Vol 16, No 4 (2019)

Immunometabolism and metainflammation in obesity
Romantsova T.R., Sych Y.P.

Recent studies have shown that immune system cells take an active part in the regulation of metabolic homeostasis. Disruption of the interaction between the immune system and metabolic processes makes a major contribution to the current epidemic of a number of non-communicable metabolic diseases. Due to central and peripheral insulin resistance, obesity is closely associated with type 2 diabetes mellitus. Many mechanisms are involved in the genesis of insulin resistance including chronic inflammation in metabolically active tissues (adipose tissue, intestines, muscles, pancreas, liver), as well as in the central nervous system. Potential triggers of obesity-induced metainflammation are cellular hypoxia, mechanical stress of the fat cells, excess of free fatty acids and lypopolysaccharides. Weight loss is a key factor to eliminating inflammation and improving tissue insulin sensitivity. This review presents literature data on the mechanisms of metainflammation in obesity. Taking into account the contribution of metainflammation to the pathogenesis of the disease, the possibilities and prospects of obesity therapy are discussed.

Obesity and metabolism. 2019;16(4):3-17
Obesity and stress: endocrine and social aspects of the problem in the modern Russian society
Mazurina N.V., Leskova I.V., Troshina E.A., Logvinova O.V., Adamskaya L.V., Krasnikovsky V.Y.

The purpose of the article is to consider stress as one of the etiological factors of obesity and metabolic syndrome. The review discusses both endocrine and social aspects of stress as a syndrome of adaptation to the current situation in Russian society.

It is emphasized that lifestyle factors contributing to the growth of overweight are gaining popularity in the society, and the high incidence of obesity is directly related to the level, quality and lifestyle of a modern man. Constant nervous tension, negative emotions, fear in conditions of abundance of food directly contributes to obesity, which is associated with a large number of other serious diseases.

Chronic hyperactivation of the hypothalamic-pituitary-adrenal axis and chronic hypersecretion of cortisol, if persistence is not a purely physiological condition. Endocrine mechanisms mediating the development of metabolic disorders on the background of chronic stress include activation of the hypothalamic-pituitary-adrenal system, changes in eating behavior, hyper-production of glucagon and triglyceride accumulation in visceral fat depots.

Processes and social changes occurring in modern society contribute to the construction of everyday socio-cultural environment characterized by increased stress. Chronic stress in combination with physical inactivity, the result of improper lifestyle of modern people, becomes an effective factor contributing to the spread among the population of Russia not only overweight, but also various forms of obesity.

It is emphasized that at the state level there is an urgent need to adopt and implement effective programs and mechanisms to ensure the population meets modern requirements and environmental standards of healthy food, rationalization of food distribution among the population, the formation of a culture of food consumption, improving the quality of life of the population and the culture of a healthy lifestyle, teaching the population the correct stress-coping behavior.

Obesity and metabolism. 2019;16(4):18-24
Sleep disorders interactions with obesity and type 2 diabetes
Brodovskaya T.O., Grishina I.F., Babykina G.G., Nikolaenko O.V., Kovin E.A., Bazhenova O.V., Beresneva V.E., Buharova S.Y.

Obesity and type II diabetes are 21st century pandemia. These metаbolic disorders are in the focus of attention of various specialties: cardiologists, endocrinologists, nutritionists, therapists, and others. The high incidence of obesity and type II diabetes cardiovascular complications, such as myocardial infarction, stroke, chronic heart failure, dementia, determine the call of risk factors search. Modifiable factors may include sleep disturbances. Recent studies have revealed a connection between changes in sleep duration and metabolic disorders. However, to date, the mechanisms underlying this association have not been established. The aim of the review is to summarize existing epidemiological and experimental observations, as well as an analysis of possible pathophysiological mechanisms linking sleep duration with obesity and type II diabetes. The article considers current data suggesting a bi-directional association of sleep disorders with obesity and diabetes. Sleep disturbances are significant determinant of developing metabolic disorders. Sleep duration correction as one of therapeutic targets for cardiovascular complications of obesity and type II diabetes prevention.

Obesity and metabolism. 2019;16(4):25-30
Unsolved issues related to multivitamin and multimineral support for patients following bariatric surgery
Malykhina A.I., Yashkov Y.I., Maksimov M.L.

