Vol 18, No 3 (2015)

Epidemiology
National register of diabetes mellitus in Russian Federation.
Dedov I.I., Shestakova M.V., Vikulova O.K.
Abstract
Clinical and epidemiological monitoring of diabetes in Russian Federation (RF) is carried out by the National diabetes register, which methodological and organizational reference center is Federal Endocrinology Research Centre. Since 2014 initiated the translation the National diabetes register on online software system in order to increase the effectiveness of the register as a scientific and analytical platform. The article include the analysis of DM prevalence, incidence,DM-related mortality,the prevalence of diabetic complications and analysis of effectiveness of diabetes care (included HbA1c) and according to the data of online register.
Diabetes mellitus. 2015;18(3):5-22
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Pathogenesis
New concepts of glucose-induced insulin secretion in the development of type 2 diabetes: clinical implications
Dedov I.I., Smirnova O.M., Irina K.V.
Abstract

The prevalence of type 2 diabetes is increasing dramatically, and the pathogenesis of the disease has been studied extensively in recent years. Of particular interest, incretins are reported to cause changes in insulin secretion that affect the natural development of the disease. The emergence of new drugs that act via the incretin axis have led many clinicians to consider their place in clinical practice.

Diabetes mellitus. 2015;18(3):23-31
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Intraperitoneal insulin infusion: on the way to the artificial pancreas
Karpel'ev V.A., Fedorova E.A., Philippov Y.I., Mayorov A.Y., Shestakova M.V.
Abstract

Creating an "artificial pancreas" (a "closed loop" insulin pump, with self-adjusting insulin abilities, based on real time continuous glucose monitoring data) – is one of the most actual medical challenges of modern engineering and cybernetics.

Artificial pancreas (AP) prototypes based on wearable insulin pump with subcutaneous insulin delivery are still problematic, mainly because of slow insulin pharmacokinetics. Intravenous insulin infusion via AP allows effectively maintain euglycaemia for inpatients, due to insulin pharmacokinetics and pharmacodynamics advantages. Unfortunately, it can’t be used for outpatients. Intraperitoneal insulin infusion is still relatively infrequently used in the world, but it is a promising alternative, compared to both previous methods due to a physiological action profile, fast insulin pharmacokinetics, relatively better safety and availability for outpatient usage.

The purpose of this review is to describe the intraperitoneal insulin infusion features for diabetes patients at a point of AP creation perspectives.

 

Diabetes mellitus. 2015;18(3):32-45
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Genetics
Polymorphism of gene UBE2E2 and the risk of developing diabetes type 2
Kazakova E.V., Wu Y., Chen M., Wang T., Sun L., Qiao H.
Abstract
Recently, the ubiquitin–proteasome pathway has emerged as a crucial pathway for protein turnover, and it has also been identified as an important factor for insulin synthesis. This pathway plays a critical role inside β cells; therefore, it has naturally been linked with various insulin-related diseases, most notably type 2 diabetes mellitus (T2DM), but also other metabolic diseases and symptoms such as obesity and atherosclerotic plaques. The UBE2E2 gene encodes ubiquitin-conjugating enzyme E2 E2 (UBE2E2), which plays an important role in the synthesis and secretion of insulin. UBE2E2  is a protein expressed in the pancreas, liver, and adipose tissue, as well as in an insulin-secreting cell line . The results of some studies have indicated that single nucleotide polymorphisms on UBE2E2 (rs6780569, rs7612463, rs9812056) are associated with T2DM risk in Japanese, Korean and Chinese populations. Therefore, the UBE2E2 gene has started to draw interest from researchers because of its newly discovered relationships with various diseases.
Diabetes mellitus. 2015;18(3):46-50
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Cardiology
Изучение количества циркулирующих прогениторных клеток эндотелия у больных сахарным диабетом 1 типа
Sokolova A.V., Kochegura T.N., Parfyonova E.V., Shestakova M.V.
Abstract

Aim

Circulating progenitor endothelial cells (CPCs) play an important role in the regeneration of damaged vascular endothelium. We aimed to study the effect of type 1 diabetes mellitus (DM) on the number of different lines of CPCs.

Methods. 

The number of different lines of CPCs was evaluated by flow cytometry in 45 patients with type 1 DM (mean age: 26,6±6,5 years) of different duration and 14 healthy volunteers.

Results. 

The number of CPCs in the peripheral blood flow of patients with type 1 DM was significanlty reduced compared with that in healthy volunteers and had a reliable inverse correlation with glycated haemoglobin (HbA1c).

Conclusions. 

