Aim.
To determine serum lipid profile in native populations (Evens, Nanais, Ulchis) of the Amur region diagnosed with type 2 diabetes mellitus.
Materials and methods.
297 Evens, 792 Ulchis, and 1,274 Nanais aged 30-70 years and older were examined. Total cholesterol, triglyceride, andhigh-density lipoprotein were measured with a Sapphire autoanalyzer (Japan) using Olveks Diagnosticim enzymatic kits (including reference sera).LDL levels were calculated by W.Fridewold formula (TC-HDL-TG/2.2) in millimol/l. Glucose tolerance test to verify type 2 DM was performed withthe measurement of blood glucose level by the glucose oxidase method. Previously diagnosed DM2 was taken into account. The results were estimatedbased on WHO criteria (1999). The study was carried out in winter time.
Conclusion.
Changes of the serum lipid profile in DM2 female aborigines of the Amur region were consistent with the literature data. Specifically, theyshow higher TC, TG,, HDL and lower LDL levels compared with DM-free women of the same population. The lowest levels of TC, TG, HDL, andLDL were documented in female Evens. Nanais and Ulchis with DM2 had similar lipid profiles.

Aim.
To elucidate peculiarities of autorosette formation (ARF), immunological status and associated factors in patients with type 2 diabetes mellitus.
Materials and methods.
The study included 148 patients with DM2 and 63 practically healthy subjects. The following parameters were measured:the number of autorosettes in peripheral blood, C-reactive protein level, and humoral immunity (from blood immunoglobulin levels); spontaneousand induced TNB tests were performed.
Results.
Patients with DM2 suffered disturbances of carbohydrate metabolism and had an elevated number of autorosettes in peripheral blood, dysimmunoglobulinemia,increased level of acute phase protein, impaired functional activity of neutrophils.
Conclusion.
Intensity of ARF increases with duration of DM2 and a rise in AP. Patients with long-standing severe DM2, AH, micro- and macroalbuminurea,hyperglycemia, and triglyceridemia experience deterioration of immunological status.

Aim.
To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease.
Materials and methods.
70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm.
Results.
At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response.
Conclusion.
The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.

The progressive loss of beta cells in Type 1 Diabetes (T1D) is a result of chronic autoimmune attack targeted at diverse molecules expressing in thepancreatic beta cells. The appearance of cellular and humoral autoimmunity precedes the clinical manifestation of T1D. There are several autoantigenswhich are supposed to be involved in pathogenesis of TD1. Zinc transporter 8 (ZnT8; Slc30A8) was identified as a novel T1D autoimmunitytarget.

This review generalizes current data on the genes responsible for combined susceptibility to type 1 diabetes and autoimmune thyroid diseases. Analysisof the role of common genetic markers facilitates understanding their contribution to the development of each of the two or several concomitantautoimmune diseases affecting a single patient

Adipose issue is a source of mesenchymal stem cells (MSC) that can be used to stimulate blood vessel growth in ischemic tissues. Various metabolicdisorders including hypeglycemia may have negative effect on therapeutic properties of these cells. Aim.
To study the influence of high glucose concentration on functional activity in human adipose tissue.
Materials and methods.
Flow cytometry and real time PCR were used to study functional activity of cultured MSC from human adipose issue at highglucose concentration.
Results.
Prolonged (10-12 days) incubation at a high glucose concentration (25 mM) suppressed the ability of MSC to stimulate angiogenesis. Also,glucose modified expression of genes activating and inhibiting angiogenesis but had no effect on MSC proliferation and apoptosis.
Conclusion.
High glucose concentration suppresses angiogenic activity of MSC in adipose tissue; it may account for incomplete restoration of bloodflow in diabetic patients.

