The study of hereditary predisposition to multifactorial diseases is essential for diagnosis and selection of the optimal treatment. The study of polymorphisms of candidate genes whose products are involved in the pathogenesis of multifactorial diseases is of great clinical importance.
Aim.
The aim of this study was to investigate the association of rs2241766 and rs1501299 polymorphisms in the ADIPOQ gene, rs2275737 and rs2275738 polymorphisms in the ADIPOR1 gene and rs11061971 and rs16928751 polymorphisms in the ADIPOR2 gene with the development of type 2 diabetes mellitus (T2DM) in the Russian population.
Materials and methods.
The study included a group of 500 patients with T2DM diagnosed based on standard diagnostic criteria (T2DM+). The control group (T2DM-) was a random sample of 500 patients with no evidence of the disease and was matched to the T2DM+ group for gender, age and body mass index. The determination of alleles and genotypes was performed using real-time polymerase chain reaction with TaqMan probes. The X² test and contingency tables were used to compare the distribution of allele and genotype frequencies. A p-value of <0.05 was considered to be statistically significant.
Results.
Comparative analysis of the distribution of alleles and genotypes indicated an association between T2DM and the disease gene polymorphic marker rs11061971 ADIPOR2 (р = 0.004 for the distribution of alleles, р = 0.011 for the distribution of genotypes). The presence of allele A and genotype AA decreased the risk of development of T2DM (OR = 0.76 and 0.75, respectively), whereas the T allele carriers and TT genotype were associated with an increased risk of developing T2DM (OR = 1.31 and 1.63, respectively). There was no statistically significant association between T2DM and polymorphic markers of ADIPOQ or ADIPOR1 genes.
Conclusions.
Based on this data, polymorphism of the ADIPOR2 gene in the Russian population is associated with the development of T2DM, but there is no association between T2DM and polymorphism of the ADIPOQ or ADIPOR1 genes.

The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus.
.
The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed..

This review presents an analysis of clinical and experimental studies related to post-transplantation diabetes mellitus (PTDM) ? a specific complication after solid organ transplantation.
A search of the databases eLibrary, PubMed and Scopus using the keywords ?posttransplantation diabetes mellitus?, ?new onset diabetes after transplantation?, ?transplantation? and ?immunosuppression? yielded in 523 results, including four from Russian literature (one original research manuscript). The analysis included original research, reviews, meta-analyses and monographs published not before 2005 in Russian and English. A total of 60 relevant original researches and reviews were included in this review.
Diagnostic criteria, disease risk factors and potential pathogenic mechanisms were all considered. The mechanisms of the diabetogenic effect of modern immunosuppressive drugs were analysed. The principles of pre- and post-transplantation screening for PTDM and optimal management strategies for patients with PTDM are presented. The current controversial issues concerning the various aspects of PTDM are discussed.

