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Barone V, Surico PL, Cutrupi F, Mori T, Gallo Afflitto G, Di Zazzo A, Coassin M. The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review. Biomedicines 2024; 12:2346. [PMID: 39457658 PMCID: PMC11505591 DOI: 10.3390/biomedicines12102346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/02/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Diabetic eye disease (DED) encompasses a range of ocular complications arising from diabetes mellitus, including diabetic retinopathy, diabetic macular edema, diabetic keratopathy, diabetic cataract, and glaucoma. These conditions are leading causes of visual impairments and blindness, especially among working-age adults. Despite advancements in our understanding of DED, its underlying pathophysiological mechanisms remain incompletely understood. Chronic hyperglycemia, oxidative stress, inflammation, and neurodegeneration play central roles in the development and progression of DED, with immune-mediated processes increasingly recognized as key contributors. This review provides a comprehensive examination of the complex interactions between immune cells, inflammatory mediators, and signaling pathways implicated in the pathogenesis of DED. By delving in current research, this review aims to identify potential therapeutic targets, suggesting directions of research for future studies to address the immunopathological aspects of DED.
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Affiliation(s)
- Vincenzo Barone
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Pier Luigi Surico
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
| | - Francesco Cutrupi
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Tommaso Mori
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Department of Ophthalmology, University of California San Diego, La Jolla, CA 92122, USA
| | - Gabriele Gallo Afflitto
- Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, 00128 Rome, Italy;
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK
| | - Antonio Di Zazzo
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Marco Coassin
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
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Tylutka A, Walas Ł, Zembron-Lacny A. Level of IL-6, TNF, and IL-1β and age-related diseases: a systematic review and meta-analysis. Front Immunol 2024; 15:1330386. [PMID: 38495887 PMCID: PMC10943692 DOI: 10.3389/fimmu.2024.1330386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024] Open
Abstract
Introduction Chronic low-grade inflammation is an important aspect of morbidity and mortality in older adults. The level of circulating pro-inflammatory cytokines (interleukin (IL)-6, tumor necrosis factor (TNF) or IL-1β) is a risk factor in cardiovascular and neurodegenerative diseases and is also associated with sarcopenia and frailties. The objective of this study was to assess each cytokine: IL-6, TNF, and IL-1β separately in the elderly with comorbidities against controls without diseases according to the data published in the available literature. Methods The electronic bibliographic PubMed database was systematically searched to select all the relevant studies published up to July 2023. The total number of the subjects involved in the meta-analysis included patients with diseases (n=8154) and controls (n=33967). Results The overall concentration of IL-6 was found to be higher in patients with diseases compared to controls and the difference was statistically significant, with a p-value of <0.001 (SMD, 0.16; 95% CI, 0.12-0.19). The heterogeneity was considerable with Q = 109.97 (P <0.0001) and I2 = 79.2%. The potential diagnostic usefulness of IL-6 was confirmed by odds ratio (OR) analysis (OR: 1.03, 95% CI (1.01; 1.05), p=0.0029). The concentration of both TNF and IL-1β was elevated in the control group compared to patients and amounted to SMD -0.03; 95% CI, -0.09-0.02, p-value 0.533 and SMD-0.29; 95% CI, -0.47- -0.12; p = 0.001, respectively. For TNF, however, the difference was statistically insignificant. Discussion IL-6, unlike TNF and IL-1β, could be a useful and convenient marker of peripheral inflammation in older adults with various comorbidities.
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Affiliation(s)
- Anna Tylutka
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, Zielona Gora, Poland
| | - Łukasz Walas
- Institute of Dendrology, Polish Academy of Sciences, Kórnik, Poland
| | - Agnieszka Zembron-Lacny
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, Zielona Gora, Poland
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Kour V, Swain J, Singh J, Singh H, Kour H. A Review on Diabetic Retinopathy. Curr Diabetes Rev 2024; 20:e201023222418. [PMID: 37867267 DOI: 10.2174/0115733998253672231011161400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 07/08/2023] [Accepted: 08/23/2023] [Indexed: 10/24/2023]
Abstract
Diabetic retinopathy is a well-recognised microvascular complication of diabetes and is among the leading cause of blindness all over the world. Over the last decade, there have been advances in the diagnosis of diabetic retinopathy and diabetic macular edema. At the same time, newer therapies for the management of diabetic retinopathy have evolved. As a result of these advances, a decline in severe vision loss due to diabetes has been witnessed in some developing countries. However, there is a steady increase in the number of people affected with diabetes, and is expected to rise further in the coming years. Therefore, it is prudent to identify diabetic retinopathy, and timely intervention is needed to decrease the burden of severe vision loss. An effort has been made to review all the existing knowledge regarding diabetic retinopathy in this article and summarize the present treatment options for diabetic retinopathy.
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Affiliation(s)
- Vijender Kour
- Consultant Ophthalmology, Department of Ophthalmology, Sub District Hospital, Tral, Pulwama, India
| | - Jayshree Swain
- Department of Endocrinology, IMS and Sum Hospital, Siksha O Anusandhan (SOA) University, Bhubaneswar, India
| | - Jaspreet Singh
- Department of Endocrinology, IMS and Sum Hospital, Siksha O Anusandhan (SOA) University, Bhubaneswar, India
| | - Hershdeep Singh
- Consultant Neurosurgeon, Department of Neurosurgery, Fortis Ludhiana, Bhubaneswar, India
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Yu W, Yang B, Xu S, Gao Y, Huang Y, Wang Z. Diabetic Retinopathy and Cardiovascular Disease: A Literature Review. Diabetes Metab Syndr Obes 2023; 16:4247-4261. [PMID: 38164419 PMCID: PMC10758178 DOI: 10.2147/dmso.s438111] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 12/21/2023] [Indexed: 01/03/2024] Open
Abstract
Diabetic complications can be divided into macrovascular complications such as cardiovascular disease and cerebrovascular disease and microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy. Among them, cardiovascular disease (CVD) is an important cause of death in diabetic patients. Diabetes retinopathy (DR) is one of the main reasons for the increasing disability rate of diabetes. In recent years, some studies have found that because DR and CVD have a common pathophysiological basis, the occurrence of DR and CVD are inseparable, and to a certain extent, DR can predict the occurrence of CVD. With the development of technology, the fundus parameters of DR can be quantitatively analyzed as an independent risk factor of CVD. In addition, the cytokines related to DR can also be used for early screening of DR. Although many advances have been made in the treatment of CVD, its situation of prevention and treatment is still not optimistic. This review hopes to discuss the feasibility of DR in predicting CVD from the common pathophysiological mechanism of DR and CVD, the new progress of diagnostic techniques for DR, and the biomarkers for early screening of DR.
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Affiliation(s)
- Wenhua Yu
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Bo Yang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Siting Xu
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Yun Gao
- Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Yan Huang
- Department of Ophthalmology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Zhongqun Wang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
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Perais J, Agarwal R, Evans JR, Loveman E, Colquitt JL, Owens D, Hogg RE, Lawrenson JG, Takwoingi Y, Lois N. Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane Database Syst Rev 2023; 2:CD013775. [PMID: 36815723 PMCID: PMC9943918 DOI: 10.1002/14651858.cd013775.pub2] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
BACKGROUND Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
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Affiliation(s)
- Jennifer Perais
- The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Ridhi Agarwal
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Jennifer R Evans
- Cochrane Eyes and Vision, Queen's University Belfast, Belfast, UK
| | | | | | | | - Ruth E Hogg
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - John G Lawrenson
- Centre for Applied Vision Research, School of Health Sciences, City University of London, London, UK
| | - Yemisi Takwoingi
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Noemi Lois
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
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Fickweiler W, Mitzner M, Jacoba CMP, Sun JK. Circulatory Biomarkers and Diabetic Retinopathy in Racial and Ethnic Populations. Semin Ophthalmol 2023:1-11. [PMID: 36710371 DOI: 10.1080/08820538.2023.2168488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Clinical staging systems for diagnosis and treatment of diabetic retinopathy (DR) must closely relate to endpoints that are both relevant for patients and feasible for physicians to implement. Current DR staging systems for clinical eye care and research provide detailed phenotypic characterization to predict patient outcomes in diabetes but have limitations. Biochemical biomarkers provide a rich pool of potential candidates for new DR staging systems that can be readily measured in accessible fluids. Circulating biomarkers that are specific to the retina and relate to angiogenesis and inflammation have been suggested as relevant for DR. Although there is a lack of multi-ethnic studies evaluating circulatory biomarkers in DR, variability in circulatory biomarkers have been reported in people from different ethnic and racial backgrounds. Therefore, there is a need for future studies to evaluate individual or combinations of biomarkers in diverse populations with DR from different ethnic and racial backgrounds.
