Vol 41, No 4 (1995)

Clinical endocrinology
Associations between insulin-dependent diabetes mellitus and HLA-DQA1 alleles
Mersiyanova I.I., Knyazev Y.A., Burdenko M.V., Sebko T.V., Yevgrafov О.V.
Abstract

The incidence of HLA-DQA1 alleles was assessed in patients with insulin-dependent diabetes mellitus (IDDM), their relatives, and healthy controls using HLA-DQA1 genotyping by digestion of PCR amplified DNA with allele-specific restriction enzymes. A significant increase in the incidence of HLA-DQA1*0301 allele was observed in diabetics although the ratio of DQA1*0301 homozygotes to heterozygotes was similar in the patients and controls. The presence of one DQA 1*0301 allele in the genome appeared to be sufficient for susceptibility to IDDM. Comparison of the incidence of other DQA1 "Arg52" alleles in diabetics and healthy controls revealed no differences between the groups. The incidence of DQA1 "non-Arg52" alleles (specifically DQA1*0201) was reduced in diabetics as compared to normal controls. The presence of these alleles may be considered as the "protective" factor.

Problems of Endocrinology. 1995;41(4):3-5
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Immunogenetic characteristics of insulin-dependent diabetes mellitus in young children
Osokina I.V., Scherbacheva L.N., Lebedev N.B., Yazdovsky V.V., Dedov I.I.
Abstract

HLA phenotype was determined in 100 children (50 girls and 50 boys) with insulin-dependent diabetes mellitus (IDDM) aged 5.9 ± 2.3 years, on an average, the mean age by the disease manifestation 2.7 + 1.1. Fifty-nine antigens belonging to classes I and II were analyzed. HLA markers of predisposition to IDDM in early childhood were revealed: DQw3 (Pcor = 3.4*10-5), DR3/DR4 (Pcor= 1.6*10-9), DR4 (Pcor = 7.8*10-12), DR3 (Pcor = 6.3*10-7), B8 (Pcor = 2.6*10-7), and the resistance marker DQw7 (Pcor = 1.1*10'8). HLA markers of predisposition to IDDM may hold promise for the study of genetically regulated mechanisms of IDDM development, serve the criteria for the prediction of disease course, and indicate the possible variants of diabetes in early childhood. Immunogenetic heterogeneity of IDDM in young children has been proved. In girls the DR4 antigen is more incident. B12 antigen is the key marker of IDDM in infants aged under one. If diabetes manifests before the age of three, the most frequent antigens are DR3 and DR3/4. DR3/4 is the precursor of grave course of diabetes and predisposition to allergic diseases. В13 indicates an etiologic relationship of diabetes with rubella. DQ1, DR1 and B35 point to relationships with varicella.

Problems of Endocrinology. 1995;41(4):5-8
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Incidence of diabetes mellitus complications as indicated by the register
Kudryakova S.V., Suntsov Y.I., Ryzhkova S.G.
Abstract

The incidence of diabetes mellitus complications was assessed on the basis of diabetes mellitus register in 1478 diabetics living in the Lenin district of Moscow. The incidence of microangiopathies was reliably higher in patients with insulin-dependent condition (IDDM) than in those with the non-insulin dependent (NIDDM) one. The incidence of retinopathies and nephropathies was much higher in women with IDDM than in men. The incidence of macroangioptithies was higher in NIDDM than in those with IDDM. The incidence of coronary disease and arterial hypertension was the highest in women with NIDDM. The incidence of complications increased with a longer standing of the disease and age of the patients.

Problems of Endocrinology. 1995;41(4):8-11
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Assessment of metabolic and hormonal shifts in patients at risk of diabetes mellitus
Tereschenko I.V., Shevchuk V.V.
Abstract

