Aim.
To study prevalence, clinical and prognostic significance of prothrombotic genotypes pre-dominant in inborn thrombophilia in patients with diabeticnephropathy (DN).
Materials and methods.
A total of 90 patients with DN were examined; 54 and 36 cases suffered DM1 and DM2 respectively. Control group comprised100 healthy subjects. PCR was used to iden-tify single nucleotide substitution (C677T) in the methylene tetrahydrofolate reductase gene (MTHFR),point mutation in coagulation factor V gene (FV), and G202210A mutation in factor II gene (FII).
Results.
The probability of DN in patients with DM1 increases in the presence of Leiden mutation and in DM2 patients in the presence of single nucleotidesubstitu-tion (C677T) in MTHFR gene and G202210A mutation in the 3-untranslated region of FII.
Conclusion.
The prevalence of the above mutations associated with blood coagulation potential in DN patients is higher than in healthy subjects.Key words: diabetes mellitus, diabetic nephropathy, gene polymorphism, methylenetetrahydrofolate reductase

Aim.
To measure concentration of carbohydrate-containing biopolymers in liver and gastric mucosa of rats with alloxan diabetes and varying stressresistance.
Materials and methods.
The ?open field? test was used to allocate the animals to 2 groups (stress-sensitive and stress-resistant). Insulin-dependentdiabetes was induced by a single s/c injection of alloxan tetrahydrate (170 mg/kg). Total glycosaminoglycanes and gyaluronidase activity were measuredin gastric mucosa.
Results.
Concentration of glycosaminoglycanes (sialic acids) in the liver increased in animals of both groups and reached a maximum on day 30.
Conclusion.
Metabolism of sialoglycoproteins in gastric mucosa was dominated by catabolic processes most intense on day 45 after induction of experimentaldiabetes

Aim.
Circulating precursors of endothelial cells (PEC) play an important role in regeneration of damaged vascular endothelium and myocardium and neovascularization of ischemic tissues. The aim of this work was to study effect of disturbed carbohydrate metabolism (DCM) on the number of PEC in patients with different forms of CHD.
Materials and methods.
The number of PEC was determined by flow cytofluometry, insulin and C-peptide levels by IFA in 78 patients aged 40-69 (mean 55.5?0.9) years. Control groups comprised 17 subjects without CHD and DCM, 33 patients were allocated to the stable angina (SA) group (48% with DCM), 28 suffered acute coronary syndrome without segment ST elevation (ACS-ST) (39% had DCM).
Results.
The number of PEC was reduced in all CHD patients, by 23% in the SA group (p<0.05) and by 43% in the ACS-ST group (p<0.001). The number of PEC in patients of the latter group was 26% smaller than in the SA group (p<0.05). Patients with SA and DCM showed a significant decrease in PEC compared with controls (p<0.05) and tendency (insignificant) toward decrease compared with SA patients without DCM. The presence or absence of DCM in the ACS-ST group did not influence the number of PEC. The number of PEC negatively correlated with blood glucose level (r=-0.23, p=0.04) and insulin concentration in SA patients (r=-0.48, p=0.01).
Conclusion.
The number of PEC in peripheral blood of patients with CHD is reduced; the decrease is especially pronounced in patients with ACS-ST. SA is associated with the most significant decrease in circulating CD34+ cells in the presence of DCM whereas DCM has no marked effect on the number of PEC in ACS-ST patients. The higher the blood glucose level the smaller the number of circulating CD34+ cells.

