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.

中文翻译：

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血浆精氨酸和瓜氨酸在糖尿病视网膜病变中升高

目的

确定 2 型糖尿病和糖尿病视网膜病变 (DR) 患者和 2 型糖尿病患者血浆中六种精氨酸相关和瓜氨酸相关代谢物（精氨酸、瓜氨酸、不对称二甲基精氨酸 [ADMA]、鸟氨酸、脯氨酸和精氨琥珀酸）水平是否存在差异对照组或增殖性 DR (PDR) 和非增殖性 DR (NPDR) 患者之间。

设计

横断面研究。

方法

从范德比尔特眼科研究所招募了患有 2 型糖尿病的成年人。排除标准包括非糖尿病性视网膜疾病。使用同位素稀释液相色谱-串联质谱 (LC-MS/MS) 对 159 名糖尿病对照和 156 名 DR 患者（92 名 NPDR，64 名 PDR）的血浆代谢物水平进行了量化。代谢物水平使用 Wilcoxon 秩和检验和调整年龄、性别、血红蛋白 A1c、糖尿病病程、他汀类药物使用和血管紧张素转换酶抑制剂或血管紧张素 II 受体阻滞剂使用的逻辑回归进行比较。对具有可用肌酐值的患者子集（135 名糖尿病对照，100 名 DR 患者 [58 名 NPDR，42 名 PDR]）进行了在回归模型中包括肌酐的二次分析。

结果

多变量逻辑回归分析确定， 与糖尿病患者相比，DR 患者的精氨酸 (OR = 1.20, [1.06-1.38], P  = .0067) 和瓜氨酸 (OR = 1.53, [1.20-1.98], P = .0025) 显着升高控制。虽然在初步分析中 NPDR 和 PDR 患者的 ADMA 存在差异（OR = 1.56，[1.15-2.16]，P  = .0051），但在调整肌酐时没有显着差异（OR = 1.30，[0.90-1.91]，P  = .15)。

结论

与糖尿病对照组相比，患有 DR 的 2 型糖尿病患者的血浆精氨酸和瓜氨酸显着升高。在调整后的分析中，NPDR 和 PDR 患者之间的测试代谢物均无显着差异。