Diabetes mellitus affects reproductive function at different levels both in men and women. It disturbs regulation of the hypothalamo-pituitary axisand impairs gonadal endocrine function at the cellular level due to direct effect of acute and/or chronic hyperglycemia, oxidative stress and microvascularcomplications. Moreover, central dysregulation aggravates hormonal disorders. Assisted reproductive technologies (ART) provide a tool for thetreatment of male and female infertility in diabetic patients although many aspects of its application await in-depth studies.

Type 1 diabetes mellitus (DM1) exerts negative impact on the formation and functioning of the reproductive system in young girls. The time of onset(especially in the prepubertal period) and duration of DM1 as well as the lack of metabolic control may cause delay of puberty, affect the age of menarche,and increase the frequency of menstrual disturbances (largely in the form oligo- and amenorrhoea). Despite extensive research devoted to thisproblem, the main cause of reproductive dysfunction in such patients remains unclear even though DM1 is known to negatively affect performanceof the hypothalamo-pituitary axis. Pathogenetic mechanisms behind reproductive disturbances include suppression of GnRH pulses due to enhancedcentral dopamine and opiate activity, decreased expression of insulin receptors on neural cells, and altered plasma leptin level. Pituitary may be affectedboth by hypothalamic activity and by lipid free radical oxidation products decreasing production of tropic hormones (LH and FSH).

Data on the worldwide prevalence of carbohydrate metabolism disturbances are reviewed. Pathogenesis of metabolic syndrome in menopausal women(menopausal metabolic syndrome) is considered, its clinical and laboratory characteristics are presented. Main therapeutic modalities (medicamenousand non-medicamentous) are discussed. Properties of the hypoglycemic drug metformin and indications to its use are described along with indicationsand contraindications to substitution hormonal therapy in women with metabolic disturbances

This article is designed to discuss data on diabetic complications negatively affecting male fertility, such as retrograde ejaculation and secondary hypogonadismthat frequently occur in patients with diabetes mellitus. It has been shown that 5 - 10% of the DM1 patients present with retrogradeejaculation associated with long-term decompensation of carbohydrate metabolism. Over 40% of the patients with DM2 have decreased total andfree testosterone levels regardless of compensation of carbohydrate metabolism. These complications are managed using neurotropic therapy (retrogradeejaculation) and stimulatory hormonal therapy (secondary hypogonadism).

With DM1 morbidity reaching epidemic growth in young people including women of childbearing age, planning and managing pregnancy in patientswith disturbances of carbohydrate metabolism acquires increasingly greater significance. Of primary importance are evening mutual influence of DM1and pregnancy (a high-risk condition) and prevention of perinatal complications resulting from poor compensation of carbohydrate metabolism.

Aim.
To evaluate effect of different factors on pregnancy course in patients with type 1 diabetes mellitus developing in the prepubertal period.
Materials and methods.
The study based at Endocrinological Research Centre included 77 women with prepubertal diabetes 18 of whom developedpregnancy that ended in delivery.
Results.
As per 2009, the age of the patients is 26,6?4,6 years. They became pregnant at 23,2?3,3 years and had had diabetes since the age of9,6?4,8 years. Their HbA_1c level before and after pregnancy was 8,6?1,4 and 6,8?1,6% respectively, the difference being insignificant (p=0,3).Significant difference was documented between these HbA_1c levels and that during pregnancy (p=0,0004 and 0.003 respectively). Nine (56,2%) patientsused ultrashort-acting insulin analogs and the remaining 7 (43,7%) recombinant human insulins. The mean insulin dose was 43,7?11 U/din the 1st trimester, 51,8?13,7 U/d in the 2bd trimester, and 45,3?10,8 U/d after delivery. 16 (88%) of the patients reported frequent hypoglycemia,five (27,8%) of them had episodes of severe daytime and nocturnal hypoglycemia. 11 (61%) developed microvascular diabetic complications beforepregnancy, with 9 (50%) having DR and 4 (22,2%) DN (microalbuminuria). The delivery occurred on weeks 36-37 in 7 (38,9%) women. Naturaland cesarean section deliveries took place in one and 17 (94,4%) patients respectively.
Conclusion.
Long-term follow-up of patients wit DM1 in accordance with algorithms of specialized medical aid to DM1 patients in Russia at a multidisciplinaryendocrinological centre decreases the risk of pregnancy and delivery complications and that of microvascular diabetic complications

The main causes behind decompensation of diabetes mellitus (DM) in pregnant women are consid-ered, such as metabolic and hormonal disturbancesinfluencing insulin requirement in different periods of pregnancy and variability of glycemia related to pharmacokinetic and pharmacodynamicproperties of insu-lin preparations. Recommended target levels of glycemia in pregnant women with DM are cited. The fre-quencyof self-monitoring blood glucose and principles of intensive insulin therapy are discussed. Advan-tages of continuous subcutaneous insulin infusionand its role in the maintenance of stable control of car-bohydrate metabolism during pregnancy are discussed.