Aim.
To elucidate the relationship between testosterone and SSBG levels in men with age-related hypogonadism and metabolic syndrome.
Materials and methods.
The study included 125 men aged 30-80 years with a diagnosis of age-related hypogonadism. In all the cases, testosterone(T) and SSBG levels were determined, free T fraction calculated, and waist circumference measured. Almost half of the patients (n=56) presentedwith metabolic syndrome (MS) and underwent measurement of basal immunoreactive insulin (IRI).
Results.
Mean age of the patients (n=125) was 54 [46; 65] years, waist circumference 108 [102; 115] cm, total T 8.3 [5.9; 11] nmol/l (norm 12 -33.5), free T 140 [99.6; 184] pmol/l (norm <250), SSBG 38,8 [28.2; 63.2] nmol/l (norm 12.9 - 61.7). Positive correlation was found between thepatients age, total T and SSBG levels (r=0.33, p<0.001 and r=0.39, p<0.001 respectively) as well as between total T and SSBG levels (r=0.48,p?0.001). The patients were divided into 2 groups depending on the presence or absence of MS. Group 1 (MS, n=56) was characterized by lowerlevels of SSBG, total and free T and more pronounced abdominal obesity compared with group 2 (without MS, n=69). 31 patients in group 1 hadmean IRI level of 26,4 [13; 36.6] mcU/ml (norm 2.3 - 26.4). There was no correlation between SSBG and IRI levels. 18 patients had elevated IRIlevels (mean 33.95 [32.4; 62.5] mcU/ml that positively correlated with SSBG levels (r=0.53, p<0.0006).
Conclusion.
Patients with age-related hypogonadism and metabolic syndrome have lower levels of SSBG, total and free T and greater waist circumferencemeasures compared with age-matched patients without MS. Despite lowered SSBG level in group 1 patients, it remains within normallimits and therefore can not be used as a diagnostic marker of age-specific hypogonadism and MS. In patients with these conditions, there isno correlation between SSBG and IRI levels; in hypogonadic patients the SSBG level is unrelated to waist measures regardless of the presenceor absence of MS.

Aim.
To study the prevalence of androgen deficiency in men with type 1 diabetes mellitus (DM1) undergoing programmed hemodialysis (PHD) andto develop methods for the treatment of metabolic disorders.
Materials and methods.
The study included 43 men with DM1 on PHD. Group 1 comprised 20 patients below 40 years of age, group 2 included23 older patients. Patients of group 1 were allocated to subgroup A (treated with testosterone and ether mixture (TEM)); and control subgroup B(n=14 and 6 respectively). Patients of group 2 were divided into subgroup C (treated with TEM) and control subgroup D (n=14 and 9 respectively).Patients in the study and control subgroups were matched for age, duration of DM1, hemodialysis (years), total testosterone (TT, nmol/l), hemoglobin(Hb, g/l) and glycated hemoglobin (HbA_1c, %) levels. All the patients were treated with epoetin-beta (EPO-b) on an individual basis depending onHb level; TEM was given thrice weekly.
Results.
Group 1: age 34.0?3.9 yr, HbA_1c 9.3?1.4%, Hb 118.1?9.6 g/l, TT 21.2?6.6 nmol/l. Group 1: age 47.3?3.5 yr, HbA_1c 9.5?1.8%,Hb 94.9?5.7 g/l, TT 9.8?3.9 nmol/l. Androgen deficiency was diagnosed in 48.8% (total group), 5.0% (group 1) and 86.9% (group 2) of the patients.Reduction of TT level was not accompanied by a significant rise in LH concentration to above normal values (p>0.05). HbA_1c level in eithergroup did not significantly change within 6 months after the onset of the study. Combined treatment with EPO-b and TEM resulted in a Hb concentrationof 118.2?6.7 g/l in subgroup A (p=0.79). Hb level in subgroup C increased to 113.5?6.3 g/l (p=0.009). Hb changes in control groups wereinsignificant. Requirement for EPO-b in subgroups A and C decreased by 32.1% (p=0.007) and 41.1% (p=0.001) respectively but remained unalteredin both control subgroups.
Conclusion.
Reduction of the TT level in men with DM1 on PHD is a function of age and constitutes an independent risk factor of anemia. Androgendeficiency and its correction have no effect on carbohydrate metabolism. Combined treatment with EPO-b and TEM increases blood Hb level in oldermen and reduces requirement for EPO-b regardless of the age.

Diabetic neuropathy is a severe complication of diabetes mellitus (DM) that considerably worsens the patients quality of life and reduces life expectancy.The FIELD study for the first time demonstrated the ability of fenofibrate to prevent macro- and microvacular complications in patientswith DM2 regardless of glycated hemoglobin level and dyslipidemia at the early stage of the disease. Neuropathy being a manifestation of microangiopathy,it suggests the possibility to treat this disorder with fenofibrate.Aim.
To study effects of fenofibrate in patients with type 2 diabetes mellitus complicated by diabetic neuropathy.
Materials and methods.
The present study included 73 patients with DM2 randomized into 2 groups to receive standard therapy (antihypertensiveand glucose control, statins) or fenofibrate (Tricor 145 mg, Solvay Pharma) in addition to the standard treatment.
Results.
Positive effect of fenofibrate on autonomous and peripheral neuropathy was apparent within 6 months after the onset of therapy when thesought parameters of AP, glycemia, and lipid spectrum were achieved. Fenofibrate improved cardiovascular function, reduced cardiac rhythm variability;QT length and dispersion, pain and paresthesia thereby enhancing quality of life and preventing cardiovascular catastrophes including death.
Conclusion.
It is concluded that supplementation of standard therapy of DM with fenofibrate is both safe and pathogenetically sound.

