Vol 61, No 6 (2015)

Original Studies
The immunohistochemical and radiological features of nonfunctioning pituitary adenomas
Lipatenkova A.K., Dzeranova L.K., Pigarova E.A., Dalantaeva N.S., Astaf'eva L.I., Shishkina L.V., Ektova A.P.
Abstract

Pituitary adenomas without clinically active hypersecretion are summarized under the term nonfunctioning pituitary adenomas (NFPAs). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties.

Aim.

To investigate the immunohistochemical and radiological features of NFPAs and assess the granins — chromogranin A (CgA), secretogranin II (SgII), secretoneurin (Sn) as immunohistochemical markers of NFPAs.

Matherial and methods.

50 pituitary adenomas excised surgically were immunostained to reveal pituitary hormones, ki-67, CgА. SgII, Sn. All patients underwent MRI, invasive growth was estimated due to J.Hardy classification (1973).

Results.

24 (51,1%) were gonadotropic tumors, 12 (25,5%) — null cell adenomas. Immunopositivity for ACTH was determined in 6 cases (12,7%), for GH in 5 (10,6%) cases, for PRL in 4 (8,5%). The median level of ki-67 was 2% (min. — 0.5%, max. — 7%). The CgA, SgII, Sn immunopositivity was found in 83, 93,6, 85,1% respectively, being more expressed in gonadotropinomas and null cell adenomas. Invasive growth was detected in 28 (44%) cases, among the invasive adenomas 22 tumors were giant. CgA expression is adverse prognostic factor, area under the curve (AUC) with 0,705. We did not find any correlation between ACTH-, STH-, CgII- and Sn- immunopositivity, ki-67 and invasive growth.

Conclusions.

Our work shows that a majority of NFPAs are truly secreting adenomas with significant numbers comprising potentially hazardous cortico- and somatotropinomas. CgA, SgII and Sn have a high expression in most of the NFPAs.

Problems of Endocrinology. 2015;61(6):4-9
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Clinical polymorphism of type 2 diabetes in children — the first study in Russia
Eremina I.A., Kuraeva T.L., Zilberman L.I., Mayorov A.Y., Koksharova E.O.
Abstract

Objective.

To elucidate the specific features of diagnostics, clinical course and manifestations of type 2 diabetes mellitus (DM2) in the children of the Russian population.

Material and methods.

A total of 80 children presenting with DM2 were enrolled in the study including 70 available for the dynamic examination, with the follow-up period of 2.6 years (1.5; 4.5). The general clinical examination of the patients was supplemented by measuring insulin secretion, studying HLA-polymorphism of the DQ and DR-genes, and determination of type 1 diabetes (DM1) — related specific antibodies (At).

Results.

The median age at diagnosis of DM2 was 13 years (11.5; 15.5). 58.8% of the children had a family history of DM2 but only 26.3% of them had classical complaints of diabetes mellitus. In 65% of the children, DM2 was diagnosed when they were passing medical examination in connection with obesity (in 51.9% with the use the oral glucose tolerance test (OGTP); 48.1% of these children had the fasting blood glucose level above 7.0 mmol/l. Ketonuria at the onset of the disease was documented in 21.3% of the patients while 85% were either obese or overweight. Antibodies (ICA and IAA) were detected in 15.2% of the children at a low titer. The HLA-genotype associated with a high risk of development of DM1 was identified in 5.5% of the cases. The glycosylated hemoglobin test revealed its mean level of 7.1% (6.3; 8.5%) at the onset of diabetes; in the majority of the children, it fell down below 6.5% within the first 3 years of the disease. During this period, insulin and C-peptide secretion remained elevated. Insulin resistance was initially documented in 81.3% of the children; the dynamic observation failed to show its appreciable decrease. Insulin therapy initiated at the onset of the disease was prescribed to 30% of the patients. After 3 years, only 8% of the children retaining endogenous insulin secretion continued to use insulin.

Conclusion.

