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Peters KS, Rivera E, Warden C, et al. Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy. Am J Ophthalmol. 2021;235:154-162doi: 10.1016/j.ajo.2021.09.021.
Peters, K. S., Rivera, E., Warden, C., Harlow, P. A., Mitchell, S. L., Calcutt, M. W., Samuels, D. C., & Brantley, M. A. (2021). Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy. American journal of ophthalmology, 235154-162. https://doi.org/10.1016/j.ajo.2021.09.021
Peters, Katherine S, et al. "Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy." American journal of ophthalmology vol. 235 (2021): 154-162. doi: https://doi.org/10.1016/j.ajo.2021.09.021
Peters KS, Rivera E, Warden C, Harlow PA, Mitchell SL, Calcutt MW, Samuels DC, Brantley MA. Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy. Am J Ophthalmol. 2021 Sep 26;235:154-162. doi: 10.1016/j.ajo.2021.09.021. Epub 2021 Sep 26. PMID: 34587493.
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Am J Ophthalmol. 2021 Sep 26;235:154-162. doi: 10.1016/j.ajo.2021.09.021. Epub 2021 Sep 26.

Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy.

American journal of ophthalmology

Katherine S Peters, Emilio Rivera, Cassandra Warden, Paula A Harlow, Sabrina L Mitchell, M Wade Calcutt, David C Samuels, Milam A Brantley

Affiliations

  1. From Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA (K.S.P, C.W, P.A.H, S.L.M, M.A.B Jr).
  2. Department of Biochemistry, Vanderbilt University, Nashville, TN, USA (E.R, M.W.C); Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA (E.R, M.W.C).
  3. Vanderbilt Genetics Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
  4. From Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA (K.S.P, C.W, P.A.H, S.L.M, M.A.B Jr). Electronic address: [email protected].

PMID: 34587493 DOI: 10.1016/j.ajo.2021.09.021

Abstract

PURPOSE: To determine if plasma levels of six arginine-related and citrulline-related metabolites (arginine, citrulline, asymmetric dimethylarginine [ADMA], ornithine, proline, and argininosuccinate) differ between patients with type 2 diabetes and diabetic retinopathy (DR) and type 2 diabetic controls or between patients with proliferative DR (PDR) and non-proliferative DR (NPDR).

DESIGN: Cross-sectional study.

METHODS: Adults with type 2 diabetes were recruited from the Vanderbilt Eye Institute. Exclusion criteria included non-diabetic retinal disease. Plasma metabolite levels were quantified in 159 diabetic controls and 156 DR patients (92 NPDR, 64 PDR) using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metabolite levels were compared using Wilcoxon Rank Sum test and logistic regressions adjusting for age, sex, hemoglobin A1c, diabetes duration, statin use, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. A secondary analysis that included creatinine in the regression model was performed for the subset of patients with available creatinine values (135 diabetic controls, 100 DR patients [58 NPDR, 42 PDR]).

RESULTS: Multivariable logistic regression analyses determined that arginine (OR = 1.20, [1.06-1.38], P = .0067) and citrulline (OR = 1.53, [1.20-1.98], P = .0025) were significantly elevated in DR patients compared to diabetic controls. While ADMA differed between NPDR and PDR patients in the primary analysis (OR = 1.56, [1.15-2.16], P = .0051), it was not significantly different when adjusting for creatinine (OR = 1.30, [0.90-1.91], P = .15).

CONCLUSIONS: Plasma arginine and citrulline were significantly elevated in type 2 diabetic patients with DR compared to diabetic controls. None of the tested metabolites significantly differed between NPDR and PDR patients in the adjusted analysis.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: ADMA; Arginine; asymmetric dimethylarginine; citrulline; diabetic retinopathy; liquid chromatography mass spectrometry; metabolomics

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