Aim.
To search for genetic markers of insulin resistance and impaired insulin secretion in pregnant women with gestational diabetes mellitus (GDM).
Materials and methods.
A total of 100 healthy pregnant women and 185 patients with GDM were available for examination. 80 patients developedGDM during current pregnancy, in 105 it was diagnosed 4-19 years ago. 25 of the 105 GDM patients had a history of type 2 DM. The following parameterswere measured: beta-cell secretory activity (proinsulin, ITI, C-peptide), total cholesterol (CH), HDL and LDL CH, triglycerides, HbA_1c,fasting glycemia. Molecular-genetic DNA testing using PCR included studies of KCNJ 11, TCF7L2, PPARG2, ADIPOQ, ADIPOR1, ADIPOR2gene polymorphism. These genes were chosen based on the published data associating them with disturbed insulin secretion and sensitivity in DM2patient.
Results.
Pregnant women with GDM and obesity showed elevated IRI and leptin levels compared with controls. This rise was accompanied bymarked insulin resistance in 75% of these patients. In 50% of the healthy women proinsulin and insulin secretion decreased. Obesity in pregnantpatients was associated with significant elevation of proinsulin, IRI, and C-peptyide levels and GDM with Lys/Lys genotype of polymorphous markerGlu23k of KCNJ11 gene, pro and ala allele of polymorphous marker A219T of ADIPOR2 gene. These associations suggest specific genetic featuresof GDM related to impaired insulin secretion and sensitivity.
Conclusion.
Studies of common genetic nature of GDM and DM2 permit to identify risk groups at the preclinical stage, plan prevention and treatmentof these disorders.

Important medico-social and economic implications of type 2 diabetes mellitus (DM2) are determined by its continuously growing prevalence, frequencyand severity of complications related to inadequate glycemic control. Large-scale studies (UKPDS, VADT, ACCORD, ADVANCE) havedemonstrated controversial effect of intensive glycemic control (estimated from HbA_1c dynamics) on diabetic macrovascular complication. At thesame time, epidemiological, experimental, and observational studies yielded conclusive evidence of postprandial glycemia (PPG) contribution tooverall glycemic control and its role in the development of macrovascular complications. For this reason, PPG control is currently given as much attentionas traditional parameters (HbA_1c and fasting glycemia). Dipeptidyl peptidase-IV (DPP-IV) inhibitors are a new class of hypoglycemic agentsthat raise levels of incretins, glucagons-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in blood by suppressing DPPIVactivity. The resulting recovery of physiological insulin secretion promotes reduction of fasting and postprandial glycemia and HbA_1c level.

Aim.
To study the prevalence of renal lesions in adult patients with type 1 and 2 diabetes mellitus in the Russian Federation.
Materials and methods.
A total of 7174 patients with DM1 and DM2 were examined in 20 regions of the Russian Federation for blood HbA_1c creatinine,urea, and cholesterol levels, albumin excretion in a single urine sample, AP, and eye fundus condition. Albumin concentration from 20 to 200mg/l was regarded as microalbuminuria (MAU) that above 200 mg/l as proteinuria (PU). The glomerular filtration rate (GFR) was calculated fromCockroft-Gault formula. Statistica-6 program was used for statistical treatment of the results of the study. They are represented as median, 25th and75th percentile values (Me [25%;75%]). Differences between all parameters is considered significant at p<0,05 level.
Results.
Pathologic albumin excretion was documented in 42,1 and 45,3% of the DM1 and DM2 patients. Its prevalence increased with age andDM duration as well as at poor AP and glycemic control. Stage 2 chronic renal disease developed in 16,5 and 23,7%, stage 3 in 4,2 and 6,3%,stage 4-5 in 0,9 and 0,2% of the DM1 and DM2 patients respectively. 15,0 and 41,2% of DM1 and DM2 patients with MAU needed additionalexamination to elucidate non-diabetic origin of CRD. 40% of the DM2 patients with impaired GFR and poor glycemic control had to be transferredto insulin therapy.

