Epidemiology
Aim.
To rate the basic epidemiological indices of type 2 diabetes mellitus in actual clinical practice using the informational database of national registry of diabetic patients.
Materials and methods.
Epidemiological analyses were performed in two administrative districts of Moscow. From 1999 to 2011 48978 adult patients with type 2 diabetes mellitus who were aged 18 years and older were registered. We used methods of clinical, analytical and statistical epidemiology with elements of descriptive research.
Results.
The prevalence rate of type 2 diabetes mellitus was 1590 per hundred thousand, most patients were in the 60?64 and 70?74 age groups, and approximately 80% of patients were older than 55 years. The morbidity rate of type 2 diabetes mellitus was 138,72 per hundred thousand and was found to be higher in women at 1,89. The mortality rate of adult patients with diabetes mellitus was 0,83, mostly in men of all ages. Cardiovascular diseases accounted for most of the registered cases of deaths (34,4%). The average life expectancy appeared to be 75,24?0,45 years, although women lived 6 years longer than men. The average duration of the disease was 10,04?0,34 years. A total of 0,4% of patients underwent hospital treatment and the average length of treatment was 17?18 days. The total number of days of disablement was an average of 307,33?30,13 days (80% of patients were older than 55 years). In the study group, a mean grade of НbА1c <7% was observed in 56,6% of patients. The prevalence rate of detected chronic complications was considerably lower compared to other epidemiological studies.
Conclusions.
Our epidemiological analyses revealed a number of features and consistent patterns dependent on sex and age indices. It is necessary to reform the system of health services of the Russian Federation and to assign some additional funding directed towards organising ubiquitous screening for early detection of complications of diabetes mellitus and timely treatment to prevent and lower the frequency of chronic complications of diabetes mellitus.
Genetics
Aims.
In this study, we evaluated the possible association of the polymorphic variants that encode key renal damage mediators (endothelial dysfunction, lipid metabolism and insulin secretion/sensitivity) with the risk of chronic kidney disease (CKD) in patients with T2DM.
Materials and Methods.
We enrolled 435 patients with T2DM using case-control study design. In 253 patients, we used non-overlapping criteria to form groups with/without CKD (defined as GFR<60 ml/min/1.73 m2) according to the duration of T2DM (?5 years/>=10 years) (n=75 and 178, respectively) and analysed the following 4 polymorphic markers: I/D in ACE, ecNOS4a/4b in NOS3, I/D in APOB and e2/e3/e4 in APOE genes. We then divided 182 patients in groups with/without CKD (n=38 and 144, respectively) regardless of the duration of diabetes and studied pro12ala in PPARG2, rs5219 in KCNJ11, rs12255372 in TCF7L2 and rs13266634 in SLC30A8 genes.
2 test, and data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Values of p <0.05 indicated statistical significance.
Results.
Four genes were found to have a significant association with CKD occurrence. For the eNOS3 the allele 4a and 4a/4a genotype was associated with a twofold CKD risk (OR=2.2/9.88) and the allele 4b and 4b/4b polymorphism were protective regarding CKD development (OR=0.44/0.45). For APOB I/D, the genotype DD was associated with lower risk of CKD [OR for DD=0.2 (95% CI: 0.05?0.88)]. In the second group, genotype TT of TCF7L2 predisposed to CKD (OR=3.03, 95% CI: 1.07?8.58). For KCNJ11 group genotype AA predisposed to CKD (OR=2.25, 95% CI: 1.02?4.97) compared to the allele G (OR=0,57, 95% CI: 0.34?0.96).
Conclusions.
In conclusion, our findings indicate a significant role of functional genetic variants associated with genes of endothelial factors (NOS3), lipid metabolism (APOB), and insulin secretion factors (KCNJ11, TCF7L2) in modulating the risk of CKD and their significant involvement in the mechanism of kidney damage in patients with T2DM.
Pathogenesis
To study the relationship between changes in the artery structure and function and peripheral lymphocyte telomere length in patients with type 2 diabetes mellitus (DM2).
Materials and methods.
A total of 50 patients with T2DM and without clinical manifestations of cardiovascular disease (CVD) were included in the study; the control group consisted of 49 people. The following tests were conducted for all study participants: carbohydrate metabolism evaluation, carotid artery duplex scan to measure intima?media complex thickness (IMT) and to determine the presence of atherosclerotic plaques, carotid?femoral pulse wave velocity (PWV) measurement and lymphocyte telomere length measurement.
