Metabolomics in Diabetic Retinopathy: A Systematic Review.
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ABSTRACT: Purpose
Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures.Methods
We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database.Results
We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism.Conclusions
This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.
SUBMITTER: Hou XW
PROVIDER: S-EPMC8340662 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionThe evidence linking dietary intake with diabetic retinopathy (DR) is growing but unclear. We conducted a systematic review of the association between dietary intake and DR.MethodsWe systematically searched PubMed, Embase, Medline, and the Cochrane Central register of controlled trials, for publications between January 1967 and January 2017 using standardized criteria for diet and DR. Interventional and observational studies investigating micro- and macro-nutrient intakes; food and beverage consumptions; and dietary patterns were included. Study quality was evaluated using a modified Newcastle-Ottawa scale for observational studies, and the Cochrane collaboration tool for interventional studies.ResultsOf 4265 titles initially identified, 31 studies (3 interventional, 28 Observational) were retained. Higher intakes of dietary fibre, oily fish, and greater adherence to a Mediterranean diet were protective of DR. Conversely, high total caloric intake was associated with higher risk of DR. No significant associations of carbohydrate, vitamin D, and sodium intake with DR were found. Associations of antioxidants, fatty acids, proteins and alcohol with DR remain equivocal.ConclusionsDietary fibre, oily fish, a Mediterranean diet and a reduced caloric intake are associated with lower risk of DR. Longitudinal data and interventional models are warranted to confirm our findings and better inform clinical guidelines.
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Project description:Aims/hypothesisProliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR.MethodsWe analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration.ResultsWe identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024).Conclusions/interpretationThese results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.
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Project description:Purpose:There is controversial data regarding the effects of dietary antioxidative supplements on diabetic retinopathy (DR). We conducted a systematic review of both observational and randomized controlled clinical trials (RCTs) to clarify whether they are effective or not. Methods:All observational and RCTs conducted by antioxidative supplements on DR published up to 1 January 2018 in PubMed, Web of Sciences, Scopus and Cochrane Library databases were included. Exclusion criteria were animal studies, and studies conducted in Type 1 diabetes mellitus (T1DM), children or pregnant women. Main outcome measures were reporting the incidence or progression of DR in T2DM by assessment of visual fields, and measurements of oxidative and antioxidative biomarkers. The quality of reporting of included articles and risk of bias were assessed. Results:Finally, we reached 14 observational studies and 7 RCTs that conducted on 256,259 subjects. Due to severe methodological heterogeneity, only qualitative synthesis was carried. All studies were reported a significantly lower level of antioxidants and higher level of oxidative stress biomarkers in DR compared with others. There was an inverse significant correlation between vitamin C and malondialdehyde (MDA) (r?=?-0.81) or DNA damage (r?=?-0.41). These figures were statistically significant between vitamin E and MDA (r?=?0.77) or superoxide dismutase (r?=?0.44). Coefficient of correlation between MDA and zinc (-0.82), coenzyme Q10 (0.56), and magnesium (-0.73) was significant. Multi-oxidants trials were shown non-significant beneficial effects on DR. Conclusions:Although our study supports the positive effects of antioxidative supplements on DR, more high quality studies are needed to confirm.
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Project description:With the increasing incidence of diabetic retinopathy and its improved detection, there is increased demand for diabetic retinopathy treatment services. Prognostic prediction models have been used to optimise services but these were intended for early detection of sight-threatening retinopathy and are mostly used in diabetic retinopathy screening services. We wanted to look into the predictive ability and applicability of the existing models for the higher-risk patients referred into hospitals. We searched MEDLINE, EMBASE, COCHRANE CENTRAL, conference abstracts and reference lists of included publications for studies of any design using search terms related to diabetes, diabetic retinopathy and prognostic models. Search results were screened for relevance to the review question. Included studies had data extracted on model characteristics, predictive ability and validation. They were assessed for quality using criteria specified by PROBAST and CHARMS checklists, independently by two reviewers. Twenty-two articles reporting on 14 prognostic models (including four updates) met the selection criteria. Eleven models had internal validation, eight had external validation and one had neither. Discriminative ability with c-statistics ranged from 0.57 to 0.91. Studies ranged from low to high risk of bias, mostly due to the need for external validation or missing data. Participants, outcomes, predictors handling and modelling methods varied. Most models focussed on lower-risk patients, the majority had high risk of bias and doubtful applicability, but three models had some applicability for higher-risk patients. However, these models will also need updating and external validation in multiple hospital settings before being implemented into clinical practice.