Aim.
To determine the level of inflammation markers and their relation to endothelial dysfunction and insulin resistance in patents with type 2 diabetesmellitus and cardiovascular form of diabetic autonomous neuropathy.
Materials and methods.
A total of 87 patients aged 45-66 years were examined for blood insulin level, insulin resistance index (HOMA-IR), CRP,and anti-inflammatory cytokine (TNF-a, IL-1-beta, IL-6) levels. Endothelial dysfunction was estimated based on quantitative Willebrand factorassay. Vegetative disorders were detected from reflex cardiovascular ECG data.
Results.
The development of cardiovascular form of diabetic autonomous neuropathy in patents with type 2 diabetes depended on diabetes duration,quality of carbohydrate metabolism compensation, levels of hyperinsulinemia and insulin resistance. Mean levels of Willebrand factors andinflammation markers in patents with type 2 diabetes and overt vegetative dysfunction were significantly higher than in diabetic patients withoutautonomous neuropathy. Correlation analysis revealed significant correlation of CRP and IL-6 levels with results of standard ECG tests.
Conclusion.
Results of the study demonstrate chronic inflammation in patents with type 2 diabetes and cardiovascular form of diabetic autonomousneuropathy. Increased level of inflammation markers and its relation to severity of vegetative disorders and endothelial dysfunction confirm the roleof inflammation in pathogenesis of nervous co-morbidity in patents with type 2 diabetes.

Autonomous cardiac neuropathy is a diabetic complication characterized by early disseminated sympathetic and parasympathetic small-fiber neuronaldegeneration. Prevalence, pathogenesis, risk factors, clinical manifestations, and early diagnosis of pathology are discussed.

As the number of cases with classical manifestations of diabetic nephropathy (DN), i.e. nodular or diffuse glomerulosclerosis, grows, an increasinglylarger number of DM patients especially those with DM2 present with renal pathology largely affecting interstitium and tubules (ischemic nephropathy,urinary infection, interstitial nephritis, etc.). The rate of renal filtration impairment in glomerular diseases (DN, glomerulonephritis) is also relatedto the severity of tubulointerstitial fibrosis (TIF). Intricate intercellular interactions activated by immune and non-immune factors have been shownto play an important role in the development of tubulointerstitial lesions. Studies of the most important factors contributing to remodeling tubulointerstitiumin DM patients may provide a deeper insight into the mechanisms of nephrosclerosis and extend possibilities for prognostication of renalfunction.

Aim.
To evaluate efficiency and tolerability of diabeton MB/metformin combination in patients failing to achieve optimal glycemic control when onmetformin monotherapy and prove advantages of this combination over combined low-dose therapy with glibenclamide and metformin.
Materials and methods.
The study included 464 patients with type 2 diabetes mellitus who poorly responded to metformin monotherapy. It was supplementedby diabeton MB. Efficiency and tolerability of combined treatment was evaluated from dynamics of glycemia and frequency of side-effects.40 patients were included in detailed comparative assessment (laboratory and instrumental, CGMS) of this monotherapy and fixed low-dose combinationof glibenclamide with metformin.
Results.
Results of comparison show that diabeton MB/metformin combination ensured most optimal glycemic control with a minimal risk of side effects.
Conclusion.
Diabeton MB/metformin combination is convenient, efficient and safe.

Цель. Оценить риски развития общей и сосудистой смертности, а также риски фатальных и нефатальных инфарктов миокарда (ИМ) и острых нарушений мозгового кровообращения (ОНМК) у больных сахарным диабетом 2 типа (СД2) в зависимости от вида пероральной сахароснижающей терапии (ПССП), назначенной после установления диагноза диабета. Материалы и методы. На основании результатов ретроспективного открытого когортного исследования проведен анализ пятилетнего риска общей и сердечно-сосудистой смертности, а также ИМ и ОНМК у лиц, заболевших СД2 в 2004 году и получавших терапию раз- личными ПССП. Для оценки рисков смерти от любых причин, смерти от сердечно-сосудистых заболеваний, ИМ и ОНМК был использован Cox-регрессионный анализ. Результаты. У больных, которым после установления диагноза ?СД2? были назначены препараты сульфонилмочевины (СМ), по сравнению с группой метформина отмечено достоверное повышение риска общей и сердечно-сосудистой смертности в два раза (р

Aim.
To assess efficiency of orthopedic footwear for diabetic patients by in-shoe computed pedobarography.
Materials and methods.
The study included 20 women with type 1 or 2 diabetes mellitus, diabetic polyneuropathy and/or angiopathy combined withmoderate foot deformity. In-shoe computed pedobarography (F-scan, Tekscan, USA) was used to study pressure distribution patterns in ordinary footwearidentical for each patient (control) and in special shoes shaped to the foot of individual patients.
Results.
Median peak pressure in orthopedic footwear was reduced by 29% compared with control value. The number of patients with overloadedfoot regions decreased from 75 to 35%, p=0,025. The change of integral load indices for clinically significant foot regions was estimated at -34%(-67%; -17%) for pressure-time integral and -26% (-65%; +7%) for force-time integral (p<0,001 in both cases).
Conclusion.
In-shoe pedography is an important tool for the assessment of reduced pressure on the foot plantar surface in orthopedic footwear fordiabetic patients. The shoe model evaluated in this work is characterized by significantly decreased pressure on the plantar surface, pressure-timeand force-time integrals.

