Plasma metabonomic profiling of diabetic retinopathy

Liyan Chen, Ching Yu Cheng, Hyungwon Choi, Mohammad Kamran Ikram, Charumathi Sabanayagam, Gavin S.W. Tan, Dechao Tian, Liang Zhang, Gopalakrishnan Venkatesan, E. Shyong Tai, Jie Jin Wang, Paul Mitchell, Chiu Ming Gemmy Cheung, Roger Wilmer Beuerman, Lei Zhou*, Eric Chun Yong Chan*, Tien Yin Wong*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

104 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1099-1108
Number of pages10
JournalDiabetes
Volume65
Issue number4
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

Bibliographical note

Funding:
This study was funded by the Singapore National Medical Research
Council’s Centre Grant CG 2013 to the Singapore Eye Research Institute and
by the Singapore Ministry of Education’s Academic Research Fund Tier 1 Grant
R-148-000-135-112 to E.C.Y.C. L.C. is supported by the Singapore National Eye
Centre’s Health Research Endowment Fund Learning Award.

Publisher Copyright:
© 2016 by the American Diabetes Association.

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