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      The relationship between carotid disease and retinopathy in diabetes: a systematic review

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          Abstract

          Background

          Since studies of the relationship between carotid disease and diabetic retinopathy (DR) have shown apparent inconsistencies, the aim of this study was to conduct a systematic review of available published data.

          Methods

          Electronic databases were searched independently by two reviewers, according to an iterative protocol, for relevant articles. The search term used was “diabetes AND (carotid disease OR intima-media OR carotid plaque OR carotid stenosis OR carotid arterial disease OR carotid artery disease OR carotid atherosclerosis) AND (retinopathy OR diabetic retinopathy)”.

          Results

          From 477 publications, 14 studies were included. There were differences in the variables used as markers of carotid disease and DR across the included studies. Ten studies used carotid disease as the dependent variable, and the remainder used DR. All but one study involved cross-sectional data. Most studies reported a statistically significant association between at least one parameter of carotid disease as assessed by ultrasound and DR presence or severity. Only four studies reported no significant association. A common limitation was the use of convenience participant sampling.

          Conclusions

          There appears to be an increased likelihood of DR when there is ultrasonographic evidence of carotid disease, and vice versa. The available studies suggest that there may be a direct relationship between DR and carotid macrovascular disease and/or that these complications co-exist due to shared risk factors. If carotid disease is detected, retinal assessment should be performed. If DR is identified, intensive cardiovascular disease risk management should be considered. Additional longitudinal studies are needed to assess the directionality of the association.

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          Most cited references34

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          Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial.

          Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022). Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.
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            Carotid intima-media thickness and plaque in cardiovascular risk assessment.

            Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular (CV) risk in multiple large studies. Careful evaluation of CIMT studies reveals discrepancies in the comprehensiveness with which CIMT is assessed-the number of carotid segments evaluated (common carotid artery [CCA], internal carotid artery [ICA], or the carotid bulb), the type of measurements made (mean or maximum of single measurements, mean of the mean, or mean of the maximum for multiple measurements), the number of imaging angles used, whether plaques were included in the intima-media thickness (IMT) measurement, the report of adjusted or unadjusted models, risk association versus risk prediction, and the arbitrary cutoff points for CIMT and for plaque to predict risk. Measuring the far wall of the CCA was shown to be the least variable method for assessing IMT. However, meta-analyses suggest that CCA-IMT alone only minimally improves predictive power beyond traditional risk factors, whereas inclusion of the carotid bulb and ICA-IMT improves prediction of both cardiac risk and stroke risk. Carotid plaque appears to be a more powerful predictor of CV risk compared with CIMT alone. Quantitative measures of plaques such as plaque number, plaque thickness, plaque area, and 3-dimensional assessment of plaque volume appear to be progressively more sensitive in predicting CV risk than mere assessment of plaque presence. Limited data show that plaque characteristics including plaque vascularity may improve CV disease risk stratification further. IMT measurement at the CCA, carotid bulb, and ICA that allows inclusion of plaque in the IMT measurement or CCA-IMT measurement along with plaque assessment in all carotid segments is emerging as the focus of carotid artery ultrasound imaging for CV risk prediction.
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              The pathologic continuum of diabetic vascular disease.

              Hyperglycemia can promote vascular complications by multiple mechanisms, with formation of advanced glycation end products and increased oxidative stress proposed to contribute to both macrovascular and microvascular complications. Many of the earliest pathologic responses to hyperglycemia are manifest in the vascular cells that directly encounter elevated blood glucose levels. In the macrovasculature, these include endothelial cells and vascular smooth muscle cells. In the microvasculature, these include endothelial cells, pericytes (in retinopathy), and podocytes (in renal disease). Additionally, neovascularization arising from the vasa vasorum may promote atherosclerotic plaque progression and contribute to plaque rupture, thereby interconnecting macroangiopathy and microangiopathy.
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                Author and article information

                Contributors
                tim.davis@uwa.edu.au
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                6 May 2020
                6 May 2020
                2020
                : 19
                : 54
                Affiliations
                GRID grid.415051.4, ISNI 0000 0004 0402 6638, Medical School, , The University of Western Australia, Fremantle Hospital, ; P. O. Box 480, Fremantle, WA 6959 Australia
                Author information
                http://orcid.org/0000-0003-0749-7411
                Article
                1023
                10.1186/s12933-020-01023-6
                7201797
                32375803
                ad1a9c1b-eb65-4a20-a08b-880156a7aa9d
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 22 February 2020
                : 25 April 2020
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Endocrinology & Diabetes
                diabetes mellitus,diabetic retinopathy,carotid disease,carotid intima-media,carotid plaque,carotid atherosclerosis

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