Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy

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 csemialdehyde, 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 b-oxidation of saturated fatty acids, fatty acid metabolism, and vitamin D 3 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.

Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?

“…Further support for an association between diabetes-induced alterations in arginase-mediated L-arginine metabolism and DR is provided by metabolomics studies of plasma samples. Comparisons of plasma metabolic profiles from type 2 diabetic patients showed dysregulation of the L-arginine pathway in patients with PDR as compared with those with NPDR [32]. A similar metabolomics profiling study performed with plasma samples from type 2 diabetic patients in China found similar impairment in the metabolism of L-arginine and L-proline in patients with PDR as compared with diabetic patients without retinopathy [33].…”

Metabolomics profiles associated with diabetic retinopathy in type 2 diabetes patients

“…In another recent study, two metabolites, arginine and carnitine, were found to be altered in DR patients, compared to diabetic controls. Arginine levels were significantly higher in the DR patients than in the diabetic controls, and carnitine concentration was elevated in the PDR patients compared to the NPDR patients [ 1 ]. However, in our study, arginine concentration was not significantly changed in the DR patients, compared to the NDR patients, and the concentration of only one carnitine, C7:DC, was significantly increased in the PDR patients, compared to the NPDR patients [ 1 ].…”

“…Arginine levels were significantly higher in the DR patients than in the diabetic controls, and carnitine concentration was elevated in the PDR patients compared to the NPDR patients [ 1 ]. However, in our study, arginine concentration was not significantly changed in the DR patients, compared to the NDR patients, and the concentration of only one carnitine, C7:DC, was significantly increased in the PDR patients, compared to the NPDR patients [ 1 ]. Furthermore, the concentrations of other carnitines, C14:1 and C16, were decreased in the DR (NPDR and PDR) patients, compared to the NDR patients (Tables 2 and S1 – S3 ).…”

Efficacy of intravitreal injection of conbercept on non-proliferative diabetic retinopathy: a retrospective study

“…7 Because diabetic retinopathy can cause a degree of blindness, it is regarded as a serious danger to human health. 8 Diabetic retinopathy can be divided into two clinical stages: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy. 9 NPDR is considered the early stage of diabetic retinopathy; the incidence of NPDR development into proliferative diabetic retinopathy is approximately 14% 10 and is increasing each year.…”