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Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Two Asian Cohorts

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Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Two Asian Cohorts Serum and urinary metabolites associated with diabetic retinopathy in two Asian cohorts AuthorBlock: Charumathi Sabanayagam3,1, Rehena Sultana1, Riswana Banu3, Zhou Lei3, Gavin SW Tan3, E Shyong Tai2, Ching-Yu Cheng1,3, Tien Yin Wong3,1 1Duke-NUS Medical School, Singapore, Singapore; 2National University of Singapore, , Singapore; 3Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; DisclosureBlock: Charumathi Sabanayagam, None; Rehena Sultana, None; Riswana Banu, None; Zhou Lei, None; Gavin SW Tan, None; E Shyong Tai, None; Ching-Yu Cheng, None; Tien Yin Wong, None; Purpose Serum metabolites have been shown to be associated with diabetes and its complications including diabetic retinopathy (DR). Metabolites in urine have recently been shown to provide information independent of serum metabolites. We examined the cross-sectional association of DR with a combination of serum and urinary metabolites in two Asian cohorts.Methods Serum (n=225) and urinary metabolites (n=33) were quantified using nuclear magnetic resonance (NMR) spectroscopy in 1869 adults with diabetes who participated in the baseline visits (2007-2011, aged ≥40 years) of two independent population-based cohort studies (Chinese, n=581; Indians, n=1288) with similar methodology in Singapore. Diabetes-specific moderate DR was assessed from retinal photographs and defined as a level>43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Multivariate logistic regression models were constructed for each metabolite (per SD increase) adjusted for age, sex, systolic blood pressure, duration of diabetes and HbA1c. Metabolites with the same direction of association in both cohorts were selected and those achieving significance corrected for multiple testing from both cohorts were meta-analysed.Results Prevalence of moderate DR was 11.2% in Chinese and 10.6% in Indians. Logistic regression identified 21 serum and 10 urinary metabolites associated with DR in one or both studies after Bonferroni correction, of which 6 serum (p<0.002) and 6 urine metabolites (p=0.005) were statistically significant in the meta-analysis. Among serum metabolites, higher levels of creatinine, total cholesterol and cholesterol esters in chylomicrons in extremely large VLDL (lipoprotein subclasses) were positively associated (odds ratios [ORs], 1.25, 1.11, 1.11) while higher levels of tyrosine, fatty acid saturation % and cholesterol esters in LDL, were inversely associated with DR (ORs 0.57, 0.60, 0.63) (Figure 1). Among urinary metabolites, higher levels of alanine, valine (aminoacids), formate (microbial), citrate (glycolysis), 3-hydroxyisovalerate, 3-hydroxy isobutyrate were inversely associated with DR with ORs ranging from 0.52 to 0.68 (Figure 2).Conclusions Our results demonstrated that adults with DR had altered serum and urinary profiles mostly confined to aminoacids, lipoprotein, glycolysis, fluid and fatty acid metabolism.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Risk Factors for Severe Diabetic Eye Disease in a Large Sample of Patients Newly-Diagnosed with Type 2 Diabetes AuthorBlock: William S. Gange1, Khristina Lung2, Benjamin Xu1, Seth Seabury2, Brian C. Toy1 1Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States; 2Keck-Shaeffer Initiative for Population Health Policy, Keck School of Medicine, Los Angeles, California, United States; DisclosureBlock: William S. Gange, None; Khristina Lung, None; Benjamin Xu, None; Seth Seabury, Precision Health Economics, LLC Code C (Consultant), Brian C. Toy, None; Purpose Diabetic eye disease is the leading cause of blindness in working-age adults in the United States. As rates of diabetes continue to rise in the United States, adequately screening all patients for diabetic retinopathy at guideline-recommended intervals remains a public health challenge. We performed a retrospective study of medical claims data for patients newly-diagnosed with type 2 diabetes (DM2), in order to better identify high risk populations who may benefit most from improved rates of screening.Methods Patients age 18 or older with newly-diagnosed DM2 from 2007-2015 were recruited from a commercial claims database. All patients were required to have continuous enrollment for 6 years: 1 year prior to and 5 years after the index diabetes diagnosis. 