Background: Diabetic retinopathy (DR) is one of the most common causes of blindness in patients with diabetes mellitus (DM) that is why it’s necessary to study the epidemiological characteristics of this complication.

Aims: The aim of the study was to evaluate the epidemiological characteristics of DR and blindness in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation (RF) for period 2013–16years.

Materials and methods: Database of Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (>18years).

Results: In 2016 the DR prevalence in RF was T1 38,3%, T2 15,0%, with marked interregional differences: 2,6–66,1%, 1,1–46,4%, respectively. The DR prevalence within 2013→2016 years was: T1 3830,9→3805,6; T2 1586,0→1497,0. Trend of new DR cases/per year increased: T1 153,2→187,8; T2 99,7→114,9. The structure of new cases of DR in 2016: non-proliferative stage (T1 71,4%, T2 80,3%), pre-proliferative stage 16,4%, 13,8%, proliferative 12,1%, 5,8%, terminal 0,2%, 0,1%, respectively, these data indicated the earlier detection of DR. The mean age of DR diagnosis increased: T1 by 1,2 years, T2 by 2,6. The average DM duration of DR determine increased T1 9,6→13,1 years, T2 6,0→9,1. The prevalence of blindness tends to decrease: T1 92,3→90,8; T2 15,4→15,2/10.000 DM adults. The amount of new cases of blindness/per year increased: T1 4,3→4,6; T2 1,2→1,4. The mean age of blindness increased: T1 39,1→41,6 years, T2 64,4→67,4; the mean duration of diabetes before blindness occur (from the time of DM diagnosis) increased: T1 20,2→21,2 years, in T2 10,7→11,3. We observed growth of DR treatment (laser surgery, vitrectomy, anti-VEGF medication) but the frequency of use in T2 patients is about 2 times less than in T1.

Conclusions: There was a decrease in the overall incidence of eye damage in diabetes (DR and blindness) in the analyzed period in RF. DR and blindness develops at advanced age and with a longer duration of diabetes. As the main directions of eye care development in diabetes it is necessary to standardize primary care in the regions, to unify the examination algorithms and methods of early diagnostic, to increase the continuity and interaction of endocrinologists and ophthalmologists in managing patients with diabetes in order to prevent the development of new cases of vision loss.

Background: Dipeptidyl-peptidase-4 inhibitors (iDPP-4) are pathogenically targeted drugs for diabetes mellitus type 2 (T2DM). Evogliptin is a new member of iDPP-4 class. The drug has the longest half-elimination period among the class, and its efficacy and safety as monotherapy have been already studied in placebo-controlled randomized clinical trials.

Aims: To study efficacy and safety of evogliptin as compared to sitagliptin in T2DM patients with unsatisfying glycemic control with metformin monotherapy via a multinational double blind randomized controlled trial. To compare the study results in Russian and Korean subpopulations.

Materials and methods: We used a combined Russian-Korean database (1:4) of EVO-COMBI trial. 281 adult T2DM patients administered metformin alone (at least 1000 mg/day) were randomized 1:1 to add on evogliptin (142 patients) or sitagliptin (139 patients) for 24 weeks once daily. The primary endpoint was change in glycated hemoglobin (HbA1c) level at Week 24 as compared to baseline. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was < 0.35 %. Subgroup analysis for between-subpopulation difference in treatment effect was also conducted.

Results: The mean between-group difference was 0.03 % [95 % CI: -0.14; 0.19 %], that confirms non-inferiority of evogliptin (mean HbA1c decrease -0.58 ± 0.70 %, p<0.001) to sitagliptin (mean HbA1c decrease -0.61 ± 0.66 %, p<0.001). Evogliptin and sitagliptin both tend to be more effective in South Korean subpopulation in terms of fasting plasma glucose lowering (p=0.030), however HbA1c decrease in subpopulations was comparable (p=0.657). Both drugs were well tolerated in both subpopulations. Adverse effects were associated mostly with gastrointestinal disorders, and the frequency was comparable between treatment groups (p>0.05). Gastrointestinal adverse effects were registered more often in Korean patients (p=0.014). There were no severe hypoglycemia. Frequency of mild hypoglycemia was comparable between evogliptin and sitagliptin (0.7 % and 5.2 %, respectively, p=0.365).

Conclusions: Evogliptin 5 mg/day is non-inferior to sitagliptin 100 mg/day in T2DM patients with unsatisfying glycemic control with metformin monotherapy. Safety profile is also comparable. Efficacy-safety profile of evogliptin is comparable in Russian and South Korean subpopulations.

