[Avandia and avandamet in the treatment of patients with diabetes mellitus type 2: effects on secretion of some fat tissue hormones].

AIM: To study effects of avandia and its combination with metformine (avandamet) on secretion of fat tissue hormones. MATERIAL AND METHODS: The examination protocol for 42 patients with type 2 diabetes mellitus (DM) aged 62.4 +/- 7.7 years comprised tests for blood levels of leptin, soluble receptor to leptin, insulin, grelin, resistin and adiponectine. RESULTS: The treatment resulted in reduction of fasting glycemia from 10.69 +/- 2.54 to 8.42 +/- 1.73 mmol/l, of glycosilated hemoglobin--from 8.1 + 1.6 to 7.75%, immunoreactive insulin--from 19.1 +/- 8.3 to 12.0 +/- 6.5 mg/ml, grelin--from 21.7 +/- 14.6 to 17.3 +/- 13.7 mg/ml, leptin--from 40.3 +/- 24.2 to 26.9 +/- 15.4 mg/ml, soluble receptor to leptin--from 17.9 +/- 4.5 to 13.1 +/- 3.5 mg/ml. LDLP and HDLP cholesterol was high. CONCLUSION: Avandia and avandamet are effective antidiabetic drugs with a beneficial effect on secretion of fat tissue hormones.

[The role of the fat tissue and its hormones in the mechanisms of insulin resistance and the development of type 2 diabetes mellitus].

The fact that fat issue is an endocrine gland secreting several hormones participating in the pathogenesis of type 2 diabetes mellitus (DM2) is universally recognized. Fat issue secretes leptin, tumor necrosis factor alpha, resistin, adiponectin, interleukin-6, free fatty acids, visfatin, omentin, perilipin, and other substances that influence the condition of insulinoresistance, one of the main factors responsible for DM2. Subcutaneous fat and visceral depot fat tissue differ in the spectrum of hormones they produce; the list of these hormones is presented in the article. The presence of abdominal or visceral obesity is combined with significant insulinoresistance, which, in its turn, increases the risk of vascular complications of diabetes. The article also cover the participation of other mechanisms - insulin secretion defect, oxidation stress, low secretion of glucagon-like peptide 1, apoptosis, an increased quantity of amyloid and the fl-cell pull in the pancreatic island--in DM2 pathogenesis. The authors present data on the secretion of leptin, resistin, adiponectin, and tumor necrosis factor a, as well as the condition of the functional activity of beta-cells and the degree of insulinoresistance in 30 DM2 patients receiving dietotherapy.

[Effect of metformin on the magnitude of oxidative stress in patients with type 2 diabetes mellitus].

The final glycated products forming in diabetes contribute to the higher atherogenic oxidative modification of low-density lipoproteins (LDL). The impact of glycemic control on the parameters of free radical oxidation was comparatively studied in patients with type 2 diabetes who received metformin (Glucophage, Nycomed) (Group 1, n = 40) and sulfanylurea preparations (Group 2, n - 30, out of them 15 patients took maninil and 15 had diabeton) good glycemic control caused the magnitude of oxidative stress to reduce, which appeared as the decreased levels of primary (lipid hydroperoxides) and secondary (malonic dialdehyde) products of free radical oxidation in LDL and as the enhanced activity of antioxidative defense enzymes. However, with the identical degree of glycemic control, which was determined by the level concentrations of HbA1c and lipids in both groups, the plasma levels of lipid peroxides decreased by more than 5 times in Group 1 patients receiving metformin than in Group 2 patients and the rate of LDL oxidability reduced by 4.5 times. Such a marked effect of metformin on the attenuated manifestations of oxidative stress is indicative of its antioxidative effect independent of the hypoglycemic effect of the drug.

[Lipid reducing and antioxidant action of mexicor in patients with diabetes mellitus type 2].