Aim.
To study lipid composition and Na⁺,K⁺-Na⁺,K⁺-ATPase activity in erythrocyte membranes of patients with type 2 diabetes mellitus and dyslipoproteinemia.
Materials and methods.
The study included 40 patients (22 men and 18 women) aged 40-65 years with DM2.
Results.
The patients had abnormal lipid composition and impaired Na⁺,K⁺-Na⁺,K⁺-ATPase activity in erythrocyte membranes. The magnitude of thesechanges depended on the duration of pathology, severity of diabetic dyslipoproteinemia, and quality of compensation of carbohydrate metabolism.
Conclusion.
Aim.
Investigation of lipid dysorganization in erythrocyte membranes in patients with type 2 diabetes mellitus yields data for the developmentof therapeutic modalities to correct dyslipoproteinemia.

Type 1 diabetes mellitus (DM1) is known to be associated with progressive destruction of pancreatic beta-cells. Apoptosis plays the key role in this destructiveprocess. The paper focuses on major mechanisms underlying activation of beta-cell apoptosis and its role in regulation of immune processes inpatients with DM1.

Type 2 diabetes is believed to develop as a result of lowered insulin secretion and insulin resistance leading to hyperglycemia. Sulfonylureas stimulateinsulin secretion and thereby decrease blood glucose level which accounts for their wide application in the treatment of diabetes. However, manyagents of this class produce side effects (increased body mass, hypoglycemia, resistance to therapy, etc.) attributable to excess stimulation of insulinsecretion. Glimepiride is as efficient as traditionally used sulfonylureas but causes a smaller rise in insulin secretion. Sulfonylurea receptors showlower affinity for glimepiride than for glibenclamide. Formation and dissociation of glimepiride-receptor complexes occur faster than those of glibenclamide-receptor complexes. In addition, therapeutic effect of glimepiride was shown to be associated with improved insulin sensitivity. It is concludedthat glimepiride is an efficacious agent for the treatment of type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) - common chronic liver disease, characterized by pathological accumulation of fat droplets, not associatedwith alcohol. NAFLD is often a component of other diseases such as metabolic syndrome, diabetes, obesity, and contributes to the prevalence of CVDamong the population.Asymptomatic disease, the difficulty of diagnosis, the lack of a unified concept of treatment NAFLD - topical issues that require more in-depth studyand worthy of attention a wide range of specialists.

Aim.
To elucidate the relationship between glycemic control (assessed by the level of HbA_1c) and psychological status of the patients.
Materials and methods.
The study included 115 patients with type 1 diabetes aged 13-27 years. The following tests were used to assess the psychological statusof the patients status (emotional state, social relations, attitude toward disease): State-trait-anxiety Inventory (Spielberger C.D., Hanin Y.L), Center for EpidemiologicStudies Depression Scale (CES-D), Social ajustment scale by A.K. Osnizkiy based on Q-Sort Adjustment Scale developed by R. Dymond andC.R. Rogers (1954), Lusher colour test , Colour attitudes test, A.M. Etkind original technique, method for the assessment of attitude toward disease developedin V.M. Bekhterev Research Psychoneurologic Institute, Sankt-Peterburg. The patients were allocated to 3 groups differing in terms of 33.3% percentile ofHbA_1c levels.
Results.
Patients with good glycemic control (mean HbA_1c level 7.4%) show the lowest level of social adaptation and emotional well-being. The reason for thisphenomenon is the excessive focus of patient on the disease and narrow scope of interests, which suggest psychological dependence on diabetes. Patients withpoor glycemic control (mean HbA_1c level 13.1%) also experience emotional discomfort due to increased anxiety. Despite the fact they exhibit a higher degreeof social adaptation than the patients of the above group, the main concern is the low level of communicative autonomy and the feeling of being unable to copewith the disease. Such personal characteristics also create a psychological dependence on diabetes, although of a different type than in the first group of patients.Patients with average glycemic control (mean HbA_1c level 9.5%) in the sample have the most favorable psychological state in comparison with the other twogroups. Their emotional state and social adaptation are significantly better than in the other two groups. These patients tend to psychological autonomy and independenceand maintain multifaceted life motivation in terms of diabetes. They perceive the disease as a given, some life condition that allows to maintaina positive psychological state, high daily activity, not to feel overwhelmed with diabetes and at the same time pay attention to diabetes self-management evennot quite sufficient.Conclusions. Glycemic control and psychological status in young adults does not coincide with each other, although there is a close relationship among them.Attitude toward the disease is the most important mediator of this relationship. Professional psychological help and educational interventions designed to developskills of the practical management of diabetes may contribute to improvement of metabolic control, psychological well-being and social adjustment of patients.

