Vol 16, No 4 (2013)

Editorial note
Message from Editor-in-Cheif
Dedov I.I.
Abstract
We are happy to congratulate our readers with the 15th anniversary of this title. The journal enters 2014 with almost one thousand published papers - a remarkable path that inspires confidence in future progress.

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Diabetes mellitus. 2013;16(4):4-5
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Epidemiology
Prevalence of type 2 diabetes mellitus and its complications among the population of Moscow Region ? a cross-sectional epidemiological study
Suntsov Y.I., Bolotskaya L.L., Rudakova O.G., Andrianova E.A., Tolkacheva A.A., Kon I.L.
Abstract
Aim.
 To estimate the prevalence of type 2 diabetes mellitus (T2DM) among the population of Moscow Region, as well as the actual prevalence of diabetes complications in individuals already diagnosed with DM.
Materials and Methods.
2403 inhabitants of Stupinksy and Domodedovsky areas aged 30 to 70 years were selected by means of random sampling for the estimation of T2DM prevalence. Another 600 individuals inhabiting Pushkinsky and Serpukhovsky areas were randomly selected for the estimation of the prevalence of DM complications (including patients with T2DM). Clinical screening was performed by the mobile diagnostic team.
Results.
HbA1c level was tested in all participants. The cut-off point for the diagnosis of DM was set for .
HbA1c>6.5% according to the WHO guidelines (2011). 204 individuals (8.49%) met this criterion and were selected for further evaluation by OGTT with the following
Results.
28.04% were positive for glycemic disorders, including T2DM (8.53%), IGT (17.07%), IFG (2.44%). The highest prevalence of T2DM was found in the elder group (60?70 years old). The prevalence of diabetic retinopathy was estimated at 26.06%, being 2 times higher among T2DM patients than previously calculated for Moscow Region by the Russian State Diabetes Register (13.2%). The microalbuminuria stage of diabetic nephropathy was diagnosed in 46.1% of diabetes patients, being 5 times more prevalent than previously estimated for Moscow Region by the Russian State Diabetes Register (5.84%).
Conclusion.
The actual prevalence of T2DM in Moscow Region is markedly higher than the registered. The prevalence of diabetes complications is also significantly underestimated. Most patients do not achieve .
HbA1c targets (<6.5%).
Diabetes mellitus. 2013;16(4):6-10
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Genetics
Genetic framework of type 2 diabetes mellitus
Bondar' I.A., Shabel'nikova O.Y.
Abstract
More than 100 genes associated with the risk of type 2 diabetes mellitus (T2DM) are now established. Most of them affect insulin secretion, adipogenesis and insulin resistance, but the exact molecular mechanisms determining their involvement in the pathogenesis of T2DM are not understood completely.
Diabetes mellitus. 2013;16(4):11-16
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Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population
Bondar' I.A., Filipenko M.L., Shabel'nikova O.Y., Sokolova E.A.
Abstract
Aim.
 To investigate the association of polymorphisms in TCF7L2 and PPARG2 genes with type 2 diabetes mellitus (T2DM) in Novosibirsk population.
Materials and Methods.
We examined 391 patients with T2DM and 556 individuals with normal glucose metabolism. Allelic identification was performed with TaqMan technique, implementing allele-specific real-time PCR.
Results.
 Analysis shows that allelic frequency distribution of rs1801282 variant of PPARG2 gene and rs7903146 variant of TCF7L2 differs significantly between the study and control groups (OR [CI 95%]=1.44 [1.12?1.85], p=0.005 and OR [CI 95%]=1.57 [1.17?2.10], p=0.003, respectively). T2DM patients with T/T genotype of rs7903146 variant of TCF7L2 gene had lower BMI (p=0.02). Observed combination of risk alleles reached 99%. Combined beta-cell dysfunction and insulin resistance genotypes were identified in 56% of tested subjects, isolated insulin resistance ? in 42.2% of subjects, and isolated beta-cell dysfunction ? in 0.8% of subjects.
Conclusion.