Results.
The vascular changes were more pronounced in patients with T2DM than in controls. The telomeres were shorter in patients with T2DM than in those without diabetes (9.53?0.1 vs 9.86?0.1, p=0.033). The participants were divided according to the telomere length. Among patients with T2DM, there were significant differences in the condition of the vascular wall [PWV: 10.58?0.1 m/s in patients with ?long? telomeres and 15.08?1.3 m/s in patients with ?short? telomeres; IMT: 0.80?0.09 mm in patients with ?long? telomeres and 0.87?0.05 mm in patients with ?short? telomeres (p=0.024)]. There were no significant differences in the arterial structure between the patient and control groups with ?long? telomeres [PWV: 10.58?0.1 m/s vs 10.5?0.5 m/s (p=0.913); IMT: 0.080?0.09 mm vs 0.73?0.03 mm (p=0.12). However, there were significant differences in the vascular wall condition between the patient and control groups with ?short? telomeres [PWV: 15.08?1.3 m/s vs, 10.7?0.5 m/s (p=0.015); IMT: 0.87?0.1 vs 0.78?0.1 (p=0.03)].
Conclusions.
The signs of vascular ageing were more pronounced in patients with T2DM than in controls. However, despite diabetes, vascular changes were minimal in patients with ?long? lymphocyte telomeres, comparable with the state of the vascular walls in healthy individuals. Thus, enhanced lymphocyte telomere length may have a protective effect on the vascular wall and may prevent damage from carbohydrate metabolism disorders.
Aim.
of the study was to assess the biochemical parameters and plasma levels of adipokines [adiponectin, adipsin, leptin, plasminogen activator inhibitor (PAI-1), resistin and visfatin], insulin, C-peptide, ghrelin and incretins [glucose insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)] in patients with morbid obesity after surgery (gastric bypass) and therapeutic correction.
Materials and methods.
A total of 75 patients (34 men and 41 women; age range: 24?67 years) diagnosed as obese were divided into two groups according to the treatment they received. Biochemical analysis was performed to estimate carbohydrate and lipid metabolism rates and plasma levels of adipokines (adiponectin, adipsin, leptin, PAI-1, resistin, visfatin), insulin, C-peptide, ghrelin and incretins (GIP and GLP-1) using the flow fluorometry.
Results.
Surgical treatment of obesity resulted in a significant decrease in BMI (from 45.67?9.87 to 32.45?5.35 kg/m2, p<0.05). Carbohydrate metabolism parameters and HOMA-IR index independent of BMI were comparable to the reference values after gastric bypass (18 months later). A direct correlation of plasma PAI-1 and leptin levels with BMI in groups with conservative (r=0.800, p=0.004 and r=0.780, p=0.010) and surgical treatment (r=-0.670, p=0.001 and r=0.760, p=0.01) was observed. Elevated leptin levels in patients with morbid obesity after gastric bypass with normal glucose and insulin levels indicated an indirect effect of leptin levels on the development of insulin resistance in metabolic syndrome.
Conclusions.
Gastric bypass is a more efficient approach to reduce obesity. Adipokine (leptin and PAI-1) production and adipose tissue mass are directly correlated.
Education and psychosociologycal aspects
To study the relationship between two components of the attitude (rational and emotional) of patients with type 1 diabetes (T1D) to the disease among themselves as well as the relationship of each component with psychological well-being of patients.
Materials and methods.
One hundred twenty-nine T1D patients (43 males, 86 females) were studied. The attitude towards the disease was studied using the Colour Attitude Test (CAT) by A.M. Etkind and the Psychological Diagnosis of the Type of Person?s Attitude to the Disease (TAD) developed at the Bekhterev Psychoneurological Research Institute (St. Petersburg). Psychological well-being was evaluated using the 36-item Short-Form Health Survey (SF-36), the State?Trait Anxiety Inventory (STAI) by C.D. Spielberger that was adapted by Y.L. Khanin, the Centre for Epidemiological Studies Depression Scale (CES-D), the self-assessment diagnostic technique by Dembo?Rubinstein and the Purpose in Life Test (PILT) by Crumbaugh & Maholick that was adapted by D. Leontyev.
Results.