AIM: To study mexicor effects on functional activity of beta-cells, insulin resistance, lipid metabolism and lipid peroxidation in patients with diabetes mellitus (DM) type 2. MATERIAL AND METHODS: Twenty patients with DM type 2 participated in a double blind randomized trial of mexicor vs placebo. Before and after therapy the following parameters were studied: plasma glucose before meal, immunoreactive insulin, glycosilated hemoglobin, cholesterol, triglycerides, LDLP and HDLP cholesterol, malonic dialdehyde, dienic conjugates, superoxide dismutase, catalase, glutathione peroxidase and alpha-tocopherol. RESULTS: Mexicor significantly improved compensation of carbohydrate metabolism by glucose and glycosylated hemoglobin in the blood, insulin resistance value, lipid metabolism and lipid peroxidation in activation of antioxidant enzymes. CONCLUSION: Mexicor in therapy of DM type 2 improves carbohydrate and lipid metabolism, lipid peroxidation, activates antioxidant defence enzymes, functional activity of beta-cells, reduces insulin resistance.

[REShENNYE I NEREShENNYE VOPROSY ENDEMIChESKOGO ZOBA I YODTsEFITsITNYKh SOSTOYaNIY (LEKTsIYa)].

Iodine deficiency, in addition to the development of an enlargement of the thyroid gland - goiter, leads to a number of other pathological conditions, which are commonly called iodine deficiency diseases. The spectrum of iodine deficiency diseases is wide and depends on the period of life when iodine deficiency affects the body. Iodine deficiency during pregnancy and embryonic development leads to a high prevalence of spontaneous abortion, especially in the first trimester of pregnancy; high perinatal and infant mortality, congenital malformations, congenital hypothyroidism with a lag in physical and mental development. In childhood and adolescence, iodine deficiency is accompanied by an increase in the thyroid gland, in some cases with a violation or delay in physical, mental and sexual development. In the mature period, iodine deficiency is accompanied by varying degrees of thyroid enlargement. Cretinism in iodine-deficient areas occurs with a frequency of 1 to 10%.

[A role of oxidative stress in the pathogenesis of diabetic nephropathy and the possibility of its correction with α-lipoic acid preparations].

Oxidative stress is an imbalance in the body between prooxidants and the antioxidant defense system, which, to varying degrees of severity, accompanies insulin deficiency or insulin resistance, which are one of the essential components of the pathogenesis of vascular complications of diabetes.  It has been established that oxidative stress in diabetes mellitus can be the result of several mechanisms: a) increased formation of reactive oxidants that are formed during the oxidation of both carbohydrates themselves and carbohydrates complexing with various proteins, as well as the result of autooxidation of fatty acids in triglycerides, phospholipids and esters cholesterol; b) reducing the activity of the antioxidant system in the body, which is represented by glutathione, glutathione peroxidase, catalase, superoxide dismutase, vitamins, K, E and C and other antioxidants (taurine, carotene, uric acid and ubiquinol); c) disorders of enzymes of polyol glucose metabolism, mitochondrial oxidation, metabolism of prostaglandins and leukotrienes and a decrease in glyoxalase activity; d) violation of the concentration or exchange of glutathione and ions of certain metals. In addition, ischemia, hypoxia and pseudohypoxia of tissues observed in diabetes mellitus are additional factors contributing to the increased formation of reactive oxidants in various organs and tissues.

[Characteristics of immune system in patients with metabolic syndrome]. / Osobennosti sostoianiia immunnoi sistemy u bol'nykh s metabolicheskim sindromom.

AIM: To characterize features of immune status in patients with metabolic syndrome (MS). MATERIAL AND METHODS: 41 MS patients entered the study (mean age 55.9 +/- 9.7 years). Blood free triiodthyronine (T3f), thyroxine (T4f), TTH, antibodies to thyroglobulin (abTG), thyroid peroxidase (AbTP) were studied with enzyme immunoassay; levels of CD3+, CD4+, CD8+, CD16+, CD72+ were studied with monoclonal antibodies; IgG, IgA, IgM were measured by radial immunodiffusion in gel by Manchini. The size and the structure of the thyroid were investigated with ultrasound. RESULTS: Thyroid pathology was in 48.8% patients with MS, chronic infectious diseases (CID)--in 51.2%. MS patients free of thyroid pathology and CID had elevated blood levels of IgG, IgA, dysimmunoglobulinemia and low relative number of CD3+ lymphocytes, close correlations of T3free with the levels of CD3+, CD4+, CD8+, T4free with CD72+ (r = -0.97 to +0.92), T4free with IgA, IgG (r = -0.96, r = -0.90), TTH and IgA (r = -0.89), weak negative correlations of uric acid with the levels of CD3+, CD4+, CD72+ and positive with CD8+, CD16+, immunoglobulins. Combination of MS with thyroid pathology and/or CID was characterized with aggravated defects in T- and B-cell immunity, fall in IgG, IgA and changed direction of correlations of thyroid and immune statuses. CONCLUSION: Immune status in MS patients was characterized by stimulation of humoral immunity, dysimmunoglobulinemia, T-cell immunity deficiency. This may be related to chronic hyperinsulinemia, dyslipidemia, antigenic stimulation with modified lipoproteins. Thyroid hormones levels positively correlate with concentrations of immunocytes and negatively--with immunoglobulins.