72,067 patients with newly-diagnosed DM2 were identified. Demographic data were collected. Patients were identified as having severe diabetic eye disease if they had an ICD-9 diagnosis code for proliferative diabetic retinopathy, vitreous hemorrhage, neovascular glaucoma, rubeosis iridis, tractional retinal detachment, or blindness, or a CPT code for pars plana vitrectomy, glaucoma drainage device, or panretinal photocoagulation within 5 years of diagnosis. Multivariable logistic regression was used to test associations between demographic factors and identification of severe disease.Results At 5 years following diagnosis with diabetes, 3.97% of patients had severe diabetic eye disease. Black patients were more likely than white patients to have severe disease (OR 1.26, p<.001). Age at diagnosis was positively correlated with severe diabetic eye disease, with patients diagnosed at ages 18-34 having the lowest risk (OR 0.75, p<.01) and those diagnosed after age 75 having the highest risk of severe disease (OR 1.63, p<.001). Smokers were more likely to have severe disease than non- smokers (OR 1.15, p<.02). Income and education level were not associated with early development of severe diabetic eye disease in this insured population.Conclusions A subset of patients with DM2 develop severe diabetic eye disease within the first 5 years after diagnosis. Black patients, older patients, and smokers were more likely to have severe diabetic eye disease, which suggests either a longer duration of undiagnosed disease, or poorer control of disease. These patients may require increased screening efforts.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Individualised Screening for Diabetic Retinopathy: the ISDR study. A Randomised Controlled Trial of Safety, Efficacy and Cost Effectiveness AuthorBlock: Simon P. Harding1,2, Christopher Cheyne3, James Lathe7, Amu Wang1, Pilar Vasquez Arango1, Irene Mary Stratton6, Jiten Vora5, Mark Gabbay4, Marta Garcia Finana3, Marilyn James7, Deborah Broadbent2,1 1Eye and Vision Science, University of Liverpool, Liverpool, ENGLAND, United Kingdom; 2St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; 3Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom; 4Health Services Research, University of Liverpool, , United Kingdom; 5Diabetes and Endocrinology, Royal Liverpool University Hospital, , United Kingdom; 6Gloucestershire Retinal Research Group, Cheltenham General Hospital, , United Kingdom; 7Division of Rehabilitation, Ageing and Wellbeing, School of Medicine, University of Nottingham, , United Kingdom; DisclosureBlock: Simon P. Harding, None; Christopher Cheyne, None; James Lathe, None; Amu Wang, None; Pilar Vasquez Arango, None; Irene Mary Stratton, None; Jiten Vora, None; Mark Gabbay, None; Marta Garcia Finana, None; Marilyn James, None; Deborah Broadbent, None; Purpose Systematic screening to detect sight threatening diabetic retinopathy is widely established but with major variations in models of delivery. Varying screen intervals informed by personal risk offers better targeting including for high risk groups, addresses the increasing prevalence of diabetes and allows reallocation of resources. However safety data especially on extended intervals is minimal. We aimed to evaluate the safety, efficacy and cost effectiveness of individualised variable-interval risk-based screening in a population setting compared to usual annual screening.Methods Masked, 2 arm, parallel assignment, equivalence RCT (largest to date in screening) with independent trials unit monitoring in people with diabetes aged ≥12 years attending screening in a single English programme. Randomisation was 1:1 to individualised screening (active group; 6, 12 or 24 months for high, medium and low risk) determined by a risk calculation engine using real-time local demographic, retinal and clinical data, compared with annual screening (control). Cost effectiveness analysis measuring payer (NHS) and societal costs took a 2 year time horizon.Results 4534 participants entered the study - after withdrawals/loss to follow-up: active 2097; control 2224. Attendance rates at first follow up visit (primary outcome, safety) were equivalent (per protocol analysis, 5% margin): active 83.6%, control 84.7% (difference 1.0, 95% CI -3.2, 1.2). STDR detection rates (secondary safety) were non-inferior (1.5% margin): active 1.4% control 1.7% (difference -0.3, CI -1.1, 0.5). 43.2% fewer screening appointments (secondary, efficacy) were required in the individualised arm. Worsening of glyceamic control was not detected. Quality of life (EQ5D5L, HUI3) was not significantly different between the groups. Incremental cost savings per person were: NHS perspective £19.73 (18.28 to 21.16); societal perspective £26.19 (24.41 to 27.87).Conclusions All parties involved in diabetes care can be reassured that extended
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