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Affiliation(s)
- Ward Fickweiler
- Research Division, Joslin Diabetes Center, Boston, MA, USA.,Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA.,Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Margalit Mitzner
- Research Division, Joslin Diabetes Center, Boston, MA, USA.,Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA
| | - Cris Martin P Jacoba
- Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA.,Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Jennifer K Sun
- Research Division, Joslin Diabetes Center, Boston, MA, USA.,Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA.,Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
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MicroRNA-150 (miR-150) and Diabetic Retinopathy: Is miR-150 Only a Biomarker or Does It Contribute to Disease Progression? Int J Mol Sci 2022; 23:ijms232012099. [PMID: 36292956 PMCID: PMC9603433 DOI: 10.3390/ijms232012099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 10/05/2022] [Accepted: 10/06/2022] [Indexed: 11/18/2022] Open
Abstract
Diabetic retinopathy (DR) is a chronic disease associated with diabetes mellitus and is a leading cause of visual impairment among the working population in the US. Clinically, DR has been diagnosed and treated as a vascular complication, but it adversely impacts both neural retina and retinal vasculature. Degeneration of retinal neurons and microvasculature manifests in the diabetic retina and early stages of DR. Retinal photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. Chronic inflammation is a hallmark of diabetes and a contributor to cell apoptosis, and retinal photoreceptors are a major source of intraocular inflammation that contributes to vascular abnormalities in diabetes. As the levels of microRNAs (miRs) are changed in the plasma and vitreous of diabetic patients, miRs have been suggested as biomarkers to determine the progression of diabetic ocular diseases, including DR. However, few miRs have been thoroughly investigated as contributors to the pathogenesis of DR. Among these miRs, miR-150 is downregulated in diabetic patients and is an endogenous suppressor of inflammation, apoptosis, and pathological angiogenesis. In this review, how miR-150 and its downstream targets contribute to diabetes-associated retinal degeneration and pathological angiogenesis in DR are discussed. Currently, there is no effective treatment to stop or reverse diabetes-caused neural and vascular degeneration in the retina. Understanding the molecular mechanism of the pathogenesis of DR may shed light for the future development of more effective treatments for DR and other diabetes-associated ocular diseases.
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Rosato C, Bettegazzi B, Intagliata P, Balbontin Arenas M, Zacchetti D, Lanati A, Zerbini G, Bandello F, Grohovaz F, Codazzi F. Redox and Calcium Alterations of a Müller Cell Line Exposed to Diabetic Retinopathy-Like Environment. Front Cell Neurosci 2022; 16:862325. [PMID: 35370555 PMCID: PMC8972164 DOI: 10.3389/fncel.2022.862325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 02/25/2022] [Indexed: 11/13/2022] Open
Abstract
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is the major cause of vision loss in the working-age population. Although DR is traditionally considered a microvascular disease, an increasing body of evidence suggests that neurodegeneration is an early event that occurs even before the manifestation of vasculopathy. Accordingly, attention should be devoted to the complex neurodegenerative process occurring in the diabetic retina, also considering possible functional alterations in non-neuronal cells, such as glial cells. In this work, we investigate functional changes in Müller cells, the most abundant glial population present within the retina, under experimental conditions that mimic those observed in DR patients. More specifically, we investigated on the Müller cell line rMC-1 the effect of high glucose, alone or associated with activation processes and oxidative stress. By fluorescence microscopy and cellular assays approaches, we studied the alteration of functional properties, such as reactive oxygen species production, antioxidant response, calcium homeostasis, and mitochondrial membrane potential. Our results demonstrate that hyperglycaemic-like condition per se is well-tolerated by rMC-1 cells but makes them more susceptible to a pro-inflammatory environment, exacerbating the effects of this stressful condition. More specifically, rMC-1 cells exposed to high glucose decrease their ability to counteract oxidative stress, with consequent toxic effects. In conclusion, our study offers new insights into Müller cell pathophysiology in DR and proposes a novel in vitro model which may prove useful to further investigate potential antioxidant and anti-inflammatory molecules for the prevention and/or treatment of DR.
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Affiliation(s)
- Clarissa Rosato
- Vita-Salute San Raffaele University, Milan, Italy
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Barbara Bettegazzi
- Vita-Salute San Raffaele University, Milan, Italy
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Pia Intagliata
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Daniele Zacchetti
- Vita-Salute San Raffaele University, Milan, Italy
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Antonella Lanati
- Vita-Salute San Raffaele University, Milan, Italy
- Valore Qualità, Pavia, Italy
| | - Gianpaolo Zerbini
- Complications of Diabetes Unit, Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Bandello
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Fabio Grohovaz
- Vita-Salute San Raffaele University, Milan, Italy
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Franca Codazzi
- Vita-Salute San Raffaele University, Milan, Italy
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
- *Correspondence: Franca Codazzi
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Ikeda T, Nakamura K, Kida T, Oku H. Possible roles of anti-type II collagen antibody and innate immunity in the development and progression of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2022; 260:387-403. [PMID: 34379187 PMCID: PMC8786754 DOI: 10.1007/s00417-021-05342-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 07/19/2021] [Accepted: 07/24/2021] [Indexed: 11/08/2022] Open
Abstract
The pathogenesis of both diabetic retinopathy (DR) and rheumatoid arthritis (RA) has recently been considered to involve autoimmunity. Serum and synovial fluid levels of anti-type II collagen antibodies increase early after the onset of RA, thus inducing immune responses and subsequent hydrarthrosis and angiogenesis, which resemble diabetic macular edema and proliferative DR (PDR), respectively. We previously reported that DR is also associated with increased serum levels of anti-type II collagen antibodies. Retinal hypoxia in DR may induce pericytes to express type II collagen, resulting in autoantibody production against type II collagen. As the result of blood-retinal barrier disruption, anti-type II collagen antibodies in the serum come into contact with type II collagen around the retinal vessels. A continued loss of pericytes and type II collagen around the retinal vessels may result in a shift of the immune reaction site from the retina to the vitreous. It has been reported that anti-inflammatory M2 macrophages increased in the vitreous of PDR patients, accompanied by the activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity. M2 macrophages promote angiogenesis and fibrosis, which might be exacerbated and prolonged by dysregulated innate immunity.
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Affiliation(s)
- Tsunehiko Ikeda
- Department of Ophthalmology, Osaka Medical and Pharmaceutical University, Takatsuki City, Osaka, Japan.
- Department of Ophthalmology, Osaka Kaisei Hospital, 1-6-10 Miyahara Yodogawa-ku, Osaka City, Osaka, Japan.
| | | | - Teruyo Kida
- Department of Ophthalmology, Osaka Medical and Pharmaceutical University, Takatsuki City, Osaka, Japan
| | - Hidehiro Oku
- Department of Ophthalmology, Osaka Medical and Pharmaceutical University, Takatsuki City, Osaka, Japan
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10
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Abstract
Diabetes mellitus is a disease of dysregulated blood glucose homeostasis. The current pandemic of diabetes is a significant driver of patient morbidity and mortality, as well as a major challenge to healthcare systems worldwide. The global increase in the incidence of diabetes has prompted researchers to focus on the different pathogenic processes responsible for type 1 and type 2 diabetes. Similarly, increased morbidity due to diabetic complications has accelerated research to uncover pathological changes causing these secondary complications. Albuminuria, or protein in the urine, is a well-recognised biomarker and risk factor for renal and cardiovascular disease. Albuminuria is a mediator of pathological abnormalities in diabetes-associated conditions such as nephropathy and atherosclerosis. Clinical screening and diagnosis of diabetic nephropathy is chiefly based on the presence of albuminuria. Given the ease in measuring albuminuria, the potential of using albuminuria as a biomarker of cardiovascular diseases is gaining widespread interest. To assess the benefits of albuminuria as a biomarker, it is important to understand the association between albuminuria and cardiovascular disease. This review examines our current understanding of the pathophysiological mechanisms involved in both forms of diabetes, with specific focus on the link between albuminuria and specific vascular complications of diabetes.
