Type 1 diabetes mellitus (T1DM) was used from the viewpoint of human immunogenetics as an example of the most widely studied immunity-mediated disease. This was done in order to develop, approve and implement a new clinical approach to determine immunity-mediated susceptibility or resistance to autoimmune diseases. The approach is based on analysis of entire HLA-DRB1 genotypes (not separate HLA-DRB1 haplotypes) of the study participants. Therefore, more effective and personalised classification of T1DM risk groups was achieved by exclusion from significant contingents.

Recently, on the pharmacological market, new drugs from the class of incretin mimetics, or glucagon-like peptide-1 (GLP-1) receptor agonists, which have proven their high effectiveness in type 2 diabetes mellitus therapy, have appeared. At present, much attention has been paid to the pleotropic effects of incretin mimetics. In a number of both experimental and clinical studies, cardioprotective effects of this medication group have been demonstrated. The present review elucidates existing data about neuroprotective effects of GLP-1 receptor agonists in brain ischaemia and in nonischaemic nervous system diseases such as diabetic neuropathy and neurodegenerative disorders. The possible mechanisms for these effects, which appear to be primarily antioxidant effects, anti-inflammatory effects, antiapoptotic effects and an increase in neurons differentiation, are discussed.

Aim.

To evaluate the prevalence of undiagnosed type 2 diabetes mellitus (T2DM) among patients with cardiovascular disease.

Materials and methods.

T2DM screening programs among patients with cardiovascular disease were held from 2013 to 2014 in several Russian cities. In total, 1001 patients aged ≥40 years with hypertension and/or atherosclerotic disease and without prior diagnosis of T2DM were screened in outpatient cardiology clinics. T2DM diagnosis was based on fasting plasma glucose levels, glycated haemoglobin (HbA1c) and/or oral glucose tolerance test (OGTT) results. Blood pressure (BP), family history of T2DM, cardiovascular disease, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were analysed.

Results.

Fasting glucose was measured in 1000 (99.8%) patients, HbA1c was measured in in 623 (62.2%) and OGTT was performed in 286 (2.6%). Fasting glucose detected 8% of newly diagnosed T2DM; among patients who underwentHbA1c measurement, the prevalence of T2DM was 10.91%, and among patients who underwent OGTT, the prevalence was 13.99%. Depending on the chosen test, the prevalence of undiagnosed pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) was in the range of 14.4%–36.4%. The majority of patients with T2DM diagnosed by OGTT did not have target blood pressure and lipid levels; 67.5% had elevated systolic BP, 47.5% had elevated diastolic BP, 90.9% had high LDL (≥1.8 mmol/l) and 52.9% had high triglyceride levels (≥1.7 mmol/l).

Conclusion.

A high prevalence of undiagnosed T2DM (from 8% to 13.99%, depending on the diagnostic criteria) and pre-diabetic state in patients with cardiovascular disease may require screening for T2DM in this high-risk group.

Objective.

To estimate annual expenditures attributed to diabetes mellitus (DM) per patient in Russia based on data from epidemiologic studies and to analyse DM cost drivers.

Methods.

The expenditures per diabetic patient were calculated as the sum of medical costs (outpatient and emergency room visits, inpatient care and medications provided during outpatient care), payments for sick leaves, disability pensions and gross domestic production (GDP) losses due to temporary disability (indirect costs). All data on resource consumption and productivity losses were derived from the dataset for Russia, collected from the point of view of a multicentre international study on the practice of DM treatment. Medication costs were based on registered governmental price lists (list of vital and essential drugs). Medical care costs were estimated using the approved public health care reimbursement rates. Disability payments were calculated on the basis of data published by the Russian Pension Fund and Social Security Fund. GDP losses were assessed using federal statistics.

Results.

The mean total annual costs per patient with DM type 1 (T1) were 81.1 thousand Russian rubles (RUR) and those per patient with DM type 2 (T2) were 70.8 thousand RUR. Although most patients with DMT2 were >60 years, approximately 25% of costs were nonmedical and caused by productivity losses; for patients with DM type 1(T1), this proportion was 35%. The medical cost structure differed depending on the type of diabetes. In T1, the main component was attributed to DM treatment; in DMT2, almost half of medical costs were due to DM complications. Medication costs accounted for 69% and inpatient care accounted for only 22% of medical costs in DMT1. For DMT2, the proportion spent on inpatient care (43%) was almost equal to medication costs (46%). Mean expenditures per patient with DM complications were higher; in the case of DMT2, the presence of complications increased the costs by 3 times. Mean medical costs were higher for patients not reaching the target level of Hb1Ac than those reaching it, despite age or the presence of complications. The results of regression analysis showed that the strongest predictors of costs growth were the number of admissions, presence of complications and insulin treatment. It was also demonstrated that the mean medical cost per patient with uncomplicated DM T2 on insulin therapy was 38.5 thousand RUR, which was comparable to the cost per patient with complications, receiving other glucose-lowering treatment (37.0 thousand RUR).

