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Type 1 diabetes mellitus is a metabolic disease that develops as a result of autoimmune destruction of β-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 β-cells.Сахарный диабет типа 1 — метаболическое заболевание, развивающееся вследствие аутоиммунной деструкции β-клеток. На современном этапе принято различать 6 стадий в развитии заболевания: 1) генетическая предрасположенность, обусловленная наличием гаплотипов генов НLA-системы I, II и III классов, а также других генов, ассоциированных с сахарным диабетом типа 1; 2) воздействие различных факторов внешней среды, которые инициируют начало аутоиммунных процессов, приводя к развитию инсулита; 3) развитие иммунологических нарушений; 4) стадия выраженных иммунологических нарушений; 5) манифестация заболевания; 6) полная деструкция β-клеток.

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 β-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.Сахарный диабет — это группа метаболических обменных) заболеваний, характеризующихся гипергликемией, которая является результатом дефектов секреции инсулина, действия инсулина или обоих этих факторов (ВОЗ, 1999 г.). В последней этиологической классификации (ВОЗ, 1999 г.) выделяют 4 клинических типа сахарного диабета: 1-й тип, 2-й тип, другие типы (инфекции, генетические нарушения и др.) и гестационный диабет. Сахарный диабет 1-го типа включает в себя заболевания, обусловленные деструкцией (β-клеток поджелудочной железы, абсолютной недостаточностью инсулина и склонно-стью к кетоацидозу. Подавляющее большинство таких случаев имеет аутоиммунный характер поражения, но есть группы пациентов, у которых не выявляются маркеры аутоиммунного процесса. Учитывая это, по данной классификации диабет 1-го типа включает в себя 2 вида: аутоиммунный и идиопатический. Идиопатический сахарный диабет называют также диабетом 1-го В типа, атипичным диабетом 1-го типа, диабетом, склонным к кетозу, тропическим диабетом.

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.В течение многих лет физические упражнения рассматривали как благотворные в лечении сахарного диабета. Эта терапия была признана полезной и широко использовалась медиками XIX и начала XX столетия. Вслед за открытием инсулина Джослин и другие исследователи рекомендовали физические нагрузки как один из трех принципов в управлении диабетом.В настоящее время в связи с развитием новых возможностей в лечении сахарного диабета физическая нагрузка не рассматривается как единственная необходимая часть воздействия на каждого пациента с диабетом, как это было в прошлом. В последние 2 десятилетия во многих исследованиях, использующих новые технологии, изучали связь между физической формой и метаболическим контролем диабета. С публикацией новых клинических обзоров в большей мере становится очевидным, что упражнения могут быть терапевтическим инструментом у разных пациентов с диабетом или риском развития диабета, но их действие, как и любой другой терапии, должно быть вполне понятно. С практической точки зрения это означает, что врачи должны понимать и анализировать как риск, так и выигрыш от физической активности для каждого отдельного больного. С другой стороны, общепризнанно, что физические упражнения связаны с улучшением качества жизни и благотворно влияют на кардиоваскулярную систему, следовательно, метаболический контроль не должен быть только одним критерием в оценке благотворного эффекта от тренирующих программ для пациентов с диабетом. Важно рекомендовать пациентам оптимальные тренировки для улучшения гликемического контроля и состояния сердечно-сосудистой системы или помочь подобрать адекватную терапию в случае самостоятельного выбора пациентом вида физической нагрузки.

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.

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.

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.

Some features of the formation, expression and inheritance of basic genetic and androgen programs of the level of unusual estrogen-binding protein (UEBP) in mature female rat hepatocytes under experimental conditions were investigated. Liver regeneration after partial (2/3) hepatectomy of mature rats was used for generation of a new population of differentiated hepatocytes. The UEBP content was determined by radioligand technique in control liver and at 2, 4, 14 days of liver regeneration and related to the total DNA content as an indicator of cell proliferative activity. It was revealed that the basic genetic program of low UEBP level of hepatocytes of ovariectomized females was fully transferred to daughter cell during cell proliferation and characterized by a temporary elevation of its expression during initial steps of liver regeneration. It was shown that the androgen program of a high UEBP level was completely and stably formed after androgen action in hepatocytes of ovariectomized females and was fully transferred to daughter cells during hepatocyte proliferation. However experimentally formed androgen program of a high UEBP level in female hepatocytes was completely revealed only during early steps of liver regeneration (the 4th day), its expression was essentially declined after regeneration process was over.

The content of unusual estrogen-binding protein (UEBP), the level of DNA and common protein as well as the organ mass were studied over time during regeneration of the rat liver of intact males and gonadectomized males and females. In 21 days after partial hepatectomy of males with intact testes complete restoration of the UEBP content was observed simultaneously with restoration of the DNA and protein levels and the organ mass. There was no temporary decline of the UEBP content per DNA unit at the early stages of regeneration. The UEBP content in the liver grows during regeneration with the elevation of the DNA level not only in males with intact testes but also in preliminarily castrated males. Different UEBR programs were revcaled by the 21st day of liver regeneration in preliminarily gonadectomized animals: the androgen program of the elevated UEBP content in males, and the basal genetic program of the low level of UEBP expression in females. A conclusion has been made that the hormonal memory of a high UEBP content may be transferred to a new generation of hepatocytes in the absence of androgens. It has been assumed that androgens cause the real determination of masculinization of the EUBP content in liver cells.