Aim.
To study the functional state of the adrenocortical system in experimental animals depending on severity of alloxan diabetes.
Materials and methods.
Diabetes in rats was induced by administering alloxan tetrahydrate at a dose of 17 mg/100 g b.w. Corticosteroids in plasma,adrenals, and 24-hr urine were measured by RIA, immunoenzyme assay, and HPLC. Hepatic aminotransferase activities were determined.
Results.
Durng the first week after induction of diabetes, the animals suffered metabolic disturbances and hypoinsulinemia the severity of which didnot significantly change up to day 30 Activation of adrenal glucocorticoid function (a rise in plasma corticosteron, urine and adrenal corticosteronand progesteron) occurred starting from days 8-9. Enhanced activity of hepatic aminotransferases confirmed physiological significance of elevatedblood corticosteron level.
Conclusion.
Physiological effects of glucocorticoids in the liver decreased by day 30 of experimental diabetes despite persisting disturbances in carbohydratemetabolism, probably due to reduced synthesis of corticosteron in adrenals and its concentration in blood.

The gastrointestinal tract produces hormones that influence glucose-induced pancreatic insulin secretion. One of them is glucagon-like peptide 1.Its synthetic analog, liraglutide, has properties that promote metabolic control in patients with type 2 diabetes mellitus and have beneficial effecton the risk factors of cardiovascular complications.

Aim.
To assess the influence of diabetic autonomous neuropathy (DAN) on left ventricular myocardial remodeling in type 1 diabetes mellitus.
Materials and methods.
The study included 78 patients (30 men and 48 women) with DM1 (mean age 28.9?8.3 years, DM1 duration9.7?7.5 years). DAN was diagnosed by standard ECG tests (Valsalva and breathing tests). The patients were examined using echocardiographywith the measurement of the thickness of interventricular septum (IVS) and left ventricle posterior wall (PW), end diastolic and systolic size (EDS and ESS) of the left ventricle, left ventricular myocardial mass (MM), MM index and relative wall thickness (RWT). LV hypertrophy(LVH) was diagnosed at MM index ?134 g/m2 in men and ?110 g/m2 in women; concentric and excentric types of LV hypertrophy wererecorded at RWT ?0.45 and <0.45 respectively.
Results.
The patients were divided into 3 groups depending on severity of DAN: well-apparent DAN (n=18), early DAN manifestations (n=40),absence of DAN (n=20). IVS thickness and RWT in group 1 were greater than in other groups. LVH occurred in 5.9, 15, and 43.8% of the patientsrespectively (?²=7.8, p=0.02). The frequency of concentric and excentric LVH did not differ. Patients with LVH showed higher values of OSBP andODBP, pulse rate, and parameters of lipid metabolism. Multifactor analysis showed that LPW and IVS thickness more frequently increased in menin proportion to age, heart rate, changes in the Valsalva index (R²=0.55, p<0.05). MM index depended on age, sex, pulse rate, and proteinurea(R²=0.59, p<0.05) while RWT depended on the heart rate and Valsalva index (R²=0.47, p<0.05).
Conclusion.
A rise in the heart rate and decrease of Valsalva index in DM1 patients with progressive cardiovascular form of DAN lead to LVH.

Aim.
To study the functional state of arterioles in patients with type 2 diabetes mellitus and concomitant arterial hypertension (AH) and evaluatethe role of sodium in mechanisms of elevation of arterial pressure (AP) in this pathology.
Materials and methods.
163 patients of whom 83 had DM2 with AH and 80 essential hypertension. They were examined by dopplerography of themicrocirclatory bed, measurement of arterial blood flow and daily sodium urinary excretion.
Results.
Patients with essential AH showed increased arteriolar circulation rate and enhanced reactivity of microvessels. These parameters werereduced in patients with DM2 and AH who consumed large amount of table salt.
Conclusion.
Mechanisms of development of essential AH and AH in DM2 are significantly different.

Type 2 diabetes mellitus is a disease in which traditional therapeutic strategies, such as optimization of the lifestyle, intake of metformin and sulfonylureasor glitazone prove secondarily inefficient in the short run. The discovery and use of new hypoglycemic agents, e.g. DPP-4 inhibitors, openup opportunities for the further improvement of glycemic control. This review contains data on mechanisms of action, efficacy and safety of DPP-4inhibitors exemplified by sitagliptin and their possible effects on the cardiovascular system.

