[Intravascular ultrasound with virtual histology in assessment of atherosclerotic plaque composition in patients with coronary artery disease and type 2 diabetes mellitus].

Type 2 diabetes mellitus (T2DM) is a serious medical and social problem leading to early disability of patients and high mortality from cardiovascular complications. The development of cardiovascular events is associated not only with the degree of coronary artery stenosis, but also with the structure of the atherosclerotic plaque. AIM: This study aimed to characterize structure and composition of coronary artery atherosclerotic plaque in target lesion of T2DM patients and patients without diabetes using intravascular ultrasound (IVUS) and IVUS with virtual histology (IVUS-VH). MATERIALS AND METHODS: We observed 25 patients with coronary artery disease (CAD) with T2DM and without T2DM, which admitted to Endocrinology Research Centre to perform percutaneous coronary intervention (PCI). Patients with CAD and T2DM were included at group 1 and patients with CAD and without T2DM were included at group 2. IVUS and IVUS-VH assessment of target lesion were performed prior to stent implantation. We observed 24 plaques at group 1 and 10 plaques at group 2. RESULTS: In grey - scale IVUS 2D analysis there were no differences in mean cross - sectional area of the vessel (12.5 [10.4; 15.8] mm2 vs. 13.5 [12,7; 16.5] mm2; p=0.223, respectively) and lumen area (3.71 [2.5; 4.5] mm2 vs. 3.2 [2.7; 3.8] mm2; p=0.589, respectively). Plaque burden were higher in patients without T2DM (71.6 [65.5; 75.7] % vs. 77.6 [74.4; 80.4] %; p=0.008, respectively). IVUS-VH analysis showed that percent of necrotic core and dense calcium areas were significantly higher in the T2DM group (31.3 [25.3; 36.5] % vs. 21.65 [14.3; 27.8] %; p=0.01 and 4.7 [2.3; 7.8] % vs. 2.45 [1.2; 4.05] %; p=0.046, respectively). Percent of the fibrotic tissue were higher in non-T2DM group (55.35 [49.7; 63.6] % vs 67.7 [61.8; 76.5] %; p=0.004, respectively). There were no differences in percent of lipidic tissue in both groups. CONCLUSIONS: IVUS-VH assessment of coronary artery atherosclerotic plaques showed greater amount of necrotic core and dense calcium in patients with T2DM compared to patients without diabetes.

[Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus and coronary artery disease: Diagnosis and severity assessment]. / Kardiovaskulyarnaya avtonomnaya nevropatiya u bol'nykh sakharnym diabetom 2-go tipa i ishemicheskoi bolezn'yu serdtsa: diagnostika i otsenka tyazhesti.

AIM: To study the nature and severity of heart rate variability (HRV) and heart rate turbulence (HRT) abnormalities in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) and to assess the prevalence of cardiovascular autonomic neuropathy (CAN) and its severity in patients with T2DM concurrent with CAD. MATERIAL AND METHODS: A total of 185 patients with T2DM and/or CAD were examined and divided into 3 groups: 1) 92 patients with CAD and T2DM; 2) 43 patients with CAD without T2DM; 3) 49 patients with T2DM without CAD. All the patients underwent 24-hour ECG monitoring with HRV and HRT analysis. RESULTS: CAN was identified and the severity of CAN was assessed based on the abnormal HRV and HRT parameters. CAN, especially severe one, was more common in Group 1 (the relative risk was 3.3 [95% CI 1.3-8.2]; p<0.05), than in Group 3. In Group 1, CAN was associated with the duration of T2DM and the level of glycated hemoglobin (p<0.05). The patients with severe CAN in Group 1 showed a 4-fold higher risk for multivessel coronary artery lesions than those without CAN (p<0.05). CONCLUSION: Glycemic control quality, T2DM duration, and obvious coronary atherosclerotic lesions were demonstrated to be associated with the presence and severity of CAN. The developed methods may be used in practice to detect and more accurately determine the severity of CAN and to predict cardiovascular risk in patients with T2DM and CAD.

[Intercurrent and autoimmune processes in type 1 diabetes mellitus]. / Interkurrentnye autoimmunnye protsessy pri sakharnom diabete 1-go tipa.