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Affiliation(s)
- Pappitha Raja
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK
| | - Alexander P Maxwell
- Nephrology Research, Centre for Public Health, Queen's University of Belfast, Northern Ireland Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland, UK
| | - Derek P Brazil
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK.
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Meng Q, Li Y, Ji T, Chao Y, Li J, Fu Y, Wang S, Chen Q, Chen W, Huang F, Wang Y, Zhang Q, Wang X, Bian H. Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy. J Adv Res 2021; 28:149-164. [PMID: 33364052 PMCID: PMC7753237 DOI: 10.1016/j.jare.2020.08.010] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 06/22/2020] [Accepted: 08/18/2020] [Indexed: 12/21/2022] Open
Abstract
Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. Because autophagy is highly regulated by estrogen, we hypothesized that estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor alpha (ERα)-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Thus, the results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis.
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Affiliation(s)
- Qinghai Meng
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu Li
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Tingting Ji
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Ying Chao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jun Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu Fu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Suyun Wang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Qi Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Wen Chen
- Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China
| | - Fuhua Huang
- Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China
| | - Youran Wang
- Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China
| | - Qichun Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xiaoliang Wang
- Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China
| | - Huimin Bian
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
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12
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Cutaș A, Drugan C, Roman G, Rusu A, Istrate D, Achimaș-Cadariu A, Drugan T. Inflammatory response and timeline of chronic complications in patients with type 1 and 2 diabetes mellitus. Int J Diabetes Dev Ctries 2020. [DOI: 10.1007/s13410-020-00824-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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13
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Ang WJ, Zunaina E, Norfadzillah AJ, Raja-Norliza RO, Julieana M, Ab-Hamid SA, Mahaneem M. Evaluation of vascular endothelial growth factor levels in tears and serum among diabetic patients. PLoS One 2019; 14:e0221481. [PMID: 31437234 PMCID: PMC6705830 DOI: 10.1371/journal.pone.0221481] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 08/07/2019] [Indexed: 01/16/2023] Open
Abstract
Objective Detection of vascular endothelial growth factor (VEGF) levels in ocular tissue may perhaps provide insight into the role of VEGF in the pathogenesis and progression of diabetic retinopathy (DR). The aim of this study was to evaluate the levels of VEGF in tears and serum amongst type 2 diabetes mellitus (DM) patients. Methods A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay. Results A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263). Conclusion VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation.
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Affiliation(s)
- Wen Jeat Ang
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Department of Ophthalmology, Melaka General Hospital, Jalan Mufti Haji Khalil, Melaka, Malaysia
| | - Embong Zunaina
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- * E-mail:
| | | | - Raja Omar Raja-Norliza
- Department of Ophthalmology, Melaka General Hospital, Jalan Mufti Haji Khalil, Melaka, Malaysia
| | - Muhammed Julieana
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Siti Azrin Ab-Hamid
- Unit Biostatistics and Research Methodology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Mohamed Mahaneem
- Department of Physiology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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14
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Sheikhrezaee M, Alizadeh MR, Abediankenari S. The tear VEGF and IGFBP3 in healthy and diabetic retinopathy. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-019-00761-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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15
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Ding Y, Ge Q, Qu H, Feng Z, Long J, Wei Q, Zhou Q, Wu R, Yao L, Deng H. Increased serum periostin concentrations are associated with the presence of diabetic retinopathy in patients with type 2 diabetes mellitus. J Endocrinol Invest 2018; 41:937-945. [PMID: 29349642 DOI: 10.1007/s40618-017-0820-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 12/27/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE To determine the association between serum periostin and the presence of diabetic retinopathy (DR). METHODS Serum periostin was detected in 114 healthy subjects, 122 patients with type 2 diabetes mellitus (T2DM) and 159 patients with DR and compared among groups. Clinical data and other laboratory measurements such as glycated hemoglobin (HbA1c), lipid profiles, serum creatinine (Cr) and high-sensitivity CRP (hsCRP) were also collected and compared among groups. For subgroup analysis, patients with DR were divided into a non-proliferated diabetic retinopathy (NPDR) group and a proliferated diabetic retinopathy (PDR) group. Multivariate analysis was performed using logistic regression models. RESULTS The serum periostin level was significantly higher in patients with diabetic retinopathy compared with healthy subjects and patients with T2DM (both P < 0.001, respectively). Also, the periostin level was significantly higher in the PDR group compared to the NPDR group (P = 0.044). Multivariate logistic regression revealed that serum periostin was independently associated with the presence of DR in patients with T2DM (P < 0.001). The receiver operating characteristic (ROC) curves for DR development using serum periostin showed that the area under the receiver operating characteristic curves (AUC) was 0.838 (P < 0.001). CONCLUSIONS The current study demonstrated that serum periostin is significantly associated with the presence of DR in patients with T2DM and is an independent risk factor of DR.
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Affiliation(s)
- Y Ding
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Q Ge
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - H Qu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Z Feng
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - J Long
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Q Wei
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Q Zhou
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - R Wu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - L Yao
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - H Deng
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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Erdenen F, Güngel H, Altunoğlu E, Şak D, Müderrisoğlu C, Koro A, Akça Güler P, Hakan Sahin ME, Simsek G, Uzun H. Association of Plasma Pentraxin-3 Levels with Retinopathy and Systemic Factors in Diabetic Patients. Metab Syndr Relat Disord 2018; 16:358-365. [PMID: 30036122 DOI: 10.1089/met.2018.0023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is mainly caused by metabolic factors, vascular inflammation, and endothelial dysfunction. We aimed to evaluate the relationship of DR with inflammatory and biochemical alterations in type 2 diabetics. METHODS A total of 89 diabetic patients with retinopathy [(DR (+) (n = 30)], without retinopathy [(DR (-) (n = 32)], and 27 control subjects were involved in the study. Demographic properties, biochemical values, ophtalmologic evaluation, C-reactive protein (CRP), and pentraxin-3 (PTX-3) levels were recorded. RESULTS There was significant difference between controls, DR (-) and DR (+) groups with regard to serum PTX-3 levels. Control group had the lowest and DR (+) group revealed the highest PTX-3 levels. Severity of retinopathy was not related with CRP or PTX-3 levels. Duration of diabetes was longer, systolic blood pressure (SBP) and urinary albumin-creatinine ratio (UACR) were significantly higher in DR (+) subjects than DR (-) subjects. Multivariate analysis revealed that PTX-3 level and SBP were the variables that had a significant effect on DR (P = 0.002, OR = 1.61, and P = 0.021, OR = 1.06, respectively). CONCLUSIONS Plasma PTX-3 levels may be a valuable predictor of DR-like factors such as duration of diabetes, hypertension, and UACR. Although inflammation has an important role in DR, we think that biomarkers reflecting inflammation is not sufficient to predict development and progression of DR; but follow up with PTX-3 levels along with ophthalmological evaluation may be useful. A single determination may not reflect the variations over time, so repeat measures may provide knowledge if PTX-3 is just a biomarker or has a causal role.
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Affiliation(s)
- Füsun Erdenen
- 1 Internal Medicine Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Hülya Güngel
- 2 Ophtalmology Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Esma Altunoğlu
- 1 Internal Medicine Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Duygu Şak
- 1 Internal Medicine Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Cüneyt Müderrisoğlu
- 1 Internal Medicine Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Atakan Koro
- 3 Department of Biochemistry, lstanbul Education and Research Hospital , Istanbul, Turkey
| | - Pınar Akça Güler
- 2 Ophtalmology Clinic, lstanbul Education and Research Hospital , Istanbul, Turkey
| | | | - Gonul Simsek
- 4 Department of Physiology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey
| | - Hafize Uzun
- 5 Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey
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17
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Aryan Z, Ghajar A, Faghihi-Kashani S, Afarideh M, Nakhjavani M, Esteghamati A. Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study. ANNALS OF NUTRITION AND METABOLISM 2018; 72:287-295. [PMID: 29694948 DOI: 10.1159/000488537] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 03/16/2018] [Indexed: 01/28/2023]
Abstract
BACKGROUND/AIMS This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). METHODS A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. RESULTS Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024-1.032) for CHD, 1.025 (1.021-1.029) for diabetic neuropathy, 1.037 (1.030-1.043) for diabetic retinopathy, and 1.035 (1.027-1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). CONCLUSION Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.
