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Diabetes mellitus is a group of metabolic diseases affecting carbohydrate, lipid, and protein metabolism. This pathology has a long history, and it was considered a disease of the kidneys until the middle of the 19th century. Descriptions have been found in Egyptian papyri, in ancient Indian and Chinese medical literature, in the writings of ancient Greek and Arab doctors. Aretaeus of Cappadocia gave the first accurate description of the disease, coining the term "diabetes". Thomas Willis first differentiated diabetes from other causes of polyuria by the sweet taste of urine. Matthew Dobson proved the presence of glucose in urine by evaporation. Claude Bernard demonstrated that hyperglycemia contributes to glucosuria. This is how the concept of the renal threshold appeared. In domestic practice, the term "renal threshold" was introduced by endocrinologist V.G. Baranov. The development of qualitative tests for determining glucose in the urine, the creation of test strips and glucometers has significantly improved the quality of life of patients with diabetes. The current stage of development of glucometry includes the determination of fasting plasma glucose, postprandial glycemia, glycated hemoglobin, as well as continuous glucose monitoring. Continuous glucose monitoring systems make it possible to estimate the time in target range, show the rate of rise or fall of glucose levels. It affects the rate and degree of carbohydrate metabolism compensation and allows for maximum control of the disease.

The main cause of death in patients with type 2 DM is cardiovascular complications resulting from the progression of atherosclerosis. The pathophysiology of the association between diabetes and its vascular complications is complex and multifactorial and closely related to the toxic effects of hyperglycemia that causes increased generation of reactive oxygen species and promotes the secretion of pro-inflammatory cytokines. Subsequent oxidative stress and inflammation are major factors of the progression of type 2 DM and its vascular complications. Data on the pathogenesis of the development of type 2 DM and associated cardiovascular diseases, in particular atherosclerosis, open up broad prospects for the further development of new diagnostic and therapeutic approaches.

Abdominal aortic aneurysm (AAA) is a complex degenerative vascular disease, with considerable morbidity and mortality rates among the elderly population. The mortality of AAA is related to aneurysm expansion (the enlargement of the aortic diameter up to 30 mm and above) and the subsequent rupture. The pathogenesis of AAA involves several biological processes, including aortic mural inflammation, oxidative stress, vascular smooth muscle cell apoptosis, elastin depletion, and degradation of the extracellular matrix. Mitochondrial dysfunction was also found to be associated with AAA formation. The evidence accumulated to date supports a close relationship between environmental and genetic factors in AAA initiation and progression. However, a comprehensive pathophysiological understanding of AAA formation remains incomplete. The open surgical repair of AAA is the only therapeutic option currently available, while a specific pharmacotherapy is still awaited. Therefore, there is a great need to clarify pathophysiological cellular and molecular mechanisms underlying AAA formation that would help to develop effective pharmacological therapies. In this review, pathophysiological aspects of AAA development with a special focus on mitochondrial dysfunction and genetic associations were discussed., (© 2021 Volha I. Summerhill et al., published by De Gruyter.)

COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.

Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. Methods: A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients' blood and stimulated by interferon-γ (IFN-γ) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-α ( r = 0.726, p = 0.027) and CCL18 ( r = -0.949, p = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS ( p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months ( p = 0.033). Conclusions: Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.

Aim: Determination of desialized apolipoprotein-B-100 (apoB-100) and lipoprotein-containing circulating immune complexes in patients with chronic kidney disease (CKD) in program hemodialysis with type 2 diabetes mellitus., Materials and Methods: We examined 81 patients with CKD (50 men / 31 women) treated with program hemodialysis, of which 36 (17/19) with type 2 diabetes mellitus, 45 (33/12) non-diabetic patients. The levels of total cholesterol, triglycerides and desialylated apoB-100 in blood plasma and lipoprotein-containing circulating immune complexes. A color duplex scan of brachiocephalic arteries was used to assess the extent of development of atherosclerosis with the determination of the thickness of the intima-medial complex., Results: Patients with diabetes had high values of total cholesterol, triglycerides (p&lt;0.05). Duplex scan of brachiocephalic arteries showed an increase in the thickness of intima-medial complex in all patients for program hemodialysis, however, in patients with diabetes, the thickness was 13% higher (p&lt;0.05). In patients with diabetes, plaques with stenosis up to 50% prevail, compared with non-diabetic patients, p&lt;0.05. The incidence was significantly higher for desialized apoB-100 by 46% in patients with diabetes on hemodialysis compared non-diabetic patients (p&lt;0.05). An increase in the level of lipoprotein-containing circulating immune complexes by 39%, (p&lt;0.05) in patients with diabetes mellitus was observed, compared with patients non-diabetic patients. The correlation between desialized apoB-100 and duplex scan of brachiocephalic arteries parameters (r=0.325), as well as between the cholesterol level and stenosis up to 50% (r=0.465) in patients with diabetes mellitus, was found to be of medium strength. The patients with diabetes and CKD, myocardial infarction developed 79% more often than in patients without diabetes (p&lt;0.05). Thus, immunogenic lipid markers of atherosclerosis can be considered both as mechanical factors of atherogenesis and diagnostic and prognostic characteristics in type 2 diabetic patients with impaired renal function and chronic renal insufficiency., Conclusion: Accelerated development of atherosclerosis with diabetes and CKD, confirmed with the help of duplex scan of brachiocephalic arteries, may be associated with an increase in the level of modified low density lipoprotein.