AIM: To estimate the prevalence of autoantibodies pathognomonic for autoimmune diseases of connective tissue and liver in patients with type 1 diabetes mellitus (DM1) and to study their clinical features in patients positive for these indicators. MATERIAL AND METHODS: A total of 84 patients (39 men and 45 women) with DM1 divided into 2 groups were examined. Biochemical, immunological, and instrumental examinations were performed. RESULTS: There was a high prevalence of markers of autoimmune diseases of connective tissue and liver in patients with DM1 and that of autoantibodies in those without its clinical symptoms or signs according to instrumental findings. CONCLUSION: The findings may suggest that patients with DM1 have a higher risk of concomitant autoimmune diseases with a probability of their asymptomatic course.

[Risk factors and glycation end products in patients with different forms of coronary heart disease and type 2 diabetes mellitus]. / Faktory rosta i konechnye produkty glikirovaniya u bol'nykh s razlichnymi formami ishemicheskoi bolezni serdtsa i sakharnym diabetom 2-go tipa.

AIM: To determine the levels of growth factors and glycation end products in patients with different forms of coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 134 patients with CHD and T2DM, including 38 patients with non-ST-elevation acute coronary syndrome (ACS), were examined. The arterial and venous serum levels of basic fibroblast growth factor-ß (FGF-ß), transforming growth factor-ß (TGF-ß), placental growth factor (PlGF), advanced glycation end products (AGEs) and their receptors (RAGE) were estimated in all the patients. RESULTS: A direct correlation was found between the degree of arterial stenosis and the level of growth factors and AGEs in the patients with T2DM; there was also a direct correlation of the examined factors with lipid metabolic parameters. There was a significant two-fold increase in FGF-ß, PlGF, and RAGE levels in the patients with ACS. CONCLUSION: Hyperglycemia was found to negatively affect the progression of atherosclerotic changes in the vessel wall and on that of fibrotic processes.

[Idiopathic diabetes].

Diabetes mellitus is a group of metabolic metabolic) diseases characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both of these factors (WHO, 1999). In the last etiological classification (WHO, 1999), 4 clinical types of diabetes mellitus are distinguished: type 1, type 2, other types (infections, genetic disorders, etc.) and gestational diabetes. Type 1 diabetes mellitus includes diseases caused by destruction (pancreatic ß-cells, absolute insulin deficiency and a tendency to ketoacidosis. The vast majority of such cases have an autoimmune nature of the lesion, but there are groups of patients who do not show autoimmune markers Taking this into account, according to this classification, type 1 diabetes includes 2 types: autoimmune and idiopathic. Idiopathic diabetes is also called type 1B diabetes, atypical type 1 diabetes , ketosis-prone diabetes, tropical diabetes.

[Role of fibroblasts in the development of diabetes mellitus and its complications].

Type 1 diabetes mellitus is a metabolic disease that develops as a result of autoimmune destruction of ß-cells. At the present stage, it is customary to distinguish 6 stages in the development of the disease: 1) a genetic predisposition due to the presence of haplotypes of genes of the HLA system of classes I, II and III, as well as other genes associated with type 1 diabetes mellitus; 2) the impact of various environmental factors that initiate the onset of autoimmune processes, leading to the development of insulin; 3) the development of immunological disorders; 4) stage of pronounced immunological disorders; 5) the manifestation of the disease; 6) complete destruction of ß-cells.

[Role of exercises in health and in diabetes mellitus].

Exercise has been seen as beneficial in the treatment of diabetes. This therapy was recognized as useful and was widely used by physicians of the 19th and early 20th centuries. Following the discovery of insulin, many researchers recommended physical activity as one of the main principles for diabetes management.Currently, due to the development of new opportunities in the treatment of diabetes mellitus, physical activity is not considered as the only necessary part of the impact on each patient with diabetes, as it was in the past. Over the past 2 decades, many studies using new technologies have explored the relationship between physical fitness and metabolic control of diabetes. With the publication of new clinical reviews, it has become increasingly apparent that exercise can be a therapeutic tool in different patients with diabetes or the risk of developing diabetes, but their effect, like any other therapy, should be understandable. From a practical point of view, this means that doctors must understand and analyze both the risk and the gain from physical activity for each individual patient. On the other hand, it is generally accepted that physical exercise is associated with an improvement in the quality of life and has a beneficial effect on the cardiovascular system; therefore, metabolic control should not be just one criterion in assessing the beneficial effects of training programs for patients with diabetes. It is important to recommend optimal training for patients to improve glycemic control and the state of the cardiovascular system, or to help select appropriate therapy if the patient independently chooses the type of exercise.