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Affiliation(s)
- Zahra Aryan
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Ghajar
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Faghihi-Kashani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Afarideh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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18
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Song SJ, Han K, Lee SS, Park JB. Association between the number of natural teeth and diabetic retinopathy among type 2 diabetes mellitus: The Korea national health and nutrition examination survey. Medicine (Baltimore) 2017; 96:e8694. [PMID: 29381952 PMCID: PMC5708951 DOI: 10.1097/md.0000000000008694] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to investigate the relationship between the number of teeth and diabetic retinopathy among Korean population.This was a retrospective analysis using data of total 45,811 individuals who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) 2008 to 2012. Among these, 2593 (5.7%) participants were identified as having type 2 diabetes mellitus. After excluding participants without ophthalmic evaluation or other variables, 2078 (80%) participants were included. Demographic factors including dental status were analyzed and compared between participants with and without diabetic retinopathy.Among the 2078 type 2 diabetes, 358 (17.2%) had diabetic retinopathy. Type 2 diabetes with fewer teeth were more likely to have diabetic retinopathy (P < .001). Multivariate analysis showed that type 2 diabetes with < 20 teeth had an 8.7-fold risk of having vision-threatening diabetic retinopathy when compared with type 2 diabetes with ≥28 teeth (95% confidence interval: 2.69-28.3) after adjusting for age, sex, body mass index, smoking, drinking, exercise, hypertension, diabetes mellitus duration, and glycated hemoglobin level.The number of teeth was found to be an independent risk factor for diabetic retinopathy. Thus, a comprehensive approach of dentists and ophthalmologists is needed to minimize the complications of diabetes mellitus. Whether the teeth number reflects microvascular changes of the retina among type 2 diabetes warrants further investigation.
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Affiliation(s)
- Su Jeong Song
- Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul
| | - Seong-su Lee
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Bucheon-si Gyeonggi-do
| | - Jun-Beom Park
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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19
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Wong ND, Zhao Y, Quek RGW, Blumenthal RS, Budoff MJ, Cushman M, Garg P, Sandfort V, Tsai M, Lopez JAG. Residual atherosclerotic cardiovascular disease risk in statin-treated adults: The Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol 2017; 11:1223-1233. [PMID: 28754224 DOI: 10.1016/j.jacl.2017.06.015] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Revised: 05/17/2017] [Accepted: 06/14/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND Residual atherosclerotic cardiovascular disease (ASCVD) risk in statin-treated US adults without known ASCVD is not well described. OBJECTIVE To quantitate residual ASCVD risk and its predictors in statin-treated adults. METHODS We studied 1014 statin-treated adults (53.3% female, mean 66.0 years) free of clinical ASCVD in the Multi-Ethnic Study of Atherosclerosis. We examined ASCVD event rates by National Lipid Association risk groups over 11-year follow-up and the relation of standard risk factors, biomarkers, and subclinical atherosclerosis measures with residual ASCVD event risk. RESULTS Overall, 5.3% of participants were at low, 12.2% at moderate, 60.3% at high, and 22.2% at very high baseline risk. Despite statin therapy, age- and race-standardized ASCVD rates per 1000 person-years for men and women were both 4.9 for low/moderate risk, 19.1 and 14.2 for high risk, and 35.6 and 26.7 for very high risk, respectively. Specific independent predictors of residual risk included current smoking, family history, diabetes, high-sensitivity C-reactive protein, low-density lipoprotein particle number, carotid intimal medial thickness, and especially coronary artery calcium score. Those on moderate- or high-intensity statins at baseline (compared with low intensity) had 39% lower risks and those who increased statin intensity 62% lower ASCVD event risks (P < .01). CONCLUSION Residual risk of ASCVD remains high despite statin treatment and is predicted by specific risk factors and subclinical atherosclerosis. These findings may be helpful for identifying those at highest risk needing more aggressive treatment.
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Affiliation(s)
- Nathan D Wong
- Division of Cardiology, Department of Medicine, University of California at Irvine, Heart Disease Prevention Program, Irvine, CA, USA; Department of Epidemiology, University of California Los Angeles, Los Angeles, CA, USA.
| | - Yanglu Zhao
- Division of Cardiology, Department of Medicine, University of California at Irvine, Heart Disease Prevention Program, Irvine, CA, USA; Department of Epidemiology, University of California Los Angeles, Los Angeles, CA, USA
| | - Ruben G W Quek
- Global Health Economics and United States Medical Organization, Amgen, Inc, Thousand Oaks, CA, USA
| | - Roger S Blumenthal
- Department of Medicine, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA
| | - Matthew J Budoff
- Division of Cardiology, Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA
| | - Mary Cushman
- Department of Pathology, University of Vermont, Burlington, VT, USA
| | - Parveen Garg
- Division of Cardiology, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Veit Sandfort
- Department of Cardiovascular Imaging, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Michael Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - J Antonio G Lopez
- Global Health Economics and United States Medical Organization, Amgen, Inc, Thousand Oaks, CA, USA
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20
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Sharma Y, Saxena S, Mishra A, Saxena A, Natu SM. Apolipoprotein A-I and B and Subjective Global Assessment relationship can reflect lipid defects in diabetic retinopathy. Nutrition 2016; 33:70-75. [PMID: 27908554 DOI: 10.1016/j.nut.2016.08.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 08/01/2016] [Accepted: 08/27/2016] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Elevated lipid levels increase complications of diabetic retinopathy (DR). Uncontrolled diabetes increases these complications and causes unintentional weight loss, indicating an apparently normal body mass index (BMI). Thus, it is easy to assume that patients with DR and a normal BMI have optimal lipid status. Apolipoprotein (Apo) A-I and Apo B levels differentially indicate serum lipid status in DR. Subjective Global Assessment (SGA) scores are associated with DR status. If SGA scores and serum Apo A-I and B levels are found to be interrelated, their relationship can reflect lipid defects in patients with DR despite apparently normal BMI. The aim of the present study was to investigate the possible relationship between serum Apo A-I and B levels and SGA scores of patients with DR. METHOD This was a case-control study conducted from November 2011 to April 2014. Serum Apo A-I and B levels and SGA scores were calculated for 40 healthy controls, 48 individuals without DR, 49 nonproliferative DR cases, and 48 proliferative DR cases. Pearson's correlation analysis was applied between Apo A-I, Apo B, Apo B/Apo A-I ratio, and SGA scores. RESULTS Negative correlation was observed between serum Apo A-I level (r = -0.567, P < 0.001) and positive correlation between serum Apo B level (r = 0.451, P < 0.001) and Apo B/Apo A-I ratio (r = 0.597, P < 0.001) with escalating SGA scores. CONCLUSION To our knowledge, this is the first study to report a novel correlation between serum Apo A-I, Apo B and Apo B/Apo A-I ratio and SGA scores. SGA scores can help predict lipid abnormalities in patients with DR even when they have an apparently normal BMI.
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Affiliation(s)
- Yashodhara Sharma
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Sandeep Saxena
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India.
| | - Arvind Mishra
- Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Anita Saxena
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Shankar Madhav Natu
- Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
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21
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Application of multiplex immunoassay technology to investigations of ocular disease. Expert Rev Mol Med 2016; 18:e15. [PMID: 27577534 DOI: 10.1017/erm.2016.15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Eye-derived fluids, including tears, aqueous humour and vitreous humour often contain molecular signatures of ocular disease states. These signatures can be composed of cytokines, chemokines, growth factors, proteases and soluble receptors. However, the small quantities (<10 µl) of these fluids severely limit the detection of these proteins by traditional enzyme-linked immunosorbent assay or Western blot. To maximise the amount of information generated from the analysis of these specimens, many researchers have employed multiplex immunoassay technologies for profiling the expression or modification of multiple proteins from minute sample volumes.
