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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.

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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.

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The allele and genotype frequency distributions of the D11S2008 tetranucleotide microsatellite linked with the catalase (CAT) gene were compared between patients with insulin-dependent diabetes mellitus (IDDM) with (N = 72) and without (N = 82) coronary heart disease (CHD), and between IDDM patients with normal arterial tension (N = 82) and with arterial hypertension (N = 42). In total, eight alleles were found. The alleles varied in length from 120 to 148 bp and included from 15 to 22 tetranucleotide repeats. The groups did not differ in D11S2008 allele and genotype frequencies; the only exception was that the frequency of genotype 18/19 in patients with CHD (31.9%) was significantly higher than in the controls (18.3%). Thus, the D11S2008 polymorphic locus located in proximity to the catalase gene proved to be weakly associated with CHD, but not associated with arterial hypertension, in IDDM patients. Genotype 18/19 was associated with a higher risk of CHD.

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The insertion/deletion polymorphism (I/D) of the angiotensin I-converting enzyme gene (ACE) was examined in type I diabetes mellitus patients (DM) with (n = 31), or without (n = 33) retinopathy, and in type 2 DM patients with either myocardial infarction (MI; n = 75), or with (n = 37), or without (n = 178) retinopathy. No association between the ACE gene and retinopathy in type 1 and type 2 DM patients was revealed. In the type 2 DM patients with MI, a statistically significant (P < 0.05) elevation of the D allele frequency (64%) compared to that without MI (55.3%), together with statistically nonsignificant prevalence of the DD homozygotes (41% versus 30.6%) was observed. Our data indicate that the D allele (RR 1.43) and DD genotype (RR 1.75) are risk factors for myocardial infarction in the type 2 DM patients.

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Results of clinical and laboratory examinations of 161 diabetics are presented. The main factors or risk of nonproliferative diabetic retinopathy are the duration and degree of compensation of diabetes mellitus, development and stage of diabetic nephropathy, the latter factor replacing in experiments with simulation of diabetic retinopathy the level of arterial hypertension, and the blood serum content of high-density lipoprotein cholesterol and ratio of total cholesterol to high-density lipoprotein cholesterol. The factors of risk of proliferative diabetic retinopathy are duration and degree of compensation of diabetes mellitus, development and stage of diabetic retinopathy with this latter factor replacing in simulation of diabetic retinopathy the level of arterial hypertension, and the blood serum levels of triglycerides, low-density lipoprotein cholesterol, fibrinogen, soluble fibrin-monomer complexes, as well as fibrinolytic activity.

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Because little is known about disordered metabolism of uric acid as a pathogenetic mechanism of renal damage in non-insulin-dependent diabetes mellitus (NIDDM) it was studied in 75 NIDDM and 48 IDDM patients. Clinical examination of the patients included evaluation of purin metabolism according to serum uric acid, diurnal urine excretion, uric acid clearance. Hyperuricemia occurred more frequently in NIDDM. Positive correlation was observed between hyperuricosuria and the severity of diabetic nephropathy which was more pronounced in IDDM.

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Use of laser doppler flowmeter helped reveal in patients with diabetes mellitus a decrease of volumetric bloodstream in the capillaries of skin in the absence of clinical and biochemical evidence of microcirculatory disorders. Bloodstream parameters were correlated to the findings of objective methods of diagnosis at the stage of manifest clinical signs of vascular involvement of various localizations. Laser doppler flowmeter may be used for preclinical diagnosis of renal and ophthalmic involvement in diabetics with types I and II conditions as a method to monitor the therapy efficacy in patients with apparent clinical signs of microangiopathies. We should like to emphasize the possibility of mass screenings of patients and the simple technique of using the device, as well as the possibility of assessing the bloodstream not only in the skin, but in the organs and retina as well.

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Besides the known factors contributing to the pathogenesis of diabetic nephropathy, the role of immune mechanisms in types I and II diabetes is discussed of late; the contribution of autoimmune mechanisms to pathogenesis of noninsulin-dependent diabetes (NIDDM) is virtually unknown. Seventy-six patients with NIDDM and 48 with insulin-dependent condition were examined. Under study were levels of antibodies to FxIA and renal glomerular basal membrane antigens in the blood sera of donors and patients with types I and II diabetes, as well as concentrations, size, and pathogenicity of immune complexes. Antibodies to FxIA antigen were detected in patients with both types of diabetes with diabetic nephropathy. Detection of circulating antibodies to FxIA antigen in more than 70% of diabetics in the absence of protein in the urine may be used as a test system for the laboratory diagnosis of diabetic nephropathy prestage and as a criterion for prescription as early as at the initial stages of nephroprotective agents.

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Twenty-five patients with type I diabetes mellitus (8 women and 7 men) aged 19 to 54 with a disease duration of 3 to 19 years were treated by Russian semisynthetic short-acting human insulin mono-H. The daily dose varied from 24 to 44 U. The drug therapeutic efficacy was assessed from the terms of attainment of carbohydrate metabolism compensation, glycosylated hemoglobin level, and changes in daily insulin requirement. Clinical safety of the drug was assessed from changes in antiinsulin antibody level, incidence and severity of hypoglycemia, absence of lipodystrophy and other adverse reactions. The drug was found effective for the treatment of patients with type I diabetes. Its hypoglycemic effect was similar to that of actrapid, a porcine insulin. Fractionated insulin therapy resulted in the majority of patients in a reduction of glycosylated hemoglobin level, of daily requirement in insulin, and of antiinsulin antibody titer.

