Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes

Abstract

The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used. The level of 25 compounds was significantly (p < 0.001) altered in the aqueous humor of the patient group. The concentration of a single compound, N-acetylornithine, makes it possible to discriminate between control and diabetes (sensitivity and specificity equal to 1). In addition, receptor operating characteristic curve and principal component analysis for the above-mentioned six compounds yielded significantly (p < 0.001) altered in the aqueous humor of the patient group. In addition, receptor operating characteristic curve and principal component analysis for six compounds yielded cut-off values and remarkable sensitivity, specificity, and segregation ability. The altered level of N-acetylornithine may be due to an increased amount of acetate in diabetes. It is of interest to further investigate whether this alteration is related to the pathogenesis of the disease. The increase in the amino form of pyruvate, alanine, in diabetes is also relevant because it could be a means of reducing the formation of lactate from pyruvate.

Advancing Personalized Medicine by Analytical Means: Selection of Three Metabolites That Allows Discrimination between Glaucoma, Diabetes, and Controls

“…The altered concentration of some metabolites found in the AH of patients in comparison to healthy individuals is providing valuable insights into the pathophysiological mechanisms of multiple diseases, including, but not limited to, open-angle glaucoma and type 2 diabetes [ 5 , 14 ], but a diagnostic tool is missing. Our laboratory has recently provided metabolomics-based evidence of altered arginine metabolism as a principal factor in Parkinson’s disease [ 20 ].…”

“…In our previous publications concerning the composition of AH, we were interested in looking for differentially concentrated metabolites and why they could give insight into disease mechanism. We discovered that glutamine, kynurenine, acyl-carnitine and lysophosphatidylcholine levels are altered in the AH of glaucoma patients [ 14 ], that biogenic amines are differentially concentrated in the AH of type 2 diabetes patients [ 5 ] and that the metabolism of arginine is altered as deduced from the composition of the AH of Parkinson’s disease patients [ 20 ]. In the present study, we use the data from previous studies to develop a novel methodology for disease diagnosis and management considering the perspective of personalized medicine.…”

“…Data (concentration of every metabolite in each sample) used in the present study are available in previously published papers [ 5 , 14 ]. We used R 4.3.0 software to conduct linear discriminant analysis (LDA) with leave-one-out cross-validation to control for overfitting.…”

“…In fact, we have recently identified new biomarkers after comparing the concentration of small metabolites in the aqueous humour (AH) of healthy controls, patients with open-angle glaucoma, and patients with type 2 diabetes. Instead of glucose, one molecule, acetyl-ornithine, makes it possible to detect if a given AH is from a patient with type 2 diabetes or a healthy control [ 5 ].…”

Simultaneous Comparison of Aqueous Humor and Serum Metabolic Profiles of Diabetic and Nondiabetic Patients Undergoing Cataract Surgery—A Targeted and Quantitative Metabolomics Study

“…According to a recent review [ 8 ], only two untargeted metabolomics studies investigated differences in AH composition in patients with and without diabetes [ 9 , 10 ], while three additional studies were focused on patients with proliferative stage diabetic retinopathy [ 11 , 12 , 13 ]. More recently, the first metabolomics analysis of AH in diabetic macular edema [ 14 ] and the first targeted metabolomic study of AH in DM were published [ 15 ].…”