Vol 15, No 4 (2018)

Advantages and disadvantages of different methods for diagnosis of visceral obesity
Brel N.K., Kokov A.N., Gruzdeva O.V.

This analytical review is devoted to the study of visceral obesity as a risk factor for the development and progression of cardiovascular diseases. The presented review discusses the evolution of methods for diagnosis of visceral obesity, their advantages and limitation for various ectopic fat depots.

Obesity and metabolism. 2018;15(4):3-8
Metabolic aspects of the relationship of asthma and obesity
Kytikova O.Y., Antonyuk M.V., Gvozdenko T.A., Novgorodtseva T.Р.

Asthma and obesity are serious medical and social world problems, and their combined course is characterized by a decrease in the quality of life, an increase in the frequency and duration of hospitalization. The present review summarizes the current views on the mechanisms of formation of asthma phenotype combined with obesity, role of leptin and adiponectin imbalance in the development of systemic inflammation in obesity in the pathophysiology of asthma, it’s interrelations with metabolic syndrome. We present data that shows that syndrome is closely related not only to the debut of asthma, but also to a decrease in its control. Along with obesity, the role of other components of metabolic syndrome, in particular insulin resistance, as a predictor of asthma development is considered. Insulin resistance may be the most likely factor in the relationship between asthma and obesity, independent of other components of the metabolic syndrome. Insulin resistance associated with obesity can lead to disruption of nitric oxide synthesis. We reveal common mechanism of metabolic disorders of nitric oxide and arginine in metabolic syndrome and asthma and show that insulin resistance treatment can be therapeutically useful in patients with asthma in combination with obesity.

Obesity and metabolism. 2018;15(4):9-14
Original paper
Influence of exogenous melatonin on the oxidative status and the state of peroxidation of proteins in a rat model of alimentary obesity
Davydov V.V., Medvedev D.V., Shodiev D.R., Nekrasova M.S.

Not only lipids, but also proteins are exposed to the action of reactive oxygen species (ROS). Oxidative modification of proteins (PBS) leads to a change in their native conformation with the formation of large aggregates, it causes inactivation of enzymes, disrupts the metabolism and functioning of cells. In addition, there is a growing interest in studying the hormone of the pineal gland called melatonin, as well as its synthetic analogues as the leading protection factors in the oxidative stress conditioned by disturbed physiological rhythms, including obesity. The peculiarities of protein peroxidation in the case of alimentary obesity, as well as the conditions affecting to this process, in contrast to lipid peroxidation (LPO), have not been studied sufficiently, that has determined the purpose of this study.

Aim. To evaluate the effect of exogenous melatonin on the oxidative status and features of PBS in rats with alimentary obesity.

Methods. The study was conducted on 27 white Wistar male rats with body weight 160–180 grams. Animals were divided into 3 series of 9 rats in each: 1 series – intact animals; 2 series – animals with alimentary obesity, followed by the introduction of 0,9% sodium chloride solution in a volume of 2 ml for 12 days; 3 series – animals with alimentary obesity followed by melatonin administration at a dose of 2 mg / kg rats for 12 days. Alimentary obesity was reproduced by feeding animals with high-calorie carbohydrate-fatty food, consisting of a laboratory feed "Assortment Agro" (42.5%), butter (25%) and sweet condensed milk (32.5%) for seven weeks. The maximum physical working capacity and resistance of rats to severe hypobaric hypoxia were determined. PBS was determined by the method of R. Levine in the modification of E.E. Dubinina. In addition, the lipid peroxidation marker – TBA-reactive products (malonic dialdehyde MDA) was determined.

Results. It has been established that the PBS in alimentary obesity is not specific, it is reflected in the increase in the areas of absorption of light from both the visible and ultraviolet of aldehyde and ketondinitrophenylhydrazones. In parallel with this, there was a marked increase in the concentration of TBA-reactive products in the blood serum in this pathology, as well as a significant decrease in the resistance of rats to hypobaric hypoxic hypoxia and maximum physical activity. The daily administration of a 2 mg/kg melatonin suspension to rats with alimentary obesity for 12 days leads to a significant decrease in the concentration of TBA-reactive products, however, the PBS is not significantly affected.