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Stable compensation of diabetes mellitus, including normolipidemia, underlies the therapy of diabetic angiopathies. Mevacor represents a nonactive lactone form of a certain hydroxy acid, a potent inhibitor of endogenous synthesis of cholesterol, conducive to blood cholesterol reduction. The aim of the present study was the assessment of the efficacy of this drug in therapy of patients with diabetes mellitus. Ten patients were administered mevacor in a dose of 20 mg for a month. Such therapy was conducive to a significant reduction of the levels of cholesterol, LNP cholesterol, triglycerides, and cholesterol/LVP ratio. It also promoted a reduction of the content of lipid peroxidation products in the blood, these products being an active factor of vessel destruction. The levels of hydroperoxides, blood serum and red cell malonic dialdehyde, and superoxide dismutase were also reduced. These results necessitate addition of mevacor to a complex of therapy for diabetes to normalize lipid metabolism.

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Patients with types I and II diabetes mellitus without the clinical signs of nephroangiopathy were subjected to a comprehensive study of renal function. Using the method for determination of endogenous creatinine clearance (140 patients), radionuclide methods (in 350 patients) and beta-2-microtest (in 130 patients) the impairment of renal filtration function was established in 30.8, 67.6 and in 52% of the patients, respectively. In 16.3% of the patients, there was an impairment of the proximal part of the canaliculi. The determination of proteinuria selectivity in polyacrylamide gel revealed latent proteinuria in 70% of the patients and enabled one to specify the spectrum of uroproteins. The informative value of the methods suggested was supported by the results of morphologic studies of biopsy specimens of the kidneys and skin. The importance of the specification of the preclinical stage of diabetic nephroangiopathy was determined by the possibility of the reverse development of the pathological alterations at the given stage. The authors describe the experience gained with the correction of functional disorders by means of programmed administration of insulin using the apparatus Biostator, application of diamicron and angioprotectors.

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A total of 43 patients aged 16-62 with moderately severe and severe type I diabetes mellitus of 2-27 years duration were observed. The patients were admitted to hospital with decompensation of metabolic processes. In order to achieve compensation monocomponent insulins were administered in an individual dose depending on the levels of glycemia and glucosuria and a scheme of drug administration (2 times continuously, i.v. using the Biostator apparatus). The duration of therapy was 4 months. A hypoglycemic effect in relation to immunological and hemorheological indices was assessed. A hypoglycemic effect was noted in all the patients. A positive effect of high-purity insulins on immunological and hemorheological indices was revealed. These insulins can be used for prevention of diabetic angiopathies.

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A degree of a decrease in the content of urocanic acid in washes-off from the skin surface of patients with decompensated diabetes mellitus depends on a period and gravity of disease that may be indicative of disorders of the adenylate cyclase system (or one of its links). Change in the content of urocanic acid in the epidermis of patients with diabetes mellitus treated with the Biostator apparatus, correlates with change in the content of glucagon and blood sugar. The authors discuss a possibility to use the test of urocanic acid determination for the prediction and assessment of the efficacy of therapy of patients with diabetes mellitus.

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Altogether 100 patients with insulin-dependent diabetes mellitus of a labile course were treated using the Biostator unit (artificial pancreas). The control group (20 persons) was treated with divided doses of insulin within a day. A study was made of glycemia, the range of its deviations, daily glucosuria, diuresis, the basal level of C-peptide and glucagon in the study and control groups prior to and after treatment. Statistically significant improvement of the values in the study group was observed, that, in the authors' opinion, can be attributed to the improvement of insulin-glucagon ratio at the expense fo an increase in the basal secretion of C-peptide as a result of the use of the artificial pancreas.

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The authors present for the first time their results concerned with the determination of selective proteinurea by disc electrophoresis in polyacrylamide gel in patients with insulin-dependent and insulin-independent diabetes mellitus with and without the clinical signs of kidney affection. A study was made of the uroproteinograms of these patients before and after the correction of carbohydrate metabolism by means of programmed insulin administration. A conclusion was made of a possibility to use the above method for early detection of diabetic nephropathies. Programmed insulin administration using the Biostator apparatus was shown to improve tubuloglomerular functions, that was expressed in the lowering of proteinurea and in some cases in the improving of the qualitative composition of uroproteins.

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The clinicofunctional characteristics of the kidneys were estimated, biopsy of the kidney and skin with an immunohistochemical study was performed and some immunity values considered in 17 patients with type I diabetes mellitus. The study was performed with respect to the degree of expression of the clinical signs of nephropathy including the preclinical stage, too. Three types of morphological changes in the kidney and skin were singled out. Initial tubuloglomerular disorders occurred at the preclinical stage of nephroangiopathy. The nature of changes in the skin coincided mostly with changes in the kidney lagging behind in some cases. The results confirmed the leading role of metabolic derangements in the genesis of microangiopathies and a necessity of a good compensation of diabetes for its prevention. The immunohistochemical and immunological findings did not make it possible to exclude the immune mechanisms in the development of diabetic nephroangiopathy.

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Phagocytic function of polymorphonuclear leukocytes was studied in patients with insulin-dependent and insulin-independent diabetes. A total of 52 patients were examined; the patients were mainly young, suffering from insulin-dependent diabetes with or without angiopathies. The leukocyte phagocytic activity was studied with the use of the direct method developed by G. I. Podoprigora and V. N. Andreev in 1976. All phagocytosis parameters were shown to be reduced, the relationship between these parameters distorted, and digestion impaired, especially in patients with diabetic functional angiopathy and with the Kimmelstiel-Wilson syndrome. A trial is described of correcting phagocytosis disorders by means of a Biostator apparatus (an artificial pancreas, functioning according to the feedblack principle). Such investigation was the first attempted in this country, no data on the leukocyte phagocytic activity before and after treatment with the use of an artificial pancreas apparatus were reported in foreign literature. Clinical application of the method is described.

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