Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy

• Type of Material: Article
• Authors: Katherine Sumarriva, Vanderbilt University; Karan Uppal, Emory University; Chunyu Ma, Emory University; David J. Herren, Vanderbilt University; Yating Wang, Emory University; Isaac M. Chocron, Vanderbilt University; Cassandra Warden, Vanderbilt University; Sabrina L. Mitchell, Vanderbilt University; L. Goodwin Burgess, Vanderbilt University; Megan P. Goodale, Vanderbilt University; Melissa P. Osborn, Vanderbilt University; Allison J. Ferreira, Vanderbilt University; Janice C. Law, Vanderbilt University; Edward F. Cherney, Vanderbilt University; Dean P Jones, Emory University; Milam A. Brantley, Jr, Vanderbilt University
• Language: English
• Date: 2019-07-01
• Publisher: Association for Research in Vision and Ophthalmology (ARVO)
• Publication Version: Final Published Version
• Copyright Statement: Copyright 2019 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.19-27321
• Title of Journal or Parent Work: Investigative Ophthalmology & Visual Science
• ISSN: 0146-0404
• Volume: 60
• Issue: 8
• Start Page: 3119
• End Page: 3126
• Grant/Funding Information: Supported by National Institutes of Health (Bethesda, MD, USA) Grants R01 EY022618, P30 EY008126, P30 ES019776, U2C ES030163, and S10 OD018006; a grant from the International Retinal Research Foundation (Birmingham, AL, USA); and an unrestricted departmental grant to Vanderbilt University Medical Center from Research to Prevent Blindness (New York, NY, USA).
• Keywords: Science & Technology; RISK; Life Sciences & Biomedicine; metabolomics; diabetic retinopathy; MASS-SPECTROMETRY; arginine; citrulline; ASYMMETRIC DIMETHYLARGININE ADMA; Ophthalmology; PREVALENCE; carnitine; COMPLICATIONS; MELLITUS; HIGH-RESOLUTION METABOLOMICS
• Research Categories: Health Sciences, Opthamology; Health Sciences, Medicine and Surgery

Abstract

Purpose: To determine plasma metabolite and metabolic pathway differences between patients with type 2 diabetes with diabetic retinopathy (DR) and without retinopathy (diabetic controls), and between patients with proliferative DR (PDR) and nonproliferative DR (NPDR). Methods: Using high-resolution mass spectrometry with liquid chromatography, untargeted metabolomics was performed on plasma samples from 83 DR patients and 90 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis, and linear regression was used to adjust for age, sex, diabetes duration, and hemoglobin A1c. Pathway analysis was performed using Mummichog 2.0. Results: In the adjusted analysis, 126 metabolic features differed significantly between DR patients and diabetic controls. Pathway analysis revealed alterations in the metabolism of amino acids, leukotrienes, niacin, pyrimidine, and purine. Arginine, citrulline, glutamic γ-semialdehyde, and dehydroxycarnitine were key contributors to these pathway differences. A total of 151 features distinguished PDR patients from NPDR patients, and pathway analysis revealed alterations in the β-oxidation of saturated fatty acids, fatty acid metabolism, and vitamin D3 metabolism. Carnitine was a major contributor to the pathway differences. Conclusions: This study demonstrates that arginine and citrulline-related pathways are dysregulated in DR, and fatty acid metabolism is altered in PDR patients compared with NPDR patients.