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Project description:To determine whether the recommended screening interval for diabetic retinopathy (DR) in the UK can safely be extended beyond 1?year. Systematic review of clinical and cost-effectiveness studies. Nine databases were searched with no date restrictions. Randomised controlled trials (RCTs), cohort studies, prognostic or economic modelling studies which described the incidence and progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes mellitus of either sex and of any age reporting incidence and progression of DR in relation to screening interval (vs annual screening interval) and/or prognostic factors were included. Narrative synthesis was undertaken. 14,013 papers were identified, of which 11 observational studies, 5 risk stratification modelling studies and 9 economic studies were included. Data were available for 262,541 patients of whom at least 228,649 (87%) had type 2 diabetes. There were no RCTs. Studies concluded that there is little difference between clinical outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there was high loss to follow-up (13-31%), heterogeneity in definitions of low risk and variation in screening and grading protocols for prior retinopathy results. Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between 1-year and 2-year screening intervals. The lack of experimental research designs and heterogeneity in definition of low risk considerably limits the reliability and validity of this conclusion. Cost-effectiveness findings were mixed. There is insufficient evidence to recommend a move to extend the screening interval beyond 1?year.
| S-EPMC4717369 | biostudies-literature
Project description:ObjectiveTo determine the diagnostic accuracy of telemedicine in various clinical levels of diabetic retinopathy (DR) and diabetic macular oedema (DME).MethodsPubMed, EMBASE and Cochrane databases were searched for telemedicine and DR. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). Measures of sensitivity, specificity and other variables were pooled using a random effects model. Summary receiver operating characteristic curves were used to estimate overall test performance. Meta-regression and subgroup analyses were used to identify sources of heterogeneity. Publication bias was evaluated using Stata V.12.0.ResultsTwenty articles involving 1960 participants were included. Pooled sensitivity of telemedicine exceeded 80% in detecting the absence of DR, low- or high-risk proliferative diabetic retinopathy (PDR), it exceeded 70% in detecting mild or moderate non-proliferative diabetic retinopathy (NPDR), DME and clinically significant macular oedema (CSME) and was 53% (95% CI 45% to 62%) in detecting severe NPDR. Pooled specificity of telemedicine exceeded 90%, except in the detection of mild NPDR which reached 89% (95% CI 88% to 91%). Diagnostic accuracy was higher with digital images obtained through mydriasis than through non-mydriasis, and was highest when a wide angle (100-200°) was used compared with a narrower angle (45-60°, 30° or 35°) in detecting the absence of DR and the presence of mild NPDR. No potential publication bias was detected.ConclusionsThe diagnostic accuracy of telemedicine using digital imaging in DR is overall high. It can be used widely for DR screening. Telemedicine based on the digital imaging technique that combines mydriasis with a wide angle field (100-200°) is the best choice in detecting the absence of DR and the presence of mild NPDR.
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Project description:AimTo summarize findings from studies reporting the prevalence and incidence of diabetic retinopathy and diabetic maculopathy in African countries in light of the rising prevalence of diabetes mellitus.MethodsUsing a predefined search strategy, we systematically searched MEDLINE, EMBASE, Science Citation index and Conference Proceedings Citation index, African Index Medicus and the grey literature database 'OpenSIGLE' for studies published between January 1990 and February 2011. Included studies reported prevalence or incidence of diabetic retinopathy or diabetic maculopathy of subjects with diabetes resident in African countries.ResultsSixty-two studies from 21 countries were included: three population-based surveys; two cohort studies; five case-control studies; 32 diabetes clinic-based, nine eye clinic-based and 11 other hospital-based surveys. Included studies varied considerably in terms of patient selection, method of assessing the eye and retinopathy classification. In population-based studies, the reported prevalence range in patients with diabetes for diabetic retinopathy was 30.2 to 31.6%, proliferative diabetic retinopathy 0.9 to 1.3%, and any maculopathy 1.2 to 4.5%. In diabetes clinic-based surveys, the reported prevalence range for diabetic retinopathy was 7.0 to 62.4%, proliferative diabetic retinopathy 0 to 6.9%, and any maculopathy 1.2 to 31.1%. No obvious association between prevalence and income level of the country was detected.ConclusionsLarge, community-based cross-sectional and cohort studies are needed to investigate rates and determinants of prevalence of diabetic retinopathy, incidence and progression in Africa. Consensus is needed on the most appropriate methods of identification and classification of retinopathy for research and clinical practice. Estimates of prevalence of diabetic retinopathy, proliferative diabetic retinopathy and maculopathy are comparable with recent European and American studies.