In the review article the authors discuss unsolved issues regarding vitamin and mineral support of patients undergoing bariatric/metabolic operations. Many patients refer for the surgery already having deficiencies of macro- and micronutrients and need preoperative preparation for improving of vitamin-mineral status. Vitamin-mineral support is indicated after each bariatric operation, however the volume of nutritive support and the choice and doses of vitamins and minerals can be varied depending on type of surgery. Hypoabsorptive procedures such as duodenal switch or SADI-S (Single anastomosis duodeno–ileal bypass with sleeve gastrectomy) usually demand more significant protein, calcium and iron supplementations together with administration of multivitamin complexes containing fat-soluble vitamins. Existing standard vitamin-mineral complexes may not contain necessary doses of iron, calcium, fat-soluble and other vitamins as well as some microelements like cooper, zink, selenium etc. Thus, sufficient vitamin-mineral support may need up to 10 tablets or pills daily depending on kind of surgery. That can influence on patient’s compliance, lead to refusal of supplementations and thus to undesirable metabolic consequences after surgery. The authors have concluded about necessity of working out of cost-effective domestic series of vitamin-mineral combinations with high bio-availability specially adapted to every class of bariatric/metabolic operation. To author’s opinion this can lead to better patient’s compliance and can prevent undesirable side effects after metabolic surgery.

Obesity and metabolism. 2019;16(4):31-36
Raynaud’s phenomenon in the endocrinologist’s practice
Panevin T.S., Alekperov R.T., Melnichenko G.A.

Raynaud’s phenomenon or syndrome (RS) is an episodic attacks of transient digital ischemia resulting from vasospasm of the digital artery, precapillary arterioles, and skin arteriovenous shunts in response to exposure to cold temperature or emotional stress. Prevalence averages 3–5%. The high prevalence of RS in the population, as well as the frequent association with other, often life-threatening, diseases and conditions, determines its clinical significance. In 80–90% of cases, RS is idiopathic. It is assumed that the spasmodic reactivity of the vessels is caused by a violation of the central and local dysregulation of vascular tone. The most important role is played by vascular endothelial, intravascular and neuronal disorders.

In at least 10% of cases, this is a secondary phenomenon. Most often, RS is associated with systemic rheumatic diseases. Along with this, endocrine diseases can develop, including those affected by the pituitary, thyroid and parathyroid glands, adrenal glands, and diabetes mellitus. In some cases, RS may be the only symptom of endocrine pathology. In general, SR is a condition with a favorable outlook and a stable course. The most informative instrumental method for the differential diagnosis of primary and secondary syndrome is the capillaroscopy of the nail bed.

Obesity and metabolism. 2019;16(4):37-45
Original paper
The treatment of the metabolic syndrome with stapleless one-anastomotic gastric bypass: a randomized clinical trial compared to stapler method
Ospanov O.B., Yeleuov G.A., Bekmurzinova F.K.

BACKGROUND: The authors have developed an original method of laparoscopic gastric bypass significantly reducing financial costs when conducting this surgical treatment of obesity. In the presented article for the first time describes the evaluation of the effectiveness of the proposed to introduce a new type of staplerless gastric bypass compared to the standard stapler method.

AIMS: to evaluate the effectiveness of the author’s method of laparoscopic gastric bypass for the treatment of metabolic syndrome with obesity.

MATERIALS AND METHODS: This prospective, randomized controlled trial presents the results of surgical treatment of 80 patients with metabolic syndrome. Patients were randomized into two groups of 40 people. In the first group, the author’s method of laparoscopic mini-gastric bypass with a band-separated pouch was implemented, and in the second group, the standard laparoscopic mini-gastric bypass with a standard (stapler-separated) gastric pouch was used. Procedures were performed in the period from 2015 to 2016 with an average follow up period of 3 years. The postoperative change of weight loss and the changes of the main manifestations of the metabolic syndrome, as well as the change in the cardiovascular risk index in the comparison groups were assessed.

RESULTS: In both groups there were no significant differences by sex and age. In the first group there were 39 women and 1 man, and in the second group 36 women and 4 men aged 36.75±8.6 years and 40.47±11.0 years, respectively (p=0.097). Three years after surgery, all 80 patients were examined using analysis of variance. At the same time, it was revealed that the change in body mass index after operations, which was 14.02±5.05 kg/m2 in the first group, and 12.38±5.7 kg/m2 (p=0.170) in the second group, was found equally good bariatric effect of two compared methods of gastric bypass.