The role of the pituitary gland was investigated in the regulation of the level of rat liver androgenic receptors (AR) and in the realization of polydifferentiating action of gonadal hormones. The level of AR in the female and male rat liver was shown not to depend directly on the presence of the pituitary gland or STH administration. The pituitary gland is not a mediator in the realization of polydifferentiating action of androgens and estrogens. STH enhances the development of a positive effect of androgens on the level of AR.

A study was made of the specificities of polydifferentiating action of androgens (A) and estrogens (E) on the level of androgen receptors (AR) of the rat liver cytosol. Androgen receptors were shown to be detected in the neonatal period of ontogenesis, their level was progressively on the increase with the body development. Sex differences in their content were revealed in mature animals only. The AR level is a reversibly controlled, but unprogrammed sex-related sign. The effects of sex steroids are dose-related and modulated reciprocally by the action of endogenous A and E. The action of physiological doses of A and E is characterized by slow development of the effect. Correlation between the level of AR and the efficacy of A action on the content of these proteins was revealed.

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 concentration of receptors to E2 decreased in the uterine cytoplasm of rat uterus and increased in the nuclei during sexual maturation. With ageing this index in the cytoplasm and the nuclei of the uterus fell, and failed to alter during pregnancy. After ovariectomy the concentration of the receptors increased in the uterine cytoplasm, but no marked changes in the receptors occurred in the nuclei. No significant changes were revealed in the receptors to E2 in sexual maturation, pregnancy and ovariectomy in the cytoplasm and the nuclei of the kidneys and the liver. Administration to rats of E2 produced a reduction of the concentration of receptors to E2 in the cytoplasm of the uterus, kidneys and the liver and an increase in their content in the nuclei of the uterus and the liver.

A new modification of specific estrogen-binding protein (SEBP) assay in the liver was used to measure the content of this protein at different stages of ontogenesis in male and female rats after administration of testosterone propionate (TP). It was shown that liver capability to form SEBP could be initially programmed by androgens. The crucial period of the SEBP-determining action of androgens in females is not restricted, since potential capability of androgens of primary induction of SEBP may be realized both neonatally and in the course of pubertation. The emergence of SEBP in the liver of males may be the result of natural pre(neo)natal androgenization. Androgens do not play any decisive role in the control of the level of induced SEBP, inasmuch the content of SEBP in the liver of non-pubertal and pubertal males does not appreciably change after TP administration but grows with pubescence. SEBP is capable of long-term existence in the absence of androgens. The presence of the ovaries produces an inhibitory effect on the level of androgen-induced SEBP and the time of its existence after TP discontinuation. Hypophysectomy does not provoke SEBP emergence in pubertal intact and ovariectomized females but prevents its induction with androgens. Adrenal- and thyroectomy produce no influence on the SEBP-programming effect of TP or promote its spontaneous appearance in the same groups of female rats.

The paper is concerned with differential quantification of the level of androgen receptors (AR) in the liver cytosol of male and female rats as well as in the prostatic cytosol. AR affinity to synthetic androgen R1881 was shown to be similar in all investigated tissues. In male rats the AR content in the liver cytosol was 20.5 +/- 2.1 fmol per 1 mg of protein, lower (p less than 0.05) than in the prostatic cytosol (30.8 +/- 2.5 fmol per 1 mg of protein). Sex differentiation of the liver AR content with 3-fold predominance in males was determined. Gonadectomy of mature rats caused leveling down of sex differences in the liver AR content as a result of a decrease in AR concentration in castrated males and its increase in ovariectomized females. Sex differentiation of the liver AR content could be an additional factor enhancing the multiple differentiating action of androgens on the male rat liver.

Some properties of the macromolecules, specifically binding estradiol (E2) of salt chromatin extracts of the nuclei of the kidneys, liver, prostate, testes and the uterus of rats were studied. Examination of competition of various unlabeled hormonal preparations with 3H-E2 for the binding sites demonstrated the E2-binding macromolecules of the nuclei of all the organs under study to have a high hormonal stereo-specificity. The E2-binding macromolecules of the nuclear extracts of the kidney, liver and the uterus were sensitive to the action of pronase. In sedimentation with ammonium sulfate of proteins from the 0.3 M NaCl extracts of the nuclei of the kidneys and liver, but not of the uterus, the supernatent fraction of the salt-treated extracts showed an additional (in comparison with control) specifically E2-binding macromolecule activity, sensitive to the action of pronase. An analogous effect of the appearance of additional binding activity could be obtained in heating of the nuclear extracts of the kidney and the liver at 60--100 degress C for 5 minutes.

