Diabetes mellitus is one of the leading causes of death in modern society, primarily due to its cardiovascular complications. This factor drives search for novel pharmacologic agents to affect not only glycemic levels, but also the cardiovascular prognosis in diabetic patients with ischemic heart disease. Recent studies demonstrate that aside from basic blood glucose lowering action, metformin shows beneficial influence on blood rheology and vascular tone, hemostasis, oxidative stress, lipid spectrum and delivers and an ant-ischemic effect. Here we review clinical and experimental evidence on cardio- and vasoprotective effects of metformin, highlighting their molecular mechanisms.

Aim.
To study the heart rate variability via 24-hours ECG monitoring in male patients with metabolic syndrome (MS) and no signs of ischemic heart disease (IHD).
Materials and Methods.
131 males aged 29 to 60 years with no evidence for IHD were enrolled for this study and underwent 24-hoursECG monitoring procedure.
Results.
We determined that MS in males is associated with dysautonomia, accompanied by decrease in sympathetic heart stimulation (specifically, in LF and VLF parameters) and left ventricular diastolic abnormalities that correlate with abdominal obesity.
Conclusion.
MS in males is associated with dysautonomia, accompanied by decrease in sympathetic heart stimulation (specifically, in LF and VLF parameters) and left ventricular diastolic abnormalities that correlate with abdominal obesity.

Although collateral circulation is the essential means of perfusion for ischemized myocardium, its efficiency varies substantially within and between the species. There is both experimental and clinical evidence for association of glycemic disorders with inadequate col- lateral circulation. Current article reviews general mechanisms of collateral circulation failure due to such metabolic disturbances with regard for stages of arteriogenesis. We also highlight horizons of further studies in this field.

Aims.
To assess plasma level of N-terminal precursor for brain natriuretic peptide (proBNP) in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension without overt heart failure ? and further estimation of its correlation with data from echocardiog- raphy and clinical parameters (severity of ischemic heart disease (IHD), age, sex, duration of T2DM and hypertension experience, characteristics of glucose and lipid metabolism, renal function.
Materials and methods.
We examined 94 patients with T2DM and arterial hypertension (aged 40?65 years), determining character- istics of glucose and lipid metabolism and renal function. We also performed six minute walk test, ECG, echocardiography and blood tests for N-terminal proBNP (NT-proBNP) in all study subjects. Acquired data was compared to the group of 30 healthy controls.
Results.
We observed an increase in plasma NT-proBNP in patients with IHD, history of left venctricular (LV) myocardial infarction or clinical signs of heart failure (II NYHA class and higher). Results from patients with T2DM and arterial hypertension but without IHD did not significantly differ from control group. Plasma NT-proBNP levels correlated with left ventricular ejection fraction, left ventricular EDD and ESD, but not with LV diastolic function parameters. Duration of T2DM and arterial hypertension, HbA_1c levels,27Сахар ный диабет КардиологияСахарный диабет. 2013;(1):27?32BMI, lipid and uric acid metabolism parameters had no influence on plasma NT-proBNP in diabetic patients.
Conclusion.
According to our study, NT-proBNP was elevated in T2DM patients with IHD (and a history of LV myocardial infarc- tion in particular) or clinical evidence for heart failure beyond II NYHA class, thus indicating unfavorable prognosis for this group of patients and need for correction of therapy with subsequent re-evaluation of plasma NT-proBNP.

Aims.
To evaluate transcutaneous oximetry as a method for diagnostics and monitoring in patients with diabetes mellitus (DM) and critical limb ischemia (CLI) after percutaneous transluminal balloon angioplasty (PTBA).
Materials and Methods.
We enrolled 126 patients with DM and CLI for participation in this study (148 limbs in total). 22 patients underwent PTBA on both lower limbs, and 104 ? on single limb. Transcutaneous oximetry and duplex ultrasonography of lower limb arteries was performed prior to PTBA with subsequent examinations on 5-7th days, 1st, 3rd and 6th month after intervention. Transcu- taneous oxygen tension (TcpO2) was measured by Radiometer (Copenhagen) oximeter system. Duplex ultrasonography was performed on Voluson 730? Expert system (GE Medical Systems Kretztechnik GmbH&Co OHG, Austria).
Results.
Multiple factor analysis suggests that results of TcpO2 monitoring prior to and after PTBA are influenced by presence of ischemic heart disease, severe lower limb infections, serum creatinine, arterial hypertension and lower limb reperfusion edema. We observed a strong correlation of TcpO2 with the degree of anterior tibial artery and dorsal pedis artery occlusion.
Conclusion.
Transcutaneous oximetry allows evaluation of CLI severity and efficiency of PTBA in the majority oа patients with DM and CLI. Certain comorbidities impose limitations on this technique. Efficiency of endovascular intervention should be evaluated based on complex non-invasive examination, clinical data and signs of CLI.

