetic patients. In the present study, we investigated whether FA reduces vascular permeability by inhibiting cyclooxygenase-2 (COX-2), a critical mediator of inflammation, and reducing overexpression of fibronectin (FN) and collagen IV (Coll IV), two basement membrane (BM) components upregulated in diabetic retinopathy. Rat retinal endothelial cells (RRECs) were grown in normal (N:5 mM glucose) or high glucose (HG:30 mM glucose) medium with or without FA for 7 days...
November 2015: Experimental Eye Research
https://www.readbyqxmd.com/read/26238659/feno%C3%AF-brate-suppresses-cellular-metabolic-memory-of-high-glucose-in-diabetic-retinopathy-via-a-sirtuin-1-dependent-signalling-pathway
#10
Shuzhi Zhao, Jun Li, Na Wang, Bingqing Zheng, Tao Li, Qing Gu, Xun Xu, Zhi Zheng
Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid‑lowering therapeutic agent in clinical use, exerts a potential anti‑inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+‑dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR)...
October 2015: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26209985/the-use-of-fenofibrate-in-the-management-of-patients-with-diabetic-retinopathy-an-evidence-based-review
#11
Neil Sharma, Ju-Lee Ooi, Jong Ong, Douglas Newman
BACKGROUND: Diabetic retinopathy is a significant cause of vision impairment, especially affecting those of working age. There are two large, randomised controlled trials examining the effect of fenofibrate on diabetic retinopathy. OBJECTIVE: We summarise their findings, and report on the available safety data. DISCUSSION: The FIELD study reported that patients treated with fenofibrate had a statistically significant relative risk reduction in the need for laser treatment for maculopathy and proliferative retinopathy...
June 2015: Australian Family Physician
https://www.readbyqxmd.com/read/26055067/relationship-of-fibroblast-growth-factor-21-with-baseline-and-new-on-study-microvascular-disease-in-the-fenofibrate-intervention-and-event-lowering-in-diabetes-study
#12
RANDOMIZED CONTROLLED TRIAL
Kwok-Leung Ong, Andrzej S Januszewski, Rachel O'Connell, Luke Buizen, Alicia J Jenkins, Aimin Xu, David R Sullivan, Philip J Barter, Russell S Scott, Marja-Riitta Taskinen, Kerry-Anne Rye, Anthony C Keech
AIMS/HYPOTHESIS: Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study. METHODS: Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants...
September 2015: Diabetologia
https://www.readbyqxmd.com/read/25989912/non-traditional-systemic-treatments-for-diabetic-retinopathy-an-evidence-based-review
#13
REVIEW
Rafael Simó, Stefania Ballarini, José Cunha-Vaz, Linong Ji, Hermann Haller, Paul Zimmet, Tien Y Wong
The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising...
2015: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/25949071/diabetic-retinopathy-and-systemic-factors
#14
REVIEW
Robert N Frank
Diabetic retinopathy, an oculardisease, is governed by systemic as well as local ocular factors. These include primarily chronic levels of blood glucose. Individuals with chronically elevated blood glucose levels have substantially more, and more severe, retinopathy than those with lower blood glucose levels. The relationship of blood glucose to retinopathy is continuous, with no threshold although individuals with hemoglobin A1c levels (a measure of chronic glycemia) <6.5%, generally develop little or no retinopathy...
April 2015: Middle East African Journal of Ophthalmology
https://www.readbyqxmd.com/read/25772642/is-fenofibrate-a-reasonable-treatment-for-diabetic-microvascular-disease
#15
REVIEW
Rafael Simó, Olga Simó-Servat, Cristina Hernández
Type 2 diabetes is a pandemic disease, and its prevalence is increasing mainly due to an increase in obesity and life expectancy. Diabetic complications and their comorbidities constitute the most important economic cost of the disease and represent a significant economic burden for the healthcare systems of developed countries. Despite improving standards of care, people with diabetes remain at risk of the development and progression of microvascular diabetic complications. Therefore, the identification of novel therapeutic approaches is necessary...