The main indicators of blood pressure, as well as laboratory data reflecting the state of carbohydrate and fat metabolism, statistically significantly decreased in both groups to normal values, which suggests a pronounced metabolic effect of both gastric bypass methods. It was established that cardiovascular risk in the first group decreased from 5.4±0.9 to 2.9±0.4 (p<0.001), and in the second group from 5.1±1.1 to 3.1±0.32 (p<0.001).

CONCLUSIONS: The results of the use of various types of laparoscopic gastric bypass in the surgical treatment of metabolic syndrome after three years indicate a significant reduction in body weight, normalization of carbohydrate and fat metabolism.

In a comparative aspect, the author’s and standard gastric bypass techniques equally positively affect the elimination of the main manifestations of the metabolic syndrome, but the proposed author’s method has insignificant advantages in terms of weight loss.

Obesity and metabolism. 2019;16(4):46-54
The relationship of eating behavior with biochemical blood parameters in children and adolescents born preterm
Podporina M.A., Rafikova Y.S., Saprina T.V., Loshkova E.V., Mikhalev E.V.

BACKGROUND: Prematurity is a risk for the formation of adverse metabolic disorders, the components of which can progress and lead to obesity. However, at the moment, the presence and nature of interrelations of metabolic parameters with the type of nutrition have not been established, there is also no clear idea of the age and structure of the initial manifestations of metabolic shifts, the prevalence of eating disorders in children born prematurely.

AIMS: To determine the frequency and structure of the initial manifestations of the metabolic syndrome (abdominal obesity, impaired glucose tolerance, dyslipidemia, hypertension); to establish associations of types of eating behavior with biochemical parameters characterizing the adverse metabolic phenotype in children and adolescents born prematurely.

MATERIALS AND METHODS: The study involved 123 children: in the main group (group 1) there were children and adolescents aged 10-17 years 11 months who were born prematurely (less than 37 weeks at birth and less than 2500 grams at birth), in the control group (group 2) included full-term children (more than 37 weeks and more than 2500 grams at birth). The study included clinical anthropometry with measurement of body weight, height, waist circumference (WC) and hips (HC), followed by calculation of body mass index (BMI) and ratio of WC/HC, measurement of blood pressure (BP). Eating behavior (EB) was assessed using a modified validated Dutch Eating Behavior Questionnaire (DEBQ).

RESULTS: WC equal to or above the 90th percentile were only in children from the main group (4 children (9.7%).There were not observed such parameters in the control group (χ²=4.63, p=0.047). BP higher than the 95th percentile was observed mainly in children born prematurely: 19 children (46.3%) against one (3.3%) of the control group (χ²=21.94, p <0.001). Eating disorders are often found in both groups (59 of 123 (47.9%)): the control group had 35 of 65 (53.8%) children against 24 of 58 (41.4%) of the main group (p>0.05).

CONCLUSIONS: The components of metabolic syndrome are registered more often in children born prematurely. Eating disorders are often found in both groups.

Obesity and metabolism. 2019;16(4):55-65
The role of obesity in the implementation of genetic predisposition to the development of essential hypertension in men
Moskalenko M.I., Ponomarenko I.V., Polonikov A.V., Sorokina I.N., Batlutskaya I.V., Churnosov M.I.

BACKGROUND: Obesity is considered a non-infectious pandemic, and the increase in its spread is a serious medical and social problem. High values of body mass index closely correlate with arterial hypertension and its complications, but the effect of obesity on the realization of hereditary susceptibility to essential hypertension (EH) remains poorly understood.

AIMS: To study the associations of polymorphic loci of MMPs with the development of EH in men depending on the presence of obesity.

MATERIALS AND METHODS: The study was conducted in a case-control design. Surveyed 821 men – 564 patients with hypertension and 257 patients of the control group. Groups of patients and controls were divided into subgroups depending on the presence of obesity. All men were genotyped for eight polymorphic loci of MMPs. Nonsynonymous SNPs were detected using the software SIFT (https://sift.bii.a-star.edu.sg/). The regulatory potential was studied using the HaploReg service (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php). The association of SNPs with the expression level was detected using GTEx-portal (http://www.gtexportal.org).

