卷 86, 编号 10 (2014)

AIM. To study the secretion of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 2 (GLP-2) in response to a carbohydrate load in people with risk factors for type 2 diabetes mellitus (DM2) in relation to the type of carbohydrate metabolic disturbances and age. MATERIALS AND METHODS. One hundred and twenty-seven patients having DM2 risk factors who had not previously received glucose-lowering therapy underwent an oral glucose tolerance test (OGTT). The plasma levels of glucose, insulin, glucagon, GLP-1, GIP, and GLP-2 were determined at 0, 30, and 120 minutes of the test. RESULTS. According to the findings, the patients were divided into 3 groups: 1) normal glucose tolerance; 2) prediabetic states (impaired glucose tolerance and/or impaired fasting glycemia); 3) new-onset DM2. OGTT showed that the secretion of GLP-1 was lower and that of GIP and GLP-2 was higher in patients with DM2. GLP-1 secretion decreased with patient age. CONCLUSION. During OGTT, there is a statistically significantly difference in the secretion of incretin hormones in persons with varying degrees of carbohydrate metabolic disturbances: the peak GLP-1 secretion is the highest in healthy individuals and lowest in the patients with DM2; on the contrary, the peak GLP2 and GIP secretions are the highest in the patients with DM2. This may suggest that GLP-1 and the two other hormones (GLP-2 and GIP) show opposite effect in the regulatory mechanisms of carbohydrate metabolism. GLP-1 secretion is decreased with age, which may be one of the reasons for the higher prevalence of DM2 among the elderly.

AIM. To study the prognostic value of multifocal atherosclerosis (MFA) in patients with diabetes mellitus (DM) at high risk for myocardial ischemia who need coronary angiography (CAG). MATERIALS AND METHODS. The investigation included 148 patients: 25 with type 1 DM (DM1), 73 with type 2 DM (DM2), and 50 without DM who had undergone CAG. Duplex ultrasound scanning of lower limb vessels and brachiocephalic and renal arteries was carried out in all the patients. RESULTS. Involvement of two or more vascular beds was noted in 60% of the patients with DM1, in 68.4% of those with DM2, and in 34% of those without DM (p < 0.05). Regression analysis showed that the risk factors of MFA were defined to be myocardial infarction (MI) in the history (OR=2.4; p=0.02), DM (OR=3.9; p=0.0002), smoking (OR=2.4; p=0.05), elevated creatinine (OR=6.5; p=0.002) and fibrinogen (OR=6.8, p=0.004) levels. Among the DM patients, there were 26.5% of those who had achieved a main assessment criterion (a combined end point (CEP)), such as death, urgent hospitalization for heart failure, nonfatal MI, nonfatal stroke, lower extremity amputation, double creatinine levels, and achievement of end-stage renal failure during a 24-month follow-up. In patients without carbohydrate metabolic disturbances, this indicator was 12% (p=0.01). During the prospective study, a total of 6.1% of patients died in the DM group; all the patients in the non-DM group completed the study. Calculation of survival rates by the Kaplan-Meier method indicated that the DM patients with concurrent atherosclerotic lesion had achieved CEP significantly more frequently than the comparison group. Such differences were absent among the persons without carbohydrate metabolic disturbances. CONCLUSION. The regression analysis has shown that prior MI, DM, smoking, creatinine and fibrinogen levels are factors associated with the development of MFA in the examined groups. In the patients with DM, concurrent atherosclerosis of two or more vascular beds is an important factor for the progression of cardiovascular and renal diseases.

AIM. To investigate the relationship of resistin, adiponectin, leptin, and hormone metabolic parameters in patients with hypothyroidism. MATERIALS AND METHODS. Ninety-three women aged 58.0 (53.0-63.0) years with hypothyroidism were examined. A control group consisted of 10 women aged 48 (47-50) years. Anthropometric characteristics, glucose and lipid metabolic parameters, and leptin, resistin, adiponectin levels were studied. RESULTS. The patients with hypothyroidism were found to have statistically significantly enhanced insulin resistance (IR) and compensatory hyperinsulinemia in the presence of android fat distribution. The found atherogenic dyslipidemia manifested itself as an increase in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and atherogenic index and as a reduction in high-density lipoprotein cholesterol. The concentration of leptin and resistin was increased and that of adiponectin was reduced in the patients with hypothyroidism. There was a correlation of leptin and adiponectin with fat metabolic parameters. CONCLUSION. The women with hypothyroidism had enhanced IR, as well as compensatory hyperinsulinemia in the presence of android fat distribution. Hypothyroidism is accompanied by the development of atherogenic dyslipidemia. The concentration of leptin and resistin was elevated and that of adiponectin was reduced in the examinees.