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22
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Zhu B, Wu X, Ning K, Jiang F, Zhang L. The Negative Relationship between Bilirubin Level and Diabetic Retinopathy: A Meta-Analysis. PLoS One 2016; 11:e0161649. [PMID: 27571522 PMCID: PMC5003343 DOI: 10.1371/journal.pone.0161649] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 08/09/2016] [Indexed: 12/22/2022] Open
Abstract
Objectives Findings on the relationship between total bilirubin level (TBL) and diabetic retinopathy (DR) are inconsistent. Thus, we carried out a meta-analysis to investigate the relationship between TBL and the risk of DR. Methods Relevant studies were selected from six databases up to 31 May 2016 using a search strategy. The relevant data were extracted from the included studies according to the inclusion and exclusion criteria, and the mean value with standard errors or odds ratio (OR) with 95% confidence intervals (CIs) were calculated. We compared TBL in patients with DR with that in patients with diabetes but without retinopathy (NDR), and analyzed the dose-response relationship between TBL and the risk of DR. Results Twenty-four studies were selected in this meta-analysis. Twenty studies were included to calculate the pooled SMD, and the results showed that TBL in the DR group was lower than that in the NDR group (SMD: –0.52, 95% CI: –0.67, –0.38). Nine studies were included to calculate the pooled ORs, and the results showed that there was a significant negative relationship between TBL and the risk of DR (OR: 0.19, 95% CI: 0.14, 0.25). Six studies were included to investigate the dose-response relationship between TBL and the risk of DR, and we found a nonlinear relationship between TBL and the risk of DR. The results of our meta-analysis were found to be reliable using subgroup and sensitivity analyses. Conclusions The results of our meta-analysis indicate that higher TBL may be protective against DR in subjects with diabetes, and TBL could be used as a biomarker to predict the risk of DR.
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Affiliation(s)
- Bo Zhu
- Department of Cancer Prevention and Treatment, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China
- * E-mail:
| | - Xiaomei Wu
- Department of Clinical Epidemiology and Evidence Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Kang Ning
- Department of Occupational Health, Liaoning Disease Prevention and Control Center, Shenyang, People’s Republic of China
| | - Feng Jiang
- Center of Health Management, Shenyang 242 Hospital, Shenyang, People’s Republic of China
| | - Lu Zhang
- Department of Cancer Prevention and Treatment, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China
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Pan J, Liu S, Farkas M, Consugar M, Zack DJ, Kozak I, Arevalo JF, Pierce E, Qian J, Al Kahtani E. Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes. Mol Vis 2016; 22:636-45. [PMID: 27307695 PMCID: PMC4902182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 06/09/2016] [Indexed: 10/25/2022] Open
Abstract
PURPOSE The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes. METHODS A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups. RESULTS Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7% and 91.5%, respectively. CONCLUSIONS Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings.
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Affiliation(s)
- Jianbo Pan
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Sheng Liu
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Michael Farkas
- Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA,Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
| | - Mark Consugar
- Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA,Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
| | - Donald J. Zack
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Igor Kozak
- Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia
| | - J. Fernando Arevalo
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD,Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia
| | - Eric Pierce
- Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA,Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
| | - Jiang Qian
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD,The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
| | - Eman Al Kahtani
- Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia
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Azab N, Abdel-Aziz T, Ahmed A, El-deen I. Correlation of serum resistin level with insulin resistance and severity of retinopathy in type 2 diabetes mellitus. JOURNAL OF SAUDI CHEMICAL SOCIETY 2016. [DOI: 10.1016/j.jscs.2012.07.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Abstract
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is a major cause of vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. Severe stages of DR include proliferative DR, caused by the abnormal growth of new retinal blood vessels, and diabetic macular oedema, in which there is exudation and oedema in the central part of the retina. DR is strongly associated with a prolonged duration of diabetes, hyperglycaemia and hypertension. It is traditionally regarded as a microvascular disease, but retinal neurodegeneration is also involved. Complex interrelated pathophysiological mechanisms triggered by hyperglycaemia underlie the development of DR. These mechanisms include genetic and epigenetic factors, increased production of free radicals, advanced glycosylation end products, inflammatory factors and vascular endothelial growth factor (VEGF). Optimal control of blood glucose and blood pressure in individuals with diabetes remains the cornerstone for preventing the development and arresting the progression of DR. Anti-VEGF therapy is currently indicated for diabetic macular oedema associated with vision loss, whereas laser photocoagulation prevents severe vision loss in eyes with proliferative DR. These measures, together with increasing public awareness and access to regular screening for DR with retinal photography, and the development of new treatments to address early disease stages, will lead to better outcomes and prevent blindness for patients with DR.
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Yang XF, Deng Y, Gu H, Lim A, Snellingen T, Liu XP, Wang NL, Domalpally A, Danis R, Liu NP. C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Int J Ophthalmol 2016; 9:111-8. [PMID: 26949620 DOI: 10.18240/ijo.2016.01.19] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 05/27/2015] [Indexed: 11/23/2022] Open
Abstract
AIM To investigate the relationship between C-reactive protein (CRP) and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS Community-based observational cohort study. There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing. Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire, ocular and anthropometric examinations and laboratory investigation. The presence and severity of DR were assessed by seven fields 30° color fundus photographs. Subjects were then classified into groups with no DR, any DR, or vision-threatening DR. CRP was analyzed from serum of study subjects. RESULTS A total of 1007 patients with T2DM were included for analysis, including 408 (40.5%) men and 599 (59.5%) women. The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men (P=0.004, OR 0.37, 95% CI 0.18-0.74). After adjusting for possible covariates, higher levels of CRP were associated with lower prevalence of any DR (P=0.02, OR 0.55, 95% CI 0.35-0.89), but not associated with vision-threatening DR (P=0.62, OR 0.78, 95% CI 0.28-2.14). After stratification by sex, the inverse association between CRP and DR was found to be statistically significant in men (P=0.006, OR 0.35, 95% CI 0.16-0.73), but not in women (P=0.58, OR 0.88, 95% CI 0.29-1.16). CONCLUSION The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.
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Affiliation(s)
- Xiu-Fen Yang
- Department of Ophthalmology, the Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Yu Deng
- Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Hong Gu
- Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Apiradee Lim
- Department of Mathematics and Computer Science, Faculty of Science and Technology, Prince of Songkla University, Pattani Campus, Muang Pattani 9400, Thailand
| | | | - Xi-Pu Liu
- Sekwa Research Institute, Beijing 100088, China
| | - Ning-Li Wang
- Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Amitha Domalpally
- Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison 53705, Wisconsin, USA
| | - Ronald Danis
- Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison 53705, Wisconsin, USA
| | - Ning-Pu Liu
- Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
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Paterniti I, Di Paola R, Campolo M, Siracusa R, Cordaro M, Bruschetta G, Tremolada G, Maestroni A, Bandello F, Esposito E, Zerbini G, Cuzzocrea S. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. Eur J Pharmacol 2015; 769:313-23. [PMID: 26607470 DOI: 10.1016/j.ejphar.2015.11.035] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/05/2015] [Accepted: 11/18/2015] [Indexed: 01/19/2023]
Abstract
Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.
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Affiliation(s)
- Irene Paterniti
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Rosanna Di Paola
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Michela Campolo
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Rosalba Siracusa
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Marika Cordaro
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Giuseppe Bruschetta
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Gemma Tremolada
- Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
| | - Anna Maestroni
- Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Bandello
- Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
| | - Emanuela Esposito
- Department of Biological and Environmental Sciences, University of Messina, Italy
| | - Gianpaolo Zerbini
- Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy
| | - Salvatore Cuzzocrea
- Department of Biological and Environmental Sciences, University of Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, USA.
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Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. EYE AND VISION 2015. [PMID: 26605370 DOI: 10.1186/s40662-015-0026-2 10.1186/s40662-015-0026-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, a further one third of DR is vision-threatening DR, including diabetic macular edema (DME). The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR. Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME, especially those involved in inflammation and oxidative stress. Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility. In this review, major trends in the prevalence, incidence, progression and regression of DR and DME are explored, and gaps in literature identified. Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
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Affiliation(s)
- Ryan Lee
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Charumathi Sabanayagam
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
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Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. EYE AND VISION (LONDON, ENGLAND) 2015. [PMID: 26605370 DOI: 10.1186/s40662-015-0026-2+10.1186/s40662-015-0026-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, a further one third of DR is vision-threatening DR, including diabetic macular edema (DME). The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR. Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME, especially those involved in inflammation and oxidative stress. Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility. In this review, major trends in the prevalence, incidence, progression and regression of DR and DME are explored, and gaps in literature identified. Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
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Affiliation(s)
- Ryan Lee
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Charumathi Sabanayagam
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
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Yekta Z, Xie D, Bogner HR, Weber DR, Zhang X, Harhay M, Reese PP. The association of antidepressant medications and diabetic retinopathy among people with diabetes. J Diabetes Complications 2015; 29:1077-84. [PMID: 26233573 DOI: 10.1016/j.jdiacomp.2015.06.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Revised: 05/25/2015] [Accepted: 06/22/2015] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To determine if the use of antidepressants was associated with lower odds of diabetic retinopathy and if so, to determine if this association was mediated by decreased inflammation as measured by C-reactive protein (CRP). DESIGN This was a cross sectional study of 1,041 participants with type 2 diabetes 40-85years old from the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression was used to examine the association between the outcome of diabetic retinopathy and the primary exposure of antidepressant medication usage. We also determined whether CRP meets standard criteria as a mediator between antidepressant use and diabetic retinopathy. RESULTS Participants using antidepressants were less likely to have diabetic retinopathy (OR 0.50, 95% CI: 0.31-0.82). CRP did not meet one of the criteria for mediation. However, CRP was an effect modifier such that the association of antidepressant use and diabetic retinopathy was only present among participants with CRP ≥0.3mg/dl. Among the antidepressant drug classes, selective serotonin reuptake inhibitor (SSRI) users had significantly lower odds of developing diabetic retinopathy compared to non-users of antidepressants. CONCLUSIONS Using representative survey data of US adults with type-2 diabetes, this study found that antidepressant use was associated with lower odds of diabetic retinopathy. Further longitudinal and experimental studies are necessary to confirm this finding and to determine if there is a role for antidepressants in preventing diabetic retinopathy in select patient populations.