Aims.
To estimate an impact of glycemic variability on the development of gastroesophageal reflux disease (GERD) in adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
We enrolled 33 patients with T1DM aged from 12 to 17 years. 24-h pH-monitoring was performed with ?Gas- troskan 24? system (Istok-Sistema, Fryazino); 24-h continuous glucose monitoring utilized CGMS MMT-7310 (Medtronic Minimed, USA) with subsequent night-time analysis.
Results.
As compared to stable night-time glycemia controls (SD <2.0 mmol/L), patients with higher night-time glycemic variability (SD>2.0 mmol/L) showed longer period of esophageal acidification (17% [2?58]; p<0.001), higher incidence of acid reflux events with duration above 5 min (2 ev. [1-10]; p<0.001), longer period of most protracted acid reflux event (63 min [5?132]; p<0.001), as well as higher prevalence of pathologic acid GER events (76.4%; p<0.001) during night-time. Increase in glycemic instability positively correlated with incidence and severity of acid GER events. 6-8 months follow-up supported these findings.
Conclusion.
Glycemic variability in adolescents with T1DM is a significant risk factor for development of GERD with hypomotor dysfunction according to pH-monitoring.

Aims.
To study the dynamics of body weight, waist circumference, blood lipid and insulin demand in patients with type 2 diabetes mellitus (T2DM) during first year of combined treatment with metformin and insulin analogues, compared with insulin analogue monotherapy.
Materials and Methods.
We examined 78 patients with T2DM on newly initiated insulin therapy, including 54 females and 24 males. Median age was 56 [51.0; 64.0] years, median disease duration ? 9 [6.8;14.0] years. Participants were subdivided in two groups. First group was comprised of 48 subjects (33 females and 15 males), who received monotherapy with insulin analogues (glargine, de- temir, biphasic Aspart 30 and Humalog Mix 25 or rapid-acting lispro and aspart). Second group included 30 patients (18 females and12 males), who were treated with combined therapy (insulin analogues plus metformin). We measured HbA_1c, plasma lipid composition, BMI, waist circumference and insulin demand initially and after one year of follow-up.
Results.
We showed that combined therapy vs. insulin monotherapy allows better glycemic compensation while reducing insulin demand and lowering risks for weight gain.
Conclusions.
Combined insulin analogue plus metformin treatment delivers better metabolic control in patients with T2DM and is as- sociated with lower risks for body weight gain and increase in insulin demand against monotherapy with insulin analogues.

Body weight (BW) excess is a characteristic problem for type 2 diabetes mellitus (T2DM) both as its pathogenetic feature and as a side effect of blood glucose lowering therapy. In the latter case reduction of glycosuria and frequent hypoglycemic events are primarily blamed for BW gain, but additional factors like direct effect of insulin on lipogenesis and influence of its supraphysiologic levels on regulation of appetite via CNS structures are also under discussion.Advances of the last years have brought new hope due to introduction of drug classes that do not affect BW. However, fraction of patients dependent on exogenous insulin shows stable trend for growth. Deterioration of beta-cell secretory capacity makes insulin an ultimately indispensable tool in the foreseeable future. As so, insulin therapy modalities with minimal impact on BW are preferable. In this regard human insulin analogues of both rapid and prolonged action have certain advantages.Current article addresses influence of pre-mixed insulin preparation NovoMix 30 (Novo Nordisk, Denmark) on BW. A summary of several studies of substantial duration (up to 3 years) suggests a neutral effect on BW in various categories of T2DM patients (including obese and elder patients).Therapy with pre-mixed preparations is an adequately safe and effective T2DM treatment modality and is advantageous for patients in whom BW gain is particularly unfavorable.

The interrelationship between diabetes mellitus (DM) and bone disorder is still not fully understood. Whereas type 1 diabetes mellitus (T1DM) is characterized by decrease in bone density, a number of studies failed to discover such phenomenon in type 2 diabetes mel- litus (T2DM), ? or even uncovered some evidence for higher density, as measured against groups of control. At the very same time both types of DM are associated with elevated risk of bone fracture, which points out at some deterioration of bone tissue ?quality?. Current article discusses various mechanisms of bone damaging in DM, as well as possible causes for difference in the severity of bone disorders, known between the two types of DM. Regarding higher risk of foot fracture in patients with DM, we specifically address distal polyneuropathy as a plausible factor for bone tissue deterioration.