RESULTS: It was found that in obese men allele A (OR=2.01; p=0.01) and genotype GG (OR=0.42, p=0.01) of rs11568818 MMP7 are associated with the essential hypertension. In men without obesity allele 6A (OR=1.32; p=0.04) of rs3025058 MMР3 and genotypes GG (OR=1.52; p=0.04) and GA (OR=0.63; p=0.03)) of rs17577 MMP9 are associated with the development of the disease. These SNPs located in region of promoter and enhancer histone marks, in the region of hypersensitivity to DNAse-1, in binding sites of regulatory proteins and transcription factors. These SNPs associated with the level of gene expression.

CONCLUSIONS: In this study we established associations with the development of EH of SNP rs11568818 MMP7 in obese men and of SNPs rs3025058 MMР3 and rs17577 MMP9 in non-obese men.

Obesity and metabolism. 2019;16(4):66-72
Case Report
Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report)
Dzeranova L.K., Povaliaeva A.A., Romanova A.A., Przhiyalkovskaya E.G., Pigarova E.A., Fedorova N.S.

This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients’ glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice.

Obesity and metabolism. 2019;16(4):73-79
Use of teriparatide in treatment of severe osteoporosis in geriatric practice: a clinical case review
Dudinskaya E.N., Tkacheva O.N., Machekhina L.V., Ostapenko V.S., Brailova N.V.

Elderly and senile people are characterized by a high prevalence of osteoporosis, which, in turn, increases the risk of fractures, including the repeated ones. Fractures in osteoporosis are an extremely unfavorable complication of the disease, leading to catastrophic consequences in old age. The prevalence of osteoporotic fractures progressively increases with age. At present, the cumulative frequency of hip fractures in women over 80 is about 30%. The proportion of vertebral fractures in women older than 80 years is up to 40% of all vertebral osteoporotic fractures. Despite the tremendous successes achieved in the diagnosis and treatment of osteoporosis, the disease itself and related fractures remain a serious medical, economic and social problem. Prevention of recurrent fractures in geriatric patients is a system of preventive, rehabilitative and therapeutic measures aimed at reducing the risk of falls, choosing an effective therapy, and reducing the risk of recurring fractures. A serious problem in the treatment of osteoporosis in older people is the inefficiency of the antiresorptive therapy due to an age-related decrease in bone formation. There are frequent cases of a continuing decrease in bone density, the occurrence of repeated fractures during ongoing therapy of osteoporosis. Often the therapy of choice in this case is bone-anabolic therapy with teriparatide, which allows one to achieve good results in the accumulation of bone mineral density. In this article, we will present the clinical case of an elderly patient with severe osteoporosis, in which teriparatide became the drug of choice.

Obesity and metabolism. 2019;16(4):80-89
Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review)
Shifman B.M., Dzeranova L.K., Pigarova E.A., Tiulpakov A.N., Fedorova N.S.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of the adrenal cortex characterized by impairment of cortisol biosynthesis (with possible impairment of aldosterone biosynthesis) and excessive pituitary ACTH release, which promotes oversecretion of intact pathways products: 17-hydroxyprogesterone (17OHP), progesterone, and adrenal androgens – androstendione and testosterone. 21-hydroxylase deficiency, being the most common cause of congenital adrenal hyperplasia is a chronic disorder, that requires life-long glucocorticoid treatment, that aims both to replace cortisol and prevent ACTH-driven androgen excess. Nevertheless, reaching the optimal glucocorticoid dose is challenging because currently available glucocorticoid formulations cannot replicate the physiological circadian rhythm of cortisol secretion. The difficulties in striking the balance between uneffective normalizing of ACTH-level and excess glucocorticoid exposure leads to different abnormalities, that starts to develop at first months of life and progress, frequently gaining especial clinical meaning in adult age. In the present clinical case we introduce 35 years old male patient with salt-wasting form of 21-hydroxylase deficiency, which had either complications considered to progress due to insufficient glucocorticoid therapy, and some metabolic abnormalities, associated with supraphysiological doses of glucocorticoids.

Obesity and metabolism. 2019;16(4):90-102

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