[Carbohydrate metabolism in patients after pancreatoduodenal resection]. / Sostoianie uglevodnogo obmena u bolnykh posle pankreatoduodenalnoi rezektsii.

The authors studied carbohydrate metabolism 4 weeks to 12 months after pancreatoduodenal resection (PDR) in 21 patients whose ages ranged from 40 to 55 years. Seven of them had been operated on for carcinoma of the major duodenal papillas and the other patients for carcinoma of the major duodenal papillas and the other patients for carcinoma of tree pancreas. The control group was formed of 10 healthy volunteers of the same age as the patients of the two groups under study; 10 patients who were subjected to PDR with pancreatojejunostomy and 11 patients in whom resection of the pancreatic stump was completed by intraductal occlusion of the formed stump. None of them had disorders of carbohydrate metabolism before the operation. The patients were examined by the oral test for glucose tolerance (OTGT, 75 g of glucose) with glycemia determination and by intravenous glucose tolerance test (i.v. GTT) with determination of glycemia and C-peptide. It was found that the glycemia curves obtained during OTGT did not have a diabetic character according to the WHO criteria. In performing TTG, the coefficient K was diabetic in both groups. Study of the C-peptide level during the i.v. GTT showed that in the group with occluded ducts the level of the C-peptide and the nature of its secretion differed obviously from those in the other groups under study, which testified to disturbances in the homeostai mechanisms.

[Analysis of nuclear families with two or more patients with insulin-dependent diabetes mellitus with diabetic siblings]. / Analiz iadernykh semei s dvumia i bolee bol'nymi insulinzavisimym sakharnym diabetom sibsami.

HLA haplotype distribution was analyzed in nuclear families of patients with insulin-dependent diabetes mellitus. Sixteen families with two or more diabetic siblings were examined, a total of 69 subjects, 33 of these diabetic siblings and 36 normal subjects (siblings and parents). The data were processed using the involved sibling pairs method based on a mixed model making use of a conditional probability approach. The ratio of diabetic sibling pairs concordant by 2 haplotypes, 1 haplotype, and discordant by 2 haplotypes was 9:5:2 vs. 1:2:1 expected according to Mendel's accidental distribution (p < 0.025). Increased incidence of siblings concordant by 2 haplotypes proves the presence in the HLA domain of one or several genes responsible for the development of diabetes mellitus. Siblings identical by two HLA haplotypes with the diabetic proband are at a higher risk of developing this disease.

[Humoral autoimmunity markers in autoimmune endocrine diseases]. / Markery gumoralnogo autoimmuniteta pri autoimmunnykh éndokrinnykh zabolevaniiakh.

To clarify the value of autoantibodies as risk factors of complications in various endocrine abnormalities, the incidence of autoantibodies to thyroid microsomal antigen (ATMA), thyroglobulin, and the surface antigens of the rat islet, adrenal cortex, adenohypophyseal cells and human skin fibroblasts was studied in patients with insulin-dependent mellitus (IDDM), at the onset of the disease and during one-year insulin therapy, non-insulin-dependent diabetes mellitus (NIDDM), Hashimoto thyroiditis, Graves' disease, diabetes associated with thyroidal dysfunction, euthyroid polynodular goiter, Schmidt and polyglandular syndromes and in the population. The antibodies were determined by ELISA. Polyclonal activation of the immune system was found in all abnormalities, except in polyglandular in children. The proportion of patients with more than one type of antibodies was minimal (26.4%) in IDDM and maximal (62.0%) in Graves' disease. Among IDDM patients, polyclonal activation of the immune system was observed more often in women than in men (48.5 vs 8.5%). The persistence of antibodies to fibroblasts in IDDM patients was associated with the development of vascular complications. The latter were observed in 4 of 7 patients who had these antibodies during a year and in none of negative patients. Thus, fibroblast antibodies may have a predicative significance for the development of late diabetic complications. The highest prevalence of these antibodies was discovered in Graves' disease (37.9%) wherein the antibodies may be involved in the development of exophthalmus and pretibial mixedema. Thyroidal dysfunction developed in all IDDM patients with ATMA preserved during a year and in none ATMA-negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cellular immunity in patients with newly detected insulin-dependent diabetes mellitus]. / Osobennosti kletochnogo immuniteta u bol'nykh s vpervye vyiavlennym insulinzavisimym sakharnym diabetom.