The asymptomatic onset of type 2 diabetes mellitus in the children and adolescents emphasizes the importance of its active diagnostics during the pubertal period in the high risk groups comprising the patients with obesity and the family history of DM2. In one third of the children, the diagnosis of DM2 was possible only with the use the oral glucose tolerance test. DM2 in the children and adolescents is characterized by clinical polymorphism in the form of acute manifestations in 21% of the cases and the absence of obesity and insulin resistance in 15 and 18% respectively. This finding suggests the necessity of differential diagnostics of such cases from DM1 and MODY. Rather high insulin and C-peptide secretion persists for 3 years after the onset of DM2 in the children. Therefore, they do not need insulin therapy during this period. The presence of ICA and IAA antibodies at low titers does not compromise diagnosis of DM2.

Problems of Endocrinology. 2015;61(6):10-16
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Changes in diabetes mortality in Sasovo district of Ryazan region during 2003—2013 years
Asfandiyarova N.S., Nizov A.A., Zdol'nik T.D., Shatrova I.V., Budylin A.A.
Abstract

Aim.

To study the overall mortality, mortality from cardiovascular diseases and cancer (CVD, C) in patients with diabetes mellitus (DM) in Sasovo District of Ryazan Region during 2003—2013 years.

Material and Methods.

We studied the diabetes overall mortality, CVD and cancer mortality dynamics in Sasovo District of Ryazan region during 2003—2013 years. In 2003, the population of the district was 52 100 people, in 2013 — 45 316. In 2003 years, it was registered 550 patients with diabetes, in 2013 years — 736.

The coefficients of overall mortality, mortality from diseases were calculated according to standard formulas per 1000 population.

Results.

It was revealed the reduction of total and cardiovascular mortality in the population (p<0,001) during period of observation. There is a trend towards reduction in total mortality and mortality from CVD in diabetic patients (p>0,05), but it is in 2—3,4 times higher than among the population The main causes of death in diabetic patients are CVD (67.8%) and cancer (10.9%), the dynamics of these figures were not observed.

Conclusions.

CVD and cancer are the leading cause of death in diabetes. Absence of changes in the level of CVD mortality, suggests the need for preventive measures for influence on this risk factor.

Problems of Endocrinology. 2015;61(6):17-22
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Insulin resistance: associations of personal characteristics and factors of lifestyle
Motovilin O.G., Surkova E.V., Mayorov A.Y., Mel'nikova O.G., Koksharova E.O., Fedorova E.A., Andreeva S.I.
Abstract
Objective — to study the relationship of IR with some clinical characteristics (body weight, BMI, level of HbA1c) and social and psychological parameters in patients with type 2 diabetes and IGT.

Material and methods.

IR was assessed by determining fasting blood glucose and insulin (HOMA — homeostasis model assessment, the calculation of the IR index), patients were tested by using valid questionnaires (Strategic Approach to Coping Scale, The Level of Subjective Control, Self-attitude Questionnaire), and life style questionnaires.

Results.

Multiple associations of IR index with personal characteristics are revealed. The psychological profile of a patient with a high IR includes the reduction of positive self-attitude, uncertainty in their own abilities, especially in the interpersonal relationships. Such features can provoke rejection of the active and targeted overcome the difficulties of life, the desire to avoid decisions, and if it is impossible — aggressive reactions with defensive character and reflect the uncertainty in their forces. The association of body weight and results of psychological tests were detected: the more the worse self-attitude in a number of aspects. The correlations of IR index and weight with some characteristics of lifestyle (dietary habits, especially sleep) were also revealed.

Conclusions.

The observed association of IR and personal characteristics and lifestyle features are of interest and required larger studies.

Problems of Endocrinology. 2015;61(6):23-30
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Case Reports
Rare form of Permanent Neonatal Diabetes Mellitus (PNDM) due to novel mutation in EIF2AK3 gene (Wolcott—Rallison syndrome)
Tikhonovich Y.V., Stotikova O.V., Rubtsov P.M., Tiulpakov A.N.
Abstract

Wolcott—Rallison syndrome (WRS) is a rare genetic disease inherited in autosomal recessive way. Сlinical manifestations develop in early infancy with symptoms of permanent neonatal diabetes mellitus (PNDM), skeletal dysplasia, short stature and hepatic dysfunction. The condition has poor prognosis and most patients die at a young age due to episodes of acute liver or renal failure. To date about 60 genetically proved cases of WRS have been reported worldwide. The disease is most common in countries where consanguineous marriages are frequent, such as the Saudi Arabia (60% cases of PNDM patients), India, Turkey, Pakistan and North Africa. In Russian Federation WRS patients have not been described earlier.

