The present work is devoted studying of epidemiological situation of diabetes mellitus (DM). The data on prevalence and incidence of DM and itsmicrovascular complications among adult population in the different countries of the world is presented. The analysis of numerous researches allowsto speak about high prevalence of this disease all over the world and to allocate a number of the most significant risk factors of development andprogressing of diabetic complications.

Aim. To analyse effects of sulodexide on endothelium-dependent vasodilation (EDVD) of brain vessels in animals with experimental diabetes mellitus. Materials and methods. The study was performed on 45 Wistar male rats (180-219 g b.w.) allocated to 3 equal groups. Group 1 served as control, group 2 included rats with DM given physiological saline, group 3 was comprised of animals with DM given sulodexide (30 LRU for 4 weeks). The endothelial dysfunction (ED) was simulated by inducing DM (single v/v injection of 50 mg/kg streptozotocin). A month later, the endothelium-dependent and independent vasodilation was tested by registration of circulation in brain vessels in the projection of the middle cerebral artery, determination of Pourcelot?s and Gosling?s indices before and after administration of 0.001 mg/kg acetylcholine (Acros organics, USA), 300 mg/kg L-arginine (Acros organics, USA), 0.007 mg/kg nitroglycerin (MTKh, Moscow), 10 mg/kg nitro-L-arginine (Acros organics, USA). Samples for immunohistochemical analysis were prepared using antibodies against e-NOS and endothelin-1 (Novocastra TM) as recommended by the manufacturer. STATISTICA/w7.0 program for Windows (StatSoft Inc., USA) was used for basic statistical analysis of the results of all experiments. Results. Administration of acetylcholine to DM rats caused a much greater (2.58-fold) decrease of EDVD than in control animals whereas endothelium-independent vasodilation remained unaltered (following nitroglycerin administration); Pourcelot?s and Gosling?s indices significantly increased. DM rats given sulodexide showed lower Pourcelot?s and Gosling?s indices than untreated animals. Thus, impaired expression of antibodies against e-NOS and enhanced expression of anti-endothelin-1 antibodies (specific markers of endothelial disturbance) suggest development of ED in DM and endothelium protection by sulodexide that increases the eNOS level and decreases the endothelin-1 level thereby improving EDVD. Conclusion. Administration of sulodexide to DM rats increases the eNOS level and decreases the endothelin-1 level thereby improving EDVD.

Aim.
Comparative analysis of the levels of the membrane attack complex (MAC) - an end product of complement activation, and of hemolytic activitiesof C1 and C3 complement components in sera of patients with diabetes mellitus 2 (DM2) and healthy subjects.
Materials and methods.
37 DM2 patients (7 men, 26 women, mean age 58?9 years (M?б) and 37 healthy subjects without a family history of hereditarydiabetes (17 men, 20 women, mean age 52?12 years). Serum MAC levels were measured by ELISA, C1 and C3 hemolytic activities by usingrabbit antibody-sensitized ram erythrocytes and C1, C3-deficient sera.
Results.
Mean values of all measured parameters in DM2 patients were significantly higher than in controls.
Conclusion.
Pathogenesis of DM2 is characterized by hyperactivation of the complement system including both the classical and terminal cascadesand by hyperproduction of its cytotoxic products.

The CD40 receptor-CD40 ligand system, along with other signal molecules, plays an important role in the development of immune and inflammatoryreactions. CD40R and CD40L are expressed in lymphocytes, monocytes, platelets, endothelial and smooth muscle cells, pancreatic beta-cells, adipocytes,and other cells. The CD40-CD40L system participates in the formation of immune and inflammatory reactions in the cardiovascular system,platelet production and development of autoimmune diseases. Signals mediated through CD40 receptors are involved in the autoimmune process intype 1 diabetes, inflammation of adipose tissue in DM2, development of atherosclerosis and diabetic nephropathy. Therefore, the CD40-CD40Lsystem can be regarded as a universal pathogenetic factor responsible for immune and inflammatory processes, hyperglycemia, and vascular complications.Measurement of CD40 expression in lymphocytes, monocytes, and adipocytes and sCD40L in blood and urine can be used to diagnose andforetell immune and inflammatory processes associated with diabetes mellitus. HMG-CoA reductase inhibitors (statins) and disaggregants (aspirin,clopidogrel) inhibit activity of the CD40-CD40L system. Further studies of possibilities of pharmacological correction of this system may provide abasis for the development of new therapeutic modalities for the management of diabetes and its complications.