| S-EPMC4463765 | biostudies-literature
Project description:BackgroundThe relationship between uric acid (UA) and diabetic retinopathy (DR) remains ambiguous, and the results of current studies on the UA levels in patients with DR are conflicting. A meta-analysis was performed to provide a better understanding of the relationship between UA levels and DR.MethodsPubMed, Web of Science, Embase, and the Cochrane Library databases were searched until December 11, 2021 to identify eligible studies, that compared the UA levels of the case group (patients with DR) and control group (controls with diabetes and healthy participants). The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to evaluate the difference in UA levels between the case and control groups.ResultsTwenty-one studies involving 4,340 patients with DR and 8,595 controls (8,029 controls with diabetes and 566 healthy participants) were included in this meta-analysis. We found that patients with DR had significantly higher UA levels than those in the controls with diabetes (WMD = 36.28; 95% CI: 15.68, 56.89; P < 0.001) and healthy participants (WMD = 70.80; 95% CI: 19.85, 121.75; P = 0.006). There was an obvious heterogeneity among the 21 studies (I 2 = 97%, P < 0.001). Subgroup analyses of different phases of DR showed that UA levels were significantly increased in participants with proliferative diabetic retinopathy (PDR) (WMD = 46.57; 95% CI: 28.51, 64.63; P < 0.001) than in controls with diabetes; however, the difference is not statistically significant when comparing UA levels in patients with non-proliferative diabetic retinopathy (NPDR) and controls with diabetes (WMD = 22.50; 95% CI: -6.07, 51.08; P = 0.120). In addition, UA levels were higher in participants with a body mass index (BMI) ≥25.0 kg/m2 and over 15 years of diabetes. Univariate meta-regression analysis revealed that BMI (P = 0.007, Adj R 2 = 40.12%) and fasting blood glucose (FBG) (P = 0.040, Adj R 2 = 29.72%) contributed to between-study heterogeneity.ConclusionsIn conclusion, our study provides evidence that UA levels are higher in patients with DR than those in the controls, but this difference is not statistically significant in the early phases. UA might be a potential biomarker for identifying disease severity in patients with DR, rather than predicting the onset of DR among patients with diabetes. However, more prospective and high-quality clinical evidence is required to confirm these present findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297708.
| S-EPMC9197488 | biostudies-literature
Project description:Background:Diabetic retinopathy (DR) is a significant global public health and economic burden. DR accounts for approximately 15-17% of all cases of total blindness in the USA and Europe. Telemedicine is a new intervention for DR screening, however, there is not enough evidence to support its cost-effectiveness. The aim of this study is to review the most recent published literature on economic evaluations of telemedicine in DR screening and summarize the evidence on the cost-effectiveness of this technology. Methods:A systematic search of PubMed, Embase and Google Scholar for relevant articles published between January 2010 and January 2020. Studies were included if they met the following criteria: (1) recruited subjects with either type 1, type 2 diabetes (2) evaluated telemedicine technology (3) patients underwent primary screening for DR (4) compared a telemedicine-based intervention with standard care (5) performed an economic evaluation or provided sufficient data for evaluating the cost-effectiveness of the technology used. Results:Of 2238 articles screened, seven studies were included. Four of the studies were conducted in developed countries: The United States, Singapore and two studies in Canada. Three studies were conducted in developing countries: India, Brazil and South Africa. The patient populations in all studies were diabetic patients over the age of 18, previously not screened for DR. All seven studies used a telemedicine program which included capturing a retinal image and subsequently transmitting it to an ocular imaging center to assess the severity of DR. All studies compared telemedicine to a standard screening method for DR, including the option of no screening as standard of care. Although telemedicine requires initial and maintenance costs, it has the potential to provide significant cost savings by increasing patients' working ability, increasing independent living ability, increasing quality of life and reducing travel costs. Conclusions:Diabetic retinopathy telemedicine technology has the potential to provide significant cost savings, especially in low-income populations and rural patients with high transportation costs.
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