Correlation between molecules, which reflect malfunctioning of cellular respiration, degree of oxidative stress, and glycated hemoglobin in retinopaties with type 2 diabetes

Introduction. The pathogenetic role of biochemical changes in the development of diabetic retinopathy (DR) is undoubted and determines the importance of studies that reveal metabolic disorders of both individual molecules and show the relationships between them. Because of some commonalities between tissue respiration, monosaccharide and tryptophan exchange, and activation of lipid peroxidation (LP), there is an interest in studying the relationship between metabolites of these pathways in retinopathy.

Aim. The aim is to study the content of metabolites of the kynurenic pathway and intermediate product of lipid peroxidation in blood, and to reveal the correlation between them and glycated hemoglobin’s (HbA1c) level in retinopathy with type 2 diabetes.

Materials and methods. The 1st group (control group) included 21 healthy people; the 2nd group included 21 people with «prediabetes», the 3rd group - 21 patients with type 2 diabetes, the 4th group - 63 people with type 2 diabetes and diabetic retinopathy (DR) of varying severity levels. The content of kynurenines in the blood plasma (kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA)) of all participants, as well as the concentration of malondialdehyde (MDA) was determined by high-performance liquid chromatography using a Shimadzu LC-20 chromatograph (Japan). The level of glycated hemoglobin (HbA1c) was determined using Beckman Coulter AU 480 (USA) biochemical analyzer. The results were calculated using Jamovi program version 2.3.

Results. In the group of people with «prediabetes», the values of all studied parameters in the blood plasma were increased in comparison with the control group. In the group of patients with type 2 diabetes, the levels of KYN, 3- НKYN and MDA significantly exceeded those in the group of people with «prediabetes». In the group of people with DR, all indicators remained high, the values of 3-НKYN and KYNA showed a statistical difference compared to the group of patients with diabetes. When conducting a correlation analysis, corellations were identified between the level of HbA1c on the one hand and the values of KYN (r=0.77; p ˂ 0.001), concentrations of 3-НKYN (r=0.80; p ˂ 0.001), KYNA (r= 0.72; p ˂ 0.001) and MDA (r=0.84; p ˂ 0.001) – on the other. There was a correlation between HbA1c level and fundus scale (r=0.82; p ˂ 0.001) and between concentrations (of 3-HKYN) and MDA (r=0.50; p=0.002).

Conclusion. An increased level of glycosylated hemoglobin and lipid peroxidation products in the blood during retinopathy against the background of type 2 diabetes, an increase in the concentrations of KYN, 3-HKYN, KYNA, and the presence of correlations between these indicators serve as the basis for proving the relationship of uncontrolled hyperglycemia with changes in cellular respiration and the development of oxidative stress. Hypoxic effects and the accumulation of intermediate metabolic products of the kynurenine pathway contribute to progressive neurovascular damage to the retina, activation of lipid peroxidation processes and inflammation.

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