Pharmacoepidemiological research is the first stage of the clinical and economical evaluation of treatment with pharmaceutical agents. It plays an important role in providing reliable information about treatment regimens for patients with type 2 diabetes mellitus (T2DM). The results of the analysis of the utilisation of hypoglycaemic drugs are country specific and are associated with different epidemiological characteristics of the disease, cost of drugs and financing of the healthcare system. Analytical pharmacoeconomic studies allow the evaluation of the rational use of drugs, characteristics of treatment in clinical practice and their conformity to national and international clinical guidelines.
Aim.
To study the characteristics of treatment with insulin and oral hypoglycaemic drugs in Moscow-based patients with T2DM and to calculate the average cost of hypoglycaemic drugs per person per year.
Materials and methods.
A retrospective cohort pharmacoepidemiological study was performed by analysing information from the national register of diabetic patients from two administrative districts in Moscow. In total, 48,978 adult patients (older than 18 years) were registered with T2DM between 2000 and 2012. The study of treatment regimens was conducted using the standard international ATC/DDD methodology, and the correlation of fixed dose to appointed daily dose was calculated. The annual average cost of treatment for patients with T2DM, including different hypoglycaemic drugs (insulin and oral hypoglycaemic drugs) in the form of monotherapy and different combinations, was calculated. The average annual cost of hypoglycaemic therapy for patients with T2DM was calculated for the first time in the Russian Federation.
Results.
The majority of study patients received hypoglycaemic drugs (98.5%), and only 1.5% of the patients diagnosed with T2DM were on dietetic therapy. Of the patients receiving drugs, 90% received oral hypoglycaemic drugs, and 10% received insulin (basal-bolus regimen 4.6%, basal insulin with oral hypoglycaemic drugs 3.8% and ?MIX-insulin? 1.1%). The most frequently prescribed oral hypoglycaemic drugs were derivatives of sulphonyl urea and metformin (87% and 71%, respectively), and 12% of the patients received premixed combinations of these drugs. Other groups of oral hypoglycaemic drugs accounted for only a small proportion of oral hypoglycaemic drugs (approximately 2%) and included glinide (1.8% of the patients), thiazolidinedione (0.4%) and inhibitors of alpha-glucosidase (0.17%). In the group of derivatives of sulphonyl urea, the most frequently prescribed drugs were glibenclamide (46.4%), gliclazide (38.7%) and glimepiride (14%). The average annual treatment cost per patient was 7,467 rubles.
Conclusion.
The pharmacoeconomic analysis revealed that the treatment of T2DM was insufficiently effective in 48% of the patients (HbA_1c>7%). Most patients received monotherapy with metformin or derivatives of sulphonyl urea, among which glibenclamide was the most frequently prescribed drug. The treatment of patients with T2DM in 2011 was characterized by a low frequency of insulin prescription, rare usage of other groups of oral hypoglycaemic drugs (only 2%) and a mismatch between fixed dose and appointed daily dose. The average annual cost of hypoglycaemic drugs per patient with T2DM in 2011 in Moscow was 7,467 rubles.

The most common mental disorder in patients with diabetes mellitus (DM) is depression (DS). Despite the large number of papers about DS in DM, its prevalence in type 1 DM (T1DM) remains unclear.
Aim.
The aim of this study was to investigate the prevalence of DS in T1DM and its possible association with metabolic control disorders.
Materials and Methods.
The study included 163 patients with T1DM. The patients were aged 18?65 years, and the mean duration of T1DM was 11.18 years (range 4.28?22.33 years). The control group included 75 apparently healthy individuals. The subjects underwent physical examination, and the standard self-report Hospital Anxiety and Depression Scale questionnaire was administered to evaluate the level of anxiety and DS. Psychological counselling was conducted to diagnose DS and its severity. The continuous glucose monitoring system (CGMS) was used to monitor interstitial fluid glucose levels. Statistical analysis was conducted using SPSS Statistics 17.0 and StatSoft Statistica 6.0.
Results.
The prevalence of DS among the patients with T1DM was much higher (approximately two-fold) than the prevalence among the healthy individuals. Female sex and age over 40 years were associated with the presence of DS.
Conclusion.
The development of DS in patients with T1DM is accompanied by poor glycaemic control and increased risk of hypoglycaemic episodes.

Aim.
The aim of this study was to investigate cardiac autonomic function as assessed by ST dynamics during and post-exercise in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
The study included 71 young patients with T1DM. The patients were aged 9?18 years and had no history of macrovascular disease or renal disease, including microalbuminuria. Cardiac autonomic function was assessed using cardiovascular tests and 24-h ECG monitoring with automatic calculation of QT interval and heart rate variability parameters. Each patient underwent the physical working capacity 170 test.
Results.
The prevalence of cardiovascular autonomic neuropathy (CAN) was 30.9%. The frequency of asymptomatic ST-segment depression increased during exercise in 10 (45.5%) patients with CAN (CAN+) compared with 9 (18.4%) patients without CAN (CAN-; p=0.042). During the recovery period, asymptomatic ST-segment depression was present in the first minute in 8 (36.4%) CAN+ patients compared with 1 (2%) CAN- patient (p=0.0003) and in the second minute in 5 (22.7%) CAN+ patients compared with 1 (2%) CAN- patient (p=0.0095).
Conclusion.
Children and adolescents with T1DM and impaired autonomic function have increased prevalence of asymptomatic ST-segment depression during and post-exercise. The presence of cardiovascular risk factors in children and adolescents with T1DM and CAN may contribute to the increased cardiovascular morbidity and mortality during adulthood in patients with T1DM.

