Vol 15, No 3 (2012)

Associations of vascular endothelial growth factor (VEGF) gene and cytokine (IL-1B, IL-4, IL-6, IL-10, TNFA) genes combinations with type 2 diabetes mellitus in women
Konenkov V.I., Shevchenko A.V., Prokof'ev V.F., Klimontov V.V., Korolev M.A., Fazullina O.N., Lapsina S.A., Koroleva E.A.
Abstract
Aim.
To study the association between vascular endothelial growth factor (VEGF) and cytokine (IL1B, IL4, IL6, IL10 and TNFA)gene polymorphism combinations with type 2 diabetes mellitus (T2DM) in women.
Materials and methods.
374 Caucasian women without carbohydrate metabolism disorders from 23 to 68 years of age and 212 womenwith T2DM from 28 to 69 years of age were included in the study. The combinations of polymorphism А-2578С, С+936Т in VEGFgene with polymorphism in IL1B С-31Т, IL4 С-590Т, IL6 G-174C, IL10 A-592C and А-1082G, TNFA А-238G, A-308G and A-863Cwere studied.
Results.
Analysis revealed 52 combined genetic variations with different rate of occurrence between diabetic and control groups(р<0.002). Among variations positively associated with T2DM (n=34) high frequency of homozygote genotypes of VEGF -2578CC and+936CC, IL4 -590СС, IL6 -174GG, IL10 -592СC and -1082АА, TNFA -238GG, -308GG and -863СC, was observed. In 18 combinedgenetic variations that were negatively associated with T2DM, homozygous variant of VEGF and IL10 were equally distributed withheterozygous genotypes, while heterozygote IL1B, IL4 and IL6 genotypes were more prevalent.
Conclusion.
Combination of VEGF gene polymorphisms A-2578С and C+936Т with polymorphism in IL1B C-31Т, IL4 С-590Т, IL6G-174C, IL10 А-592C and А-1082G, TNFA A-238G, A-308G and A-863C may be genetic risk factors for T2DM in Caucasian women.
Diabetes mellitus. 2012;15(3):4-10
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Association of HLA-DQ trans-heterodimers with prevalence of type 1 diabetes mellitus in Buryat ethnic group
Ivanova O.N., Prokof'ev S.A., Bardymova T.P.
Abstract
Aims.
Search for the most pronounced HLA II markers of type 1 diabetes mellitus (T1DM) in Buryat ethnic group and analysis ofHLA-DQ trans-heterodimers.
Materials and methods.
Case control design was applied for assessment of 74 patients with T1DM and 61 healthy individuals. Alleleidentification was performed with multi-primer allele-specific PCR technique. Association of genetic markers with pathology wasevaluated according to odds ratio (OR) index. All calculations were performed with StatSoft and STATISTICA 6 software applications.
Results.
We show that regarding race-specific highly diabetogenic HLA class II haplotypes Buryat ethnic group holds intermediateposition between Mongoloids and Caucasians and none of those haplotypes are associated with T1DM. We revealed a statisticallysignificant association of T1DM with DQA1*0301+DQB1*0201+ phenotype represented by trans-coding alleles in 77% of cases. Onpopulation level DQA1*0301+DQB1*0302+ or *0201+ phenotype is found to be the most sensitive marker. It was registered in 43%of patients with T1DM against 11.5% of controls (OR 5.9; рс=0.0094). DQA1*0301+/DQВ1*0201 and DQВ1*0302 phenotype is themost specific marker, registered in 16% of patients, but not found in controls (OR 11.8; рс=0.047).Conclusions. HLA-mediated risk for development of T1DM in Buryat ethnic group is determined by HLA-DQ trans-heterodimers.
Diabetes mellitus. 2012;15(3):11-18
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Allele variants of HLA II genes DRB1 and DQB1 regarding risk for type 1 diabetes mellitus in population of Bashkortostan
Avzaletdinova .S., Morugova T.V., Mustafina O.E.
Abstract
Aims.
To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM) in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir).
Materials and methods.
We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data.
Results.
Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development.
Conclusion.
Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.
Diabetes mellitus. 2012;15(3):18-23
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Functional activity and peripheral insulin resistance in patients with different types of onset of diabetes mellitus
Nikonova T.V., Pekareva E.V., Dedov I.I.
Abstract
Aim.
To evaluate changes in functional activity and insulin resistance (IR) in patients with different types of onset of diabetes mellitus(DM).
Materials and methods.