Aim.
To study effect of sulodexide (Vessel Due F) on the functional state of endothelium in patients with diabetic retinopathy.
Materials and methods.
A total of 37 patients with DR were divided in 2 groups and treated with sulodexide. Group 1 comprised 16 patients withnon-proliferative DR, group 2 included 21 patients with preproliferative DR. The functional state of endothelium was estimated from the plasma andserum levels of endothelial factors (sVCAM, endothelin, nitric oxide, t-PA, Willebrand factor).
Results.
The measurement of the initial levels of endothelial factors in both groups revealed significant changes in endothelin, nitric oxide, and sVCAMsuggesting disturbances of endothelial function due to DR. Sulodexide therapy normalized it regardless of DR stage and thereby improved functionalactivity of retina.
Conclusion.
This study has demonstrated beneficial effect of sulodexide on endothelial function in patients with DR due to correction of the productionof vasoactive factors (endothelin, nitric oxide) and stimulation of fibrinolytic activity of the vascular wall (t-PA).

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus leading to deterioration of the patientsquality of life. Effective methods for the treatment of DPN and improvement of both quality of life and long-term prognosis of the disease remain tobe developed.To review pathogenetic mechanisms of DPN, the known methods of DPN treatment and the influence of activation of PPAR-alpha receptors onpathogenesis and outcome of DPN.

Aim.
To determine size structure and blood circulation of thymus in children with type 1 diabetes mellitus (DM1) by ultrasound.We have undertaken an ultrasonic study of thymus in 62 children aged 4-17 years with DM1 to determine its size, structure and bloodcirculation. Results.It was shown for the first time that the thymus of DM1 children is enlarged and fairly well visualized unlike that in agematchedhealthy patients in whom it is much smaller due to age-related involution and substitution of the thymic tissue by adipose one. Colorand energetic Doppler mapping showed perfect vascularization of the thymus in DM1 children compared with healthy patients in whom thismethod failed to map blood flow due to the substitution of the original thymic tissue by parenchymal and adipose tissues and dropout of bloodvessels. Conclusion the study for the first time gave evidence that thymus, the main immunogenic organ (conductor of the immune system),undergoes age-specific changes of size and structure whereas DM1 of autoimmune etiology precludes its involution.

Aim.
To evaluate the diagnostic and prognostic value of hemodynamic characteristics and endothelial function (EF), viz. endothelium-dependent vasodilation (EDVD) and vasoconstriction (EDVC), during development of diabetic nephropathy (DN).
Materials and methods.
A total of 155 children and adolescents aged 9-17 years (residents of Volgograd) with type 1 diabetes mellitus (DM1) from 1 to 14 years in duration were examined at the Endocrinological Department of the Regional Childrens Clinical Hospital. The patients were divided into 3 groups depending on DM1 duration. EF and arteriolar tone (AT) were determined by the rheovasographic method. AT was calculated from vascular distension by a pulse wave based on tetrapolar rheovasography of the shoulder and its first derivative. Rheograms were registered using the Valenta software-hardware system. EF was evaluated in a reactive (working) hyperemia test with occlusion of blood vessels in the arm for 4 min followed by decompression; these procedures resulted in an abrupt acceleration of blood flow and endothelium response to shear stress by EDVD. EDVC was determined by occlusion of blood flow in the wrist area that caused its steady decline in the brachial artery and a decrease of its diameter suggesting enhanced vascular tone. Rheovasography was performed during occlusion.
Results.
Children with DM1 showed enhanced EDVC and impaired EDVD diagnosed before manifestation of microalbuminurea (MAU) characteristic of early DM1.
Conclusion.
Changes of EF determined from AT, EDVD and EDVC in children with DM1 before manifestation of microalbuminurea make it possible to identify patients at risk of vascular complications.

Aim.
To study renal functional reserve and partial functions in patents with type 2 diabetes mellitus in the absence of renal lesionsMaterials and methods. We examined 42 patients (17 men and 24 women) aged 38-69 (mean 49.8?8.3) years with DM2 4.6?2.6 yr in duration.Control group comprised 32 practically healthy subjects. Intrarenal hemodynamics was estimated from RFR values. Ethanolamine, uric acid, Ca,and P levels were measured in sera and 24-hr urine; daily excretion of ammonia and aminonitrogen in the urine was determined.
Results.
The patients were divided into 2 groups based on the results of RFR measurement. FRF remained unaltered in 21 patients (mean 60.7?27.6%)and decreased in the absence of filtration reserve in 20 (-25.8?23.4%). Correlation analysis revealed the relationship of lipid metabolism and abdominalobesity with the renal tubular function and intraglomerular hemodynamics.
Conclusion.
Examination of DM2 patients without clinical and laboratory signs of renal lesions revealed compromised function of all nephron compartments,viz. intraglomerular hypertension, impaired stability of renal cell membranes, and tubular dysfunction. The latter is related to hemodynamic disturbances.