 Our data shows that carrier state of 12Pro rs1801284 variant of PPARG2 gene and T-allele rs7903146 variant of TCF7L2 gene are associated with T2DM in Novosibirsk population, increasing its risk 1.44 and 1.57 times, respectively. Combination of these polymorphisms was observed in 99% of patients with T2DM.
Diabetes mellitus. 2013;16(4):17-22
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Comparative analysis of HLA II allele and genotype frequency distribution in patients with type 1 diabetes mellitus and autoimmune thyroiditis
Repina E.A., Atamanova T.M., Zvereva Y.S., Tishina Y.V., Prokof'ev S.A.
Abstract
Aim.
 To compare HLA II allele and genotype frequency distribution in type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AIT) with that in isolated T1DM.
Materials and Methods.
A total of 92 T1DM patients were subdivided into two groups. The first group comprised 54 patients with established AIT comorbidity or elevation of anti-thyroid autoantibodies (ATA). Patients with isolated T1DM (ATA-negative) formed the second group. HLA-genotyping was performed by multiprimer PCR set for the three following genes: DRB1, DQA1 and DQВ1.
Results.
 Prevalence of alleles DRB1*01, *03(017), *04, *07, *11 and genotypes 01/03, 01/04, 03/04 tends to be higher among patients with AIT comorbidity. The comorbidity group was also characterized by the trend towards higher prevalence of ?marker/marker? and ?marker/non-marker? combinations favouring the former variant. Conversely, ATA-negative patients exhibited trend for higher prevalence of ?non-marker/non-marker? combination.
Conclusion.
Statistically insignificant difference between HLA II alleles and genotypes in the two studied groups suggests that primary genetic factors are common in these two diseases. Plausibly, genes other than DRB1, DQA1 and DQВ1 determine the localization of the autoimmune process.
Diabetes mellitus. 2013;16(4):23-27
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Pathogenesis
Markers for gastrointestinal autoimmune disorders in patients with type 1 diabetes mellitus
Derevyanko O.S., Dalantaeva N.S., Pekareva E.V., Ivanova O.N., Goncharov N.P., Nikonova T.V., Smirnova O.M.
Abstract
Aim.
 to assess the occurrence of autoantibodies characteristic of autoimmune pancreatitis and gastritis in patients with type 1 diabetes mellitus (T1DM), and to analyze clinical features of positive subjects.
Materials and Methods.
 84 patients (39 male, 45 female) with T1DM were subdivided into two groups and underwent biochemical, immunologic and instrumental examination.
Results.
 Markers for gastrointestinal autoimmune disorders were found to be highly prevalent in patients with T1DM, even in those asymptomatic according to instrumental diagnostic methods.
Conclusion.
Our data suggests that T1DM patients are at higher risk of corresponding, possibly asymptomatic autoimmune disorders.
Diabetes mellitus. 2013;16(4):28-32
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Analysis of the calcium-phosphorus metabolism and function of the parathyroid glands in patients with type 1 diabetes mellitus
Khantakova E.A., Khamnueva L.Y., Orlova G.M.
Abstract
Objective.
To analyze the calcium-phosphorus metabolism in patients with diabetes mellitus (DM) type 1 depending on the functional state of the kidneys.
Materials and Methods.
The study involved 235 patients with type 1 diabetic (males). One hundred and thirty-four patients entered the group without diabetic nephropathy (DN) and 101 patients entered the group with DN. To study the phosphorous-calcium metabolism in patients with type 1 diabetes there were studied the following parameters in blood plasma: the level of intact parathyroid hormone (PTH), total calcium (Ca), ionized calcium (Ca2+), serum phosphorus (P), as well as calculated CaxP product.
Results.
 In patients with type 1 diabetes in the progression of DN the increase of P was observed from stage 4 CKD and reduction of Ca ? from CKD stage 5. The increase of the level of PTH was observed from the stage of CKD 3, although isolated cases of secondary hyperparathyroidism were registered in patients with stage CKD 2. At the same time in a large group of the patients with type 1 diabetes there was observed level of PTH below the target values of the stages CKD 3, 4, 5. The deterioration of glycemic control in patients with type 1 diabetes is associated with decreased level of PTH. In patients with type 1 diabetes without DN and with DN there was observed inverse relationship between the level of glycated hemoglobin (HbA.