There were two groups of patients in the results of cluster analysis of TAD: those with rational adaptive and maladaptive attitudes towards the disease. In the group of patients with the rational adaptive attitude towards the disease, scores were higher on most scales of STAI, CES-D, SF-36 and PILT. In the result of cluster analysis of CAT, there were two groups of patients: those with favourable and unfavourable emotional acceptance of the disease. The group of patients with favourable emotional acceptance of the disease also had higher scores on most scales of STAI, CES-D, SF-36, PILT and the Dembo?Rubinstein technique. The comparative analysis of the relationship of rational and emotional components in attitude to the disease showed their incomplete coincidence among themselves.
Conclusions.
Both the rational and emotional components of the attitude towards the disease are associated with the psychological well-being of patients. Patients with the adaptive rational attitude towards the disease and a high level of emotional acceptance are characterised by a high level of psychological well-being.
Diagnosis, control, treatment
Evaluation of the itopride (Ganaton?, Abbot) therapy efficacy in the management of gastrointestinal (GI) symptoms and gastric motor function (GMF) in type 1 diabetis mellitus (T1DM) patients (pts) in the presence of GMF dysfunction and other forms of diabetic autonomic neuropathy (DAN).
Materials and Methods.
The total of 34 patients with T1DM, GMF dysfunction and DAN were selected for randomized, prospective, open-label, comparative study. The duration of the study was 6 weeks. The study group (17 pts) received itopride 150 mg total daily. The control group (17 pts) did not receive any treatment for GMF. А questionnaire was used for the assessment of gastrointestinal (GI) symptoms. Gastric emptying velocity was evaluated with 13C-octanoate breath test.
Results.
As a result of itopride therapy there was a statistically significant decrease in the amount of time (T1/2) needed for the gastric emptying. The median amount of time decreased from 89.0 [82.3; 101.0] min to 53.0 [82.3; 101.0] min (p<0.001); decrease of the incidents of gastroesophageal reflux (p=0.013) and symptoms of intestinal dyspepsia (p=0.005). In control group there was no change in parameters. There was no positive dynamics of glycaemic control parameters (fasting blood glucose, postprandial blood glucose, fructosamine), and no reduction in the frequency of hypoglycaemic episodes during the test in any of the groups.
Conclusions.
Itopride therapy in T1DM patients with GMF dysfunction and DAN in the total daily dose of 150 mg improves gastric emptying velocity. This therapy also improves symptoms of gastroesophageal reflux and intestinal dyspepsia. Improvement GMF doesn?t lead to positive dynamics of glycaemic control parameters.
Pediatric diabetology
Objective.
The objective of this study was to investigate the functional activity of neutrophil granulocytes (NGs) in children with T1DM.
Materials and Methods.
This study involved 25 children aged 7?15 years. To evaluate programmed cell death, the number of NGs expressing apoptosis markers (CD95, CD95L and BCL2) was determined. The functional activity of NGs was determined in terms of phagocytosis and the levels of myeloperoxidase, lysosomal cationic proteins and active oxygen radicals.
Results.
A reduction in the bactericidal activity of NGs with deficiencies in phagocytosis, secretion of active oxygen radicals and functional reserve was found. An increase in the apoptotic potential of NGs was demonstrated, which was accompanied by an increase in CD95 expression and a decrease in BCL2 expression. An increase in the cytotoxic potential of neutrophils in the form of enhanced levels of myeloperoxidase and lysosomal cationic proteins was revealed.
Conclusions.
Therefore, an increase in the apoptotic potential of NGs associated with functional and metabolic changes may reflect the active involvement of NGs in the immunopathogenesis of T1DM.
Аim.
Prediction of the early preclinical stage of T1DM.
Materials and methods.
We studied the predisposing and protective haplotypes (HLA-DRB1, gene DQ) together with immunological markers (ICA, GADA, IAA) in 224 discordant/concordant families.
Results.
At the Endocrinology Research Centre, population and family risks of the development of T1DM in Russia were calculated on the basis of population genetic approaches. The analysis of the prevalence of HLA genotypes among T1DM patients revealed that the high-risk haplotypes in the structure of genotype(s) DQ2 and/or DQ8 in combination with the others were 78%: of these genotypes DQ2/DQ8, DQ2/DQ2, and DQ8/DQ8 accounted for 35%; DQ2/X* and DQ8/X* accounted for 43%; and the low-risk genotype Х*/Х* accounted for 22%. The genotype Х/Х consisted of weaker predisposing haplotypes that were specific to the Russian population in combination with neutral haplotypes or those consisting of neutral haplotypes only. The analysis of patients with T1DM genotypes revealed that high-risk genotypes (DQ2/DQ8) were more common in ill children up to the age of 5 (33% of cases) than in T1DM children over 10 years (23%) (p=0.05). Conversely, the low-risk genotypes were significantly less likely to be found in children with manifestations of diabetes up to 5 years than in sick people over 10 years [5% and 13%, respectively (p <0.05)]. This is consistent with hereditary load of diabetes manifestations in young children and with the earlier data. The 16-year prospective surveillance showed that the manifestation of the disease occurred in 8.4% of siblings. The analysis of the frequency of autoantibodies revealed that autoantibodies were identified the most reliably prior to the manifestation of the disease compared with T1DM patients in the initial period and healthy siblings (eldest siblings without the disease during the whole monitoring period): 90%, 48.6% and 31%, respectively, p <0.05.