We examined 166 subjects which were subdivided into 4 study groups and 1 control group. Assessment of totalbeta-cell functional activity and degree of IR (according to HOMA-model) was conducted in patients with different variants of DM onsetand in the group of high risk for type 1 DM.
Results.
The most significant decrease in beta-cell functional activity was found in patients with type 1 diabetes mellitus (HOMA-F 8.9%).Onset of LADA (Latent autoimmune diabetes in adults) and type 2 diabetes mellitus (T2DM) was also characterized by decreasein beta-cell functional activity (HOMA-F 39.2% and 63.9%, respectively), as well as by development of IR: HOMA-IR 3.7 and 7.2,respectively.
Conclusion.
Clinical onset of LADA and T2DM occurs against the background of decreased beta-cell functional activity and compromisedperipheral insulin sensitivity.
Diabetes mellitus. 2012;15(3):24-26
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Antihyperglycemic therapy in patients with type 2 diabetes mellitus and ischaemic heart disease: management during acute period of myocardial infarction and interventional procedures
Smirnova O.M., Kononenko I.V.
Abstract
Current paper presents data from international multicenter studies performed with participation of patients with type 2 diabetes mellitus(T2DM) and ischaemic heart disease. We analyze results regarding advisability of different glycemic targets, prescription safetyof various classes of antihyperglycemic agents in patients with inschaemic heart disease, acute coronary syndrome and chronic heartfailure, as well as therapeutic approach to glycemic control in acute myocardial infarction and cardiologic interventional procedures.
Diabetes mellitus. 2012;15(3):27-38
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Ischaemic heart disease in patients with diabetes mellitus and critical lower limb ischemia
Melkozerov K.V., Kalashnikov V.Y., Terekhin S.A., Bondarenko O.N.
Abstract
Aims.
To assess prevalence of ischemic heart disease (IHD) and clinical features of asymptomatic IHD in patients with diabetes mellitus(DM) and critical lower limb ischemia (LLI).Materials and Methods.
We examined 118 patients with DM, who underwent hospitalization for critical LLI. Besides routinecardiologic examination, all patients were subject to color duplex ultrasonography of lower limbs and CT contrast angiography. Patientswith proper indications underwent coronary angiography. Statistical data was processed with SPSS v17.0.0. software package.
Results.
We have found 58.5% of patients with DM and critical LLI to suffer from IHD - and approximately 40% to have myocardialinfarction in their medical history. According to acquired coronary angiograms, 89% of asymptomatic cases were characterized byhemodynamically significant stenosis, while 68.7% of them had either three arteries affected or left main coronary artery lesions.
Conclusion.
Patients with DM and critical LLI require thorough examination, as subclinical IHD may be masked in them by lowerlimb angiopathy.
Diabetes mellitus. 2012;15(3):39-44
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Vacuum therapy for chronic wounds
Zaytseva E.L., Tokmakova A.Y.
Abstract
Chronic wound in patients with diabetes mellitus (DM) is one of the most urgent problems of modern diabetology and surgery. Numberof patients suffering from different types of chronic wounds follows increase in DM incidence. Vacuum therapy is a novel perspectivemethod of topical treatment for non-healing chronic wounds of various etiology. Current review addresses experimental and clinicalevidence for this method.
Diabetes mellitus. 2012;15(3):45-49
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Pedographic and clinical assessment of total contact cast immobilization in diabetic foot syndrome
Gorokhov S.V., Udovichenko O.V., Ul'yanova I.N., Berseneva E.A., Galstyan G.R.
Abstract
Aim.
To estimate offloading efficiency of total contact cast (TCC) and determine factors, affecting trophic ulcer response to treatment with TCC, as well as ways of their compensation.
Methods.
30 patients, receiving an outpatient treatment with TCC for diabetic foot syndrome, underwent routine clinical examination, pedography and walking activity monitoring. We assessed degree of pressure reduction on the planta and the lesion area in particular, in its correlation with treatment outcome.
Results.
According to pedography data, TCC reduced peak pressure (maximum for all plantar zones) for 20% (from -70% to 84%) and pressure in the lesion area for 55% (-100%; +359%). Similar change was observed for "pressure-time" integral. Percentage of patients with peak pressure in ulceration area <100 kPa increased from 7 (23%) to 17 (57%). Healing of the ulcer was achieved in 21 patients (70%). Mean healing time was 30 days (17-278). In 2 cases treatment with TCC was ceased prematurely at the wish of the patient, while in 7 cases (23%) - due to treatment inefficiency. Risk factors for TCC inefficiency were found to be acute stage of diabetic osteoarthropathy, resistant lesion microflora and critical level of microbial colonization according to NERDS scale (p<0.05). Patients who did not respond to TCC treatment also required antibiotic therapy significantly more often and featured skin roughness under TCC (5 from 7 against 3 from 21). Walking activity, age, duration of diabetes, HbA1c levels and percentage of smokers was not significantly different between the groups. Peak pressure in the ulceration zone was higher in patients with TCC inefficiency, although the difference was not statistically significant (156 (19-365) against 82 (12-72) kPa, p>0.05).