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Affiliation(s)
- Zahra Yekta
- Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
| | - Dawei Xie
- Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
| | - Hillary R Bogner
- Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
| | - David R Weber
- University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
| | - Xinzhi Zhang
- Health Scientist Administrator at National Institutes of Health, Bethesda, MD, USA.
| | - Michael Harhay
- Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
| | - Peter P Reese
- Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
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Ajith TA, Ranimenon. Homocysteine in ocular diseases. Clin Chim Acta 2015; 450:316-321. [PMID: 26343924 DOI: 10.1016/j.cca.2015.09.007] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 09/01/2015] [Accepted: 09/03/2015] [Indexed: 11/21/2022]
Abstract
Homocysteine (Hcy) is a derived sulfur-containing and non-proteinogenic amino acid. The metabolism of Hcy occurs either through the remethylation to methionine or transsulfuration to cysteine. Studies have identified hyperhomocysteinemia (HHcy) as one of the possible risk factors for a multitude of diseases including vascular, neurodegenerative and ocular diseases. Association of HHcy with eye diseases such as retinopathy, pseudoexfoliative glaucoma maculopathy, cataract, optic atrophy and retinal vessel atherosclerosis is established. The molecular mechanism underlying these ocular diseases has been reported as impaired vascular endothelial function, apoptosis of retinal ganglion cells, extracellular matrix alterations, decreased lysyl oxidase activity and oxidative stress. The formed homocysteine-thiolactone in HHcy has stronger cytotoxicity and pro-inflammatory properties which can induce lens opacification and optic nerve damage. The metabolism of Hcy requires enzymes with vitamins such as folic acid, vitamins B12 and B6. Despite the mixed conclusion of various studies regarding the level of these vitamins in elder people, studies recommended the treatment with folate and B12 to reduce Hcy levels in subjects with or without any defect in the enzymes involved in its metabolism. The levels of Hcy, folate, B6 as well as B12 should be measured early in patients with visual impairment that would aid to screen patients for life-threatening disorders related with HHcy. Elder patients may supplement with these vitamins in order to attenuate the ocular damages. This article discusses the association of Hcy in ocular diseases and the possible mechanism in the pathogenesis.
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Affiliation(s)
| | - Ranimenon
- Department of Ophthalmology, Dr. Ranimenon's Eye Clinic, Thrissur, 680 003 Kerala, India.
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Najafi L, Malek M, Valojerdi AE, Khamseh ME. Acute phase proteins and diabetes microvascular complications. Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-015-0389-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. EYE AND VISION 2015; 2:17. [PMID: 26605370 PMCID: PMC4657234 DOI: 10.1186/s40662-015-0026-2] [Citation(s) in RCA: 937] [Impact Index Per Article: 93.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 09/01/2015] [Indexed: 12/15/2022]
Abstract
Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, a further one third of DR is vision-threatening DR, including diabetic macular edema (DME). The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR. Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME, especially those involved in inflammation and oxidative stress. Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility. In this review, major trends in the prevalence, incidence, progression and regression of DR and DME are explored, and gaps in literature identified. Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
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Affiliation(s)
- Ryan Lee
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Charumathi Sabanayagam
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
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Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O'Neal DN, Januszewski AS. Biomarkers in Diabetic Retinopathy. Rev Diabet Stud 2015; 12:159-95. [PMID: 26676667 DOI: 10.1900/rds.2015.12.159] [Citation(s) in RCA: 198] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
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. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy.
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Affiliation(s)
- Alicia J Jenkins
- NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia
| | - Mugdha V Joglekar
- NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia
| | | | - Anthony C Keech
- NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia
| | - David N O'Neal
- NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia
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Sasongko MB, Wong TY, Jenkins AJ, Nguyen TT, Shaw JE, Wang JJ. Circulating markers of inflammation and endothelial function, and their relationship to diabetic retinopathy. Diabet Med 2015; 32:686-91. [PMID: 25407692 DOI: 10.1111/dme.12640] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/17/2014] [Indexed: 12/12/2022]
Abstract
AIM To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy. METHODS We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18-70 years. Serum markers of inflammation (high-sensitivity C-reactive protein) and endothelial function (soluble intercell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, endothelin-1 and total nitrite) were assessed using nephelometry, immunoassays and spectroscopy. Diabetic retinopathy was graded from two-field fundus photographs according to the Airlie House Classification system and was categorized into no diabetic retinopathy, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy and vision-threatening diabetic retinopathy, the latter comprising severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or clinically significant macular oedema. Multinomial logistic regression was used to assess the associations between serum markers and diabetic retinopathy. RESULTS In the study, 64% of patients (144/224) had diabetic retinopathy and 25% (57/244) had vision-threatening diabetic retinopathy. After controlling for age, gender, diabetes duration, HbA1c , systolic blood pressure, total and HDL cholesterol, smoking, the use of insulin or oral hypoglycaemic agents, nephropathy and cardiovascular disease, a positive association was found between increasing high-sensitivity C-reactive protein levels and the presence of vision-threatening diabetic retinopathy (odds ratio 1.26; 95% CI 1.05-1.51, per sd increase in high-sensitivity C-reactive protein). After stratifying by BMI ( ≥ 30 and < 30 kg/m(2) ), this association was found to be more pronounced in people with a BMI ≥ 30 kg/m(2) (odds ratio 2.9; P for interaction = 0.019). No associations were found between serum markers of endothelial activation and diabetic retinopathy. CONCLUSIONS Higher C-reactive protein levels, but not markers of endothelial function, may be related to more severe diabetic retinopathy. This finding suggests that inflammatory processes are involved in severe diabetic retinopathy, particularly in patients with a BMI ≥ 30 kg/m(2) .
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Affiliation(s)
- M B Sasongko
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Australia; Department of Ophthalmology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia
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Dave A, Kalra P, Gowda BHR, Krishnaswamy M. Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus. Indian J Endocrinol Metab 2015; 19:373-377. [PMID: 25932393 PMCID: PMC4366776 DOI: 10.4103/2230-8210.152777] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). AIMS AND OBJECTIVES The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. MATERIALS AND METHODS A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. RESULTS The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). CONCLUSIONS The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR.
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Affiliation(s)
- Apoorva Dave
- Department of Endocrinology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - Pramila Kalra
- Department of Endocrinology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - B. H. Rakshitha Gowda
- Department of Biochemistry, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - Malavika Krishnaswamy
- Department of Ophthalmology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
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Peng D, Wang J, Zhang R, Tang S, Jiang F, Chen M, Yan J, Sun X, Wang T, Wang S, Bao Y, Hu C, Jia W. C-reactive protein genetic variant is associated with diabetic retinopathy in Chinese patients with type 2 diabetes. BMC Endocr Disord 2015; 15:8. [PMID: 25887518 PMCID: PMC4350906 DOI: 10.1186/s12902-015-0006-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 02/18/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is an important microvascular complication of diabetes with a high concordance rate in patients with diabetes. Inflammation is supposed to participate in the development of DR. This study aimed to investigate whether genetic variants of CRP are associated with DR. METHODS A total of 1,018 patients with type 2 diabetes were recruited in this study. Of these patients, 618 were diagnosed with DR, 400 were patients with diabetes for over 10 years but without DR, considered as cases and controls for DR, respectively. Four tagging SNPs (rs2808629, rs3093077, rs1130864 and rs2808634) within CRP region were genotyped for all the participants. Fundus photography was performed for diagnosis and classification for DR. RESULTS rs2808629 was significantly associated with increased susceptibility to DR (odds ratio 1.296, 95% CI 1.076-1.561, P = 0.006, empirical P = 0.029, for G allele). This association remained significant after adjustment for confounding factors (odds ratio 1.261, 95% CI 1.022-1.555, P = 0.030). CONCLUSIONS In this study, we found CRP rs2808629 was associated with DR in the Chinese patients with type 2 diabetes.
