Vol 14, No 3 (2017)

Visceral obesity and cardiometabolic risk: features of hormonal and immune regulation
Kologrivova I.V., Vinnitskaya I.V., Koshelskaya O.A., Suslova T.E.

The issue of the prognostic value of obesity in the development of cardiovascular diseases still remains open. Different input of visceral and subcutaneous adipose tissue in the formation of cardiometabolic risk is highlighted in many research works. A range of epidemiological studies provides data confirming relation of the visceral adiposity with abnormal metabolic profile and increased cardiovascular risk, while subcutaneous adipose tissue is attributed with relative protective properties. Pathophysiological mechanisms mediating interconnection of visceral adiposity with the development of atherosclerosis remain studied incompletely. It was stated that sex hormones, estrogens and androgens, participate in the redistribution of adipose tissue, sustenance of energy homeostasis, influence on the secretion of adipokines and immune regulation of adipose tissue. Meanwhile cells of immune system, including cells of the adaptive immunity, widely presented in adipose tissue contribute to the development of the local subclinical inflammation and influence on the features of cardiometabolic effects of adipose tissue. The review discusses possible mechanisms, by which abovementioned relationships are executed and cardiovascular risk in obesity is realized.

Obesity and metabolism. 2017;14(3):3-10
Fragility fractures and bone remodeling in type 2 diabetes mellitus
Yalochkina T.O., Belaya Z.E.

Fracture risk is significantly increased in both type 1 and type 2 diabetes and individuals with diabetes experience worse fracture outcomes compared to normoglycemic individuals. Patients with T1DM have decreased bone mineral density (BMD), whereas patients with T2DM demonstrate increased BMD compared to healthy control. The latest studies show increased incidence of low-traumatic fractures in patients with T2DM instead of high bone mineral density (BMD). The risk of osteoporotic fractures in patients with T2DM can be explained by disease complications and increased risk of falls and consequent trauma. However, the most important cause of bone fragility in T2DM is the deterioration in bone microarchitecture, the mechanism of which is not completely understood. High BMD in patients with T2DM does not allow us to use dual-energy X-ray-absorptiometry as a “gold standard” test for diagnosticsof osteoporosis. Consequently,new risk factors and diagnostic algorithm as well as treatment strategy should be developed for patients with T2DM. In addition to this, some researchers considered that the group of T2DM is geterogenous and physicians might face patients with osteoporosis and mild diabetes that add very little to bone fragility; patients with osteoporosis and moderate or severe diabetes which also affects bone tissue –diabetoosteoporosis; and patients without osteoporosis but severe diabetes which cause bone tissue deterioration with the development of diabetic bone disease. New diagnostic tools and algorithm and new experimental research are needed for better understanding bone deterioration in patients with T2DM. This review summarizes our current knowledge on fracture rate, risk factors for fractures and causes of bone deterioration in subjects with T2DM.

Obesity and metabolism. 2017;14(3):11-18
Influence of androgen deficiency on carbohydrate metabolism in men
Mkrtumyan A.M., Egshatyan L.V.

The article provides an overview of the current literature integrating clinical data on the role of androgen deficiency in pathogenesis of metabolic malfunctions and diabetes mellitus. The combination of androgen deficiency and diabetes mellitus is a risk factor of cardiovascular diseases. Due to the fact that general physicians, endocrinologist don’t have knowledge of this problem most of androgen deficiency cases are not only remained without treatment but also not revealed.

Obesity and metabolism. 2017;14(3):19-24
Original paper
Metabolic syndrome in the inhabitants of Mountain Shoria: prevalence, variants of manifestations and ethnic peculiarities
Tsygankova D.P., Mulerova T.A., Ogarkov M.Y., Saarela E.Y., Kuzmina A.A., Barbarash O.L.

Background. Metabolic syndrome is one of the most dangerous risk factors of cardiovascular and endocrine diseases development and mortality due to them, especially among young people.

Aims: Our purpose was to study the prevalence of the metabolic syndrome, combinations of its components in indigenous and non-indigenous inhabitants of Mountain Shoria.

Materials and methods. During the period since 2012 to 2015 we have examined the inhabitants of the villages of Mountain Shoria: Ust-Kabyrza, Orton, Sheregesh by a continuous method on the basis of a name list. All the participants were examined by a cardiologist, an endocrinologist and a general practitioner, also a waist circumference and arterial blood pressure were measured. Specific diagnostic methods included an estimation of blood glucose level, triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) in blood serum.