Conclusion.
(1) TCC is an effective day-to-day offloading method, ensuring healing of trophic ulcers in 70% of cases.
(2) During acute stage of diabetic osteoarthropathy with ulceration in projection of shifting bone fragments TCC is ineffective; in this case surgical correction (wound closure) is indicated prior to TCC treatment.
(3) If ulcer is unresponsive to TCC, while ischemia and osteomyelitis are ruled out, critical microbial colonization (including resistant strains) or inadequate offloading are probable.
Diabetes mellitus. 2012;15(3):50-58
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Inсretin-based therapy in patients with type 2 diabetes and chronic kidney disease
Shamkhalova M.S., Shestakova M.V.
Abstract
The program of renoprotection in patients with diabetes mellitus (DM) is based on a conceptual model of development and progressionof diabetic kidney disease, which is the result of combined impact of genetically modulated metabolic and hemodynamic factors. Compensationof carbohydrate metabolism, which is crucial at the clinical debut of nephropathy, becomes problematic at the late stages ofchronic kidney disease (CKD). ADA (American Diabetes Association) and EASD (European Association for the Study of Diabetes)recommendations formalized in a consensus on the treatment of patients with type 2 diabetes (T2D) should only be extrapolated topatients with CKD with great prudence. Incretin-based drugs gain reputation as promising and perspective therapy for metabolic controlin patients with type 2 DM and CKD. There is an obvious need for large-scale, long-term studies involving patients with various severityof renal disease and related complications to assess the potential of this new diabetes therapy trend.
Diabetes mellitus. 2012;15(3):59-66
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Antidepressant therapy in complex treatment of painful diabetic polyneuropathy
Turbina L.G., Gordeev S.A., Zus'man A.A.
Abstract
Aims.
Comparative efficiency and safety analysis of antidepressant agents from different pharmacological classes (pipofezine and venlafaxine)in combination with carbamazepine for treatment of neuropathic pain (NP) in patients with diabetic polyneuropathy (DP).
Materials and methods.
We examined 21 male and 27 female patients with painful DP (mean age 54.3?14.2 years; mean duration ofdiabetes mellitus (DM) 8.9?5.1 years; mean duration of DP - 3.8?2.1 years). DP was diagnosed clinically and by electromyographymethod. Pain syndrome was assessed with DN4 questionnaire, visual analogue scale (VAS) and McGill Pain Questionnaire. Psycho-vegetative status was evaluated by Spielberger test with reactive and personal anxiety (RA and PA) assessment and Beck depressioninventory. All patients received symptomatic pharmacotherapy with anticonvulsant and antidepressant agent. First group (DP-1)included 23 patients on carbamazepin and pipofezine. Second group (DP-2) included 25 patients on carbamazepin and venlafaxine.
Results.
Following treatment, pain syndrome was completely compensated in 8.7% of patients from DP-1 group and 12.5% from DP-2.Decrease in pain intensity?50% from initial level was achieved in 73.9% (DP-1) and 75% (DP-2) of cases. Mean pain intensityaccording to VAS reduced from 5.2?2.1 points to 2.3?1.4 points (DP-1) and from 5.8?2.3 points (DP-2) with equal statistical significance(p<0.001). Moreover, both groups were characterized by significant decrease in all indexes of McGill Pain Questionnaire.Patients from both groups showed improvement in autonomic disorders, depression, RA and PA. DP-1 reported lower rate of side effectsfrom the treatment. Predictors of positive treatment outcome (complete compensation or pain intensity reduction?50%) were found tobe experience of DM <9.1 years, DP <3.8 years, depression score <25 points and pain intensity (VAS) <5.6 points.
Conclusion.
Our study suggests that complex treatment with venlafaxine or pipofezine may be a highly effective therapy for chronic NPand concomitant psychovegetative disorders (autonomous dysfunction, anxiety-depressive disorder), though pipofezine has a morefavourable safety profile. Optimal regime for complex treatment is pipofezine 75 mg/day (in three doses) or venlafaxine 800 mg/dayin four doses.