Coronary patients and patients with essential hypertension were found to have the highest levels of glycated hemoglobin (gly-Hb), specifically, of its HbAlc fraction, as was shown in screening of 615 subjects. Measurements of blood levels of gly-Hb and gly-albumin, study of pyruvate metabolism, oral glucose tolerance test, and glucose-insulin test in 74 patients with coronary disease and essential hypertension revealed a high prevalence of latent disorders of carbohydrate metabolism in this patient population, with disorders of carbohydrate metabolism manifesting primarily by an increase of blood levels of glycated proteins and by disorders of pyruvate metabolism. Glycation of blood proteins in patients with coronary disease and essential hypertension increases blood viscosity (1.6 ± 0.02), spontaneous platelet aggregation (46.59 + 2.07% vs. 18.1 ± 1.5% in control), reduces fibrinolysis, and is conducive to a parallel increase of the concentration of blood serum lipids. These patients develop disorders of insulin secretion after glucose loading, thyroid function is reduced with the deficit of tri-iodothyronine production (1.46 + 0.07 nmol/liter vs. 1.92 ± 0.1 nmol/liter in health, p < 0.05); hydrocortisone hypersecretion is observed (746.25 ± 49.74 nmol/liter vs. 358.23 + 9.8 nmol/liter in health, p < 0.001); hormonal dysfunction favors the formation of glucose toxicity mechanism in normal glycemia when no clinical signs of impaired glucose tolerance are seen.

Problems of Endocrinology. 1995;41(4):11-14
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Hepatobiliary function in children with insulin-dependent diabetes mellitus
Kravets Y.B., Biryulina Y.A., Mironova Z.G.
Abstract

The hepatobiliary system plays the crucial role in the development of metabolic disorders in diabetics. Involvement of the hepatobiliary system may develop at the early stages of diabetes mellitus. The present study was aimed at elucidation of the specific features of bile excretion and production in children with type I diabetes making use of present-day diagnostic methods. Fifty-two patients with type 1 diabetes aged 6 to 15 and 20 healthy controls were examined. Besides common clinical studies, fractionated duodenal probing followed by biochemical analysis of the bile, ultrasonic examination of the hepatobiliary system, and dynamic hepatobiliscintigraphy were carried out. Typical changes in liver parenchyma developing after fatty hepatosis type were found to play the main role in the structure of hepatobiliary involvement occurring in insulin-dependent diabetes. Disorders of bile excretion are caused by dyskinetic disorders of extrahepatic bile duct and choleresis changes. Bile excretion arrhythmia manifests most frequently as hypertensive dyskinesia. In patients with a longstanding disease bile excretion changes are mainly due to increased tone of the sphincter of Oddi and decelerated contractility of the gallbladder. Biochemical composition of the bile was characterized by decreased concentration of bile acids, phospholipids, and bilirubin, by a lower cholate-cholesterol coefficient, and increased levels of cholesterol and total lipids.

Problems of Endocrinology. 1995;41(4):15-17
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Ready-made human insulin pools for the treatment of diabetes mellitus
Shishko P.I., Dreval A.K., Andrianova K.V.
Abstract

Proper knowledge of insulin use is important for the effective treatment of diabetes. There is an opinion that a significant part of patients who are not currently receiving insulin do not have optimal diabetes compensation and could better control the disease when switching to insulin therapy. In mixtures of NPH and simple insulin, the latter retains its activity for a long time. This is true statement for both human and animal insulin. Unlike the previous ones, all NPH drugs currently supplied by major pharmaceutical companies have the same level of protamine and do not contain an excess of protamine that could bind added simple insulin (regular). Ready-made mixtures of human insulin are pre-mixed preparations of various durations of action.

Problems of Endocrinology. 1995;41(4):17-18
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Assessment of body composition in normal weighing and obese subjects by the bioelectrical impedance method
Bershtein L.I., Tsyrlina Y.V., Samoilova Y.B., Kovalenko I.G.
Abstract

Body composition (lean mass, fat content) was assessed in 32 women aged 21 to 78 by measuring the thickness of subcutaneous fat in 4 typical sites and urinary excretion of creatinine, and estimating whole-body bioelectrical impedance (BI) by tetrapolar analyzer attached to personal computer. Results of BI measurements better correlated with body composition values assessed from the thickness of subcutaneous fat (particularly so in subjects aged under 50 and with Broca’s index from 0 to +19%). Hence, BI assessment may be used to evaluate body composition in patients with various endocrine diseases before the treatment and to monitor its efficacy in some diseases.

