The hepatic tissue plays a key role in the regulation and maintenance of stable blood glucose levels. The liver is the main gluconeogenesis organ of the body and is under constant hormonal control to determine the metabolic activity of hepatocytes. Hormonal signals trigger multiple post-translational regulatory mechanisms that alter the activity of key enzymes of glucose metabolism. A crucial role in the long-term control of glucose production and metabolism is played by pre-translational regulation at the level of gene expression of metabolic enzymes. There is growing evidence that this regulation, which is realised via control of the activity of transcription factors, provides constant adjustment of the body to changing environmental conditions and that its disruption leads to the development of metabolic diseases associated with insulin resistance. Therefore, the study of transcription factors that regulate glucose metabolism in the liver and the search for mechanisms to control them is of great biomedical importance in the context of metabolic disease treatment research.

Aim. To determine the frequencies of alleles and genotypes of polymorphic marker rs7903146 of the TCF7L2 gene in latent autoimmune diabetes in adults (LADA) and healthy individuals. The aims of the study were also to compare the distribution of alleles and genotypes and to explore the association with the development of LADA.

Materials and methods. A total of 96 patients (46 females and 50 males) with LADA and 201 healthy individuals were examined. A quantitative determination of autoantibodies GADA, ICA, IA-2A and ZnT8 in the serum of LADA patients was performed. All patients underwent genotyping of rs7903146 of the TCF7L2 genes.

Results. There was an increased frequency of the T allele and genotype T+ of marker rs7903146 of the TCF7L2 gene in patients with LADA with low concentrations of autoantibodies compared to a group of patients with high concentrations and with controls. We observed significant associations of the T allele and genotype T+ with LADA in patients with low concentrations of autoantibodies [p = 0.02; odds ratio (OR) = 1.85; 95% confidence interval (CI) = 1.10–3.13 and p = 0.04; OR = 2.14; 95% CI = 1.01–4.53 for the T allele and genotype T+, respectively).

Conclusion. The results of the study suggest that LADA patients with low concentrations of autoantibodies have a genetically pre-determined similarity with patients with type 2 diabetes.

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis.

Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values <0.05 were considered statistically significant.

Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029). Patients with АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 0.04). The patients with GG for TNFα G(238)A and GA for TNFα G(308)A had significantly greater amplitude of post-occlusive wave increase (Apw) than patients with GA for TNFα G(238)A and GG for TNFα G(308)A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively).

Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.

Comorbid chronic venous insufficiency (CVI) and type 2 diabetes mellitus (T2DM) are common, particularly in older people. The severity of DM and its complications can worsen the course of CVI and affect its management.

Aim. To assess the impact of T2DM on lesions of the lower extremities in patients with CVI.

Materials and methods. Eighty patients with CVI of the lower limbs were examined. Forty patients had T2DM (main group) and 40 patients did not have T2DM (control group). Physical examination, clinical and biochemical tests, ultrasound scanning of veins and arteries of the lower extremities and electroneuromyography (ENMG) of the lower extremities were performed for all patients. The state of the microvasculature was studied by laser Doppler flowmetry (LDF) for 15 patients in the main group and 15 patients in the control group.

Results. T2DM exacerbated the course of CVI, which was clinically characterized by a greater severity of trophic (p = 0.0001) and oedema (p = 0.03) syndromes. Morphological changes in the venous blood flow in patients with T2DM with CVI were characterized by bilateral lesions (p = 0.03), more frequent failure of sapheno-femoral anastomosis (p = 0.02) and perforating veins of the lower leg (p = 0.0004). The pathogenesis of such complications was associated with diabetic factors, including hyperglycaemia, НbА1с > 10%, duration of DM > 10 years and the presence diabetic microangiopathy of the lower limbs. Diabetic macroangiopathy and polyneuropathy were associated with disruption of the morphological and functional characteristics of the venous system and the disruption of the microcirculation in the lower extremities, contributing to increased oedema and trophic changes. At the same time, the presence of diabetic neuropathy masked the symptoms of CVI due to reductions in pain (p = 0.0004).