Conclusion.
The 16-year prospective surveillance in families with T1DM showed that the frequency of recurring diabetes cases was 8.4%, which exceeds the siblings? rate of risk of 6.4% that had been empirically calculated 20 years ago. This may be due to an increase in the incidence of T1DM in the population and different methodological approaches (one-time screening versus long-term monitoring).
Cardiology
To evaluate the prognostic value of adipokines in patients with myocardial infarction (MI) and various glucose metabolism disorders.
Materials and Methods.
Consecutive patients aged ?80 years and diagnosed with MI (380 patients, 63.4% males) were examined. The patients were classified into four groups: I, with normal glucose tolerance; II, with prediabetes; III and IV - with newly detected and previously diagnosed type 2 diabetes mellitus, respectively. Levels of insulin, C-peptide and cortisol during glucose tolerance test and basal levels of apolipoproteins AI, B100, leptin and adiponectin were determined in 113 patients with Q MI. Cardiovascular events were analysed for the next 2 years after MI. Logistic regression analysis was used to identify the risk factors of poor prognosis after MI.
Results.
Elevated levels of leptin with decreased levels of adiponectin were observed in all MI patients independent of the degree of glucose metabolism disturbance. A linear trend of leptin level increase was observed starting from group I to group IV (Jonckheere?s test: J=2218.0; z=3.411; р=0.001). Multiple regression analysis showed that the basal insulin level was an independent predictor of death during the 2 years after MI (OR=0.639; р=0.033). MI prior to hospitalisation (OR=5.633; р=0.013), basal hypercortisolaemia (OR=5.435; р=0.016), glycaemia (OR=1.213; р=0.023) and heart rate (OR=1.051; р=0.032) on admission were associated with the occurrence of repeated MI. Leptin levels (OR=1.018; р=0.031) and creatine kinase-MB fraction (OR=1.009; р=0.018) were risk factors of the occurrence of the combined end-point of cardiovascular events.
Conclusion.
An imbalance of adipokines was observed in MI patients regardless of the presence of glucose disorders. The levels of leptin, glycaemia, insulin and basal hypercortisolaemia were significantly associated with the occurrence of cardiovascular events during the late post-infarction period.
To investigate the relationship between changes in indicators of arterial stiffness of various types of vessels, hemodynamic pulsatility, renal function and renal blood flow in patients with coronary artery disease (CAD) and arterial hypertension in the presence or absence of type 2 diabetes mellitus (T2DM).
Materials and Methods.
The study included 96 patients with CAD and arterial hypertension; among them, 54 subjects had T2DM and 42 did not. Сarbohydrate and lipid metabolism, renal function, stiffness of various types of arteries, parameters of hemodynamic pulsatility and renal blood flow were investigated.
Results.
Arterial stiffness of various types of vessels was increased in the T2DM group: carotid?femoral pulse wave velocity as a marker of aortic stiffness (a vessel of the elastic type) was increased by 16% (p <0.001), index ?.
of the common carotid artery (a vessel of the muscular elastic type) was increased by 7.6% (p <0.05) and index ?.
of the brachial artery (a vessel of the muscular type) was increased by 22% (p <0.05). The level of microalbuminuria was 5-fold higher (p <0.05) and the renal resistive index was 12.5% higher (p <0.05) in the diabetics group. Significant correlations were found between aortic stiffness, parameters of hemodynamic pulsatility (pulse pressure, measured at the brachial artery, the central pulse pressure, augmentation index) and renal function and renal blood flow in patients in both groups.
Conclusion.
The results may indicate the general pathogenetic mechanisms and the relationship between the development of increased aortic stiffness and renal dysfunction in patients with CAD, arterial hypertension and T2DM.