Background: Lipohypertrophy is primary dermal complication of insulin therapy. The data on the prevalence of lipohypertrophy in diabetic subjects are inconsistent, that may be due to the lack of sensitivity and subjectivity of palpation as diagnostic technique. Meanwhile, the reliability of lipohypertrophy detection can be increased by ultrasound.

Aims: to compare clinical and ultrasound characteristics and to determine the risk factors of insulin-induced lipohypertrophy in diabetic subjects.

Materials and methods: We observed 82 patients, including 26 individuals with type 1 diabetes and 56 subjects with type 2 diabetes. Duration of insulin therapy varied from 3 months to 37 years (median 14 years). The sites of insulin injections were assessed by palpation and ultrasound. Visualization protocol included gray-scale densitometry, strain elastography, and 3D Doppler power ultrasound. Scaled evaluation of ultrasound sings was applied. Insulin injection technique was assessed by questionnaire. Serum levels of insulin antibodies were determined by ELISA.

Results: Lipohypertrophy was revealed by palpation and ultrasound in 57 and 80 patients (70% and 98%) respectively. Total lipohypertrophy area, acoustic density and total ultrasound score showed weak positive correlations with daily insulin dose (r=0.3, r=0.3 and r=0.35, respectively, all p<0.006). Patients receiving insulin analogues had smaller area of abdominal lipohypertrophy than those on human insulin (p=0.03). A positive correlation was found between abdominal lipohypertrophy area and mean postprandial glucose (r=0.35, p=0.001). A rare needle change and injections in lipohypertrophy sites were the most common deviations in insulin injection technique (70 and 47 subjects, 85% and 53% respectively). The levels of insulin antibodies showed no association with lipohypertrophy parameters.

Conclusions: Patients with type 1 and type 2 diabetes demonstrate high prevalence of lipohypertrophy in insulin injection sites. Ultrasonography is more sensitive method of diagnostics of lipohypertrophy compared with palpation. Insulin-induced lipohypertrophy is associated with errors in injection technique and higher insulin doses.

Background: Premature aging are frequently observed among individuals with type 1 diabetes. Decrease of ovarian reserve may be one of the characteristics of such process.

Aims: To evaluate the ovarian reserve function in female patients of reproductive age with type 1 diabetes in comparison with healthy women.

Materials and methods: This study evaluated 224 Caucasian women, age 18–37 years with type 1 diabetes and 230 healthy women of comparable age. Serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and testosterone were compared on the 2–3 day of menstrual cycle as ovarian volume and antral follicle count (AFC). In addition, glycated hemoglobin level (HbA1c%) was evaluated.

Results: We reveal statistically significant difference in following parameters in diabetic women in comparison with healthy women: AMH, AFC. But even in diabetic patients parameters remained within reference ranges. There was a pronounced negative relationship between the levels of HbA1c% and AMG.

Conclusions: Ovarian reserve function parameters decrease in young women with type 1 diabetes in comparison with healthy women, but ovarian reserve parameters are in normal reference range. These findings are important in pregnancy planning consulting by gynecologists and endocrinologists. We must recommend to women with type 1 diabetes more early planning of natural pregnancy for treatment with reproductive technology in cases of prolog absence of nature pregnancy.

Background: Diabetes mellitus type 2 is metabolic disease characterized by hyperglycemia due to a defect in insulin secretion resulting in insulin resistance. This disease leads to dysfunction of various organs including eyes, kidneys, and heart. One of the alternative diets which can be consumed is a mixture of soy milk and ginger (Indonesian: Susu kedelai dan jahe (Sulehe)). Sulehe contains isoflavones, PUFAs, and gingerols that are affected by insulin resistance.

Aim: This study was aimed to discover the effect of Sulehe on peroxisome expression proliferator-activated receptor gamma (PPAR-γ) in a rat model of insulin resistance.

Methods: Twenty-four rats were divided into six study groups: (1) negative control, (2) positive control, (3) soy milk 5 g/kg BB diet, (4) ginger 500 mg/kg BB diet, (5) Sulehe (soy milk 2500 mg/kg BB + ginger 250 mg/kg BB) diet, (6) Sulehe (soy milk 5000 mg/kg BB + ginger 500 mg/kg BB) diet. This research belonged to experimental in vivo laboratory study with all replications of each treatment across all subjects is completely randomized, and data retrieval with a post-test only control group design.