1c).
Conclusion.
In patients with type 1 diabetes the progression of DN leads to various disorders of phosphorus-calcium metabolism: reduction of Ca, higher level of P, alter the function of the parathyroid glands (secondary hyperparathyroidism and reduction of PTH below the target value). Deterioration of glycemic control in patients with type 1 diabetes is associated with a reduction of PTH.
Diabetes mellitus. 2013;16(4):33-37
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Immunohystochemical study of the largest islets of human pancreas in aging and diabetes mellitus: perspectives for the transplantation
Proshchina A.E., Krivova Y.S., Barabanov V.M., Savelyev S.V.
Abstract
Aim.
 To study the distribution and cellular architecture of the largest human pancreatic islets (with a diameter of more than 200 micron) in aging and diabetes mellitus types 1 and 2.
Materials and methods.
 Antibodies to insulin, glucagon, somastatin and nturon-specific enolase were applied. The autopsy samples of the pancreatic tissue of patients with diabetes mellitus type 1 (DMT1) and type 2 (DMT2) and 2 age groups (up to 50 years old (control) and after 50 (aging control)), not suffering from diseases of the pancreas and carbohydrate metabolism malfunction were investigated.
Results.
 The number of islets with diameter more than 200 mkm compared to control group increased both in aging and diabetes groups. Their number reaches in some cases 15% (and higher in DM) of the total number of islets. These islets compared to the other are rich-vascularized. It was shown that glucagon and somatostatin-containing cells are found both on the periphery of the large islets, and inside them only in the immediate proximity of the capillaries. Insulin-containing cells form clusters, surrounded by the capillaries and the ?- and ?-cells, while the inner part of such clusters has no direct contact with the capillaries. In the large islets the number of glucagon-containing cells is often increased, and insulin-containing cells show signs of degradation.
Conclusion.
 The largest of the pancreatic islets may be useless for the transplantation, because of the high content of glucagon-containing cells, the rich vascularization and, in some cases, the limited functionality of ?-cells.
Diabetes mellitus. 2013;16(4):38-43
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Experimental Diabetology
Morphology of bronchial epithelium in rodent streptozotocin-induced diabetes mellitus
Pivovarova O.A., Mankovsky B.N.
Abstract
Aim.
 To study the morphology of bronchial epithelium in a rodent streptozotocin-induced (STZ) diabetes mellitus.
Materials and Methods.
. Diabetes mellitus was introduced in 47 white Wistar rats aged 5?6 months (body weight 234.0?2.64 g). 43 white Wistar rats of the same age were used as control subjects (body weight 242.0?2.13). Diabetes was induced by single intraperitoneal injection of STZ (SIGMA, USA) 60 mg/kg in 0.1 M citrate buffer, pH 4.5.
Results.
A statistically significant decrease in the total epithelial area by 25.9% was observed in the study group, accompanied by a reduction of the supranuclear zone by 22.1% vs. the control group.
Conclusion.
We found that bronchial mucous membrane in rodents with STZ-induced diabetes mellitus exhibits signs of atrophy and partial loss of mucous production by bronchial secretory cells.
Diabetes mellitus. 2013;16(4):44-48
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Discussion
Novel approach to pathophysiology of type 2 diabetes mellitus
Mukhamedzhanov E.K., Esyrev O.V.
Abstract
In this paper, we present a model of interplay between protein, lipid and carbohydrate metabolic pathways with regard to the carbon chain transporting systems, as well as generation and consumption of energy. This model elucidates the role of protein metabolism in the impairment of glucose tolerance during the absorption period. We also discuss the effects on energy homeostasis exercised by cytokines via mTOR pathway (the key factor of insulin signalling) considering the phenomenon of insulin resistance.
Diabetes mellitus. 2013;16(4):49-51
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Education and psychosociologycal aspects
The effects of structured self-monitoring of blood glucose on therapeutic effectiveness and adherence in patients with type 2 diabetes mellitus initiating insulin treatment
Suvorova L.A., Petrov A.V., Strongin L.G.
Abstract
Aim.
 To compare the efficiency of standard and structured approaches to self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes mellitus (T2DM) initiating insulin treatment.