Twenty-five diabetics with insulin-dependent condition were examined at the debut of the disease before insulin therapy, as were 10 healthy donors. Under study were relative and absolute counts of T lymphocytes, NK cells, B lymphocytes, DR-T lymphocytes, Th, Ts, and Th/Ts index. Patients' and donors' sera were tested for autoantibodies to P64-69kD antigenic complex. Characteristic features of cellular immunity of patients with newly-detected diabetes were disclosed. Counts of B lymphocytes and Dr-T lymphocytes were increased in all patients. A relationship was revealed between immunoregulatory Th/Ts index and clinical features of insulin-dependent diabetes. Autoantibodies to p64-68 kD andigenic complex were detected in 63-88% of patients with newly detected insulin-dependent diabetes.

[Determination of autoantibodies to pancreatic beta-cells, non-islet endocrine cells and fibroblasts in patients with newly detected diabetes mellitus]. / Opredelenie autoantitel k beta-kletkam podzheludochnoi zhelezy, neostrovkovym éndokrinnym kletkam i fibroblastam u bol'nykh s vpervye vyiavlennym sakharnym diabetom.

The clinical onset of insulin-dependent diabetes (IDD) is characterized by the onset of circulation of autoantibodies to beta-cells. Thirty-three newly detected IDD patients and 14 newly detected patients with noninsulin-dependent diabetes mellitus were examined for autoantibodies to antigen P 64-69, to surface antigen of islet cells, to thyrocyte microsomal fraction, thyroglobulin, hypophysis, fibroblasts; the levels of circulating immune complexes were measured as well. IDD debut was found associated with the appearance of antibodies to pancreatic islet cells, thyroid, thyroglobulin, hypophysis, fibroblasts, this indicating a polyclonal activation of the immunity system. A relationship was revealed between antifibroblast antibody and anti-islet-cell antibody. Antihypophyseal antibodies were detected in 43% of patients with noninsulin dependent diabetes. Nine per cent of IDD patients and 24% of patients with noninsulin dependent condition were negative in the tests.

[Lipid peroxidation and antioxidant enzymatic defense in patients with newly detected insulin-dependent diabetes mellitus]. / Perekisnoe okislenie lipidov i antioksidantnaia fermentativnaia zashchita u bol'nykh s vpervye vyiavlennym insulinzavisimym sakharnym diabetom.

Studies of lipid peroxidation and antioxidant enzymic defense in red cell membranes in 23 patients with newly detected insulin-dependent diabetes mellitus have revealed a statistically significant (2-fold) elevation of malonic dialdehyde lipid peroxidation products and a trend to a rise in the levels of lipid peroxides. This is parallelled by a certain overstrain of the cellular antioxidant defense system. The authors discuss the usefulness of administering antioxidant therapy at the onset of the disease in order to prevent the toxic injury of beta-cells and vascular endothelium cells by lipid peroxidation products.

[Dynamics of disorders of cellular and humoral immunity parameters in patients with insulin-dependent diabetes mellitus]. / Dinamika narushenii pokazatelei kletochnogo i gumoral'nogo immuniteta u bol'nykh insulinzavisimym sakharnym diabetom.