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu, Zn-superoxide dismutase (Cu, Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu, Zn-SOD was observed. The decreased activity of erythrocyte Cu, Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu, Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.

It was shown that glucose in concentration 12.5-100 mM stimulated of Cu(2+)-mediated free radical peroxidation of low density lipoproteins (LDL) from human blood plasma. On the base investigation of kinetic parameters of LDL peroxidation it was stated that intensification of this process in the conditions of our experiments is caused by formation of free radical intermediates of glucose autoxidation during active oxygen species generation in the presence of metal ions with variable valence. It was found that glucose level normalization in the blood of patients with type 2 diabetes during therapy accompanied by significant decreasing of LDL oxidizing. During therapy with sugar-lowering drug metformin which utilizate methylglyoxal the LDL peroxidation from blood diabetes mellitus in vivo inhibited in more higher degree probably in consequence of decreasing of methylglyoxal-dependent generation of superoxide anion radicals as was shown by us early [Biochemistry (Moscow), 2007, 72: 1081-1090; Biochemistry (Moscow), 20(09, 74: 461-466].

Late complications in type 2 diabetic patients are commonly associated with accelerated development of atherosclerosis. In type 2 diabetes mellitus, non-enzymatic glycosylation of apo-B that is a function of hyperglycaemia is an efficient biochemical way of low-density lipoprotein atherogenic modification. So, proper metabolic control is needed to prevent late complications of diabetes. The study was performed to estimate the effects of time-released garlic powder tablet Allicor on the parameters of metabolic control and plasma lipids in type 2 diabetes mellitus. The metabolic action of Allicor was investigated in the 4-week double-blinded placebo-controlled study in 60 type 2 diabetic patients. Fasting blood glucose was measured daily, and serum fructosamine as well as cholesterol and triglyceride levels were determined at the baseline, after 1, 2, 3 and 4 weeks. It has been demonstrated that treatment with Allicor resulted in better metabolic control due to the lowering of fasting blood glucose, serum fructosamine and serum triglyceride levels. The results of this study may allow recommending garlic powder tablets Allicor for the treatment of type 2 diabetes mellitus along with dietary treatment and/or sulfonylurea derivatives to achieve better metabolic control. The benefits from garlic preparations may lead to the reduction of cardiovascular risk in diabetic patients.

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus.

Glycosylation end-products formed during diabetes mellitus promoted atherogenic oxidative modification of low-density lipoproteins. We evaluated the effects of compensation of carbohydrate metabolism and therapy with antioxidant probucol on parameters of free radical oxidation in patients with type II diabetes mellitus. Compensation of carbohydrate metabolism reduced manifestations of oxidative stress, which was manifested in accelerated enzymatic utilization of reactive oxygen species and lipid peroxides and decreased content of free radical oxidation products in low-density lipoproteins. In patients with type II diabetes mellitus combination therapy with antioxidant probucol decreased the severity of oxidative stress and stabilized carbohydrate metabolism without increasing the dose of hypoglycemic preparations.

Glurenorm, a IInd generation sulfanylurea preparation, was used for a year as a sugar-reducing drug in 20 patients with non-insulin-dependent diabetes mellitus and concomitant diseases of the liver (cirrhosis, chronic hepatitis, n = 5) and biliferous duct (cholelithiasis, a state following cholecystectomy, chronic cholecystitis, n = 15). A year follow-up has not shown deterioration of liver function as indicated by results of liver tests (AST, ALT, acid phosphatase, gamma-glutamyltranspeptidase, bilirubin, cholesterol, triglycerides). The hypoglycemic effect of the drug proved to be inferior to that of sulfanylurea derivatives, but the absence of side effects permit higher doses of glurenorm (up to 4-6 tablets daily) as against other oral sugar-reducing drugs.

The paper presents the results of treatment with insulins of iletin-II and humulin series. Decreased insulin doses, absence of complications, stable compensation of diabetes mellitus, reduction of insulin antibodies titer suggest high clinical effectiveness of the above preparations. Because of low immunogenicity humulin insulins are preferable when compared to iletin-II ones.

Rat spleen lymphocytes were shown to bind insulin in vitro. This reaction which comes to saturation depends on both pH and temperature. In competition experiments two types of binding sites differing in their ability to bind insulin were revealed. In Zajdela hepatoma-bearing rats both Kass values and lymphocytes ability to bind insulin were increased, whereas in hepatoma G-27 bearing rats the number of receptors on lymphocytes was drastically decreased. On the second day of Zajdela hepatoma growth the number of receptors on lymphocyte was decreased 1.5-fold, then it was increased reaching the maximum up to fifth day with 5-fold augmentation. The changes in insulin-binding ability of lymphocytes were found to correlate with insulin-binding of the same rat liver plasma membranes. This finding indicates that the character of changes in insulin-binding ability is similar in various tissues of tumor-bearing rats.

Parameters of insulin binding with its specific receptors were determined in small concentrations of peripheral blood mononuclear cells. Examination of 22 patients has shown that the higher the level of insulinemia and the degree of obesity in the insulin-independent form of diabetes mellitus, the lower insulin binding. A decrease in the binding results from the reduction of the number of binding sites and partially from the affinity of type I receptors for insulin. Causes of a decrease in the number of receptors in patients with diabetes mellitus who are not suffering from obesity are discussed.