Aim.
This work was to study activation markers of apoptosis (CD95, CD95L) on peripheral blood lymphocytes of patients with type 1 diabetes mellitus (DM1) at the onset of the disease.
Materials and methods.
A total of 33 patients (25 men and 8 women) divided into 2 groups were available for biochemical, genetic, and immunological examination.
Results.
Those with the ?classical? onset of DM1 had significantly fewer CD95-expressing lymphocytes and more CD95L+ lymphocytes than control subjects. Carriers of genes responsible for high risk of DM1 showed especially large number of lymphocytes expressing CD95L.
Conclusion.
It is conjectured that DM1 is characterized by the suppression of mechanism controlling apoptosis of activated lymphocytes that may promote prolongation of the immune response.

This paper focuses on the approaches to target glycemic control in patients with type 2 diabetes mellitus. It is emphasized that timely onset of insulintherapy enhances glycemic control and reduces the risk of vascular complications. One way to achieve this goal is to use modern strategies of intensivehypoglycemic therapy with insulins having improved pharmacokinetic and pharmakodynamic properties, e.g. glargine (Lantus) and glulysine (Apidra).Results of international clinical studies confirm effi-ciency of basal and basal-plus insulin strategies allowing to achieve glycemic control in type 2diabetes without heightening the risk of hypoglycemia, development and progression of vascular complications.

AIM: To analyse starting characteristics of the Russian patient cohort included in the IMPROVE observational program with reference to its demographiccomposition and clinical features of the disease in patients allocated to different groups depending on previous treatment, reason for prescribing DiAsp 30 (NovoMix 30) therapy, and its initial dosage regime.

METHODS: The analysis covered the cohort of Russian patients included in the IMPROVE global program, an open non-randomizedobservational multicentre study of safety and effectiveness of insulin DiAsp for patients with DM2 during 26 weeks of routine clinical practice. In thepreceding period, the patients (n=4869) received either oral hypoglycemic agents (OHAs) (n=2430) or insulin +/- OHAs (n=2343); the controlgroup was comprised of 95 patients given no previous antidiabetic treatment.

RESULTS: Most patients had inadequate glycemic control prior to DiAsp therapy with the mean HbA_1c level of 9,2%. Those given no previous antidiabetictreatment showed the highest HbA_1c level (9,9%) and higher frequency of microvascular vs macrovascular complications (91 and 51% respectively).Patients that used the largest amount of antidiabetic agents developed the highest number of complications; this situation reflects therelationship between poor glycemic control and the risk of complications.

CONCLUSIONS: The Russian patient cohort is one of the three largest ones in the IMPROVE? global program. They reside in different geographic regions,have different history of antidiabetic treatment and far-from-normal HbA_1c levels as a result of altogether poor glycemic control in Russian patientswith DM2. The cohort at large exhibits a suboptimal HbA_1c level even though the majority of the patient have an access to antidiabetic therapy. Mostphysicians participating in the study refer to improved glycemic control in their DM2 patients (lowered HbA_1c, fasting and postprandial glucose levels)as the main reason for the initiation of therapy with DiAsp 30 (NovoMix 30).

Results of numerous studies give definitive evidence that phenofibrate affects activity of PPAR-a receptors in liver and thereby decreases the level oflipids responsible for the development of atherosclerosis (VLDL, small dense LDL); simultaneously, it increases the level of anti-atherogenic HDL.Activation of PPAR-a receptors in vascular cells decreases activity of inflammation markers, such as C-reactive protein, TNF-a, IL-6, fibrinogen,etc. These effects of phenofibrate eventually lead to reduced risk of macro- and microvascular diabetic complications.

This work is devoted to the analysis of results of recent clinical studies. It is argued that the absence of close association between normalized glycemiaand reduced incidence of cardiovascular disorders may be due to both relatively short duration of observations and possible effect of co-factors (e.g. hypoglycemia/drug interaction, etc.). Some results suggest the necessity of multifactor approach to the treatment of DM2 especially for the reductionof cardiovascular mortality or prevention of vascular catastrophes. Sulphonylurea derivatives are regarded as putative risk factors of hypoglycemiaor vascular disorders. A number of publications are reviewed in which glibenclamide was shown to be safe in terms of risk of myocardial infarction.