Diabetes mellitus. 2012;15(3):67-73
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Dose adjustment in insulin pump therapy: optimization of bolus calculator settings
Filippov Y.I., Ibragimova L.I., Pekareva E.V.
Abstract
Precise dosing of insulin at meals and for correction of glycemia is crucial for sustention of optimal blood glucose concentration. Moderninsulin delivery systems (such as insulin pumps) not only provide high dosing precision, but are also capable of calculating necessarydose by means of built-in software - so called bolus calculators. However, patient-oriented approach to calculator settings, as wellas their timely correction is imperative for attainment of desired precision. Though similar in their principle, various calculatorsalso feature essential peculiarities that have to be considered for optimal adjustment. The review addresses current evidence for boluscalculator efficiency, comparative analysis of these applications and description of their key distinctions.
Diabetes mellitus. 2012;15(3):74-80
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Analysis of typical approaches to outpatient management of type 2 diabetes mellitus
Sapozhnikova I.E., Tarlovskaya E.I., Avksent'eva M.V., Sanatova A.V.
Abstract
Aim.
To analyze typical outpatient management approaches to type 2 diabetes mellitus (T2DM).Materials and Methods.
We analyzed 211 files from 7 outpatient clinics, containing case records of patients, regularly examined during2009. VEN, ABC- and frequency analyses were conducted.
Results.
Prescription percentage for medications with proved prognosis improvement did not substantially differ from recommendedlevel. Main direct expenditures were related to antihyperglycemic, antihypertensive and hypolipidemic agents (class V). Inexpensivemedications without proven efficiency (class N) were prescribed more frequently than those with capacity to improve quality of life(class E). Testing for HbA1c level was found to be of inadequate frequency and thus complicated assessment of antihyperglycemic treatmentefficacy. Number of patients with improvement in arterial hypertension showed an increase, but treatment goals were not achievedin 2/3 of patients (according to office measurement). Prescription frequency of statins, though growing in the course of year, remainedinsufficient; rare testing for LDL complicated assessment of hypolipidemic treatment adequacy.
Conclusion.
Structure of pharmacological treatment is fairly adequate, but goals of multifactor therapy are not achieved in a significantpercentage of patients, which may be explained by peculiarities of diabetes pathogenesis, prescription of inadequate treatment regimensand doses and insufficient dynamic control.
Diabetes mellitus. 2012;15(3):81-86
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Influence of intensive glycemic control on development and progression of diabetic nephropathy in patients with type 2 diabetes mellitus (based on results from ADVANCE study)
Klefortova I.I.
Abstract
Current article presents data on effects of intensive glycemic control with Diabeton MR on development and progression of diabeticnephropathy in patients with type 2 diabetes mellitus (T2DM), accumulated from ADVANCE (Action in Diabetes and Vascular Disease:Preterax and DiamicroN Modified Release Controlled Evaluation study). Influence of intensive therapy with Diabeton MR wasassessed in that study separately and in conjunction with active antihypertensive treatment with perindopril and indapamide.
Diabetes mellitus. 2012;15(3):87-91
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Metabolic and cardiovascular effects of early insulin glargin prescription: based on data from ORIGIN study
Biryukova E.V., Ametov A.S., Antsiferov M.B., Zalevskaya A.G., Mel'nichenko G.A., Mkrtumyan A.M., Shestakova M.V.
Abstract
We discuss results of ORIGIN, a multicenter parallel groups study for efficiency assessment of insulin glargin against polyunsaturatedomega-3 fatty acids or placebo regarding cardiovascular and/or mortality risk reduction in patients with impaired fasting glycemia,impaired glucose tolerance or type 2 diabetes mellitus (T2DM) on its early stage and high risk for cardiovascular events. 12 537 patientstook part in this study; 6 264 were randomized in insulin glargin group, where dosage was adjusted for complete compensationof fasting glycemia (5.3 mmol/l was set as a therapeutic goal). After treatment with glargin therapeutic goal was achieved and furthermaintained for 6.2 years of follow-up. Compensation of fasting glycemia did not affect the outcome of cardiovascular diseases in patientswith early stages of dysglycemia according to primary endpoints. It was not associated with increase in general morbidity and inrisk of hypoglycemic events. Treatment with insulin glargin delayed progression from prediabetes to clinical onset for 28% (OR 0.72,CI 95% 0.58-0.91; p = 0,006), while lowering incidence of DM. Longtime treatment with insulin glargin does not increase incidenceof malignant tumors of different localization, including patients with prediabetes. Due to results of ORIGIN, insulin glargin (Lantus?)has become the most studied human insulin analogue to date.