As known insulin therapy is associated with induration of subcutaneous fat at injections sites called lypohypertrophy. It develops at any age and at anysite regardless of duration of the treatment. The size of lypohypertrophy varies in a wide range. Numerous studies have been conducted to elucidatemechanisms of lypohypertrophy (LH) and its risk factors including young age, low or high body mass index, frequency of the change of needles andinjection sites, female gender, and type 1 diabetes mellitus. It was shown that insulin crystals induce a local immune reaction and thereby interfere withadipocyte differentiation. At the same time, patients with LH have elevated titters of anti-insulin antibodies. The problem with LH is uncontrollableabsorption of insulin from injection sites. We noticed that patients with a target glucose level due to insulin therapy undergo its apparently causelessperiodic rises. Comparative ultrasonic examination of subcutaneous fat at different injection sites and control body areas revealed specific pathologicalchanges in adipose issue. This finding provided a basis for the hypothesis that LH can be detected by ultrasonography of subcutaneous fat. It wasconfirmed by the results of examination of 50 patients with DM1 treated with insulin of whom 41 were found to have pathological changes at injectionsites.

Aim.
To study efficacy of treatment with liraglutide in women with type 2 diabetes (T2D) and obesity.
Materials and methods.
A group of 12 women aged 52-58 yr with T2D duration of 3-5 years, BMI 32-35 kg/m2, abnormally high C-peptide level,and НbА1с 7.5-8.5% were treated with 1500-2000 mg metformin/day and sulfonylureas at 50% of the maximum dose. Liraglutide was given insteadof sulfonylureas by a standard method (0.6 U/day for 1 week subcutaneously and 1.2 U/day thereafter). The total duration of therapy was 3 months.We analysed blood glucose level before and 2 hr after meals, НbА1с, lipidogram, C-peptide, HOMA index, BMI, waist circumference, percent of totalfat in the body, frequency of hypoglycemia, and side effects (nausea).
Results.
All patients achieved target values of НbА1с and a significant decrease in blood glucose before and after meals, body weight, total fat content,BMI, HOMA, systolic blood pressure; HDL cholesterol increased while LDL decreased. No case of hypoglycemia was documented. All the patientshad mild nausea of short duration (2-3 days).
Conclusion.
The use of liraglutide (Victoza) in women with T2D and obesity improve carbohydrate metabolism and insulin resistance without seriousside effects.

Aim.
To estimate dynamics of secretory and motor-evacuational functions of the stomach in patients with type 1 diabetes mellitus and gastrointestinalform of diabetic neuropathy.
Materials and methods.
32 patients with DM1 without gastrointestinal pathology allocated to different groups depending on DM duration (gr. 1 lessthan 10 yr, gr. 2 over 10 yr). Vegetative equilibrium was estimated from the Kerdo index, rehabilitative potential from its basic constituent (morphophysiologicalindex). The motor-evacuational function of the stomach was studied with the use of a scintillation gamma-chamber, the gastric secretoryfunction by pH measurements.
Results.
Half of the patients in gr 2 presented with hypersympathicotony. The frequency of hypertonic form of gastric tone increased with durationof DM while the acid-producing and evacuational functions of the stomach decreased (as estimated by pH-measurement and gastroscintiographyrespectively). The propulsive function most significantly decreased in the pyloric part. The efficacy of rehabilitation of diabetic patients with gastrointestinalform of diabetic neuropathy was much lower than in those with preserved vegetative function of the stomach.
Conclusion.
Impairment of evacuational function of the stomach and duodenum with DM1 duration may be a cause of unstable blood glucose level.Hypomotor dyskinesia of the upper gastrointestinal tract due to DM1 and deficit of parasympathetic innervation occurs more frequently in patientswith low rehabilitative potential. Functional changes in the gastrointestinal tract of DM1 patients do not depend on the quality of compensation ofmetabolic disorders but correlate (r=-0.39) with DM duration. It is concluded that the gastrointestinal form of diabetic neuropathy impairs rehabilitativepotential of fhe patients.

