Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Department of Medicine, Emory University, Atlanta, Georgia, United States.
Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):3119-3126. doi: 10.1167/iovs.19-27321.
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).
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.
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.
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.
确定 2 型糖尿病伴糖尿病视网膜病变（DR）和无视网膜病变（糖尿病对照）患者以及增殖性 DR（PDR）和非增殖性 DR（NPDR）患者之间的血浆代谢物和代谢途径差异。
使用液相色谱高分辨质谱法对 83 例 DR 患者和 90 例糖尿病对照的血浆样本进行非靶向代谢组学分析。通过偏最小二乘判别分析识别有区别的代谢特征，并通过线性回归调整年龄、性别、糖尿病病程和糖化血红蛋白。使用 Mummichog 2.0 进行途径分析。
在调整分析中，DR 患者与糖尿病对照之间有 126 个代谢特征存在显著差异。途径分析显示氨基酸、白三烯、烟碱、嘧啶和嘌呤代谢发生改变。精氨酸、瓜氨酸、谷氨酸γ-亚氨基戊醛和脱氢肉碱是这些途径差异的关键贡献者。共有 151 个特征可区分 PDR 患者和 NPDR 患者，途径分析显示饱和脂肪酸β-氧化、脂肪酸代谢和维生素 D3 代谢发生改变。肉碱是导致这些途径差异的主要因素。
本研究表明，精氨酸和瓜氨酸相关途径在 DR 中失调，与 NPDR 患者相比，PDR 患者的脂肪酸代谢发生改变。