Analysis of immunocompetent cell subsets in peripheral blood of patients with insulin dependent diabetes mellitus (IDDM) and the determination of sICA-autoantibodies in their sera were performed by flow rate cytometry and compared to healthy donors and patients with noninsulin-dependent diabetes mellitus (NIDDM). It was shown that newly diagnosed IDDM was characterized by predominant disturbances of humoral immunity, and disease progression was mainly accompanied by cellular immunity disturbances. Exogenous insulin was one of the causes of such disturbances. A tendency to normalization of cellular rather than humoral immunity was observed after the onset of human monocompetent therapy of IDDM patients. It is likely that the appearance in the peripheral blood of activated T-lymphocytes accompanied by sICA-autoantibodies and increased mature B-lymphocytes and NK-cells counts corresponds to increased ADCC against pancreatic beta cells in IDDM development.

[The clinical x-ray characteristics of the soft tissues of the lower extremities in diabetics]. / Kliniko-rentgenologicheskaia kharakteristika miagkikh tkanei nizhnikh konechnostei u bol'nykh sakharnym diabetom.

The authors present the results of clinicoroentgenological and immunological investigations of the state of lower limb soft tissues in 117 patients with diabetes mellitus. Vascular wall calcification and soft tissue edema were noted practically in all the patients with a period of disease over 1 year. X-ray investigation permitted the detection of vascular lesion at early stages of complication development, in most of the patients even at the preclinical stage. A degree of lower limb vascular lesion is not related to a type of diabetes mellitus and the patients' age. There is direct correlation between the affection of the walls of medium size vessels and vessels of the fundus of the eye. The frequency and severity of lower limb vascular lesion, polyneuropathy and nephropathy grow significantly with an increase in a period of disease. A parallel decrease of immunoglobulins is noted. The affection of osseous tissue does not depend on a period of disease and shows insignificant correlation with a degree of vascular lesion.

[The insulin and proinsulin levels in patients with newly detected diabetes mellitus]. / Soderzhanie insulina i proinsulina u bol'nykh s vnov' vyiavlennym sakharnym diabetom.

Total immunoreactive insulin (IRI), proinsulin-like component, IRI, C-peptide and glucagon were determined in patients with newly detected diabetes mellitus and in healthy subjects on an empty stomach and after food testing. The results obtained have shown that a study of the serum total IRI composition combined with C-peptide determination during food testing can be used as a diagnostic test to define a type of diabetes mellitus.

[Use of human insulin preparations in the treatment of patients with insulin-dependent diabetes mellitus]. / Primenenie preparatov chelovecheskogo insulina pri lechenii bol'nykh insulinzavisimym sakharnym diabetom.

The authors presented the results of a study of human insulin drugs Monotard HM and Actrapid HM (Novo, Denmark) for type I diabetes mellitus. They stressed their efficacy in therapy of insulin dependent diabetes mellitus: a course of disease became less labile, the time of achieving compensation was reduced; the drugs proved to be effective in the treatment of post-injection insulinlipodystrophies, in body mass deficiency; a tendency to a decrease in daily insulin requirement, serum insulin binding capacity, and in increase in the content of free insulin were noted.

[Immunoenzyme detection of autoantibodies to the surface of pancreatic islet cells in diabetes mellitus and in increased risk of its development]. / Immunofermentnoe vyiavlenie autoantitel k poverkhnosti ostrovkovykh kletok podzheludochnoi zhelezy pri sakharnom diabete i pri povyshennom riske ego razvitiia.

The authors described the use of an enzyme-linked immunosorbent assay to determine islet cell surface antibodies (ICSA) in persons at high risk of developing insulin dependent diabetes (IDD) and different types of manifest disease. Among I degree healthy relatives of probands with IDD antibodies were detected in 16%. In disorder of the oral GTT (a small group) ICSA were found in 57% of examinees. In the group of IDD patients which was heterogeneous in duration of disease and age at its onset, the frequency of ICSA was 38%. The least frequency (10%) of antibodies was observed in patients with non-insulin dependent (NIDD) compensated by a diet and oral hypoglycaemic drugs. Among non-compensated NIDD patients 62% were ICSA-positive. Thus, ICSA determined by the enzyme-linked immunosorbent assay, could be employed as a marker of autoimmune damage of the insular apparatus for prognosis of the development of "primary" and "secondary" insulin dependence.