A study was made of the role of estrogens (E) in the induction and regulation of the level of specific estrogen binding protein (SEBP) in the rat liver using a differentiated quantitative method of its determination. It was shown that E could not replace androgens (A) in the primary determination of the SEPB level, neither did they prevent its A-dependent induction. Multiple administration of 0.4 microgram of estradiol (E2) caused a significant decrease in the SEPB level in intact and castrated male rats as well as in ovariectomized females with the A-induced SEPB level. Multiple administration of even 10 micrograms of E2 did not influence the SEPB level in hypophysectomized males. The rate of development of the E2 effect on the SEPB level of the mature male liver increased with the growth of the dose and duration of hormone administration. The inhibitory effect of E2 was also revealed in a single administration of 10 micrograms of the hormone. In that case the effect was observed after a 3-day lag period, and a maximum decrease in the SEPB level occurred in 6 days. The regulatory negative effect of E2 was reversible. Complete regeneration of the initial SEPB content took place 10-12 days after the development of the maximum effect of E2.

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.

A study was made of the ability of androgen-receptor complexes (ARC) of male rat liver cytosol to interact with hepatic cell nuclei and DNA in a model free-cell system and after administration of androgens to animals. In a free-cell system androgen receptors (AR) within a partially purified cytosol preparation were capable of binding strongly with hepatic cell nuclei and DNA of cellulose-conjugated cow spleen. The administration of testosterone propionate for 3 days resulted in the redistribution of liver AR between cytoplasm and nuclei during testing 1 h after the last injection. The observed regularities were unrelated to changes in AR content caused by the regulatory effect of administered androgen. Similar changes in AR content in the studied subcellular fractions were revealed 1 h after single administration of R1881 but not testosterone propionate. The revealed regularities were indicative of a possibility of AR involvement in androgenic action on the liver at the nuclear level.

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.

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.

A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier.

A method of gel-filtration of Sepharose 6B was used; Stoke's radii (a) of some forms of cytoplasmic receptors of estrogens of the uterus, kidneys, and the liver of male and female rats were determined. In the initial cytozol in elution with buffer of low ionic strength estrogenic uterine receptors were presented chiefly by the form with a congruent to 70A, and the receptors of the male and female kidneys--by the form with a congruent to 30 A; receptors of the liver of males and females were represented by both forms, in females the content of the form with a congruent to 70 A somewhat exceeded the content of the form with a congruent to 30 A. At the same time in the males the form with a congruent to 30 A prevailed. In elution with a buffer of a high ionic strength the receptors of all the organs under study eluated with a congruent to 20--26 A. Formation of a form with a congruent 20--26 A in case of receptors of the liver of males and the uterus was reversible under the action of a high salt concentration. Receptors of all the organs under study were capable of forming Ca2+-stabilized form with a congruent to 35 A in elution with a buffer of low ionic power and a congruent to 21-26 A in elution with a buffer of high ionic strength.

Several properties of estradiol (E2)-binding cytosol macromolecules in the liver of females with cholecystitis and of males with hepatic cirrhosis were studied by means of comparatively delicate methods of free- and bound hormone separation. E2-binding macromolecules with Stokes' radius of approximately 5 nm were found in the hepatic samples under study, formed with E2 complexes, similar to estrogen receptors, according to hormonal specificity of affinity and stability. Protein, similar to a specific estrogen-binding protein of the rat and guinea pig liver, was not found in the preparations examined.

The effect of some hormones of total metabolic action on a degree of sex differentiation of the liver by a specific estrogen-binding protein (SEBP) was investigated. Insulin administration did not change the SEBP level of the male rat liver. Adrenalectomy and dexamethasone administration caused no significant changes of sex differentiation of the SEBP level in the male and female rat liver. Neither did thyroidectomy cause significant changes in the SEBP level. Dose-related T3 administration decreased reversibly the SEBP level in the liver of adult male rats. The effect of T3 on the SEBP level was preserved after castration or hypophysectomy of males. T3 administration decreased a degree of determination of a raised level of SEBP in the female rat liver by androgens. STH injections were effective mainly in hypophysectomized male rats resulting, on the one hand, in an increase in the level of SEBP and creating conditions, on the other hand, for a decrease in its level caused by estradiol. It has been concluded that thyroid hormones and STH are able to be modulators of adaptive changes of sex differences of the liver by SEBP.

A study was made of specific binding of estradiol (E2) by cytosol and the extracts of the nuclei of the testes, the prostate, the kidneys and the liver of the sexually-mature male rats. In the cytosol of all the mentioned organs there were found macromolecules with a high affinity (Kac similar 1--4-10(9)M(-1)). Low capacity ti the hormone (Nc similar to (1--2)--minus 14 mol per 1 mg of protein) and a marked hormonal sterospecificity--only the preparations with an estrogenic activity, but not testosterone, 5alpha-dihydrotestosterone, progesterone and corticosterone competed for H-3--E2 binding. The capacity of cytosol of these organs to bind E2 apecifically was eliminated by pronase, but not by RNA-ase and DNA-ase. The mentioned properties of the E2-binding macromolecules of cytosol of the testes, the prostate, the kidneys and the liver permitted to refer them to the estrogenic protein-receptors. Specific E2-binding was also revealed in the extracts of the nuclei of these organs, but its level was extremely low.