Problems of Endocrinology. 1995;41(4):19-21
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Pathophysiology of the microcirculatory bed in obesity
Zelinsky В.A., Sokur S.A.
Abstract

A total of 207 patients with alimentary constitutional and hypothalamic obesity were examined in order to assess the status of the microcirculatory bed, including the status of capillary walls, hemocirculation, transcapillary metabolism, oxygen delivery to tissues in patients with various forms of obesity. Bulbobiomicroscopy, assessment of capillary wall permeability by the hydrostatic test, polarographic study of oxygen tension in the skin using oxygen and ischemic test were employed. Obese patients were found to develop appreciable microcirculatory disorders (vascular, intravascular, extravascular); capillary walls became better penetrable for liquid and proteins and the adaptation reserve of these vessels decreased, with the substrate movement from blood to tissues predominating. A correlation has been traced between the status of the circulation and capillary walls, and extravascular shifts, on the one hand, and capillary permeability, on the other. Oxygen delivery to tissues was disordered in obese patients, this manifesting by deterioration of both oxygen delivery and consumption. The degree of impairment of various components of microcirculation and oxygen supply of tissues augmented with body mass increase.

Problems of Endocrinology. 1995;41(4):21-23
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Case Reports
Syndrome Hutchinson-Gilford (progeria)
Fofanova O.V.
Abstract

Gatchinson-Guildford syndrome or progeria (senile dwarfism) is an extremely rare genetic disease in children with clinical features of premature aging. The frequency of the disease is 1 in 8 million newborns (De Busk. 1972). To date, about 70 patients with this syndrome have been described in world literature. The etiology of progeria is unclear. The genetic model of inheritance is unknown due to the extreme rarity of the syndrome and the absence of offspring in patients. However, studies by foreign scientists allow us to talk about sporadic dominant mutation as the genetic basis of this syndrome. The clinical picture of progeria is represented by symptoms of progressive premature aging. Characteristic face: exophthalmos, a thin coracoid nose, a large brain and small facial skull, a thin voice, skeletal anomalies. Puberty usually does not occur; external genitalia hypoplasia. Intelligence average or above average. This syndrome is characterized by widespread atherosclerosis with lesions of coronary and mesenteric vessels, aorta, cerebral vessels, with hyperlipidemia. Progeria as a model of premature aging is studied in various aspects: metabolic, hormonal, histological, immunological, molecular.

Problems of Endocrinology. 1995;41(4):24-26
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For practitioners
Treatment of uncomplicated non-insulin-dependent diabetes mellitus (lecture)
Dreval` A.V.
Abstract

Type II diabetes mellitus, or non-insulin-dependent diabetes mellitus (NIDDM) is a common endocrine disease, it affects up to 5-10% of the population aged 60-70 years, the frequency of NIDDM increases rapidly in individuals over 40, although it can occur at an earlier age. Mortality among patients with NIDDM is approximately 2 times higher than among people without diabetes. In particular, in patients with NIDDM under the age of 50 years, life expectancy is reduced by 5-10 years. Moreover, the life expectancy of women is less than that of men, but this difference disappears with age. The main cause of death with NIDDM is cardiovascular and cerebrovascular diseases. However, the prognosis of the disease depends not only on the degree of normalization of metabolism, but also on the effectiveness of the treatment of such often concomitant NIDDM conditions as hypertension, obesity, hyperlipidemia, as well as the elimination of bad habits, in particular smoking.

Problems of Endocrinology. 1995;41(4):27-34
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Modern aspects of nutrition planning for a child suffering from diabetes mellitus
Kasatkina E.P., Odud E.A.
Abstract

Fluctuation of blood sugar during the day in a patient with diabetes is largely determined by the nature and mode of his diet. In this regard, nutrition planning, taking into account the glycemic effect of food and the maximum compliance with the insulin therapy regimen, is one of the main links in good control of diabetes. Planning a child’s nutrition is imperative to provide for his age-related energy needs and the optimal ratio of basic food ingredients (proteins, fats and carbohydrates) without lowering the daily calorie rate. The adequacy of the energy and biological value of food to the age requirements of the child is assessed by the normal rate of physical and mental development of the sick child, as well as his good health. However, a child should not only receive food calories, proteins, fats and carbohydrates “due” to him by age, but also enjoy the food. It depends on how diverse the patient’s diet is and how the doctor takes into account the stereotype of the family’s nutrition and the patient’s eating habits: if the regimen and nature of the food recommended by the doctor is familiar and convenient for the patient, this will not create difficulties for observing the basic “dietary” rules.