Materials and Methods.
This open prospective randomized clinical trial included 51 T2DM patients who initiated insulin therapy in either outpatient or inpatient setting. Subjects were randomized in standard and structured SMBG groups, the structured group used an advanced Accu-Chek 360 View protocol. Evaluation included clinical examination and laboratory testing of HbA1c levels at the beginning of the treatment and after 3 months of the follow-up period.
Results.
70% of the structured self-monitoring group and 32% of the control group achieved therapeutic goals (p=0.008). Higher adherence was associated with better glycemic control in both groups ? and vice versa. However, among patients with low adherence, 73% of advanced SMBG group managed to achieve therapeutic goals vs. 19% in the control group (p=0.005). In addition, patients in the structured monitoring group gained less weight as compared to the control (1.0?2.88 kg vs. 3.2?2.56 kg; p=0.005).
Conclusion.
Structured SMBG commenced at the initiation of insulin therapy improves glycemic control in a greater fraction of patients, especially in those with low adherence to treatment. Structured SMBG also partially alleviates weight gain as side effect of insulin treatment.
Diabetes mellitus. 2013;16(4):52-57
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Evaluation of glycemic control, quality of life and psychological characteristics in patients with type 1 diabetes mellitus
Shishkova Y.A., Motovilin O.G., Surkova E.V., Mayorov A.Y.
Abstract
Aim.
To identify psychological characteristics associated with better glycemic control and higher quality of life (QoL) in patients with type 1 diabetes mellitus (T1DM).
Materials and Methods.
 The study included 140 T1DM patients (47 males) aged 18 to 28 years. Assessment of the QoL and associated emotional state (ES) was performed by validated localized questionnaires, supplemented with the inventories for evaluation of psychological characteristics. Based on the acquired data we performed a trilateral analysis of glycemic control, QoL and ES, followed by testing of these parameters for correlation with certain psychological characteristics, including disease attitude, mindfulness, self-attitude and self-assessment, coping strategies, autoregulation parameters and the locus of control.
Results.
 In the studied sample, better glycemic control was associated with higher QoL and more favourable ES. We also identified several psychological characteristics associated with an improvement in all three primary parameters, namely: higher level of mindfulness, internal locus of control and ergopathic attitude.
Conclusion.
 The diagnostic inventory for QoL and ES evaluation used in the present study may be helpful for psychological testing in patients with T1DM.
Diabetes mellitus. 2013;16(4):58-65
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Cardiology
Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus
Laptev D.N., Ryabykina G.V.
Abstract
Aim.
To determine the effects of hypoglycemia on the duration of QT interval, heart rate variability (HRV) and frequency of arrhythmic events, as well as to closer investigate the factors associated with the development of various heart rhythm disorders in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
 The study included 150 children and adolescents with T1DM at the age of 6?18 years. All participants underwent Holter monitoring and continuous glucose monitoring (CGM) for 24 hours. QTc and HRV parameters (SDNN, RMSSD, SVVR) were calculated automatically. Data was averaged for 5?-interval and juxtaposed with CGM. Patients identified with hypoglycemic events (blood glucose <3.5 mmol/L) during the day (7:00?23:00) and nighttime (23:00?7:00) were selected for further study. In these patients length of QTc and RR intervals, HRV parameters and arrhythmic events were analyzed and collated with CGM data.
Results.
We observed 39 episodes of nocturnal hypoglycaemia in 32 patients (21.3%) and 89 episodes of daytime hypoglycaemia in 46 patients (30.7%). Marked prolongation of QTc (hypo- vs. normoglycemia, respectively: 431 vs. 420 ms; p<0.05) and reduced HRV (hypo- vs. normoglycemia, respectively: SDNN 68 and 90 ms; RMSSD 56 and 61 ms; p <0.05) occurred during episodes of nocturnal hypoglycemia. The same pattern was observed during the day (hypo- vs. normoglycemia, respectively: SDNN 58 and 63 ms; RMSSD 32 and 36 ms; p<0.05). Eleven subjects with nocturnal hypoglycemia demonstrated either ventricular or supraventricular premature complexes. Thirty of subjects with diurnal hypoglycemia also had either ventricular or supraventricular premature complexes. Hypoglycemic episodes vs. normoglycemia were characterized by an increase in ventricular and supraventricular ectopic beats, ST segment and T-wave amplitude depression. Various rhythm abnormalities were associated with cardiovascular autonomic and peripheral neuropathy.