Aim.
To evaluate the association between coronary collateral circulation (CCC) and carbohydrate metabolism disorders (CMD) in patients with chronic coronary artery disease (CAD).
Materials and Methods.
Six hundred three patients with chronic CAD were included in this cohort cross-sectional study. Coronary angiography images were used to quantify coronary circulation, including CCC evaluation, with a modified technique proposed by Rentrop. CMD were classified according to the WHO criteria.Potential associations between CMD and CCC were evaluated using multiple linear models that incorporated major angiographic, clinical and laboratory parameters.
Results.
Among the 603 patients with chronic CAD, 47.4 had CMD, including type 2 diabetes mellitus in 24.2% of the patients, impaired glucose tolerance in 2.8%, type 1 diabetes mellitus in 1.0% and unspecified CMD in 16.1%. CMD were independently associated with lower CCC [odds ratio (OR).
= 0.96, p .
= 0.003). CMD were independently associated with a decrease in the association .
between maximum diameter stenosis and CCC (OR = 0.93, p.
= 0.005). No independent associations were found between CCC and type of anti-diabetic treatment, HbA_1c levels, insulin resistance (HOMA index), or metabolic syndrome components (body mass index, triglycerides, fasting glucose levels, LDLP cholesterol and arterial hypertension).
Conclusion.
CMD in patients with chronic CAD are .
independently associated with worse CCC. The presence of CMD weakens .
the association between maximum diameter stenosis and CCC. Metabolic syndrome components, blood glucose control and anti-diabetic treatment modality were not found to influence CCC.

Aim.
The aim of this study was to investigate late diabetic complications in patients with Type 1 diabetes mellitus (T1DM) who received simultaneous pancreas-kidney transplantation (SPK).
Materials and Methods.
The study included 16 patients with T1DM who received SPK. All patients underwent clinical examination and diagnostic investigation.
Results.
After SPK, 93.75% of the patients had a functioning pancreas transplant, and 100% had a functioning kidney transplant within 4?48 months [mean 21 months (10 is revealed; 36)). All patients had euglycaemia according to daily monitoring. The mean level of glycated haemoglobin (HbA_1c) before surgery was 9.1% (range 8.7%?11%) and was 5.7% after surgery (5.55%?5.9%; p < 0.0001). The baseline level of insulin was 12.5 ?IU/ml (11.4?15.3 ?IU/ml) and the baseline level of C-peptide was 2.02 ng/ml (1.07?2.77 ng/ml). Normal renal function was observed (glomerular filtration rate 76 ml/min/1.73 m2 (68?90 ml/min/1.73 m²). Other laboratory findings included haemoglobin 127 g/l (120?130 g/l), serum parathyroid hormone 77.5 pg/ml (61?85 pg/ml), serum phosphate 1.2 mmol/l (1.07?1.3 mmol/l) and blood pressure 110(100?120)/70(64?80) mmHg. In 37.5% of the patients, vitrectomy and additional laser panretinal photocoagulation were performed for proliferative diabetic retinopathy. Other ophthalmological disorders included newly diagnosed cataract (81.25%), secondary cataract (25%) that required YAG discission in three patients, glaucoma (25%) and macular oedema (12.5%). Ulcers of the lower extremities were observed in 31.25% of the patients, and chronic osteoarthropathy was observed in four. One patient underwent amputation of index and ring fingers and resection of the first and third metatarsal heads to treat osteomyelitis. One patient underwent balloon angioplasty and stenting for advanced atherosclerotic stenosis of blood vessels of the lower extremities.
Conclusions.
Euglycaemia and recovery of renal function 6?48 months after SPK resulted in a significant decrease in diabetic complications without clinical signs of regression in some patients. However, some patients suffered progression of complications, reflecting their multifactorial causes. These findings highlight the need for timely diagnosis, treatment and long-term follow up to improve the quality of life and prognosis in patients with T1DM receiving SPK.