Conclusion.

Costs for patients with DM complications are considerably higher than those for patients without complications. Therefore, the key point in controlling the growth of the DM economic burden is to minimise and/or prevent the development of DM complications, which could be achieved by timely DM diagnosis and appropriate glucose-lowering therapy.

Objective.

Using continuous glucose monitoring to determine diagnostic optimisation of metabolic status and perioperative management techniques in coronary heart disease and diabetes mellitus type 2 (DMT2) in order to reduce the risk of perioperative complications.

Materials and Methods.

We examined 80 patients with ischaemic heart disease, aged 39 to 71 years. Patients were divided into four groups. Separation criteria were the presence of diabetes and the method of myocardial revascularisation. For all patients in the intra- and early postoperative periods the continuous glucose monitoring was performed by CGM System Gold MMT-7102W (Medtronic, USA); also blood glucose level has been controlled by sample testing of venous blood (laboratory glucose oxidase electrochemical method) and capillary blood by portable blood glucose meter (OneTouch Ultra, LifeScan, USA).

Results.

In our study, average blood glucose levels from the results of measurements with CGMS at different operative stages and in the early postoperative period in four groups of patients were measured. Glucose level monitoring in diabetic patients during coronary revascularisation demonstrated that perioperative hyperglycaemia in patients with coronary artery disease who underwent cardiopulmonary bypass was observed regardless of whether they had metabolic carbohydrate disorders during the preoperative period. The most significant changes in glucose were observed in these patients at the stage of cardiopulmonary bypass, while in patients with T2DM, the glycaemic response to intervention (even with satisfactory preoperative compensation of carbohydrate metabolism) was more intense and less manageable than that in surgical patients without diabetes. When operating on a beating heart, intraoperative hyperglycaemia was observed more frequently in patients with T2DM than in controls at the stage of bypass, but glucose indicators were significantly lower than in groups of patients with T2DM who underwent cardiopulmonary bypass.

Conclusion.

Given the lack of significant differences between the laboratory glucose rates, data from CGM System Gold and OneTouch Ultra demonstrated that continuous glucose monitoring can reliably assess the presence or absence of metabolic changes in the perioperative period and thus reduce the likelihood of complications.

Glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are new classes of hypoglycemic agents with numerous pleiotropic effects. The review summarises data about the influence of GLP-1 analogues and DPP-4 inhibitors on structural and functional changes in diabetic kidneys. Growing evidence indicates that the kidney is one of the loci of the effects and degradation of GLP-1. The potency of the effects of GLP-1 in diabetic kidneys can be reduced by decrease in GLP-1 receptor expression or enhancement of GLP-1 degradation. In experimental models of diabetic nephropathy and non-diabetic renal injury, GLP-1 analogues and DPP-4 inhibitors slow the development of kidney fibrosis and prevent the decline of kidney function. The mechanisms of protective effect include hyperglycaemia reduction, enhancement of sodium excretion, suppression of inflammatory and fibrogenic signalling pathways, reduction of oxidative stress and apoptosis in the kidneys. In clinical studies, the urinary albumin excretion reduction rate while using the GLP-1 analogue and DPP-4 inhibitor treatment was demonstrated in patients with type 2 diabetes. Long-term impact of these agents on renal function in diabetes needs further investigations.

Aim.

The study of ion- and osmoregulating renal functions in patients with type 2 diabetes mellitus (T2DM) for individual predictive assessment of renal response to exenatide treatment.

Materials and methods.