Diabetic foot
Reliable data on the efficacy of treatment for diabetic foot (DF) ulcers (DFUs) is essential for planning outpatient services, comparison of several DF clinics, pharmacoeconomic studies and prognosis of healing time. However, no reports based on Russian DF cases have been published to date.
Aim.
The aim of our study was to analyse of the outcomes of routine DFU treatments at one DF outpatient clinic (DFOC).
Materials and methods.
We analysed the medical records of all patients admitted to one DFOC for foot/leg ulcers in 2012 (72 patients, 77 episodes of treatment, 124 ulcers in total). The median age of the patients was 66 years (range: 45?90 years), 51% patients were females and 49% were males. Three (4%) patients had type 1 diabetes mellitus, whereas the rest had type 2 diabetes mellitus. The median duration of ulcer prior to the initiation of treatment was 31 days (range: 1?392 days). A total of 106 (85%) cases involved DFUs, whereas 18 (15%) involved leg ulcers in patients with diabetes. One patient had a combination of foot and leg ulcers. Examination and treatment of all patients were conducted by a single experienced doctor according to international and national guidelines. The follow-up time ranged from 8?20 months.
Results.
Lower extremity ischemia was observed in 39% cases. The healing rate for all ulcers at 3, 6 and 12 months was 34%, 51% and 65%, respectively. At follow-up time, ulcers remained unhealed in 16% patients and 9% survived amputations [1 (1%), below knee; 6 (8%), minor)]. Furthermore, 4% patients died on account of cardiovascular events. The results of the present study were comparable to those reported in other countries. Modern and effective treatment modalities (such as contact casting and revascularisation) were not used extensively; therefore, their active utilisation is necessary to improve treatment outcomes.
Conclusions.
- The healing rate for ulcers in our cohort was 34%, 51% and 65% at 3, 6 and 12 months, respectively.
- Treatment efficacy should be improved by increasing the use of total contact casting and revascularisation.
- Person-related measures (i.e. healing of all ulcers in a patient) are optimal for most cases, although ulcer-related measures can be significant in cases where several ulcers are detected in a patient.
- Our studied cohort is typical for a DFOC; therefore, our data can be used for planning outpatient services, evaluation of other DFOCs and pharmacoeconomic studies.
To evaluate the efficiency of topical negative pressure wound therapy (NPWT) compared with standard therapy for the regeneration of the soft tissues of the lower extremities in patients with diabetic foot syndrome.
Materials and Methods.
The effects of negative pressure therapy on the clinical (size, tissue oxygenation), histological (light microscopy) and immunohistochemical (CD68, MMP-9, TIMP-1) aspects of repair of the soft tissue of the lower extremities in patients with diabetes mellitus were compared with those of standard treatment. Thirty-one patients with diabetic foot ulcers were included in the study from the moment of debridement until the plastic closure of the wound. During the perioperative period, 13 patients received NPWT (-90 to -120 mmHg) and 18 patients received standard therapy.
Results.
A reduction of the wound area (26.6%?17.2%) and the depth of the defects (40.5%?25.6%) were achieved with negative pressure therapy compared with baseline data. In the control group, the corresponding values were 25.3%?19.4% and 21.8%?21.6%, respectively. The results of transcutaneous oximetry showed a greater increase in the level of local hemodynamics in the study group (p <0.04). An important criterion for wound preparation for a plastic closure is filling it with granulation tissue by more than 75%. In the study group, 95% of patients had wounds filled with 89.9%?17% of abundant granulation tissue. The histological data of the study group show a significant reduction of oedema by 80% (p <0.05), improved extracellular matrix organization (p <0.05), 90% (p <0.05) dissolution of inflammatory infiltrate and the formation of healthy granulation tissue (p <0.05). Immunohistochemical analysis demonstrated a significant decrease in the number of macrophages in the dermis (CD68 expression) (p <0.05). In both groups, the level of MMP-9 was decreased. However, the ratio of MMP-9:TIMP-1 was lower in the study group (p <0.05).
Conclusion.
The findings suggest that negative pressure therapy (-90 to -120 mmHg) is more efficient compared with standard treatment and achieves more rapid reduction of the area and depth of the wound, increased local microcirculation and decreased inflammation. These findings were confirmed histologically and immunohistochemically. The high efficiency of this method significantly reduced the time required for preparing the wound for the next surgical treatment.
Ophthalmology
News
Memorable events

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
ISSN 2072-0378 (Online)