Conclusion. Alimentary obesity in rats, simulated by the maintenance of animals on a high-calorie carbohydrate-fat diet, leads to an increase in the proportion of visceral fat in the body, an increase in the activity of PBS in the form of an increase in the level of carbonyl derivatives, a significant increase in the concentration of MDA, and a significant decrease in the stability of rats to hypobaric hypoxic hypoxia and maximum physical activity. When a melatonin suspension was administered at a dose of 2 mg/kg for 12 days, a stable high level of carbonyl derivatives was observed, in comparison with the intact series, which was explained by the need to use a greater concentration of the drug to increase its exposure time, which requires further study.

Obesity and metabolism. 2018;15(4):15-21
Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity
Tikhonenko E.V., Babenko A.Y., Shlyakhto E.V.

Background: Type 2 diabetes mellitus (DM2), which mainly develops from visceral obesity, is a socially significant disease. Reduction of losses from DM2 is a priority in modern medicine development. Glucagon-like peptide-1 receptor agonists (aGLP-1) present one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight in DM2. Taking into account predictors of response to the therapy will allow to reach trearment targets with the highest probability, maintaining a safety of treatment, to optimize recommendations for administration of aGPP-1 as much as possible.

Aims: To assess dynamics of metabolic parameters, to identify predictors of reduction in blood glucose, body weight and other metabolic parameters on aGLP-1 therapy in patients with DM2 with body mass index (BMI) ≥35 kg/m2.

Materials and methods: The study involved 33 patients (10 men, 23 women), who had been treated with aGLP-1, the observation period for 24 weeks was planned. 3 patients terminated the participation before the appointed time (1 – due to pancreatitis development 2 – due to the lack of financial opportunity to purchase the drug). So, 30 patients (10 men, 20 women) were included in the final analysis. Examination consisted of the survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated at baseline and after 24 weeks of treatment.

Results: The study found that patients who achieved weight loss ≥ 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after standard breakfast test (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had a mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1c was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, we revealed the statistically significant decrease in triglycerides level, blood pressure by end of the treatment period.

Conclusions: Results indicate the different predictors for reduction in weight, glycemia and blood pressure on aGLP-1 therapy. In addition to the metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics of patients help to estimate an expected effect of aGLP-1 therapy. When being identifying, the predictors of weight loss and the predictors of carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for this group of drugs administration in DM2.

Obesity and metabolism. 2018;15(4):22-30
Тhe prevalence of metabolically healthy obesity: data from the epidemiological survey in of Novosibirsk
Mustafina S.V., Shcherbakova L.V., Kozupeeva D.A., Malyutina S.K., Ragino Y.I., Rymar O.D.

Background: Obesity is associated with numerous metabolic complications, such as type 2 diabetes mellitus (DM2), dyslipidemia, arterial hypertension (AH), cardiovascular diseases and some forms of cancer. Nevertheless, the literature describes a group of obese individuals who are more resistant to the development of metabolic disorders. At present, this phenomenon is known as "Metabolically healthy obesity", "metabolically healthy obesity" (MZO). Despite the presence of excess weight or obesity, a favorable metabolic profile can be observed in this cohort of patients, characterized by preserved insulin sensitivity, absence of arterial hypertension, normal lipid, hormonal profile, absence of inflammation and unchanged hepatic transaminases.

Aims: To study the prevalence of metabolically healthy obesity (MHO) and its characteristics in men and women at the age of 45–69 years in Novosibirsk.

Materials and methods: To study covered 3197 persons from the base of the international project HAPPIE. They had a body mass index (BMI ≥ 30 kg/m²). «Metabolically healthy obesity» was determined as obesity (BMI ≥ 30 kg/m², with 2 and fewer components of metabolic syndrome (MS) by criteria NCEP ATP III, 2001. Statistical analisys SPSS-13.