In total, 41 patients with T2DM were included in the study (12 males, 29 females). Compensated and subcompensated heart failure was observed in 80% and 20% of the patients, respectively. Nephropathy in the microalbuminuria stage was diagnosed in 34% of these patients. The patients’ ages ranged from 34 to 82 years. The mean duration of T2DM was 7 ± 1 years. The mean value of glycated haemoglobin was 8.1 ± 0.4 mmol/l. The control group included 16 healthy women, aged 24‒36 years. Ion- and osmoregulating renal functions and glycaemia levels were assessed after water loading and exenatide treatment (5 µg). Blood serum and urine osmolalities were measured using a micro-osmometer (Advanced Instruments 3300). Capillary blood glucose concentrations were determined using a test system (Accu-Chek Go). Serum and urine levels of urea, protein, creatinine, cholesterol, triglycerides, HDL, LDL, alanine aminotransferase and aspartate aminotransferase as well as cations were determined on a biochemical analyser (Erba XL-200 and Architect c8000), flame photometer (Sherwood-420) and atomic absorption spectrophotometer (Shimadzu AA-6200).

Results.

Reabsorption of solute-free water on the background of endogenous vasopressin action was not disturbed in patients with T2DM. An increase in solute free water clearance in response to water load occurred in healthy subjects as well as in patients with T2DM. After exenatide administration, a correlation between the changes in urinary sodium excretion and blood glucose levels was found (p <0.01). The increase in diuresis in oedema exenatide-treated patients was attributed to the rise of renal sodium excretion; there is a strong correlation between values of sodium excretion during the control period and after exenatide injection (p <0.001).

Conclusions.

The results indicate the prognostic significance of initial kidney function to assess the capacity for removal of water and ions and the subsequent reactions to exenatide.

Intensification of antihyperglycaemic treatment in patients with poorly controlled type 2 diabetes mellitus who were on insulin therapy remains a difficult issue. Results from clinical trials with the sodium-glucose linked transporter (SGLT-2) inhibitor dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus using insulin are summarised and discussed in the article.

The Somogyi phenomenon or rebound hyperglycaemia is known as the counterregulatory response to asymptomatic nocturnal hypoglycaemia; the Somogyi phenomenon occurs with high fasting blood glucose levels and hyperglycaemia the following morning. Most published trials, however, do not agree with this theory. Although data from some experimental studies may suggest a pathophysiological link. Perhaps, the differences in research results are caused by the evolution of blood glucose monitoring methods. Nevertheless, it cannot be excluded that the results of Michael Somogyi’s studies were misunderstood.

Introduction.

In the early 2000s, in type 2 diabetes mellitus (T2DM) treatment, a fundamentally new class of drugs appeared—the incretin mimetics. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors allowed the safety of the T2DM therapy to be increased by reducing several parameters, including hypoglycaemia incidences, risks of cardiovascular complications and weight gain. Market approval of a new Russian drug in this group will ensure modern, efficient and affordable care for our patients.

Aim.

To study the efficacy and safety of a new DPP-4 inhibitor (gosogliptin) in comparison with that of vildagliptin as monotherapy as well as in combination with metformin in patients with T2DM who were not previously treated with drug therapy.

Materials and methods.

The study SRX-1374-02 involved 299 patients. In total, 149 patients were randomised to the gosogliptin group and 150 were randomised to the vildagliptin group. The groups were comparable with respect to baseline characteristics. In the first 12-week stage, patients received treatment with one of the study drugs as monotherapy. The decision was then made whether to continue the monotherapy regimen or to add metformin during the next 24 weeks. Dose titration of the study drugs and the addition of metformin were performed on the basis of glycaemia levels. The total treatment duration was 36 weeks.

Results.

After 12 weeks of monotherapy, НbА1с levels significantly decreased by -0.93% and -1.03% in the gosogliptin and vildagliptin groups, respectively. After the administration of combination therapy the decrease in НbА1с continued and was -1.29% in the gosogliptin + metformin group and -1.35% in the vildagliptin + metformin group when compared with baseline values. The difference in НbА1с reduction between the groups during both treatment periods was ≤0.1% (upper level of CI <0.4%), which led to the conclusion about the superior efficacy of gosogliptin over that of vildagliptin as monotherapy and in combination with metformin. By the end of the 36-week treatment period, НbА1с reached the target level of ≤7.0% in 56.4% and 55.4% of patients in the gosogliptin and vildagliptin groups, respectively (statistically significant differences between treatment groups were not found, p = 0.74).

Conclusion.

The results showed that gosogliptin is an effective hypoglycaemic agent from the group of DPP-4 inhibitors and can be recommended for use in patients with T2DM both as monotherapy and in combination with metformin.