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Affiliation(s)
- Danfeng Peng
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Jie Wang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Rong Zhang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Shanshan Tang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Feng Jiang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Miao Chen
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Jing Yan
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Xue Sun
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Tao Wang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Shiyun Wang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Yuqian Bao
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Cheng Hu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Weiping Jia
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 10/06/2014] [Accepted: 12/10/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
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Rajab HA, Baker NL, Hunt KJ, Klein R, Cleary PA, Lachin J, Virella G, Lopes-Virella MF. The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes. J Diabetes Complications 2015; 29:108-14. [PMID: 25441222 PMCID: PMC4426877 DOI: 10.1016/j.jdiacomp.2014.08.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 07/22/2014] [Accepted: 08/12/2014] [Indexed: 01/29/2023]
Abstract
AIMS This study was undertaken to determine whether levels of inflammation and endothelial dysfunction biomarkers in serum samples collected at baseline in the Diabetes Control and Complications Trial (DCCT) cohort could predict the development of retinopathy. METHODS Levels of clotting/fibrinolysis, inflammation and endothelial dysfunction biomarkers were measured in 1391 subjects with type 1 diabetes to determine whether their levels predicted increased risk to develop or accelerate progression of retinopathy during 16years of follow-up. RESULTS Using regression models adjusted for DCCT treatment group, duration of diabetes, baseline retinopathy scores, HbA1c and albumin excretion rate, the baseline levels of sE-selectin and PAI-1 (active) were significantly associated with increased risk of a 3-step progression in retinopathy score in the primary prevention cohort (PPC). After adjusting for additional covariates (e.g., ACE/ARB and statin therapy), this association persisted. Levels of active and total PAI-1 in the same group were also significantly associated, after similar adjustments, with the time to progress to severe non-proliferative retinopathy during the follow-up period (54 and 29%, respectively of increased risk). No associations were observed in the secondary intervention cohort for any of the outcomes. CONCLUSIONS High levels of sE-selectin and PAI-1 are associated with the development of retinopathy in patients with uncomplicated type 1 diabetes.
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Affiliation(s)
- Hussein A Rajab
- Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA
| | - Nathaniel L Baker
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Kelly J Hunt
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Richard Klein
- Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA
| | - Patricia A Cleary
- The Biostatistics Center, George Washington University, Washington DC, Washington DC, USA
| | - John Lachin
- The Biostatistics Center, George Washington University, Washington DC, Washington DC, USA
| | - Gabriel Virella
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
| | - Maria F Lopes-Virella
- Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
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Xu C, Wu Y, Liu G, Liu X, Wang F, Yu J. Relationship between homocysteine level and diabetic retinopathy: a systematic review and meta-analysis. Diagn Pathol 2014; 9:167. [PMID: 25257241 PMCID: PMC4207897 DOI: 10.1186/s13000-014-0167-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 08/16/2014] [Indexed: 02/06/2023] Open
Abstract
Background The relationship between homocysteine (Hcy) and diabetic retinopathy (DR) remains unclear to date. Therefore, a systematic review and meta-analysis was performed on the relationship between Hcy level and DR. Methods Studies were identified by searching PubMed, Embase, and Web of Science databases until 5 May, 2014. Results A total of 31 studies involving 6,394 participants were included in the meta-analysis. After pooling the data from each included study, the blood Hcy concentration in the DR group was observed to be higher than that in the control group [WMD = 2.55; 95% confidence interval (CI), 1.70–3.40], and diabetes mellitus (DM) patients with hyperhomocysteinemia were at a risk for DR [odds ratio (OR) = 1.93; 95% CI, 1.46–2.53]. Considering the different DM types, hyperhomocysteinemia in T1DM (OR = 1.83, 95% CI, 1.28–2.62) was associated with DR rather than in T2DM (OR = 1.59, 95% CI, 0.72–3.51). Considerable statistical heterogeneity in the overall summary estimates was partly explained by the geographical differences. Conclusions Results from this current meta-analysis indicate that hyperhomocysteinemia is a risk factor for DR, especially proliferative DR. Differences between geographical regions were observed in the relationship between hyperhomocysteinemia with T1DM risk. Given the heterogeneous results, the relationship between high Hcy and DR needs further investigation. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_167
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The role of microglia in diabetic retinopathy. J Ophthalmol 2014; 2014:705783. [PMID: 25258680 PMCID: PMC4166427 DOI: 10.1155/2014/705783] [Citation(s) in RCA: 117] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Revised: 07/08/2014] [Accepted: 07/31/2014] [Indexed: 02/06/2023] Open
Abstract
There is growing evidence that chronic inflammation plays a role in both the development and progression of diabetic retinopathy. There is also evidence that molecules produced as a result of hyperglycemia can activate microglia. However the exact contribution of microglia, the resident immune cells of the central nervous system, to retinal tissue damage during diabetes remains unclear. Current data suggest that dysregulated microglial responses are linked to their deleterious effects in several neurological diseases associated with chronic inflammation. As inflammatory cytokines and hyperglycemia disseminate through the diabetic retina, microglia can change to an activated state, increase in number, translocate through the retina, and themselves become the producers of inflammatory and apoptotic molecules or alternatively exert anti-inflammatory effects. In addition, microglial genetic variations may account for some of the individual differences commonly seen in patient's susceptibility to diabetic retinopathy.
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Cekić S, Cvetković T, Jovanović I, Jovanović P, Pesić M, Stanković Babić G, Milenković S, Risimić D. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy. Bosn J Basic Med Sci 2014; 14:177-84. [PMID: 25172979 DOI: 10.17305/bjbms.2014.3.21] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Accepted: 07/19/2014] [Indexed: 11/16/2022] Open
Abstract
The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.
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Affiliation(s)
- Sonja Cekić
- Ophthalmology Clinic for Eye Diseases, Clinical Centre Niš, Faculty of Medicine, University of Niš.
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Lois N, McCarter RV, O’Neill C, Medina RJ, Stitt AW. Endothelial progenitor cells in diabetic retinopathy. Front Endocrinol (Lausanne) 2014; 5:44. [PMID: 24782825 PMCID: PMC3988370 DOI: 10.3389/fendo.2014.00044] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 03/21/2014] [Indexed: 12/30/2022] Open
Abstract
Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication.
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Affiliation(s)
- Noemi Lois
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK
| | - Rachel V. McCarter
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK
| | - Christina O’Neill
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK
| | - Reinhold J. Medina
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK
| | - Alan W. Stitt
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK
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Zeng J, Chen B. Epigenetic mechanisms in the pathogenesis of diabetic retinopathy. Ophthalmologica 2014; 232:1-9. [PMID: 24714375 DOI: 10.1159/000357824] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2013] [Accepted: 12/08/2013] [Indexed: 11/19/2022]
Abstract
Diabetic retinopathy (DR), which arises as a result of an increasing incidence of diabetes mellitus, has gradually become a common disease. Due to its complex pathogenesis, the treatment means of DR are very limited. The findings of several studies have shown that instituting tight glycemic control in diabetic patients does not immediately benefit the progression of retinopathy, and the benefits of good control persist beyond the period of good glycemic control. This has led to the concept of persistent epigenetic changes. Epigenetics has now become an increasingly important area of biomedical research. Recently, important roles of various epigenetic mechanisms have been identified in the pathogenesis of diabetes and its complications. The aim of this review is to provide an overview of the epigenetics and epigenetic mechanisms in diabetes and diabetes complications, and the focus is on the emerging evidence for aberrant epigenetic mechanisms in DR.
