title: Plasma Metabonomic Profiling of Diabetic Retinopathy.
abstract: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested population-based case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Liyan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
authors.forename: Hyungwon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Charumathi
authors.initials: C
authors.lastname: Sabanayagam
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Gavin S W
authors.initials: GS
authors.lastname: Tan
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Dechao
authors.initials: D
authors.lastname: Tian
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkatesan
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Chiu Ming Gemmy
authors.initials: CM
authors.lastname: Cheung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Signature Research Program in Neuroscience & Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Roger Wilmer
authors.initials: RW
authors.lastname: Beuerman
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Signature Research Program in Neuroscience & Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore zhou.lei@seri.com.sg phaccye@nus.edu.sg ophwty@nus.edu.sg.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore zhou.lei@seri.com.sg phaccye@nus.edu.sg ophwty@nus.edu.sg.
authors.forename: Eric Chun Yong
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore Saw Swee Hock School of Public Health, National University of Singapore, Singapore zhou.lei@seri.com.sg phaccye@nus.edu.sg ophwty@nus.edu.sg.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D012846:Singapore
chemical_list: D015415:Biomarkers