The number of CPCs in the peripheral blood flow of patients with type 1 DM depended on the level of DM compensation. Of the different lines of CPCs, Lin-CD34+ cells were significantly reduced by 42% (p=0,006), Lin-CD34+c-Kit- cells by 42% (p=0,007) and Lin-CD34+c-Kit+ cells by 41% (p=0,022). Thus, the number of CPCs in the peripheral blood of patients with type 1 DM is reduced with higher levels of HbA1c.

Diabetes mellitus. 2015;18(3):51-56
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Diabetic foot
The clinical course of critical limb ischaemia and the role of endovascular revascularisation in patients with diabetes
Bondarenko O.N., Galstyan G.R., Dedov I.I.
Abstract

Recent data suggest that chronic critical limb ischaemia (CLI) is the most important reason for amputation among diabetic patients. The high prevalence of CLI in this patient group is associated with specific clinical and morphological properties of peripheral arterial disease. Percutaneous transluminal angioplasty is an appropriate primary therapy, but it is not considered early in the disease process, and is instead reserved as a limb salvage strategy. Low primary patency, despite optimal clinical effects, remains a typical issue of percutaneous transluminal angioplasty for diabetic patients in particular. Thus, the indications, technical success and clinical results of endovascular revascularisation need to be clarified in patients with diabetes. Although difficult, the procedure can be effective through a multidisciplinary approach.

Diabetes mellitus. 2015;18(3):57-69
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Clinical and morphological characteristics with markers of reparation in neuropathic diabetic foot ulcers.
Komelyagina E.Y., Kogan E.A., Antsiferov M.B.
Abstract

Aim. 

To compare the clinical and morphological characteristics of chronic diabetic foot ulcers and the markers of repair.

Materials and Methods.

We included 26 patients with neuropathic diabetic foot syndrome who had signs of severe peripheral neuropathy. Biopsies were performed from the margin and central part of the lesion and were fixed in a 10% formalin solution before being placed on paraffin slides and stained with hematoxylin and eosin. We assessed the percentages of necrotic, granulation and fibrotic tissues and the severity of vascular hyalinosis. Immunohistochemistry was performed with initial antibodies to Ki-67 (a marker of proliferation), smooth muscle actin (a marker of myofibroblast synthesis) and cytokeratin (a marker of epithelisation). For analysis, the samples were divided into three groups by the length of time the ulcer had been present: group 1 (≤90 days; 9 samples), group 2 (91–365 days; 10 samples) and group 3 (>365 days; 9 samples).

Results. 

The patients of group 3 were older than those of groups 1 and 2 (53.7±2.7 vs 51.7±5.9 vs 59.9±5.6 years; p=0.04). There were no differences in the duration of diabetes, glycated haemoglobin or severity of neuropathy. The percentage of necrotic tissue was higher in group 1 (33.7%±21.7% vs 11.0%±3.9% vs 12.8%±6.1%; p=0.02) and the percentage of fibrotic tissue was highest in group 3 (21.1%±21.0% vs 35.5%±19.8% vs 54.4%±23.9%; p=0.001). However, the amount of granulation tissue was not different between the groups (45.2%±21.1% vs 53.5%±21.1% vs 32.8%±26.3%; p=0.4). There was also no difference in the severity of vascular hyalinosis between the groups (p=0.9). Expression of Ki-67 was higher in groups 1 and 2, implying a greater capacity to regenerate. The expression of smooth muscle actin and cytokeratin was higher in groups 1 and 2 but without statistical significance.

Conclusion. 

The morphological characteristics and regenerative capacities of neuropathic diabetic foot ulcers differ with the duration the ulcer has been present. Patients with ulcers for less than 1 year were characterised by higher cell proliferation but lower fibrosis. Neuropathic diabetic foot ulcers that are unable to heal over a year are characterised by incomplete regeneration and higher levels of fibrosis. Thus, different treatment approaches are needed depending on how long an ulcer has been present.

Diabetes mellitus. 2015;18(3):70-76
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Diagnosis, control, treatment
Frequency of type 2 diabetes in family and it’s changes in diabetic patients affected or not affected with cancer
Berstein L.M., Teslenko S.Y., Vasilyev D.A., Kovalenko I.M.
Abstract

Aims

To study at greater than before material the prevalence of type 2 diabetes (T2DM) in relatives of suffering from T2DM patients with cancer and compare the features of antidiabetic therapy in cancer patients with a familial and non-familial form of diabetes.

Materials and Methods. 