Conclusion.
 During episodes of hypoglycemia, HRV parameters decrease, QT elongates and episodes of arrhythmia occur more frequently. History of autonomic and peripheral neuropathy contributes to the development of arrhythmias.
Diabetes mellitus. 2013;16(4):66-71
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Correlation between arterial wall stiffness, N-terminal prohormone of brain natriuretic peptide, functional and structural myocardial abnormalities in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy
Serhiyenko V.A., Serhiyenko A.A., Mankovsky B.N.
Abstract
Aim.
To assess arterial wall stiffness, plasma levels of of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), as well as functional state and structure of the myocardium in patients with type 2 diabetes mellitus (T2DM) and cardiac autonomic neuropathy (CAN).
Materials and Methods.
The study involved a total of 65 patients with T2DM. 12 had no evidence of cardiovascular disease (CVD) or CAN, 14 were diagnosed with subclinical stage of CAN, 18 ? with functional stage, and 21 ? with organic stage. We measured aortic pulse wave velocity (PWV), aortic augmentation index (AIx), brachial artery AIx, ambulatory arterial stiffness index (AASI) and plasma levels of NT-proBNP. Clinical examination included ECG, Holter monitoring, ambulatory BP measurement and echocardiography.
Results.
 Patients with isolated T2DM showed a trend for increased vascular wall stiffness. PWV was increased in patients with subclinical stage of CAN. Aortic and brachial AIx, PWV and AASI were elevated in patients with functional stage of CAN, PWV being significantly higher vs. subclinical CAN subgroup. Organic stage was characterized by pathologically increased values of all primary parameters; PWV and AASI were significantly higher compared with other groups. Development and progression of CAN was accompanied by an increase in NT-proBNP plasma levels. Concentration of NT-proBNP was in direct correlation with left ventricular mass (LVM) and PWV. PWV and LVM values also directly correlated between themselves.
Conclusion.
Development and progression of CAN in patients with T2DM is accompanied by an increase in vascular wall stiffness. The elevation of plasma NT-proBNP in patients with T2DM correlates with the development of CAN and is significantly and independently associated with an increase in LVM and PWV. Our data suggests the pathophysiological interconnection between metabolic, functional and structural myocardial abnormalities in patients with T2DM and CAN.
Diabetes mellitus. 2013;16(4):72-77
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Ophthalmology
Anti-VEGF agents in the treatment of diabetic macular edema
Konenkov V.I., Klimontov V.V., Chernykh V.V., Tjan N.V.
Abstract
Diabetic macular edema (DME) is a common complication associated with the loss of visual acuity in diabetic patients. Intravitreal injections of vascular endothelium growth factor (VEGF) inhibitors (anti-VEGF therapy) have been proposed recently as a new treatment option for patients with DME. In this review we summarized results of randomized clinical trials of VEGF inhibitors in DME patients. The results indicate that all studied inhibitors (ranibizumab, bevacizumab, pegaptanib and aflibersept) reduce the retinal thickness and improve of visual acuity in DME when are used as a monotherapy or in combination with the laser treatment. Optimal course duration and effectiveness predictors of anti-VEGF therapy in DME should be elucidate in the future studies.
Diabetes mellitus. 2013;16(4):78-84
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Diabetic foot
Clinical outcomes of lower limb peripheral vascular disease after endovascular intervention in patients with diabetes mellitus, critical limb ischemia and chronic kidney disease
Ayubova N.L., Bondarenko O.N., Galstyan G.R., Manchenko O.V., Dedov I.I.
Abstract
Aim.
To assess the extent of the lower limb arterial calcification and to evaluate the long-term outcomes of percutaneous transluminal balloon angioplasty (PTBA) in patients with diabetes mellitus (DM), critical limb ischemia (CLI) and chronic kidney disease (CKD).
Materials and Methods.