The diabetic population faces 80% increased risk of cellulitis, 4-fold increased risk of osteomyelitis and 2-fold risk of both sepsis and death caused by infections.
Study objectives.
The present study was carried out to assess the clinical aspects and microbiological profile of organisms isolated from 25 patients undergoing diabetic limb amputations.
Materials and Methods.
In 25 diabetes persons who underwent limb amputation, grading of ulcers was done according to Wagner system. Material was stained with Gram stain. Potassium hydroxide wet mounts were also studied. Culture was done in blood agar, MacConkey agar, Sabouraud dextrose agar tube slants and brain heart infusion broth and examined for growth. The histopathology sections were also studied and special stains were done.
Results.
Of 25 cases, 16 were males and 9 were females. The age ranged from 30 to 90 years (mean: 58?10.91). Majority of ulcers were grade 3. Osteomyelitis was seen in 13 (52%) cases; acute in 2 (8%), chronic in 3 (12%) and acute exacerbation of chronic osteomyelitis in 8 (32%) cases. On culture Proteus mirabilis was isolated in majority of cases followed by Escherichia coli. In 20 cases more than one bacterium were isolated. Candida was cultured in 8 cases followed by Trichosporon in 2 and Fusarium in one case. On histopathology Candida was seen in 3 cases, while one case showed spores of Trichosporon. 80% cases with osteomyelitis had polymicrobial infection.
Conclusions.
The isolation of etiologic agent helps in administering appropriate antibiotic regimens, thus reducing the problem of multidrug resistance, morbidity and surgical limb amputations in patients suffering from diabetes mellitus.

Aim.
To investigate the efficacy and safety of combined glimepiride and metformin therapy in patients with type 2 diabetes mellitus (T2DM).
Materials and methods.
A multi-centre, open-label, prospective, observational study was conducted. A total of 1200 patients with T2DM inadequately controlled with metformin, glimepiride or combination of metformin + glimepiride were enrolled. Change in serum glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG), and postprandial blood glucose (PPG) levels; weight; waist circumference and hypoglycemic episodes were evaluated.
Results.
Baseline HbA_1c levels (8.24% ? 0.42%) were significantly reduced after 12 weeks of treatment (7.48% ? 0.48%) and at the end of the study.
(6.88% ? 0.56%). Target HbA_1c levels (?7%) were achieved in 65.1% of patients at the final visit at 24 weeks. FPG and PPG levels decreased by 1.45 ? 1.14 mmol/l and 2.17 ? 1.27 mmol/l respectively (p < 0.001). No severe hypoglycemic events were reported. Body mass index reduced by 0.85 ? 1.28 kg/m² (p < 0.001).
Conclusion. .
Combined glimepiride and metformin therapy significantly improved long-term glycemic control in patients with T2DM during the period of 24 weeks.
without additional risk of hypoglycemic events or weight gain.

This article describes the clinical case of a patient with early development of terminal complications of type 1 diabetes with chronic decompensated carbohydrate metabolism. For 1 year, the patient was treated with hemodialysis and she subsequently underwent successful kidney transplantation.

Vladimir Dilman ? an internationally renowned endocrinologist, oncologist, and gerontologist whose name is firmly entrenched into the history of medical science. The eve of his 90th birth anniversary is a particularly appropriate time to remember the achievements of Vladimir Dilman. Prof. Dilman predicted what has become a cornerstone of modern theories of origin of many chronic age-associated diseases, highlighting the role of the increase of hypothalamic sensitivity to the inhibitory action of peripheral hormones in the development of main non-communicable diseases.
The appreciation of the principal works of V. M. Dilman and his scientific biography not only increases our understanding of this subject, but provides a stimulus to independent research by younger generations and experienced specialists in the field of me.
dical science and .
practice, including e.
ndocrinology and diabetology.