[Functional state of the sympathetic-adrenal system at the stages of developing late complications of diabetes mellitus]. / Funktsional'noe sostoianie simpatiko-adrenalovoi sistemy na étapakh formirovaniia pozdnikh oslozhnenii sakharnogo diabeta.

AIM: To study a functional state of the sympathico-adrenal system in patients with diabetes mellitus (DM) in developing late complications. MATERIAL AND METHODS: The study included 81 DM patients: free of late complications and diabetic autonomic neuropathy (DAN) (n = 24); with DAN (n = 6); with DAN and nonproliferative retinopathy (n = 8); with DAN and nephropathy stage 1-2; with DAN and diabetic retinopathy, sensory polyneuropathy (n = 23); with diabetic nephropathy stage 4 (n = 14). Blood levels of epinephrine, norepinephrine, dopamine were measured using liquid chromatography with electrochemical detection. A spectral analysis of the cardiac rhythm was made with application of the program "Mars". RESULTS: In patients with DM progression there was imbalance of autonomic nervous system, sympathetic hypertonicity, parasympathetic hypotonicity, subnormal power of the central regulatory contour. Dissociation was found between the degree of hypersympathicotonia and a fall of blood catecholamines concentration related to severity of the disease complications. CONCLUSION: Dissociation between sympathetic hypertonicity and low concentration of blood catecholamines is prognostically unfavourable and predicts development of arrhythmia and asystole. Augmentation of centralization of the systems regulating autonomic nervous system reflects tension of the regulatory systems and predicts disruption of adaptation.

Interrelation between compensation of carbohydrate metabolism and severity of manifestations of oxidative stress in type II 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.

[Polymorphic locus D6S392 near the Mn-dependent superoxide dismutase gene is associated with diabetes mellitus in the Moscow population]. / Polimofnyi lokus D6S392 riadom s genom Mn-zavisimoi superoksiddismutazy sviazan s sakharnym diabetom v Moskovskoi populiatsii.

AIM: Distribution of alleles of tetranucleotide microsatellite D6S392 located nearby the gene of Mn-dependent superoxide dismutase (SOD2) was studied in healthy donors (n = 143), patients with insulin-dependent (n = 166) and insulin-independent (n = 101) diabetes mellitus (IDDM and IIDM). MATERIALS AND METHODS: Alleles of the polymorphic locus D6S392 were amplified using polymerase chain reaction (PCR) on the basis of genome DNA isolated from the venous blood of the examinees. PCR products were analysed with gel-electrophoresis in polyacrylamide gel. Significance of differences of allele and genotypes distribution in the population control and patients were assessed with Fisher's criterion and Bonferroni's corrections. RESULTS: Locus D6S392 contains 31 allele from 210 to 330 pn in length and 37 to 67 tandem repeats. Compared to controls, IDDM patients had less frequent incidence of low molecular allele 41 and 42 as well as allele 62. CONCLUSION: Polymorphic locus D6S392 is closely associated with development of DM in Moscow population. This may indicate possible participation of the gene SOD2 in development of this pathology.

[Tonocardin in complex treatment of diabetes mellitus concurrent with hypertension]. / Tonokardin v kompleksnom lechenii sakharnogo diabeta, sochetaiushchegosia s gipertoniei.