Type 2 diabetes mellitus (T2 DM) is often seen in patients with obesity. Bariatric surgery, aimed to decrease body weight, can often help those patientsto improve glycemic status. After some of bariatric operations patients reach normoglycemia in few days, the fact that cant be explained onlyby reduction in weight. Recent trials revealed that the reorganization of gastrointestinal tract provides hypoglycemic effect of such operations. Thisarticle explains the role of proximal and distal gut in pathophysiology of T2 DM.

Aim.
To study effect of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells (CPC) in patients with coronary heart disease(CHD) and postinfarction heart failure (ischemic cardiomyopathy).Methods.
The number of CPC (CD34+ cells) was determined by flow cytophotometry in 47 patients with CHD including 14 with CHD + DM2; 12patients without CHD and DM2 made up the control grouP. Enzyme-linked immunosorbent assay was used to measure N-terminal precursor of brainnatriuretic peptide (NT-proBNP), immunoreactive insulin (IRI) and C-peptide levels.
Results.
The number of CPC in patients with ischemic cardiomyopathy without DM2 was 33.4% greater than in controls. In patients with cardiomyopathyand DM2 the number of CPC depended on the quality of diabetes compensation. It was lowest in case of decompensated DM2 (HbA_1c=9.5?1.8%).In patients with compensated/subcompensated DM2 (HbA_1c=6.8?0.3%) it was significantly higher than in controls and patients with ischemiccardiomyopathy without DM2 (mean 46.5 (p=0.006) and 40.0% (p=0.02) respectively).
Conclusion.
The number of CPC in peripheral blood of patients with ischemic cardiomyopathy and DM2 correlated with the level of DM compensation.It was lowest in patients with decompensated DM2 and exceeded the normal number in patients with CHD without DM2. The number of CPC inverselycorrelated with blood glucose level. Positive correlation of CPC number with IRI and C-peptide levels was documented in control subjects and patientswith CHD without DM2.

Aim.
To study physical abilities of patients in the late postoperative period after surgical treatment of complicated diabetic foot syndrome.
Materials and methods.
This questionnaire study included 116 patients operated in the Department of Purulent Surgery, Sverdlovsk Regional ClinicalHospital No 1, between 01.01.2005 and 31.12.2007. Their physical ability to perform simplest indoor actions was compared with that of 84 DMpatients without diabetic foot syndrome.
Results.
In less than half of the patients the support function of the lower leg recovered within 1-3 years after discharge due to the presence of nonhealingor new wounds, the necessity of unloading, and the absence of prosthetic treatment. Physical abilities were especially poor after above-the-ankleamputations. The operated patients retained the ability to perform simplest indoor actions comparable with that of control subjects depending on DMduration and BMI.
Conclusion.
The latter parameter should be corrected as appropriate before the discharge of the patients from the hospital.

Functional microcirculatory abnormalities in the foot have been given much attention in the recent years for their potential pathogenetic role in thedevelopment of diabetic neuropathy and diabetic foot syndrome. This paper reviews data on the disturbances of skin microcirculation in lower extremitieswith reference to the role of neuropathy and endothelial dysfunction in this pathology. Possible relationships between end-stage renal disease, highplantar pressure and compromised skin microcirculation are discussed. The influence of several drugs on foot skin microcirculation and prospects fortheir use for therapeutic purposes are considered.

Aim.
Assessment of vascular stiffness and endothelial function in patients with type 1 diabetes at different stages of diabetic nephropathy and without it.
Materials and methods.
We examined 93 patients with DM1 aged 18 to 40 years, and disease duration of more than 5 years. The criterion for forming groups is the stage of diabetic nephropathy. Control group consisted of 23 healthy people. The study included an evaluation of the contour of pulse wave analysis, and conducting tests with reactive hyperemia on the unit Angioskan (LTD Angioskan, Russia). Prior to the study of each patients written informed consent.
Results.
In conducting the analysis of the pulse wave contour index of aortic stiffness was significantly higher in all groups of patients with diabetic nephropathy (DN) compared with healthy subjects. However, when comparing patients with T1D without DN and the control group, significant differences of stiffness index (SI) was not been determined. It should be noted that the increase in value of SI is almost independent of the presence of hypertension in the patient groups. In the analysis of reflection index (RI) values of statistically significant relationships were found. In analyzing the test data with reactive hyperemia we showed a reduction in growth of the signal amplitude in a significant number of patients, which is a sign of endothelial dysfunction, and occurs even in patients without clinical and laboratory signs of kidney damage. However, along with a decrease of this index, a large number of patients have paradoxically high its value, which may indicate a high level of basal nitric oxide.
Conclusion.
Increase in the stiffness of the aorta, the progression of DN may be an early marker of macrovascular lesions even in patients without hypertension. Reduced growth of the amplitude of the signal after occlusion in patients with no signs of kidney disease, indicates the presence of endothelial dysfunction even in the preclinical stage of diabetic nephropathy. Paradoxically high increase of the amplitude of the signal can indicate the presence of abnormally high basal level of nitric oxide, which is a marker of inflammation, high-risk factor of progression of angiopathies and fibrosis.