94 patients with CLI formed two groups (CKD-positive and CDK-negative). Quantitative assessment of tibial arterial calcification was performed with non-contrast CT. Outcomes of angioplasty were monitored during the 18?6 months of the follow-up period by means of duplex ultrasonography.
Results.
 Long-term outcomes of PTBA were significantly worse in patients with CKD. Nevertheless, limb preservation and survival rates were relatively satisfactory in both groups (74% and 72%, respectively).
Conclusion.
PTBA in patients with DM, CLI and CKD presents a technical challenge. Despite that, in many cases the endovascular intervention allows avoiding high-level amputations and improves survival rates.
Diabetes mellitus. 2013;16(4):85-94
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Diagnosis, control, treatment
Efficacy and safety of glimepiride as initial treatment in Russian patients with type 2 diabetes mellitus
Ametov A.S., Abaeva F.T.
Abstract
Aim.
 To investigate the efficacy and safety of glimepiride as initial mono-therapy in type 2 diabetes patients (T2DM).
Materials and Methods.
This is a multi-center, open-label prospective observational study. 245 treatment-naive T2DM patients, who had not achieved glycemic goals on lifestyle therapy during first 12 weeks after the diagnosis, were enrolled in this study. Anti-diabetes treatment was initiated with glimepiride and continued during the 6-month follow-up period. Prescription of the initial dose (1 mg per day) and further dose adjustments were carried out by the attending physician in accordance with the glimepiride data sheet. Dynamics of HbA1c, fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPPG), weight and waist circumference, as well as the incidence of hypoglycemia were the evaluated parameters.
Results.
The baseline HbA1c (mean: 7.9?0.5%; female: 7.8?0.4% ; male: 8.0?0.6%) was significantly reduced at week 12 (mean 7.2?0.6%, p<0.001; female: 7.1?0.5%; male: 7.2?0.6%), and at the final visit (6.6?0.7%, p<0.001; female: 6.6?0.7; male: 6.5?0.7). 71.7% of the subjects achieved the HbA1c target (<7%) at the end of the study. FPG and 2hPPG levels decreased by 2.3?1.3 mmol/L and 3.1?1.9 mmol/L, respectively (p<0.001). Of note, FPG and PPG at baseline were 8.2?1.2 mmol/L and 10.5?1.9 mmol/L, respectively. The incidence of hypoglycemia (as defined by BG <3.9 mmol/L in the presence of the relevant symptoms) was 10.2%. Nocturnal symptomatic hypoglycemia was observed in 1.6% of cases. No severe hypoglycemic events were reported.
Body weight and BMI reduced by 1.0 kg and 0.4 kg/m2, respectively, during the follow-up period. The mean glimepiride daily dose at the end of the follow-up was 2.8?1.3 mg. Observed reduction in weight and low incidence of hypoglycemia could be attributed to continued effects of the lifestyle therapy and relatively short history of T2DM (average duration of diabetes was 1.4?2.4 years (median 0.5 years).
Conclusion.
 Glimepiride effectively improved glycemic control in treatment-naive T2DM patients over a 6-month period. The use of glimepiride in this population also showed a favorable safety profile. This data provides further rationale for the use of glimepiride for the initiation of pharmacological therapy in T2DM patients.
Diabetes mellitus. 2013;16(4):95-100
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Ten years of NovoMix 30 in Russian and international clinical practice
Surkova E.V.
Abstract
Insulin treatment for type 2 diabetes mellitus is challenging in elderly people. Biphasic insulin preparations technically simplify this task, but also increase compliance and facilitate the achievement of therapeutic goals.
Diabetes mellitus. 2013;16(4):101-107
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Short Messages
Meeting of the expert committee on the use of pre-mixed insulin preparation Humalog Mix 50 in type 2 diabetes mellitus
 
Abstract

The panel of experts has a held a discussion on effectiveness and tactics of glycemic control by pre-mixed insulin preparations in T2DM. Special attention was paid to the aspects of treatment with Humalog Mix 50, including indications and contraindications, potential for the achievement of therapeutic goals and optimization of patient monitoring.

Diabetes mellitus. 2013;16(4):108-110
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