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Affiliation(s)
- Jun Zeng
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha City, PR China
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Kuo JZ, Wong TY, Rotter JI. Challenges in elucidating the genetics of diabetic retinopathy. JAMA Ophthalmol 2014; 132:96-107. [PMID: 24201651 DOI: 10.1001/jamaophthalmol.2013.5024] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
IMPORTANCE In the past decade, significant progress in genomic medicine and technologic developments has revolutionized our approach to common complex disorders in many areas of medicine, including ophthalmology. A disorder that still needs major genetic progress is diabetic retinopathy (DR), one of the leading causes of blindness in adults. OBJECTIVE To perform a literature review, present the current findings, and highlight some key challenges in DR genetics. DESIGN, SETTING, AND PARTICIPANTS We performed a thorough literature review of the genetic factors for DR, including heritability scores, twin studies, family studies, candidate gene studies, linkage studies, and genome-wide association studies (GWASs). MAIN OUTCOME MEASURES Environmental and genetic factors for DR. RESULTS Although there is clear demonstration of a genetic contribution in the development and progression of DR, the identification of susceptibility loci through candidate gene approaches, linkage studies, and GWASs is still in its infancy. The greatest obstacles remain a lack of power because of small sample size of available studies and a lack of phenotype standardization. CONCLUSIONS AND RELEVANCE The field of DR genetics is still in its infancy and is a challenge because of the complexity of the disease. This review outlines some strategies and lessons for future investigation to improve our understanding of this complex genetic disorder.
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Affiliation(s)
- Jane Z Kuo
- Medical Genetics Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California2Department of Ophthalmology, University of California San Diego, La Jolla3Department of Ophthalmology, Chang Gung Memorial Hospital and
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jerome I Rotter
- Medical Genetics Institute and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California6Institute for Translational Genomics and Population Sciences, Los Angeles Bio Medical Research Institute, Harbor-UCLA Medical Center, To
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Expression and significance of HIF-1 α and VEGF in rats with diabetic retinopathy. ASIAN PAC J TROP MED 2014; 7:237-40. [DOI: 10.1016/s1995-7645(14)60028-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 12/15/2013] [Accepted: 01/15/2014] [Indexed: 11/19/2022] Open
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Azad N, Agrawal L, Emanuele NV, Klein R, Bahn GD, McCarren M, Reaven P, Hayward R, Duckworth W. Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care 2014; 37:501-6. [PMID: 24101699 PMCID: PMC3898766 DOI: 10.2337/dc13-1193] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 10/01/2013] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To test the hypothesis that high levels of plasminogen-activating inhibitor (PAI)-1 and fibrinogen at baseline were associated with the onset or progression of diabetic retinopathy (DR) during the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS The VADT was an open-label, prospective, randomized controlled trial to test the effect of standard glycemic control (STD) compared with intensive control (INT) on cardiovascular events in patients with advanced type 2 diabetes mellitus (T2DM). Diabetic retinopathy (DR) outcomes were also collected. Incidence and progression of DR were assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later taken in 858 of a total of 1,791 participants who completed both eye examinations. RESULTS Assignment to INT was not independently associated with decreased risk of onset of DR. However, after adjustment for multiple covariates, baseline level of PAI-1 was an independent risk factor for the onset of DR. The risk for incidence of DR increased by 12% for each 10 ng/dL increase in baseline PAI-1 concentration (odds ratio [OR] 1.012 [95% CI 1.00-1.024], P = 0.042). Assignment to INT was not independently associated with decreased risk of progression of DR. However, there was an interaction between glycemic treatment assignment and fibrinogen level at baseline. INT was associated with decreased progression of retinopathy in those with fibrinogen <296 mg/dL (OR 0.55 [95% CI 0.31-1.00], P = 0.03). CONCLUSIONS The results require confirmation but are consistent with greater hypercoagulabilty and inflammation, as measured by higher levels of PAI-1 and fibrinogen, being related to DR and responsiveness to INT.
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Polat SB, Ugurlu N, Yulek F, Simavli H, Ersoy R, Cakir B, Erel O. Evaluation of serum fibrinogen, plasminogen, α2-anti-plasmin, and plasminogen activator inhibitor levels (PAI) and their correlation with presence of retinopathy in patients with type 1 DM. J Diabetes Res 2014; 2014:317292. [PMID: 24818165 PMCID: PMC4003747 DOI: 10.1155/2014/317292] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 03/16/2014] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND. Diabetic retinopathy (DR) is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative) were associated with abnormally modulated hemostatic parameters in patients with T1DM. METHOD. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP. We compared these subgroups with each other and the control group (Group IV) according to the serum fibrinogen, plasminogen, alpha2-anti-plasmin ( α2-anti-plasmin), and PAI. RESULTS. We detected that PAI-1, serum fibrinogen, and plasminogen levels were similar between the diabetic and control groups (P = 0.209, P = 0.224, and P = 0.244, resp.), whereas α2-anti-plasmin was higher in Groups I, II, and III compared to the control group (P < 0.01, P < 0.05, and P < 0.001, resp.). There was a positive correlation between serum α2-anti-plasmin and HbA1c levels (r = 0,268, P = 0.031). CONCLUSION. To our knowledge there is scarce data in the literature about α2-anti-plasmin levels in type 1 diabetes. A positive correlation between α2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control.
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Affiliation(s)
- Sefika Burcak Polat
- Endocrinology and Metabolism Department, Ataturk Training and Research Hospital, Yildirim Beyazit University, 6800 Ankara, Turkey
- *Sefika Burcak Polat:
| | - Nagihan Ugurlu
- Ophthalmology Department, Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - Fatma Yulek
- Ophthalmology Department, Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - Huseyin Simavli
- Ophtalmology Department, Izzet Baysal Government Hospital, Bolu, Turkey
| | - Reyhan Ersoy
- Endocrinology and Metabolism Department, Ataturk Training and Research Hospital, Yildirim Beyazit University, 6800 Ankara, Turkey
| | - Bekir Cakir
- Endocrinology and Metabolism Department, Ataturk Training and Research Hospital, Yildirim Beyazit University, 6800 Ankara, Turkey
| | - Ozcan Erel
- Department of Biochemistry, Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
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Tomić M, Ljubić S, Kaštelan S, Gverović Antunica A, Jazbec A, Poljičanin T. Inflammation, haemostatic disturbance, and obesity: possible link to pathogenesis of diabetic retinopathy in type 2 diabetes. Mediators Inflamm 2013; 2013:818671. [PMID: 24363502 PMCID: PMC3865689 DOI: 10.1155/2013/818671] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/20/2013] [Accepted: 10/21/2013] [Indexed: 11/18/2022] Open
Abstract
PURPOSE The pathogenesis of diabetic retinopathy (DR) is insufficiently understood but may possibly involve chronic, low-grade inflammation. The aim of this cross-sectional study was to investigate the relationship between inflammatory and haemostatic markers, other markers of endothelial dysfunction and anthropometric parameters, and their association with DR in patients with type 2 diabetes. METHODS According to the DR status patients were divided into three groups: no retinopathy, mild/moderate nonproliferative (NPDR), and severe NPDR/proliferative retinopathy (PDR). RESULTS The groups did not differ in the levels of inflammatory and haemostatic markers, other markers of endothelial dysfunction, and anthropometric parameters. After dividing the patients according to the level of obesity (defined by BMI, WC, and WHR) into three groups ANOVA showed the differences in C-reactive protein according to the WC (P = 0.0265) and in fibrinogen according to the WHR (P = 0.0102) as well as in total cholesterol (P = 0.0109) and triglycerides (P = 0.0133) according to the BMI. Logistic regression analyses showed that diabetes duration and prolonged poor glycemic control are the main predictors of retinopathy in patients with type 2 diabetes. CONCLUSION Interrelations between obesity, inflammation, haemostatic disturbance, and other risk factors may possibly play an important additional role in endothelial dysfunction involved in the pathogenesis of diabetic retinopathy.
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Affiliation(s)
- Martina Tomić
- Department of Ophthalmology, University Clinic Vuk Vrhovac, Clinical Hospital Merkur, Zajčeva 19, 10000 Zagreb, Croatia
| | - Spomenka Ljubić
- Department of Endocrinology and Metabolic Diseases, University Clinic Vuk Vrhovac, Clinical Hospital Merkur, Zajčeva 19, 10000 Zagreb, Croatia
| | - Snježana Kaštelan
- Department of Ophthalmology, Clinical Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia
| | | | - Anamarija Jazbec
- Faculty of Forestry, University of Zagreb, Svetošimunska 25 p.p. 422, 10002 Zagreb, Croatia
| | - Tamara Poljičanin
- Croatian National Institute of Public Health, Rockefellerova 7, 10000 Zagreb, Croatia
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