Problems of Endocrinology. 2015;61(6):31-35
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Reviews
Novel approaches of glucose-lowering therapy in type 2 diabetes and chronic kidney disease
Trubitsyna N.P., Severina A.S., Minara S.S., Shestakova M.V.
Abstract

Frequency of the diabetes mellitus (DM) and chronic kidney disease (CKD) steadily increases around the world. Compensation of a carbohydrate metabolism plays a key role in prevention of development and progressing of CKD in patients with DM, that was proved in the largest researches. However at later stages of CKD compensation of a carbohydrate metabolism is extremely complicated because of high risk of hypoglycemia due to decrease in a renal gluconeogenesis, insulin and anti-hyperglycemic agents cumulation, inadequate level of glycated hemoglobin due to nephrogenic anemia. Thus, great care and an individual approach in choosing and intensification of hypoglycemic therapy are required in patients with diabetes. Incretin drugs have taken a worthy place in the international and national guidelines for the treatment of patients with type 2 diabetes mellitus (DM2). Inhibitors of dipeptidyl peptidase-4 (DPP-4) showed a favorable efficacy and safety profile in patients with normal renal function and patients with CKD.

Problems of Endocrinology. 2015;61(6):36-43
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Promising pharmacological targets for the treatment of the diseases associated with the impaired insulin receptor signaling pathway
Gorbunov E.A., Brigadirova A.A., Kachaeva E.V., Putilovskiy M.A., Tarasov S.A.
Abstract

Diabetes mellitus (DM) is one of the most widespread chronic diseases in the world. In DM type 2, peripheral tissues demonstrate strong resistance to endogenous insulin (insulin resistance) which is caused by impaired ability of the hormone to stimulate glucose uptake in target cells (muscle, adipose or brain tissue, liver, etc.) and to reduce blood glucose level. Research data suggest that all mentioned reasons are most likely to be based on a disruption of signal transduction from insulin receptor (IR) into insulin-dependent intracellular signaling cascades. Contemporary DM treatment strategy is aimed at the maintenance of optimal blood glucose level by improving insulin production and increasing insulin sensitivity of tissue as well as prevention of macro- and microvascular complications and decrease of their intensity. At the same time, the search for new targets for creation of innovative anti-diabetic compounds can be considered a promising task due to the optimization of existing approaches and development of the novel ones taking into account results of the latest research into DM etiology and pathogenesis. A special position among possible targets is occupied by insulin receptor (IR) and IR-associated signaling pathways. Belonging to tyrosine kinase receptor family, IR has been actively studied during the last decades. This review considers in particular the IR structure and functioning of receptor-associated signaling pathways. The paper contains data on novel ligand-mimetics and IR sensitizers as well as other molecules, which affect different components of IR-associated signaling pathways, thus exerting significant antidiabetic effect. Action of these compounds is aimed at improvement of basic metabolic disorders resulting in hyperglycemia and is mainly carried out due to the following effects: activation and potentiation of insulin signaling, increase of insulin sensitivity of peripheral tissues; recovery of insulin secretion physiological mechanisms; reduction of glucose production in liver.

Problems of Endocrinology. 2015;61(6):44-54
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Clinical guidelines
Russian national guidelines on insulin pump therapy and continuous glucose monitoring for diabetes mellitus patients. DRAFT
Shestakova M.V., Mayorov A.Y., Philippov Y.I., Ibragimova L.I., Pekareva E.V., Laptev D.N., Glazunova A.M.
Abstract
Insulin pump therapy (continuous subcutaneous insulin infusion, CSII) and continuous glucose monitoring (CGM) are high-tech treatment and diagnostic tools for diabetes patients management which are actively used worldwide. CSII initiation and pump-users supervision became a part of routine clinical practice in Russia along with the CGM. Present project of clinical guidelines is based on international and domestic experience in CSII and CGM for diabetes treatment. Guidelines should ensure uniformity of CGM and CSII usage in Russia by health care professionals and diabetes patients and provide them an international experience to guarantee height performance of the technology. This article contains a preliminary version of the guidelines (draft) prepared for further expert’s discussion and review. The final version of the clinical guidelines will be sent to the Ministry of Health of the Russian Federation for approval.
Problems of Endocrinology. 2015;61(6):55-78
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