Conclusion. Diabetes exacerbates the course of CVI due to poor glycaemic control (HbA1c > 10%), long duration of diabetes (>10 years) and the presence of macroangiopathy in the lower extremities. Diabetic neuropathy of the lower limbs and diabetic microangiopathy aggravates the venous disease through disruption of microcirculation and increases the expression of trophic changes in the lower extremities.

The use of modern pharmaceuticals and cardiovascular disease (CVD) treatment methods has increased life expectancy and improved the quality of life of both patients with normal carbohydrate metabolism and diabetes mellitus (DM). This study provides a review of the literature on glycaemic control and choice of glucose-lowering therapy in patients with type 2 DM (T2DM) and CVD. According to the latest recommendations for the prevention of CVD, the target level of glycated haemoglobin (HbA1c) should be less than 7.0% and 7.5%–8.0% in older patients to decrease the risk of hypoglycaemia. The target blood glucose level is 7.7–10 mmol/L. The results of randomized clinical trials (RCTs) revealed that the adverse effects of second-generation sulfonylureas include critical hypoglycaemia episodes and increases in CVD-associated complications and mortality. Metformin reduces the risk of CVD in comparison with second-generation sulfonylurea derivates and insulin. Thiazolidinediones are not currently used for patients with CVD, and the safety of GLP-1 analogues and SGLT-2 inhibitors is still under investigation. When metformin therapy is ineffective, DPP-4 inhibitors should be prescribed and renal function should be monitored. Metformin is contra-indicated in patients with severe chronic heart failure (CHF) and acute myocardial infarction (AMI) because of the risk of lactic acidosis with tissue hypoxia. Thus, insulin is the drug of choice for glycaemic control in CVD patients with chronic kidney disease, severe heart failure or other acute clinical conditions.

Studies on the cardiovascular safety of new anti-diabetic drugs have drawn attention to the problem of heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). This has included one controversial study about hospitalization associated with HF in patients treated with dipeptidyl-peptidase-4 inhibitors (I-DPP4) compared with placebo. Until recently, HF was not considered to be a vascular or chronic complication of diabetes. It is well known that patients with T2DM generally have a higher risk of developing HF. In addition, the mortality risk of patients with HF and diabetes is significantly higher than that among patients with HF without carbohydrate metabolism disorders. Among patients with HF, hyperglycaemia requiring anti-diabetic therapy is much more common than among patients without HF. Therefore, it is important to address this issue in terms of the pathogenesis of HF in patients with T2DM, the influence and dynamics of glycaemic control and methods to achieve glycaemic control, including the selection of various types of anti-diabetic drugs.

Aim. To compare the effectiveness of "Glautex" drainage and the Ahmed valve for the treatment of secondary neovascular glaucoma in patients with diabetes.

Material and methods. We observed 28 eyes with neovascular glaucoma in 28 patients with proliferative diabetic retinopathy. The mean age of patients was 56.61 ± 1.43 years (range: 40–65). There were 11 males and 17 females. Patients were divided into two groups based on the drainage device used. The first group included 13 patients (13 eyes) for whom "Glautex" drainage was used, while the second group included 15 patients for whom the Ahmed valve model FP7 (New World Medical Inc., USA) was used.

Results. The absolute hypotensive effect [normalization of intraocular pressure (IOP) without the use of drugs] 1 year after surgery was 46.1% (6/13) in group I and 60% (9/15) in group II. The relative hypotensive effect (normalization of IOP during treatment with glaucoma drugs) 1 year after surgery was 53.8% (7/13) in group I and 80% (12/15) in group II. Hyphema in the early postoperative period was observed in 30.7% (4/13) and 26.6% (4/15) of patients in groups I and II, respectively. Hypotension with choroid detachment was observed in 23.1% (3/13) of group I patients and 13.3% (2/15) of group II patients. Migration of the tube to the scleral layers occurred after implantation of the Ahmed valve in 6.6% (1/15) of patients.