Results. All the subjects (460 persons) were divided into age (18–39 years, 40–59 years, 60 years and older), ethnic (the Shors and the non-Shors) and gender (men and women) groups. Generally, the metabolic syndrome was diagnosed in 40.2% of inhabitants of Mountain Shoria. Metabolic syndrome (MS) was presented in 12.4% of indigenous men and in 47.8% of non-indigenous examined men (р=0.00001). MSwasrevealedin 36.8%, of Shor-women and in 60.7% of non-Shor women (р=0.00002). The most common variant of 3-component MS was abdominal obesity + arterial hypertension + hyperglycemia and the rarest was – abdominal obesity + TG + hyperglycemia. The most common variant of 4-component MS was a combination of abdominal obesity + hyperglycemia + arterial hypertension + HDL-C, the rarest was abdominal obesity + arterial hypertension + TG + HDL-C. Different variants of 3-component and 4-component MS occurred with similar frequency in all age groups of the Shors and non-Shors.

Conclusions. Generally MSoccurred more frequently in non-indigenous inhabitants than in indigenous inhabitants. Only in women of young age group this pathology was revealed with the similar frequency among both ethnic groups. Among all the inhabitants of Mountain Shoria the most frequent clinical variant of 3-component MS was a combination of abdominal obesity + arterial hypertension + hyperglycemia and of 4-component variant – a combination of abdominal obesity + hyperglycemia + arterial hypertension + HDL-C.

Obesity and metabolism. 2017;14(3):26-31
Expression of microRNA related to bone remodeling regulation in plasma in patients with acromegaly
Grebennikova T.A., Belaya Z.E., Nikitin A.G., Brovkina O.I., Solodovnikov A.G., Dzeranova L.K., Melnichenko G.A.

Backgraund. MiсroRNA are small regulatory factors that regulate gene expression by post-transcriptional regulation of mRNA, playing an important role in numerous cellular processes including organogenesis, apoptosis, cell proliferation and differentiation. Acromegaly causes bone fragility, but the pathogenetic mechanism is generally unknown.

Aim. To evaluate levels of microRNA related to bone remodeling regulation in plasma samples from patients with acromegaly

Materials and methods. Fasting plasma samples were taken and stored in aliquot at ≤ -80°C from consecutive subjects with clinically evident and biochemically confirmed active acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). miRNeasy Serum/Plasma Kit, TaqMan Advanced miRNA cDNA Synthesis Kit, TaqMan Advanced miRNA Assays were used to assay plasma miRNA expression. Insulin-like growth factor 1 (IGF1) was measured by immunochemiluminescence assay (Liaison).

Results. We enrolled 40 subjects 22 patients suffered from acromegaly and 18 matched healthy controls) matched by sex, age and BMI. The median age of patients with acromegaly was 42 years (Q25;Q75 – 37;43) with no difference among the groups, p=0.205; BMI – 28 (24;32) kg/m2, p=0.253. The median IGF1 in subjects with acromegaly – 622 (514;1000) ng/ml was significantly higher as compared to the control group (p<0.001). Patients with acromegaly had significantly higher expression of microRNA-100-5р (p=0.051), microRNA-550а-5р (p=0.048), microRNA-7b-5р (p=0.005) and microRNA-96-5р (p=0.042) among 27 bone-specific microRNA tested in plasma

Conclusions. This study reveals that several microRNAs, known to regulate bone remodeling can be detected in plasma samples of patients with acromegaly and may be suggested as biomarkers for skeletal involvement in patients with acromegaly.

Obesity and metabolism. 2017;14(3):32-37
TGF-β and FRF-21: association with coronary artery disease in patients with type 2 diabetes and obesity
Shvangiradze T.A., Bondarenko I.Z., Troshina E.A., Nikankina L.V., Kukharenko S.S., Shestakova M.V.

Backgraund: Obesity and type 2 diabetes mellitus (T2DM) are associated with with an increased risk of cardiovascular disease (CVD) and coronary artery disease (CAD), in particular.

Obesity lead to several fibrotic processes, including activation of transforming growth factor β (TGF-β). Recent data indicate the involvement of Fibroblast growth factor 21 (FGF-21) as an important metabolic regulator, and even biomarker of metabolic changes in obesity and T2DM. Impact of metabolic dysregulation that accompany obesity and T2DM in CAD development remain a great challenge.

Aims: To study TGF-β and FGF-21 level in patients with obesity and T2DM.

Materials and methods: TGF-β and FGF-21 were identified in peripheral blood samples of 66 patients with obesity, aged 48-65 years. 1st group included 21 patients with CHD and T2DM; 2nd group (22 patients)- with T2DM and excluded CHD; 3rd group (20 patients) with normal glucose metabolism and excluded CHD.

Results: TGF-β was lower in patients with CHD (group 1) than in the group of "metabolically healthy" obesity (p=0.022).

TGF-β in patients with T2DM negatively correlated with LDL cholesterol (r=-0.426, p=0.038) the degree of internal carotid artery stenosis (r=-0.426, p=0.024). Patients with verified CHD had a negative correlation with the processes of heart muscle remodeling (thickness of the left ventricular posterior wall (r=- 0.386, p=0.029) interventricular septum (r=-0.335, p=0.031). All patients with obesity had significantly increased level of FGF-21 compared with the control group (p=0.031) FGF-21 positively correlated with BMI (r=0.473, p=0.033)

Conclusions: TGF-β has negative correlations with the factors that can influence prognosis and the severity of the CVD/. There were found correlations of FGF-21, TGF-β with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CAD.