Results: The mean PPAR-γ activity in normal (control) rats was 578 ± 82.02. Sulehe (soy milk 5000 g + ginger 500 mg) diet can increase rat PPAR-γ activity up to 1158 ± 53.74. The significant different result achieved when p-value on ANOVA analysis is less than 0.05 (p<0.05). According to the ANOVA analysis, there was a significant difference in PPAR-γ in the combination of soy milk + ginger 500 mg, with a difference of −345.5, compared with control.

Conclusion: In summary, Sulehe may be a potential agent to influence PPAR-γ expression.

Background: The increased serum uric acid (SUA) levels have been linked to macro vascular disease in Type 2 Diabetes Melitus. The correlation between serum uric acid levels and diabetic peripheral neuropathy has not been addressed properly.

Objective: The aim of this study was to determine the correlation between high serum uric acid levels and diabetic peripheral neuropathy.

Methods: This was a case-control design study and the sampling was done consecutively by following the inclusion and the exclusion criteria. The diabetic peripheral neuropathy was evaluated using Electroneuromyography (EMNG) and the serum were taken for uric acid level examination. Chi square test was used for the correlation analysis.

Result: Thirty subjects were enrolled and divided into an experimental group of 15 subjects and a control group of 15 subjects as well. We found that the diabetic peripheral neuropathy did not show a significant correlation with high serum uric acid levels, p=0,136 and OR 3,143 (CI 95% 0,681-14,503).

Conclusions: There was no correlation between high serum uric acid levels with diabetic peripheral neuropathy.

In this work systematization (classification) of biochemical and physiological processes that cause disorders in the human body during the development of diabetes mellitus is carried out. The development of the disease is considered as the interaction and mutual reinforcement of two groups of parallel processes. The first group has a molecular nature and it is associated with impairment of ROS-regulation system which includes NADPH oxidases, RAGE receptors, mitochondria, cellular peroxireductase system and the immune system. The second group has a pathophysiological nature and it is associated with impairment of microcirculation and liver metabolism. The analysis of diabetes biochemistry based on different published references yields a creation of a block diagram evaluating the disease development over time. Two types of autocatalytic processes were identified: autocatalysis in the cascade of biochemical reactions and "cross-section" catalysis, in which biochemical and pathophysiological processes reinforce each other. The developed model has shown the possibility of using pharmacologically active natural metabolite glycine as a medicine inhibiting the development of diabetes. Despite the fact that glycine is a substitute amino acid the drop in the glycine blood concentration occurs even in the early stages of diabetes development and can aggravate the disease. It is shown that glycine is a potential blocker of key autocatalytic cycles, including biochemical and pathophysiological processes. The analysis of the glycine action based on the developed model is in complete agreement with the results of clinical trials in which glycine has improved blood biochemistry of diabetic patients and thereby it prevents the development of diabetic complications.

Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists.

The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week.

Type 2 diabetes mellitus (DM) is a global epidemic associated with severe vascular complications development. Diabetic neuropathy is the most common chronic complication of DM that worsens patients’ life quality and prognosis. Therefore, studies dealing with DM and diabetic neuropathy underlying mechanisms are extremely relevant. The review discusses current views on vitamin D role in glucose metabolism and inflammatory processes. It is reported that vitamin D deficiency can contribute to insulin resistance development, and change in vitamin D receptor activity or extra- and intracellular calcium concentration due to vitamin D deficiency can affect pancreatic β-cells function and lead to decrease in insulin production. Key pathogenic mechanisms of diabetic neuropathy as well as possible relationship between vitamin D deficiency and neuropathy development are in focus of this review. Results of recent clinical trials regarding vitamin D supplementation in patients with DM are also discussed. The presented data suggest that vitamin D deficiency can be considered as a non-classical risk factor for the development of not only DM but its complications as well.

In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- and hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed.

A case report of type 2 diabetic patient with critical limb ischemia (CLI) after successful endovascular revascularization is reported. The diagnosis of CLI was established according to clinical data and results of lower limb ischemia assessment by non-invasive methods. The unique feature of this case is presentation of results of the new method of lower limb ischemia assessment – fluorescent angiography in near infrared range using indocyanine green (ICG). Following parameters of fluorescent angiography in near infrared range are analyzed in different regions of interest: Tstart(sec) – the time of fluorescence occurrence (Istart, unit) in the analyzed area after intravenous administration of ICG; Tmax (sec) – time to achieve maximum fluorescence (Imax, unit) after intravenous injection of ICG; Tmax – Tstart (sec) – the time difference between Imax and Istart. In this clinical case, the time of achievement Istart, Imax, Tmax – Tstart in different regions of interest decreased after successful endovascular revascularization of lower limb arteries.