Problems of Endocrinology. 1995;41(4):34-35
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Experimental endocrinology
Role of GABA-A and GABA-B receptors of the brain in the hypothalamo-pituitary-testicular regulation by the negative feedback mechanism
V. Naumenko Y.V., Amikishiyeva A.V., Serova L.I.
Abstract

The role of gamma-aminobutyric acid (GABA) of the brain and its receptors in the hypothalamo-pituitary-testicular (HPT) regulation by the negative feedback mechanism was for the first time studied in sham-operated and unilaterally castrated adult Wister rats. Increased level of GABA in the central nervous system following an injection of GABA transaminase inhibitor, aminoacetic acid, into the lateral ventricle of the brain was associated with activation of a compensatory increase of testosterone level in the blood, caused by unilateral castration. GABA effect is mediated through the receptors. Muscimol stimulation of GABA-A receptors of the central nervous system activated and their blocking with bicucullin inhibited a compensatory increase of testosterone level in the blood caused by hemicastration. Baclofen stimulation of cerebral GABA-B receptors was associated with an inhibition and their saclofen blocking with stimulation of the level of male sex steroid hormone in the blood following unilateral castration. A conclusion is made about participation of GABAergic mechanisms of the brain in the regulation of HPT function via the negative feedback mechanism

Problems of Endocrinology. 1995;41(4):36-38
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Parathyroidin effect on cerebrovascular resistance
Chursina Y.Y., Khudaverdyan D.N.
Abstract

Effects of parathyroidin in various doses on cerebrovascular resistance was studied in narcotized cats by resistography. Changes in systemic arterial pressure were recorded in parallel with this. A hypotensive dose-dependent effect of the drug was revealed, which manifested at the first minute by reduction of both arterial and perfusion pressure. The reduction of perfusion pressure reflecting a drop of cerebrovascular resistance was less pronounced than arterial pressure decrease. The said parathyroidin effect did not depend on its hypercalcemic effect which manifested much later. A suppressive action of exogenous parathyroid hormone on the transmembranous release of calcium ions in the smooth-muscle cells of the vessels is believed to underlie the detected hemodynamic shifts. These data may be useful in designing schemes of therapeutic correction of cerebral circulation disorders

Problems of Endocrinology. 1995;41(4):38-41
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Relationship between functional activity of the adrenals and gonads in monkeys during puberty
Butnev V.Y., Goncharov N.P.
Abstract

Testicular and adrenocortical endocrine function was followed up for 1 year in pubertal male Papio hamadryas. Blood levels of androgens (testosterone, dihydrotestosterone, dehydroepiandrosterone), corticosteroids (hydrocortisone, progesterone, 17-hydtpxyprogesterone, 17-hydroxvpregnanediol), and aldosterone were radioimmunoassayed. An increase of androgen levels (testosterone and dihydrotestosterone) in the blood of experimental animals during puberty was associated with a reliable reduction of corticosteroid concentration, most expressed in monkeys with the maximal increase of testosterone content. The detected hormonal changes did not influence the mineralocorticoid function of the adrenal cortex, because aldosterone level was unchanged over the entire follow-up period.

Problems of Endocrinology. 1995;41(4):41-43
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Reviews
Immunotherapy for insulin-dependent diabetes mellitus
Dedov I.I., Abugova I.A., Shamhalova M.S., Shishko P.I.
Abstract

The autoimmune nature of insulin-dependent diabetes mellitus (IDDM) is currently undeniable. In the 80s, some features of its pathogenesis were determined: on beta cells of patients with newly diagnosed IDDM, overexpression of class I HLA antigens was detected; on beta and alpha cells of isolated islets of Langerhans, expression of class II HLA antigens in combination with tumor necrosis factor (TNF-alpha) and gamma-interferon (gamma-IF) was detected; the presence or absence of Asp-57 in the N-end of the beta1 domain of the HLADQ beta chain has been shown to be positively associated with IDDM in humans and NOD mice; it was revealed that macrophage interleukin-1 (IL-1) and TNF-alpha have a damaging effect on beta cells: IL-1 exhibits selective beta-cell cytotoxicity in low molar concentrations, and the effect of IL-1 is potentiated by TNF-alpha; it was determined that early infiltration during the development of inflammation of pancreas in BB rats is caused by macrophages and monocytes; destruction of beta cells is performed by T-helpers and natural killers. Thus, the autoimmune concept of the disease necessitates the use of immunotherapy to slow the development of IDDM.

Problems of Endocrinology. 1995;41(4):43-48
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