Obesity and metabolism. 2017;14(3):38-42
The autoimmune IgG4 -associated endocrine pathology
Yukina M.Y., Troshina E.A., Platonova N.M., Nuralieva N.F.

Immunoglobulin G4-associated diseases (IgG4-AD) arethe group of chronic progressive autoimmune fibro-inflammatory pathology of various organs and tissues, characterized by their enlargement and abundant infiltration of immunoglobulin G4-positive plasma cells, as well as an increase in the level of serum immunoglobulin G4 (IgG4).In most patients, the disease is characterized by a mild course.However, there is evidence of a high incidence of malignancies in patients with IgG4-AD.Among endocrine IgG4-associated pathologies, pancreatitis with outcome in diabetes mellitus, hypophysitis and thyroiditis are described.

Laboratory examination usually reveals an increased level of IgG4. However, the concentration of IgG4 could not be used as the only diagnostic criterion.The possibility of plasmablastsdetermining as a marker of the disease is discussed.Among the imaging techniques CT, MRI and 18F-FDG-PET/CT are used.However, the most informative method of diagnosis is biopsy.

Randomized clinical trials to determine clear recommendations for the treatment of IgG4-AD were not conducted.In most cases, glucocorticoids are prescribed, and immunosuppressive therapy is sometimes used.According to the results of recent studies, the genetically engineered drug rituximab is relatively effective in inducing remission of the disease.Given the high recurrence rate and the risk of malignancy, patients with IgG4-AD require careful long-term follow-up.

Thus, the review describes the clinical manifestations of IgG4-AD, examines the possibilities of their diagnosis and presents the existing methods of treatment.However, given the fact that IgG4-AD became a separate group of autoimmune pathology less than 20 years ago, there are insufficient data on these diseases. Researches related to epidemiology, pathophysiology, diagnosis and effective treatment of IgG4-AD are actual.

Obesity and metabolism. 2017;14(3):43-47
Case Report
Challenges in differential diagnosis between primary and secondary forms of hyperparathyroidism
Mokrysheva N.G., Eremkina A.K., Mirnaya S.S., Kovaleva E.V.

Hyperparathyroidism is a disease characterized by excessive secretion of parathyroid hormone (PTH) in the chief cells of parathyroid glands. There are three types of hyperparathyroidism: primary, secondary, and tertiary depending on the cause of this disease. By the secondary hyperparathyroidism calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) lead to disturbance of phosphorus-calcium exchange and to development of a parathyroid glands hyperplasia. Treatment of secondary hyperparathyroidism with vitamin D showed the efficiency not only in normalization of clinical laboratory indicators but also in involution of changes in parathyroid glands. We represent the clinical case of a patient with secondary hyperparathyroidism caused by hypovitaminosis D, parathyroid hyperplasia more than 1 cm. The long-term oral therapy with active vitamin D led to the positive dynamics of PTH levels, as well as complete reduction of parathyroid lesion.

Obesity and metabolism. 2017;14(3):48-53
Options for individualizing therapy for postoperative central diabetes insipidus
Dzeranova L.K., Mikaylova D.S., Pigarova E.A., Mokrysheva N.G., Rozhinskaya L.Y., Grigoriev A.Y., Ivashchenko O.V.

Postoperative diabetes insipidus is a common life-threatening morbidity after pituitary surgery. More frequent neurosurgeon interventions make drugs’ adjustment very important for higher life quality in the case of postoperative complications. We present the case of personalized adjustment of drug dosage to treat postoperative diabetes insipidus in patient undergoing reccurent transnasal adenomectomy.

Obesity and metabolism. 2017;14(3):54-57
Pathogenic relations between metabolic and gynecologic disorders in acromegaly: a clinical case report
Lutsenko A.S., Vorotnikova S.Y., Stanoevich I.V., Zenkova T.S., Azizyan V.N., Grigoriev A.Y., Belaya Z.E.

Acromegaly is a neuroendocrine disorder with multiple comorbidities. In this article, we present a patient with long-term active acromegaly, without clinical remission after repeated neurosurgery and long-term treatment with somatostatin analogue. After the first neurosurgical treatment, cyclic ovarian function improved. Taken together with progressing metabolic disorders, it led to clinical manifestation of adenomyosis, which presented by algomenorrhea, menometrorrhagia and severe anemia. Due to clinical manifestation and extent of the disease, the patient underwent hysterectomy. Histologically we observed adenomyosis II with 2/3 myometrialpenetration. This clinical case highlights the importance of gynecological assessment among patients with acromegaly of late reproductive and premenopausal period.

Obesity and metabolism. 2017;14(3):59-63

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