The review is devoted to the pharmacological effects, the results of clinical trials, safety and the research perspectives of the first incretinomimetic exenatide

Quality of life (QoL) studies are very important in many chronic diseases. Diabetes srongly impacts on QoL because of complex control and treatmentregiments and multiple somatic symptoms (acute and chronic complications). In turn, QoL has a significant impact on the prognosis of the disease.The paper reviws QoL definitions, evaluation approaches in medicine, list of examination tools.

Aim.
To study changes of metabolic parameters and neurologic manifestations in patients with type 2 diabetes mellitus and concomitant primaryhypothyroidism under effect of combined therapy.
Materials and methods.
62 patients with distal neuropathy (DN) including 16 with DM2 and primary hypothyroidism (PHT) (group 1), 32 DM2patients without thyroid pathology (group 2), and 15 patients with PHT without DM (group 3). The patients were matched for age and durationof all above diseases. They were treated by alpha lipoic acid-based drugs: thioctacid, thiogamma, berlithion, octolipen (600 U/d i/v), vitamins B:milgamma, combilipen (2 ml/d i/m) for 12 weeks. All measurements were made at admittance, 21 days and 12 weeks after it. The efficacy of therapywas estimated from changes in HbA_1c levels, fasting and postprandial glycemia, lipid metabolism. DN was diagnosed using NSS, TSS, NDS, NDSm,and NIS-LL scales.
Results.
Combined therapy of patients with DM2 and PHT resulted in a decrease of HbA_1c levels within 12 weeks, fasting and postprandialglycemia within 21 and 12 weeks respectively. Compensation of PHT led to a decrease of total cholesterol and triglyceride levels within 12 weeks.Subcompensation of carbohydrate metabolism (postprandial glycemia) improved neurologic symptoms within 21 weeks in all patients (NSS and TSSscales). The same effect was documented within 12 weeks in patients without thyroid pathology (NSS, TSS, NDS, NDSm, and NIS-LL scales). Inthose with PHT beneficial effect was revealed only using the NIS-LL scale. The worst outcome of therapy estimated from NSS, TSS, NDS, NDSm,and NIS-LL scales was documented in patients with DM2+PHT probably due to additional effect of thyroid pathology on the severity of DN.
Conclusion.
The use of NSS, TSS, NDS, NDSm, and NIS-LL scales makes it possible to reveal changes in the severity of sensorimotor disturbancesin DN patients depending on metabolic parameters modified by pathogenetic therapy.

According to the International Diabetes Federation there are at least 285 million people suffering from diabetes mellitus (DM) in the world, and by2030 this figure is likely to be more than 438 million people, mostly at the expense of patients with type 2 diabetes (T2DM) . According to the Stateregister of diabetic patients on January 1, 2010 in Russia there are over 3.1 million patients with diabetes, among them 2,822,634 with T2DM.Diabetes is the leading cause of blindness in adults aged 20-74 years, non-traumatic lower limb amputations, and the last stage of kidney failure.More than 50-80% of patients with diabetes die of cardiovascular complications. In addition, people with T2DM live almost 10 years less than peoplewithout diabetes. With regard to the effective management of diabetes, there is strong evidence showing that improved glycemic control can significantlyreduce the risk of late complications of the disease. The project Consensus of the Russian Association of Endocrinologists (RAE) was publishedin 2011. The main emphasis in this project is on individual approach to treatment of the patient. According to the recommendations of experts RAEmonotherapy antidiabetic agents in combination with lifestyle modification is possible only at the initial level of HbA_1c 6,5-7,5%. At the initial levelof HbA_1c 7,6-9,0% combined therapy should be started immediately, and at the level of HbA_1c above 9.0% insulin therapy should be assigned. It isimportant to note that the priority in the choice of treatment should be safety and efficacy. For one of the most efficient is the combination of metforminand DPP-4 inhibitor

Glibenclemide is the most effective drug among oral hypoglycemic ones. The efficacy of this drug is determined by its unique chemical structure thatcontains sulfonylurea, not only ring, but also benzamid group in the side chain. This provides the maximum affinity for SUR 1 on the betbeta-cell ATP-dependentK+ channels and ability to associate with SUR 2A cells in the peripheral tissues such as cardiomyocytes, smooth muscle cells of the vascular walland adipocytes. However, this feature can increase the risk of hypoglycemic states and have a negative effect on the cardiovascular system. We considerdata from clinical studies proving the efficacy and safety of the drug, which were based on evidence of long-term observations, and which demonstratedreduced risk of vascular complications of diabetes, compatibility with drugs of other groups, and possibility to use in elderand multimorbid patients. Glibenclamidewas evaluated by prestigious H.G. Creutzfeldt Drug Prize in 2010. It is the only SCI listed essential medicine of the World Health Organization.