Information about diabetes history in family was collected during two subsequent periods (May 2009-February 2011 and March 2011-July 2014 years) in cancer patients (totally,1955 people; 1351 of them with T2DM and 604 without diabetes), as well as in patients with T2DM without cancer (n=379). All patients answered questions about diabetes in their mothers, fathers, siblings, and other relatives. In cancer patients with T2DM, data on the type of antidiabetic therapy for at least 6 months prior to enrolling into the hospital were collected.

Results. 

A lower frequency of family diabetes in diabetic patients with cancer (28,5±1,2% vs 38,0±2,5%, p<0.01 in T2DM without cancer) was revealed. By 2011–2014 the prevalence of family diabetes was grown significantly and virtually in a similar degree in both groups (+17,9% in ‘T2DM with cancer’ and +19,3% in ‘T2DM without cancer’). T2DM patients with cancer and family history of diabetes used metformin prior hospitalization more often than same patients without familial T2DM.

Conclusion

Reaffirming the earlier data on more infrequent occurrence of family diabetes in T2DM patients with cancer compared with T2DM patients without cancer, we were able to demonstrate roughly the same increase in the detection of familial diabetes in these groups of patients in a rather short period of time. The use of metformin – one of the potential factors contributing to the probable and unexpected decrease of cancer risk in T2DM patients with familial type of diabetes. Other possible causes of this phenomenon deserve further study in view of the growing epidemic of diabetes and obesity.

Diabetes mellitus. 2015;18(3):77-84
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The role of dipeptidyl peptidase 4 inhibitors in fat metabolism in patients with type 2 diabetes and obesity
Ametov A.S., Gusenbekova D.G.
Abstract

Objective

To evaluate the influence of combined therapy of sitagliptin and metformin on fat metabolism in patients with type 2 diabetes mellitus.

Methods. 

The study included 82 patients (age, 55.3±9.1 years) with obesity and lipid metabolism disorders. None of the patients had reached their target glycated haemoglobin levels after metformin and diet therapy. Patients in group 1 (n=42) received 1.5–2-g metformin daily before the study and were switched to a formulation of 100-mg sitagliptin and 2-g metformin once a day. Patients in group 2 (n=40) were on a diet therapy before inclusion and were started on 2-g metformin/day. The following were evaluated at baseline and after 6 months of therapy: fasting glucose levels, postprandial glucose levels, glycated haemoglobin, weight, body mass index, waist circumference and lipid profile; insulin, proinsulin, leptin and adiponectin levels; insulin resistance using the homeostatic model assessment (HOMA) of β-cell function (HOMA-β) and insulin resistance (HOMA-IR). In addition, magnetic resonance imaging was performed to assess the amount of visceral fat for the total cohort.

Results. 

After 6 months, glycated haemoglobin decreased by 18.52% (p <0.001) in group 1 and by 8.17% (p <0.001) in group 2. Fasting plasma glucose and postprandial glucose levels in group 1 were reduced by 21% (p <0.001) and 26.35% (p <0.001), respectively; the corresponding reductions in group 2 were 1.45% (p >0.05) and 5.31% (p <0.05), respectively. HOMA-β increased by 33% in group 1 (p <0.001) and by 11% in group 2 (p >0.05). Adiponectin levels increased by 27.06% (p <0.001) in group 1 and by 7.16% in group 2 (p <0.001). Leptin levels were reduced by 30.47% (p <0.001) in group 1 and by 5.41% in group 2 (p <0.001). Magnetic resonance imaging showed a 7.52% reduction in visceral fat for group 1 (p <0.001) and a 1.76% reduction for group 2 (p <0.01). The comparison of subcutaneous fat dynamics did not show statistically significant differences between the groups.

Conclusion. 

Compared with metformin monotherapy, sitagliptin and metformin combination therapy had a prominent effect on non-glycaemic parameters, with more marked decreases in visceral fat and leptin and increases in adiponectin levels.

Diabetes mellitus. 2015;18(3):85-92
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Reproductive health
Diagnostic and treatment of retrograde ejaculation as a manifestation of urogenital form of autonomic diabetic polyneuropathy
Kurbatov D.G., Galstyan G.R., Rozhivanov R.V., Lepetukhin A.E., Shwarts Y.G.
Abstract

Background

Retrograde ejaculation in patients with type 1 diabetes mellitus is a complication of autonomic neuropathy that causes excretory infertility. It can be partial (reduction of ejaculate) or total (absence of ejaculate) and occurs in 10%–20% of men with type 1 diabetes mellitus.