AIM. To evaluate the efficiency of treatment for renal anemia in patients with chronic glomerulonephritis (CGN), by using erythropoietin and its combination with hypoxic altitude chamber training (HACT). MATERIALS AND METHODS. Sixty-three patients (41 men and 22 women) (mean age 37.1±13.3 years) with CGN during the predialysis phase of chronic kidney disease (CKD) complicated by anemia. Hemoglobin (Hb), packed cell volume (PCV), and red blood cell indices (mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC)), platelet count, serum iron, fibrinogen, C-reactive protein (CRP) and creatinine levels were determined in all the patients at baseline and during a prospective follow-up. Glomerular filtration rate (GFR) was measured using with the Rehberg-Tareev test. Along with standard renal protective therapy, all the patients received either epoetin beta (n=31; Group 1) or its combination with HACT (n=32; Group 2). In Group 1 patients (n=31), erythropoietin (EPO) was given in an initial dose of 20-50 IU/kg thrice daily, followed by the dose being adjusted until the target Hb level was reached. Group 2 patients (n=32) received HACT cycles by the standard procedure in combination with EPO given in lower doses (20-50 IU/kg once weekly). A prospective follow-up of the patients was carried out during one year. RESULTS. Following one year, the number of patients who had achieved the target Hb level was 74.1% in Group 1 and 87.5% in Group 2. Over time, there were increases in the concentration of Hb (from 108.6±19.4 to 124.5±14.09 g/l; p<0.05), PCV, and red blood cell indices (MCV, MCHC) in the patients receiving EPO (Group 1). Besides an anti-anemic effect, there was a significant decrease in the concentrations of fibrinogen from 6655 (4884-7634) to 3776 (3330-4884) mg/dL; (p<0.05), serum creatinine from 159 (89-261) to 138 (79-258) µmol/l (p<0,05), proteinuria from 2.955 (1.024-6.745) to 2.069 (0.539-4.279) (p<0.05), which was accompanied by an increase in GFR from 62.3 (37.0-107.4) to 76.9 (46.0-96.0) ml/min (p<0.05). In Group 2, the rise in the concentration of Hb (from 114.1±11.7 to 132.0±16.5 g/l (p<0.05), PCV, MCV, and MCHC proved to be more pronounced than that in Group 1 (p<0.05) and accompanied by an elevation in the counts of platelets (from 222.7±19.8·109/l to 249.3±21.9·109/l (p<0.05)) and red blood cells (from 4.0±0.4·1012/l to 4.34±0.3·1012/l (p<0.05)). There was a more marked reduction in the degree of proteinuria from 3.092 (0.764-7.694) g at baseline to 1.600 (0.677-4.078) g one year later (p<0.05) than that in Group 1 (p<0.05). The increase in GFR from 60.1 (46.0-96.0) to 79.4 (44.0-120.0) ml/min (p<0.05) and the fall in the concentration of fibrinogen from 5555 (4884-7770) to 4107 (3776-5328) mg/dL (p<0.05) and serum creatinine from 166 (92-273) to 147 (92-152) µmol/L (p<0.05), which were observed in Group 2, were comparable to those in Group 1. CONCLUSION. Epoetin beta used in patients with CGN has an anti-anemic effect and leads to improved renal nitrogen-excretory function. Erythropoietin in combination with HACT used in CGN provides a higher anti-anemic efficacy and a more pronounced antiproteinuric effect.

AIM. To characterize the 2013-2014 epidemic season from the results of detection of influenza infection in patients; to provide the molecular genetic characteristics of the strains isolated from deceased patients. MATERIALS AND METHODS. The investigators examined 1203 patients (387 children, 509 people older than 16 years of age, 307 pregnant women) admitted to Moscow Clinical Infectious Diseases Hospital One with the clinical signs of acute respiratory viral diseases. Nasal lavage and autopsy specimens were used to isolate viral strains, then to sequence genomic fragments, and to determine receptor specificity. RESULTS. Out of the 1203 examinees, 284 (23.6%) were influenza-positive: 221 (77.8%), 24 (8.5%), and 39 (13.7%) patients had influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B, respectively. Influenza was notified in 42,7% of the pregnant women. There was a preponderance of its moderate form; its severe form developed in single cases having comorbidities. One fatal outcome was registered. The intake of antiviral medications in the first 48 hours of the disease could prevent complications. The investigators revealed mutations in the strain isolated from the bronchoalveolar lavage fluid of a patient with severe pneumonia complicated by acute respiratory distress syndrome. CONCLUSION. There is evidence that there are mutant A(H1N1)pdm09 viruses that have high pneumotropicity. The high risk of their circulation in the population and the risk of severe influenza forms involving the lower respiratory tract remain. Early antiviral therapy in the first 36-48 hours diminishes the clinical manifestations of influenza and reduces the risk of developing complications.