The safety of antidiabetic medications has received much attention in the resent past. Although concerns on the safety of glibenclamide therapy iscontroversial, some studies showed an increased risk of cardiovascular morbidity (f.e. myocardial infarction) and risk of mortality in subjects usingglibenclamide, but not other SU (gliclazide or glimepiride)

Aim.
DIAMOND (DIAMicrON in Daily practice) is an open non-randomized observational trial aimed to estimate the efficacy and safety of gliclazide(Diamicron MB) in routine clinical practice.
Materials and methods.
394 patients with poor control of type 2 diabetes mellitus (T2 DM), previously treated with diet or one of oral antidiabeticdrug (OAD), were switched to Diamicron MB. Previous therapy was left unchanged, except for a sulfonylurea or glinide that were canceled.
Results.
After 6 months of Diamicron MB therapy (30% monotherapy, 70% combined therapy) target HbA_1c<7% was reached in 64,7% of patients,HbA_1c<6,5% in 30,71% patients. Statistically significant reduction of body weight, systolic and diastolic blood pressure, microalbuminuria ratewas reached. The number of patients with microalbuminuria decreased from 29,19% to 22,59%, with proteinuria from 5,08% to 3,30%. No severehypoglycemia was registered, light hypoglycemia was seen in 2,28% of patients.Conclusions. Diamicron MB was effective and well-tolerated and showed low risk of hypoglycemia with no severe adverse effects in daily routinepractice. Diamicron MB demonstrated nephroprotective features as a result of better glycemic control.

Aim.
To perform cost-effectiveness analysis of prescription of pharmaceutical products and dressing materials and their consumption volume for inandout-patient treatment of diabetic foot syndrome (DFS). To analyse efficacy of the treatment in terms of modern therapeutic standards.
Materials and methods.
This retrospective study is based on the medical documentation of 139 DM1 and DM2 patients with DFS from differentmedical facilities of Moscow (2007). 72 patients were given general out-patient care by surgeons of city polyclinics, 50 ones received specialized aidin the regional Diabetic Foot Cabinet. 67 patients were hospitalized: 20 for general care in the department of purulent surgery of a military hospital,27 for specialized care in the department of purulent surgery of a city hospital, 20 for high-technology care in the endocrinological clinic of the FirstMoscow State Medical University.
Results.
Therapeutic strategy for DFS patients used in the regional Diabetic Foot Cabinet met the current therapeutic standards. General out-patientcare by surgeons of city polyclinics was at variance with the algorithms adopted in this country. Pharmacoeconomic analysis of the spectrum of pharmaceuticalproducts used for in- and out-patient treatment of DFS patients revealed frequent and ungrounded application of drugs whose woundhealing effect remains to be confirmed (pentoxifylline, thioctoic and alpha-lipoic acids).
Conclusion.
Additional training courses for surgeons of Moscow polyclinics are needed to improve the quality of medical aid to DFS patients. Suchpatients must be referred to regional Diabetic Foot Cabinets. Pentoxifylline, thioctoic and alpha-lipoic acids need to be substituted by pharmaceuticalswith validated therapeutic efficacy.

In Russia, sulfonylurea drugs are extensively prescribed to patients with type 2 diabetes mellitus. This work was designed to study pharmacoeconomicaspects of application of 2nd generation sulfonylureas based on the results of the GUIDE study comparing effects of therapy with gliclazide modifiedrelease (diabeton MV) and glimepiride (amaryl). The two drugs are known to be equally effective, but gliclazide creates a much smaller risk ofhypoglycemia than glymepiride. Cost-effectiveness analysis showed that the use of gliclazide cuts the costs of therapy by 40%. It is concluded that thechoice of gliclazide modified release is economically more feasible than glimepiride.

We describe the case of Liver transplantation on the occasion biliary cirrhosis in the patient with diabetes mellitus

We describe the case of Mauriac syndrome in young adult with prolonged poorly controlled type 1 diabetes mellitus.