The content of carbonyl compounds (methylglyoxal and TBA-reactive substances) and components of the glutathione system (activities of glutathione-dependent enzymes, content of oxidized and reduced glutathione) and their interrelationships were studied in men of young reproductive age with type 1 diabetes mellitus at the stages of normo-and microalbuminuria. In patients with normoalbuminuria, the level of methylglyoxal, reduced and oxidized glutathione, and glutathione reductase activity were increased and the content of TBA-reactive substances was decreased. In the group with microalbuminuria, an increase in content of methylglyoxal and activity of glutathione-dependent enzymes relative to the control values were observed; the content of TBA-reactive substances was increased and glutathione reductase activity was decreased relative to the group with normoalbuminuria. In patients with microalbuminuria, a strong correlation between the mean glomerular filtration rate and the blood level of methylglyoxal was revealed.
Diabetes mellitus (DM) is a public health problem worldwide. Despite the presence of various sugar-lowering drugs, correcting hyperglycemia and preventing late DM complications remain a difficult task. Unfortunately, DM complications are often detected at late stages, when there are irreversible changes and a global decrease in the function of damaged organs and systems. One of the most dangerous complications leading to early death of patients is diabetic nephropathy. However, the problem of finding early markers of renal damage that can detect the earliest renal damage in global clinical practice remains unresolved. The following are the modern markers that are likely to be able to timely reflect the preclinical manifestations of diabetic nephropathy (DN): Type-IV collagen, NGAL, b2MG, cystatin C, E-cadherin, podocalyxin, and nephrin. Heparan sulfate, mindin, TGF-β, ICAM-1, KIM-1, uromodulin, and LFABP are also being studied. The task of modern medicine is to find the most sensitive of these markers to diagnose DN in a timely manner.
Научный центр проблем здоровья семьи и репродукции человека, Иркутск ОБОСНОВАНИЕ. Диабетическая нефропатия (ДН) -специфическое поражение почек, которым страдают до 40% пациентов с сахарным диабетом 1 типа (СД1). До сих пор имеется недостаточно знаний об активности реакций окислительного стресса у больных СД1 с разным уровнем альбуминурии.ЦЕЛЬ. Оценить у мужчин с СД1 и разными уровнями альбуминурии уровни показателей окислительного повреждения липидов, ДНК и антиоксидантной защиты. МАТЕРИАЛЫ И МЕТОДЫ. Исследование проводилось в течение 2018-2019 гг. В основную группу были включены 56 мужчин репродуктивного возраста с СД1, разделенных на 2 группы: 24 пациента с альбуминурией уровня А1 (группа А1) и 32 пациента с альбуминурией уровня А2 (группа А2). Контрольную группу составили 28 здоровых мужчин. Произведена оценка содержания показателей окислительного стресса, а также активности различных звеньев системы антиоксидантной защиты. Использованы спектрофотометрические, флуориметрические и иммуноферментные методы исследования.РЕЗУЛЬТАТЫ. У пациентов группы А1 в сравнении с контролем отмечались более высокие значения медианы первичных -диеновых конъюгатов, вторичных -кетодиенов и сопряженных триенов, конечных -шиффовых оснований продуктов липопероксидации и 8-гидрокси-2'-деоксигуанозина в сравнении с контролем. Подобные изменения были выявлены также у пациентов группы А2. Межгрупповые различия касались повышенных значений медианы вторичных продуктов перекисного окисления, реагирующих с тиобарбитуровой кислотой, и 8-гидрокси-2'-деоксигуанозина у пациентов группы А2 в сравнении с группой А1. Активность системы антиоксидантной защиты в группе А1 относительно контроля характеризовалась повышенными значениями медиан глутатионпероксидазы, восстановленного и окисленного глутатионов и ретинола. У пациентов группы А2 в сравнении с контролем отмечались более высокие значения медиан глутатионпероксидазы, восстановленного и окисленного глутатионов. Корреляционный анализ в группе А1 показал наличие тесных взаимосвязей длительности заболевания с продуктами липопероксидации, уровня гликированного гемоглобина с 8-гидрокси-2'-деоксигуанозином. В группе А2 отмечались зависимости показателей соотношения альбумин/креатинин с длительностью заболевания и скорости клубочковой фильтрации с уровнем креатинина.ЗАКЛЮЧЕНИЕ. У мужчин с СД1 вне зависимости от уровня альбуминурии отмечаются более высокие значения параметров окислительного повреждения липидов и ДНК, а также наличие тесных взаимосвязей этих показателей с длительностью заболевания, что может быть использовано для разработки потенциальных стратегий профилактики и ранней терапии ДН.
Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30–300 mg/day and albumin/creatinine ratio 3–30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.
The authors ground the necessity of managing risks of venture entrepreneurship; construct algorithm of formation and introduction of a system of risk-management while operating venture entrepreneurship; analyze the rationality of its realization at the regional scale and influence on venture entrepreneurship; and conduct regressive analysis of dependence of financial economic state of enterprise LLC 'Innovazstroy' on introduction of the developed system of risk-management. The study is a regression analysis, with which the authors calculated the coefficient covariance determination of approximation and draw conclusions about the dependence between introduction of risk-management system and growth of clear profit of LLC 'Innovazstroy'. Developed as a result of the study the model of quantitative and qualitative measuring risk small enterprises all over the world use: risk evaluation (VAR), maximal potential risk (MPE), risk-appétit and risk stock, in order to measure and to unite market, credit, operational and other risks. It is necessary for entrepreneur to know actual cost of risk, which influences on their activity.
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