Aim.
To evaluate the frequency of H.pylori infection and efficiency of its eradication in patients with type 2 diabetes mellitus.
Materials and methods.
The study included 40 patients with DM2 and 38 diabetics with chronic gastritis (CG). H.pylori was detected by urease assayusing 13C-urea. The degree of stomach bacterial contamination was assessed by a semiquantitative histological method. Control groups comprisedpatients with gastric ulcer and CG having undisturbed carbohydrate metabolism.
Results.
The frequency of H.pylori infection was virtually identical in patients with and without DM2 regardless of gastric problems. However, comparativeanalysis revealed significant correlation between the graveness of infection and duration of DM2 (r=0.84; p<0.05). The efficiency of H.pylorieradication by first-line therapy in DM2 patients was significantly lower than in controls (p<0.05).
Conclusion.
Frequent intake of antibiotics was a key factor responsible for resistance to eradication therapy. This funding should be taken into accountwhen prescribing anti-helicobacter therapy to patients with DM2.

Diabetic retinopathy (DR) is a main cause of blindness throughout the world, with chronic hyperglycemia and arterial hypertension being the keycontributors to the development of this microvascular complication. A few international multicentre studies have recently been conducted to assesseffect of intensive control of glycemia and AH on the development and progress of DR in type 1 and 2 DM patients. Results of DCCT, UKPDS,DIRECT, ADVANCE, and AdREM studies are reviewed.

Results of 31 controlled randomized studies of insulin glargine given to patients with diabetes mellitus are reviewed to evaluate the frequency of malignantneoplasms. 52 tumours were diagnosed in 45 (0.8%) patients on insulin glargine therapy and 48 tumors in 46 (0.9%) patients using other insulins(mostly NPX insulin). The incidence of breast cancer was equal (0.1%) in both groups (4 and 6 cases respectively). These data indicate thatthe use of insuline glargine does not increase the risk of malignancy, e.g. breast cancer.

Aim.
To assess efficiency and safety of therapy at the onset and after intensification of the treatment with biphasic insulin aspart 30/70 (NovoMix 30)in patients with type 2 diabetes who failed to reach the desired level of glycemic control by using other forms of insulin.
Materials and methods.
The study included the Russian cohort of patients participating in the global IMPROVE program - a multi-center and multinationalopen observational non-randomized study for the evaluation of safety and efficiency of biphasic insulin aspart 30. Patients with type 2 diabetesmellitus were treated during 26 weeks under conditions of routine clinical practice. A total of 4869 patients enrolled in the program receivedantidiabetic treatment in the period preceding the study. 2430 of them were given oral hypoglycemic (OHG) agents alone and 2343 insulin +/- GHG.95 patients were preciously untreated. The dosage regime was prescribed by the attending physician on an individual basis. Most patients were poorlycompensated prior to the onset of the study. Their mean HbA_1c level of 9.2% amounted to 9.9% in the untreated patients. Results of the treatment were analysed by the standard statistical methods for the entire cohort and for separate groups formed depending on previous therapeutic modality.
Results.
Six months after beginning of treatment with NovoMix 30, the HbA_1c level significantly decreased by 2.34% in the entire cohort, 2.50% inthe previously untreated patients, and 2.13% in the two treated groups (p<0.0001). Fasting and postprandial glucose levels also fell down. The frequencyof severe hypoglycemia decreased from 0.093 to 0.002 per previously treated patient per year (p<0.0001) and mild hypoglycemia from 10.09to 5.32 per patient per year (p<0.0001). Only 6 (<0.1%) serious adverse events were documented in the cohort of 4869 patients which correspondsto ~2400 patient-years of NovoMix 30 therapy.
Conclusion.
The use of NovoMix insulin in routine clinical practice permits to optimize glycemic control without a rise in the frequency of hypoglycemiaand increase of body weight in DM2 patients who failed to reach the desired level of glycemia with other insulin preparations.