Conclusion. Comparative analysis of the outcomes of surgical treatment of secondary neovascular glaucoma in patients with diabetes showed that the most effective method to lower IOP was implantation of an Ahmed valve. The valve preserved visual function during the 1-year follow-up period and resulted in failed outcomes in only 20% of patients. The hypotensive effect of sinus trabeculectomy was observed in 53.8% of patients with "Glautex" drainage. There was a progressive decrease in visual function and the need for reintervention in 46.1% of group 1 patients.

A critical aspect of the treatment of most patients with type 2 diabetes mellitus (T2DM) is the initiation (and subsequent intensification) of insulin therapy when lifestyle interventions and oral anti-hyperglycaemic drugs fail to maintain or improve glycaemic control. There are several insulin treatment options available, including basal insulin, basal-bolus insulin and premixed insulin. Each of these options has advantages and disadvantages. The insulin lispro premixed insulin analogues, mix 25 (25% insulin lisproand 75% insulin lispro protamine suspension) and mix 50 (50% insulin lispro and 50% insulin lispro protamine suspension), which include intermediate- and rapid-acting components, were recently added to Russia’s national drug reimbursement program, increasing the treatment options for patients with T2DM. The aim of this review is to provide Russian physicians with current information on the efficacy and safety of insulin lispro, with a focus on insulin lispro mixtures, for the treatment of T2DM.

The quality, pharmacokinetic and pharmacodynamic profiles, safety and immunogenicity must be compared to demonstrate the bio-similarities of recombinant human insulin and insulin analogues. To confirm these bio-similarities in clinical studies, it is necessary to adhere to a multi-phased approach, starting with the pharmacokinetics and pharmacodynamics of the study drugs. In this article, in accordance with modern approaches to drug research, evaluation of the pharmacokinetics and pharmacodynamics of recombinant human insulin and analogues of human insulin (biosimilar drugs) is performed in a double-blind, randomised crossover euglycaemic hyperinsulinaemic clamp study.

This article describes the main approaches to the evaluation of the pharmacokinetic and pharmacodynamic parameters of recombinant human insulin preparations and insulin analogues during a euglycaemic hyperinsulinaemic clamp study. The inclusion criteria for the sample selection, design and conditions of the study, methods for the suppression of endogenous insulin, recommendations for doses of drugs, duration of the study and choice of primary and secondary pharmacokinetic and pharmacodynamic parameters for bio-similar insulin products (which depend on the duration of their effects) are described.

Background. A pharmaco-epidemiological study comparing the dynamics of different anti-diabetic drugs in patients with type 2 diabetes mellitus (T2DM) in Russia was conducted using data from a diabetes registry.

Objective. To assess and compare the frequency of the prescription of oral anti-diabetic medications (OAMs) and insulin and the average cost of anti-hyperglycaemic therapy with different OAMs in 2014 and 2011.

Material and methods. A retrospective cohort study was conducted using national diabetic registry data from the city of Moscow. Data for 270,073 patients (≥18 years old) with T2DM registered by 31 December 2014 were analysed using international the ATC/DDD methodology. The average indicated and actual daily dosage ratio was calculated. The cost of anti-hyperglycaemic therapy for оne person/year was calculated.

Results. There were no significant differences in prescribed OAMs between 2011 and 2014, despite the availability of new OAM classes (data for 2011 were published in «Diabetes mellitus», 2015, p. 32–46). The tendency to prescribe two groups of OAMs remained unchanged during the 4-year period (Metformin in 40% of patients and sulfonylurea derivatives, in combination or as a monotherapy, in 49.3%). The percentage of patients with T2DM who received insulin therapy increased from 10% in 2011 to 19.2% in 2014. The absence of a significant increase in the average cost of anti-diabetic therapy by 2014 can be explained by an increase in the prescription of different Russian generics for metformin, sulfonylurea derivatives and insulin, which were cheaper than foreign analogues by 30%–60%.

Conclusions. The main trends in the treatment of patients with T2DM by 2014 included less frequent combination therapy with metformin and PSM and more frequent monotherapy or combination therapy with insulin. Despite the appearance of new OAM classes in the market, the overall consumption pattern in 2014 did not exceed 5%. The average cost of anti-diabetic therapy for one patient with T2DM in 2014 in Moscow was 7,727 rubles per year.