Type 2 diabetes mellitus (DM2) is a chronic progressing disease associated with insulin resistance and impaired insulin secretion insufficient toovercome insulin resistance that deteriorates as a result of glucose toxicity and beta-cell apoptosis. Combination of metformin and sulfonylureas (SU) iscurrently regarded as an effective strategy of hypoglycemic therapy having effect not only on the main stages of pathogenesis but also on t dangerousrisk factors leading to adverse events (hypoglycemia, body weight increment, cardiovascular disorders). Amaryl, SU of the 3d generation, meets allcriteria of safety and efficacy for combined hypoglycemic therapy due to its high affinity to a specific subunit of SU receptors-1 on beta-cells coupled toshort-term stimulating action on insulin secretion. Moreover, it has a unique SU-unrelated extrapancreatic mechanism of action. The efficacy andsafety of Amaryl was confirmed in a number of clinical studies which gives reason to recommend it for inclusion in any modern hypoglycemic therapywith a minimal risk of hypoglycemia, lack of weight increment, positive effect on the cardiovascular system and progress of atherosclerosis

Aim.
To study efficacy of glycemic control in terms of reduced HbA_1c level using glyclazide modified release (MR) in patients with DM2 and differentclinical characteristics at the initial stage of therapy in the framework of ADVANCE study (Action in Diabetes and Vascular Disease: Preterax andDiamicron Modified Release (MR) Controlled Evaluation).
Materials and methods.
A total of 11140 patients aged 55 years or older with DM2 and one or several cardiovascular risk factors were randomized forthe study. They were randomly distributed between 2 groups, one to receive intensive hypoglycemic therapy with glyclazide MR the other to be treatedin a standard mode as recommended by local, regional or national guidelines after a 6 week introductory phase. The efficacy of therapy was assessedbased on the following criteria: absolute change in HbA_1c level (difference between the last and the first values obtained during the randomizationperiod), real HbA_1c level achieved, percent of patients with target HbA_1c level (<7.0, <6.5 or <6.0%) in the end of the follow-up (median 5 yr).Also, the efficacy was evaluated in subgroups formed based on the patients age and sex, DM duration, BMI, starting HbA_1c level, and the use ofhypoglycemic agents.
Results.
Mean HbA_1c level decreased by the end of the 5 year follow-up period from 7.5 to 6.5 and 7.3% in patients given intensive and standardhypoglycemic therapy respectively. Intensive therapy allowed to achieve the target HbAc1 level (<7.0, <6.5 or <6.0%) in a greater number of patientsof all subgroups (p<0.0001). The key independent predictors of HbA_1c reduction were its initial level, duration of DM, and BMI in the early phaseof the study. Patients given intensive therapy did not increase mean body mass and had only rare episodes of severe hypoglycemia even if somewhatmore frequent than in the control group.
Conclusion.
Intense hypoglycemic therapy with glyclazide MR is well tolerated and equally efficient in DM2 patients with a wide range of clinicalcharacteristics.

Intensive combined therapy including modification of the lifestyle, intake of metformin and/or sulfonylureas, insulin treatment in the absence ofadequate HbAc1 control, hypolipidemic, early antihypertensive and antithrombotic therapy not only decreases the frequency of DM2 complicationsbut also reduces the total cost of the treatment (1.8 times compared with traditional therapy). Reduction in cardiovascular mortality achieved inSTENO-2 was due to intense control of risk factors at early stages of therapy with the use of modified release gliclazide (Diabeton MV). This treatmentis considered to be not only more efficacious than routine therapy but also to significantly reduce the cost of the management of DM2

The majority of diabetes cases are referred to two pathogenetic forms, DM1 and DM2. Other variants are much rarer. One of them is DM resultingfrom disturbances in the pancreatic exocrine apparatus, e.g. pancreatitis, underlain by a different pathogenetic mechanism. A case of diabetes mellitusassociated with biliary recurrent pancreatitis is described. The importance of comprehensive examination of such patients and their specific treatmentis emphasized