Aim

The aim of the study was to assess the effectiveness of a new endoscopic method for retrograde ejaculation correction and antegrade ejaculation restoration.

Materials and methods

We included 30 patients with type 1 diabetes mellitus who had spermatozoa present in their post-orgasmic urine and ultrasonographic evidence of impaired or absent bladder neck closure. The mean age of participants was 32 (30–35) years, mean duration of diabetes was 17 (12–22) years and mean preoperative glycated haemoglobin level was 7.4% (6.9%–8.0%). All participants had total retrograde ejaculation. We used conventional irrigated urethrocystoscopy under local anaesthesia. During urethroscopy, bladder neck gaping was observed in all cases. Biocompatible material was injected at three points under the mucous layer of the posterior urethra, reaching the closing of the opposite edges of the urethra. A spermiogram was examined 1 week after the operation.

Results. 

Restoration of antegrade ejaculation was achieved for 22 patients (73%), and the effects persisted for a mean of 7 (2–12) months. The spouses of four men became pregnant after surgery. In one case, the pregnancy resulted in a spontaneous abortion at gestational week 8, but the other three cases continued normally.

Conclusion.

This new method provides a highly effective means of restoring the physiological passage of the ejaculate. The operation is a low-invasive endoscopic procedure that does not disrupt urination, and it is possible to receive ejaculate of sufficient.

Diabetes mellitus. 2015;18(3):93-98
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Case report
Development of metabolic syndrome at a young age as a manifestation of familial partial lipodystrophy type 3 (PPARG mutation): the first description of its clinical case in Russia
Sorkina E.L., Kalashnikova M.F., Likhodey N.V., Koksharova E.O., Ustyuzhanin D.V., Mayorov A.Y., Shestakova M.V., Tiulpakov A.N.
Abstract

Metabolic syndrome (MS) is extremely common (20%–25% of the world’s population), and its diagnostic criteria are defined and well known. It has been shown that patients who have MS are twice as likely to die from a cardiovascular complication and three times as likely to suffer from it compared with patients without MS. However, the underlying cause of MS remains to be clearly elucidated, although inherited factors, such as insulin resistance (IR), and external factors are considered to play a key role in this process. Special attention should be paid to MS in young patients, who may present the first manifestation of inherited lipodystrophy. The study describes the first known family in Russia (three clinical cases) with familial partial lipodystrophy (FPLD) type 3 caused by heterozygous p.R212Q PPARG mutation (MIM#601487). The study reports rare forms of inherited IR, such as FPLD, and contributes to a better understanding of common disorders such as MS.

Diabetes mellitus. 2015;18(3):99-105
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The History
To the 110 anniversary since the birth of professor E.A.Vasyukova
Ametov A.S., Doskina E.V., Kochergina I.I., Smirnova O.M., Mishina E.E.
Abstract

110 years ago was born famous scientist, talented teacher and doctor, organizer of public health, honoured worker of science of RSFSR, doctor of medicine, professor Ekaterina Alekseevna Vasyukova. Ekaterina Alekseevna had long and difficult career path - from research assistant to the director of the All-Russian Institute of Experimental Endocrinology(now Endocrinology Research Centre), was head of it for 10 years, a long time was head of the Department of Endocrinology at the Central Institute of Advanced Medical Ministry of Health (now the Academy of Postgraduate Education). She had more than 200 publications, including 14 monographs, collections and algorithms in endocrinology. Under her leadershipthere were defended 16 doctoral and 63 master's theses. The main areas of her research were the methods of diagnostics and treatment of diabetes, Cushing's disease, thyroid diseases, abnormalities of reproductive growth. In 1971 she had identified the current trends in the nativeclinical endocrinology, which were the relationship between the central nervous system and the endocrine glands; immunopathology in endocrinology; study of the prevalence and prevention of diabetes. EkaterinaAlekseevnawassensitive person, a great clinician, a professional teacher. She had great authority and respect among the medical community of our country and abroad.

Diabetes mellitus. 2015;18(3):106-109
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News
ADA Congress 2015 in Boston (USA) - an overview of the main topics
Nikonova T.V.
Abstract

From July 5 to July 9, 2015 in Convention Center in Boston (USA) there took place anniversary 75th session of the annual congress of the American Diabetic Association (ADA). The congress united more than 14000 participants from 124 countries. Programs of scientific sessions of the congress included the most topical issues of diabetology: modern approaches to diagnostics, prevention and treatment of DM and its complications, the results of the international researches of anti-diabetic preparations, problems connected with diabetes 2 types and obesity and many others.

Diabetes mellitus. 2015;18(3):110-113
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