Cerebrovascular accident (CA) is a nowadays widely spread, highly incapacitating and often lethal event that poses a prominent clini- cal problem. Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) ? an ?epidemic? of the century, ? are known to be its primary risk factors. Hyperglycemia promotes CA risks by induction of protein glycosylation, elevation of blood plasma atherogenic potential, activation of coagulation system with higher risk for thrombosis and disturbance of microcirculation on tissue and organ lev- els. Influence of hyperglycemia on severity and extent of neurologic damage is still under evaluation. Development of macroangiopathy is thought to be associated with media calcification, distal polyneuropathy and renal disorders, all of which are cardiovascular risk factors. Application of so-called metabolic drugs resulted in certain disillusionment, as these agents failed to prove their efficacy during clinical trials. Incidence of pulmonary edema in patients with ischemic CA and T2DM is important as it dictates the necessity for use of loop diuretics. Incidence and severity of heart failure and its correlation with degree of glycemic disorders, incidence of pulmonary em- bolism, as well as tactics of management and prognosis in patients with ischemic CA and T2DM, remains a relevant research problem.

Aims.
To assess the risk for sleep apnea in patients with various types of glycemic disorders by means of Epworth Sleepiness Scale andSleep Apnea Screening Questionnaire.
Materials and Methods.
We examined 744 residents of Mozhaisk Region, that were considered to have high risk for development of type2 diabetes mellitus (T2DM), as estimated by FINDRISK Questionnaire. Patients, who scored 12+ were cleared for participation in this study. Combined score from Epworth Sleepiness Scale and Sleep Apnea Screening Questionnaire was applied for diagnosis of sleep apnea, supplemented with specific questions about snoring and episodes of apnea. Glycemic disorders were diagnosed with standard glucose tolerance test.
Results.
42.7% of examined patients (n=318) were diagnosed with various types of glucose disorders. Prevalence of abdominal obe- sity (according to waist circumference measurement) comprised 59.3% in male patients and 54.1% in females. We observed positive correlation between body mass index (BMI) and snoring ? 0.3 (p=0.0001), BMI and apnea ? 0.2 (p=0.0001), BMI and daytime sleepiness ? 0.1 (p=0.007); we also observed direct correlation between age and snoring ? 0.2 (p=0.0001), as well as age and sleep apnea ? 0.1 (p=0.028). Risk for sleep apnea was found to be 4.7 times higher in patients with arterial hypertension. After adjustment71Диагностика, контроль и лечениеСахарный диабет. 2013;(1):71?77Сахар ный диабетfor age risk of apnea remained 2.8 times higher in patients with T2DM, 1.9 times higher in subjects with impaired glucose tolerance and1.6 times higher in subjects with impaired fasting glycaemia. Relative risk for snoring in patients with various types of glycemic disorders was 1.1-1.2 against normoglycemic controls. We estimated that all types of glycemic disorders increase risk for apnea 1.2?1.6 times.
Conclusion.
Glycemic disorders, body weight excess, obesity and arterial hypertension are risk factors for snoring and sleep apnea. Corresponding patient categories should be screened for sleep apnea by questionnaire survey to identify those in need of further complex examination and treatment.

Aims.
To determine vascular channel reserves in patients with systemic atherosclerosis and type 2 diabetes mellitus (T2DM). Materials and Methods.
Study included 143 patients with systemic atherosclerosis, 40 of them also suffered from T2DM. We applied laser Doppler flowmetry (LDF) to evaluate vascular channel reserves and transcranial spectrometry to assess cerebral oxygenation status.
Results.
We found that 60% of patients with systemic atherosclerosis and T2DM show microcirculation parameters below critical level, which indicates failure of collateral circulation. This group also showed lower efficiency of cerebral perfusion and more pronounced vascular constriction in response to functional load as compared to diabetes-negative controls.
Conclusion.
Patients with T2DM, accompanied with systemic atherosclerosis showed lower circulation efficiency and more pronounced autonomous dysregulation of cerebral circulation against patients without diabetes mellitus.

DCCT (Diabetes Control and Complications Trial) study established that intensified insulin therapy in multiple daily injections (MDI) or continuous insulin infusion (CSII) regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM) as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus?) and glulisine (Apidra?) insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

Diabetes mellitus is a heterogeneous group of diseases that, although unified by a number of characteristics, require a differential thera- peutic approach. Current review discusses key pathogenic features of type 2 diabetes mellitus that determine therapy goals and options in management. We further enunciate and pathogenetically substantiate a new "gravicentric" concept for treatment of type 2 diabetes mellitus that differs in many ways from the common contemporary approach.