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      Plasma Metabonomic Profiling of Diabetic Retinopathy.

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          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.

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          Author and article information

          Journal
          Diabetes
          Diabetes
          American Diabetes Association
          1939-327X
          0012-1797
          April 2016
          : 65
          : 4
          Affiliations
          [1 ] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
          [2 ] 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.
          [3 ] 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.
          [4 ] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore.
          [5 ] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
          [6 ] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.
          [7 ] Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
          [8 ] 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.
          [9 ] Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.
          [10 ] 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.
          [11 ] 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.
          [12 ] Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore zhou.lei@seri.com.sg phaccye@nus.edu.sg ophwty@nus.edu.sg.
          [13 ] 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.
          Article
          db15-0661
          10.2337/db15-0661
          26822086
          2219741e-fa01-49a0-aa41-afd5d434fcfd
          History

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