Diabetes mellitus. 2012;15(3):92-100
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Pharmacoeconomic assessment of type 2 diabetes mellitus care on the base of Endocrinology Research Centre, Moscow
Dedov I.I., Shestakova M.V., Tarasov E.V., Shestakova E.A.
Abstract
Aims.
To assess the development of medical care and pharmacological treatment at Endocrine Research Centre (ERC), Moscow, forthe period of 2010-2011 years.Materials and Methods.
We analyzed files of 100 patients with type 2 diabetes mellitus (T2DM), who underwent hospitalization to ERCafter January 1, 2010. Key parameters were assessed by means of a study chart, applied for every patient file. Mean values, medians,fractions and confidence intervals (CI) were calculated for studied parameters. Various methods of parametric and non-parametricstatistics were used for comparison of acquired values.
Results.
Files of 100 patients with T2DM, hospitalized to Endocrinology Research Centre, were analyzed to obtain clinical characteristicsand evaluate initial (prior to hospitalization) and optimized (after hospitalization) therapeutic schemes, as well as spendingpatterns. Mean patient age exceeded 63 years, mean duration period of T2DM was greater than 14.4 years. 86% of patients weredecompensated for glycemic metabolism. 8% were diagnosed with less than 3 diabetes complications, 66% were found to have from 3to 6 complications. Almost all studied cases (98%) featured elevated blood pressure, 63% - diabetic retinopathy on different stages,59% - IHD, 51% - cataract, 49% - CKD. Lower limb angiopathy was found in 30% of cases, diabetic foot syndrome - in 15%.2 patients lost their vision due to diabetic complications and 3 patients experienced lower limb amputation. Arterial hypertension wascompensated in 14 cases from total of 98.Correction of therapy decreased fraction of patients on oral hypoglycemic agents and intermediate acting insulin (NPH), while prescriptionfrequency of short acting insulin and rapid acting human insulin analogues (as well as long acting analogues) showed oppositetrend. Optimization of therapy also included prescription of hypolipidemic drugs for majority of patients, as well as various agents forcorrection of coagulation abnormalities, treatment for CVD and other complications of T2DM.Due to described measures cost of per day treatment for 100 patients increased 2.28 times: from 8 982 RUB to 20 440 RUB (averagecost per day increased from 89.8 RUB to 204.1 RUB).Following the correction, fraction of patients with fasting glycemia <6.5 mmol/l increased from 16% to 45%. Fraction of patients withpostprandial glycemia >9.0 mmol/l dropped from 37% to 9%, and that with postprandial glycemia >10.0 mmol/l - from 27% to 1%.Mean fasting glycemia level decreased from 8.6 mmol/l to 6.8 mmol/l.Conducted analysis shows that prime expenditures (more that 36% from total cost structure) were associated with hospital stay (includingintensive care unit).
Conclusion.
Considering expanding nature of DM epidemic, there is an urgent need for effective healthcare management and preventionof severe cardiovascular complications. Priority should be established on balancing efficiency of hypoglycemic agents with theirsafety for short- and long-term prognosis.
Diabetes mellitus. 2012;15(3):101-109
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Overcoming marked insulin resistance in a patient with type 2 diabetes mellitus by means of insulin pumptherapy
Artemova E.V., Kononenko I.V., Smirnova O.M., Mayorov A.Y.
Abstract
Patients with type 2 diabetes mellitus (T2DM) often feature resistance to endogenous and exogenous insulin which is a serious problemto overcome. Current paper presents clinical case of T2DM characterized by marked insulin resistance, where high dosage regimenfailed to compensate carbohydrate metabolism. Regarding the case in question we discuss chronic insulin overdosage as one of the possiblefactors to interfere with compensation of diabetes, as well as capacity of insulin pump therapy to resolve such complicated clinicalsituation.
Diabetes mellitus. 2012;15(3):110-116
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Expert committee on introduction of incretin-based therapy in Russia: advance and failure
 
Abstract

Short resume of expert committees meeting about problems of using of incretin-based therapy in Russian Federation.

Diabetes mellitus. 2012;15(3):117-120
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In Memorian: Sergey Prokof'ev
 
Diabetes mellitus. 2012;15(3):121-121
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Instructions for authors
 
Diabetes mellitus. 2012;15(3):122-123
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