Aim.
To carry out cost-effectiveness analysis of treatment options for type 2 diabetes using different groups of medicines, to prognosticate late diabeticcomplications and the cost of their management.
Materials and methods.
A total of 3678 DM2 patients (with mean HbAc1 level 9.3%) were examined in 23 regionsin the framework of the Diabetesmellitus subprogram of the Federal target program "Prevention and control of socially significant diseases". Two hypothetical therapeutic modalitieswere considered: treatment with NovoMix 30 and oral hypoglycemic (OHG) agents. The CORE model was used to analyse anticipated expendituresand DM outcomes.
Results.
Simulation revealed a greater decrease of HbA_1c levels (-1.7%), reduction of total cholesterol, LDL, systolic AP (-4.1%) and risk of cardiovasculardiseases coupled to increase of HDL in patients treated with NovoMix 30. Maximum life expectancy was 17.2 yr compared with 16.5 yrin the OHG group and overall cost of the treatment 1,650,725 and 1,586,234 rubles respectively. Savings for the treatment of diabetes using NovoMix30 amounted to 19,832 rubles per patients due to reduced indirect expenditures including management of renal, cardiac, ophthalmologic , and cerebrovascularcomplications.
Conclusion.
Simulation of late results of DM2 treatment demonstrated enhanced pharmacoeconomic efficiency of modern insulin analogs comparedwith OHG agents.

Aim.
To evaluate results of panretinal laser coagulation (PLC) for severe non-proliferative and early proliferetaive diabetic retinopathy (DR) in patientswith type 1 diabetes mellitus (DM1).
Materials and methods.
58 patients with DM1 were observed. All of them were treated by panretinal laser coagulation after subtenon administrationof triamcinolone (40 mg) under ultrasonic control.
Results.
PLC at the stage of severe non-proliferative DR stabilized its development in 35% of the patients and caused its reverse development withresolution of oedema and intraretinal hemorrhage, normalization of vein diameter, and improvement of visual acuity in 30%. In 35% of these casesPLC caused neovascularization within 1.6?0.9 years after treatment. Reverse development of DR after PLC was documented in 46.3% cases withearly proliferative DR but stabilization of DR occurred rarer than in the previous group (14.6%) and hemorrhage into the vitreous body more frequently(12 cases in 41 and 2 in 40 respectively, p = 0.0007). Patients with severe non-proliferative DR tended to have reduced requirement for vitrectomyafter PLC compared with those having early proliferative DR (1 case of 40 and 6 of 41, p = 0.052).Conclusion: The above results suggest the necessity of early PLC in DM1 patients.

Aim.
To assess current criteria for type 2 diabetes mellitus.
Materials and methods.
This screening study involving 2,368 residents of two municipal districts of the Moscow region was designed to elucidate differencesin the prevalence of abnormalities of carbohydrate metabolism depending on diagnostic criteria (WHO and ADA).
Results.
The prevalence of early disorders of carbohydrate metabolism and DM2 among the adult population of Moscow region is 17,1 and 7,2 respectivelyusing WHO criteria and 40,0 and 5,9% by ADA criteria.
Conclusion.
Refusal to undergo OGTT during screening decreases detectability of early metabolic disorders by 28,8 and 6,1% using WHO and ADAcriteria respectively. When screening is aimed to diagnose DM2 alone, OGTT can be omitted in subjects with fasting plasma glucose level below4,7 mmol/l. If it is aimed to diagnose both DM2 and impaired glucose tolerance, OGTT is not needed in subjects with fasting plasma glucose levelbelow 4,2 mmol/l. The use of ?combined? diagnostic criteria (i.e. OGTT according to ADA, but not WHO) significantly increases the prevalence ofmetabolic disorders from 24,9 to 48,8%.

Diabetes mellitus (DM) is a polygenous multifactor disease that may be triggered by a viral infection that causes death of beta-cells by at least two mechanisms,virus-mediated autoimmunity and direct cell injury. A case of DM1 following infectious mononucleosis is described to illustrate the necessityof a combined approach to the examination of patients and prescription of treatment.