AIM. To evaluate the efficacy of the combined drug furamag (furasidine potassium and magnesium hydroxycarbonate) in combination with the third-generation cephalosporin cefotaxime versus cephalosporin monotherapy for nosocomial urinary tract infections (NUTI). MATERIALS AND METHODS. The randomized open-label comparative parallel group clinical trial enrolled 52 male and female patients aged over 18 years with a documented diagnosis of NUTI. Group 1 (a study group) took oral furamag 300 mg/day in combination with intravenous cefotaxime 6 g/day; Group 2 (a control group) received cefotaxime monotherapy. The duration of therapy in both groups was 7 to 10 days until the efficiency levels were achieved. RESULTS. A final efficiency analysis was made in 24 and 25 patients from Groups 1 and 2 who had different forms of NUTI (catheter-associated NUTI, cystitis, pyelonephritis). On day 3 of treatment, most patients were noted to have a decreased systemic inflammatory response; lower C-reactive protein and procalcitonin levels being in the study group patients. The clinical efficiency of antibacterial therapy, which had been evaluated both immediately after treatment termination and during further control, did not substantially differ in the furamag/cefotaxime combination and control groups although there was an obvious tendency towards the more marked effect of combined therapy 7-14 days after treatment (11.8% efficiency differences; p>0.05). Analysis of bacteriological efficacy revealed its most pronounced and clinically significant differences between the groups: the cefotaxime/furamag combination led to higher pathogen eradication in all follow-up periods: after 3 days of treatment (82.6%) and following a complete therapy cycle (95.8%) versus the cefotaxime monotherapy group (43.5 and 70.8%, respectively; p<0.01). Microbiological results showed that the major NUTI pathogens (Escherichia coli, enterococci) were more susceptible to potassium furasidine (furamag) versus cefotaxime. The in vitro higher activity of furamag versus cefotaxime was attended by the significantly higher eradication of one of the two important NUTI pathogens - Enterococcus faecalis. CONCLUSION. Furamag used in combination with the third-generation cephalosporin cefotaxime showed a higher bacteriological efficacy and a rapider reduction in the symptoms of a systemic inflammatory response in patients with NUTI. On the basis of the findings, the above combination of furamag and cefotaxime may be recommended as first-line therapy for NUTI when multidrug-resistant nosocomial infection pathogens are widely distributed now.

The incidence of chronic viral hepatitides (CVH) has increased 2.2-fold in the Russian Federation over the past decade. This increase is mainly determined by an almost threefold rise in the incidence of chronic hepatitis C (CHC): from 12.9 in 1999 to 39.1 per 100,000 population in 2012. The calculated data of hepatitis C burden in the Russian Federation show that in 2010 the total medical and social losses and expenses associated with hepatitis C and its implications were 48.47 billion rubles or 0.108% of the gross domestic product, the direct medical costs were 17.1 billion (35.28%) rubles, GDP losses were 26.05 billion (53.75%) rubles, and the disability payments were 5.32 billion (10.97%) rubles. The patients (mean age 45 years) with liver cirrhosis (LC) were 15.2% in the structure of the CHC patients (mean age 37 years) admitted to Moscow infectious diseases hospitals in 2010. Analysis of the regional registers of the Russian Federation, the proportion of patients with LC among those with CHC was 18%. The existing forms for recording morbidity and mortality from poor CHC outcomes cannot significantly estimate the true disease stage distribution of patients and hepatitis C-associated disability and mortality rates. In this connection, it is necessary to introduce a federal register and to change recording forms for patients with viral hepatitides. Standard interferon, pegylated interferon alpha 2a and pegylated alpha 2b, and the HCV protease inhibitors telaprevir, boceprevir, and simeprevir have been registered for the treatment of hepatitis C in the Russian Federation.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MEN1 tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MEN1 gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

Type 1 diabetes mellitus (DM1) is a chronic disease that may affect survival and quality of life in patients due to the development of acute and chronic complications. This review highlights the publications during the past decade on survival and the degree (stabilization/regression) of complications, such as diabetic retinopathy, nephropathy, neuropathy, and macrovascular events in DM1 patients with end-stage renal disease after simultaneous pancreas-kidney transplantation.

Gestational diabetes mellitus (GDM) is hyperglycemia that is first detected during pregnancy and does not meet the criteria for manifest diabetes. The incidence of GDM worldwide varies from 1 to 14% and that in Russia is as high as 4%. Hyperglycemia during pregnancy is associated with the development of preeclampsia, the birth of a big baby, emergency cesarean section, birth trauma, and neonatal hypoglycemia. The fact that there is no well-organized screening for GDM in our country leads to that the diagnosis of this condition is delayed for 4-20 weeks in 50-60% of cases. The risk group distribution of pregnant women leads to the diagnosis of GDM only in 50% of cases. At the same time, pregnancy is accompanied by physiological insulin resistance so the latter itself is a clinically important risk factor for carbohydrate metabolic disturbances. The Hyperglycemia and Adverse Pregnancy Outcomes (HYPO) study has indicated that the previously used diagnostic criteria for GDM require reconsideration. There is a need for uniform standards for the diagnosis and treatment of carbohydrate metabolic disturbances during pregnancy. The concepts "diabetes mellitus (DM)" and "manifest (new-onset DM during pregnancy" and directly "GDM" require clear clinical and laboratory definitions. Furthermore, GDM is a risk factor for obesity, type 2 DM and cardiovascular diseases in the mother and her offspring in future.

The 2013 European Society of Hypertension guidelines, including treatment policy changes presupposing that one two-component combination of antihypertensive agents may be substituted for another and their full-dose combinations may be prescribed if monotherapy is ineffective, are discussed. A rationale is provided for the most effective two-component full-dose combinations of antihypertensive drugs.