AIM: To examine the effect of the alpha 1-adrenoblocker tonocardin (doxazosin) on the course of arterial hypertension (AH) and on carbohydrate and lipid metabolism and insulin resistance in patients with type 2 diabetes mellitus (DM) concurrent with AH. MATERIALS AND METHODS: 18 patients with type 2 DM concurrent with AH, treated with tonocardin for at least 12 weeks were examined; the fasting glycemia, the levels of blood glycosylated hemoglobin, serum total cholesterol and triglycerides, and the degree of insulin resistance (intravenous insulin load or insulin tolerance test and the insulin resistance index estimated by the HOMA method) were determined. RESULTS: Tonocardin treatment lowered systolic BP (from 159 +/- 19.83 to 136.57 +/- 17.43 mm Hg; by 14.5%), diastolic BP (from 93.38 +/- 12.98 to 79.12 +/- 11.69 mm Hg; by 15.28%), fasting glycemia (from 9.32 +/- 1.61 to 7.05 +/- 1.51 mmole/l; by 24.36%), glycosylated hemoglobin Ai (from 9.63 +/- 1.86 to 8.59 +/- 0.98%; by 10.8%), total cholesterol (from 6.09 +/- 0.57 to 5.4 +/- 0.4 mmole/l; by 11.4%), triglycerides (from 2.11 +/- 0.57 to 1.88 +/- 0.52 mmole/l; by 11%), glycemia after 30-min insulin load (from 9.32 +/- 1.61 to 5.77 +/- 1.57; by 39% and from 7.05 +/- 1.51 to 4.2 +/- 1.25 mmole/l; by 44% at the beginning and end of the follow-up, respectively), insulin resistance index (from 9.87 +/- 2.45 to 6.57 +/- 1.99; by 33.5%). CONCLUSION: The findings suggest that tonocardin exerts an antihypertensive effect and positively affects carbohydrate and lipid metabolisms, and diminishes insulin resistance in patients with type 2 DM concurrent with AH.

[Association between insertion-deletion polymorphism of the angiotensin-converting enzyme gene and development of angiopathies in patients with non-insulin dependent diabetes mellitus from the Chuvash Republic]. / Assotsiatsiia mezhdu insertsionno-deletsionnym polimorfizmom gena angiotenzin-prevrashchaiushchego fermenta i razvitiem angiopatii u bol'nykh insulin-nezavisimym sakharnym diabetom iz respubliki Chuvashiia.

Insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene was analyzed in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in the control group consisting of healthy subjects. The insertion allele (I) and genotype II were found to be associated with NIDDM. The frequencies of diabetic retinopathy and nephropathy in NIDDM patients were not associated with this polymorphism. However, an association was found between the DD genotype of the ACE gene and diabetic angiopathy in lower extremities.

[Analysis of polymorphic variants of renin-angiotensin system genes in polymetabolic syndrome and non-insulin-dependent diabetes]. / Analiz polimorfnykh variantov genov renin-angiotenzinovoi sistemy pri polimetabolicheskom sindrome i insulin-nezavisimom sakharnom diabete.

Polymorphisms of the genes for angiotensin-converting enzyme (ACE) and angiotensinogen, the proteins of the renin-angiotensin system (RAS), were tested for association with the polymetabolic syndrome (PMS) and non-insulin-dependent diabetes mellitus (NIDDM) in the Moscow population. The insertional (I) allele and genotype II of the ACE gene proved to be associated with PMS. A significant difference in allele and genotype frequency distributions of the (CA)n microsatellite of the 3'-untranslated exon of the angiotensinogen gene was revealed between randomly sampled individuals and patients with PMS and IDDM from the Moscow population.

[Indications for surgical treatment of diffuse toxic goiter]. / O pokazaniiakh k khirurgicheskomu lecheniiu diffuznogo toksicheskogo zoba.

The results of examination and treatment in 129 patients with toxic goiter (TG) were analyzed. Thyroid status, stable intrathyroid iodine content, thyroid-stimulating hormone (TSH) receptor antibody titer, the volume and echostructure of thyroid tissue were studied either during their first visit and during conservative treatment. The findings suggests that the relapse rate is higher with slow reduction in thyroxine levels and prolonged suppressed TSH during treatment, with higher TSH receptor antibody titer after treatment, with large thyroid volumes when TG manifests it self and in the absence of positive changes in the volume and echostructure of thyroid tissue during treatment, with lower intrathyroid iodine content and its greater reduction during treatment. Earlier surgical intervention should be recommended 2 patients having these risk factors (their combination, in particular).