May 2015: Current Diabetes Reports
https://www.readbyqxmd.com/read/25525608/effects-of-fenofibrate-on-adiponectin-expression-in-retinas-of-streptozotocin-induced-diabetic-rats
#16
Ying-Jung Hsu, Lu-Chun Wang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao Yang
Adiponectin has been associated with increased risks of microvascular complications in diabetes; however, its role in the development of diabetic retinopathy (DR) is unknown. Fenofibrate is a lipid-lowering agent that has been shown to be capable of preventing DR progression. We investigated the expression of adiponectin and its receptors in DR and evaluated the effects of fenofibrate on their expression. The mRNA and protein levels of adiponectin and its receptors were elevated in retinas of streptozotocin-induced diabetic rats and were suppressed following fenofibrate treatment...
2014: Journal of Diabetes Research
https://www.readbyqxmd.com/read/25524951/serum-25-hydroxyvitamin-d-a-predictor-of-macrovascular-and-microvascular-complications-in-patients-with-type-2-diabetes
#17
RANDOMIZED CONTROLLED TRIAL
Markus Herrmann, David R Sullivan, Anne-Sophie Veillard, Thomas McCorquodale, Isabella R Straub, Russell Scott, Markku Laakso, Duncan Topliss, Alicia J Jenkins, Stefan Blankenberg, Anthony Burton, Anthony C Keech
OBJECTIVE: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial...
March 2015: Diabetes Care
https://www.readbyqxmd.com/read/25172198/the-effects-of-medical-management-on-the-progression-of-diabetic-retinopathy-in-persons-with-type-2-diabetes-the-action-to-control-cardiovascular-risk-in-diabetes-accord-eye-study
#18
RANDOMIZED CONTROLLED TRIAL
Emily Y Chew, Matthew D Davis, Ronald P Danis, James F Lovato, Letitia H Perdue, Craig Greven, Saul Genuth, David C Goff, Lawrence A Leiter, Faramarz Ismail-Beigi, Walter T Ambrosius
PURPOSE: To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. DESIGN: Double 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7...
December 2014: Ophthalmology
https://www.readbyqxmd.com/read/25133794/effects-of-fenofibric-acid-on-diabetic-macular-edema-the-macufen-study
#19
RANDOMIZED CONTROLLED TRIAL
Pascale Massin, Tunde Peto, Jean-Claude Ansquer, Patrick Aubonnet, For The MacuFEN Study Investigators
PURPOSE: Fenofibrate reduced progression of diabetic retinopathy in two large randomized studies. The effect of 135 mg fenofibric acid on diabetic macular edema (DME) was evaluated in subjects with existing DME. METHODS: In this double-blind, randomized, placebo-controlled study, 110 subjects with DME not requiring immediate photocoagulation or intraocular treatment with adequate diabetes and blood pressure control received either fenofibric acid or placebo once daily for 1 year...
October 2014: Ophthalmic Epidemiology
https://www.readbyqxmd.com/read/25108226/peroxisome-proliferator-activated-receptor-%C3%AE-protects-capillary-pericytes-in-the-retina
#20
Lexi Ding, Rui Cheng, Yang Hu, Yusuke Takahashi, Alicia J Jenkins, Anthony C Keech, Kenneth M Humphries, Xiaowu Gu, Michael H Elliott, Xiaobo Xia, Jian-Xing Ma
Pericyte degeneration is an early event in diabetic retinopathy and plays an important role in progression of diabetic retinopathy. Clinical studies have shown that fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has robust therapeutic effects on diabetic retinopathy in type 2 diabetic patients. We evaluated the protective effect of PPARα against pericyte loss in diabetic retinopathy. In streptozotocin-induced diabetic mice, fenofibrate treatment significantly ameliorated retinal acellular capillary formation and pericyte loss...
October 2014: American Journal of Pathology
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