Results: The prevalence of metabolic healthy obesity (MHO) was 42% (38% for men and 43% for women). The examined people with MHO have reliably more favorable average level of TG, HDL-cholesterol, indicators of blood glucose, systolic arterial pressure and diastolic arterial pressure and less waist circumference. In the groups withMHO and MS abdominal obesity is common in men at 95 and 71%, in women at 99 and 90%; hyperTG – in men at 74 and 9%, in women at 72 and 5,5%; lower level HDL-cholesterol in 16 and 1% for men, and in 44,5% and 3% for women; AP in 96 and 77% and 94 and 71% in men and women respectively, the frequency fasting of hyperglycaemia 77 and 21% in men and 60 and 5% in women was markedly different. According to the data obtained by us, the frequency in the sample is high and amounted to 42%. In the subgroup the most commonly found is the MHO phenotype – 53%, than in the men -38%, р <0,001

Conclusions: According to our data, the frequency of metabolic healthy obesity in the sample is high and amounted to 42%. In the female subgroup, a metabolically healthy phenotype is more common 43% than in the male 38%, p <0.001. Metabolically healthy obese individuals are characterized by a significantly lower incidence of fasting hyperglycaemia and dyslipidemia.

Obesity and metabolism. 2018;15(4):31-37
The spermatogenesis and antioxidative activity of an ejaculate in young men with post pubertal visceral obesity and normal andrological anamnesis
Rozhivanov R.V., Kurbatov D.G.

Background: Taking into account a common development of a visceral obesity at men, research of its influence on a spermatogenesis and antioxidative activity of an ejaculate is actual.

Aims: Assessments of spermatogenesis and antioxidative activity of ejaculate in young men with post pubertal visceral obesity and normal andrological anamnesis in comparing with healthy men.

Materials and methods: 80 men with post pubertal and nutritional visceral obesity in the age of until 30 years and 30 healthy men have been included in cross-section research. The assessments of waist circumference, levels of gonadotropins and total testosteron, antioxidant activity of an ejaculate, its electronic-microscopic examination was carried spent. Statistically significant counted differences between groups at p <0.05.

Results: In young men with post pubertal visceral obesity and normal andrological anamnesis the spermatogenesis was significantly worse in comparing with healthy men. These differences were were significant for waist circumference more more then 98 cm. Antioxidative activity of ejaculate in men with visceral obesity also was significantly lower in comparing with healthy men. The maximal expressiveness of sperm pathogenetic disorders was in men with waist circumference more then 102 cm.

Conclusions: In young men with post pubertal visceral obesity and normal andrological anamnesis the spermatogenesis is worse compared to healthy men. If the waist circumference less than 102 cm, the spermatogenesis is normal in most cases, but antioxidant activity of an ejaculate is pathological and mediated through oxidative stress.

Obesity and metabolism. 2018;15(4):38-43
Evaluation of relationship between obesity and asthma severity
Rabieepour M., Seyed Mokhtari S., Mamizadeh H.

Background: The prevalence of both obesity and asthma has risen in recent years. We sought to investigate whether obesity may be related to asthma.

Materials and methods: In this analytical study, 177 patients with asthma were enrolled. Obesity was defined as a body mass index (BMI) greater than 30. Asthma severity was defined by using the National Heart Lung and Blood Institute 1997 guidelines.

Results: Of the 177 patients, there were 80 males and 97 females. 38.4 percent of the sample was obese. There is no significant relationship between BMI and asthma severity (P=0.76) but as established by Pearson’s correlation coefficient a positive and significant correlation is present between BMI and FEV1/FVC values (r=0.32 & P=0.0001). Females with asthma were significantly more overweight than males (p = 0.001).

Conclusions: In our study, there was a significant correlation between body mass index and sex of patients with asthma. Women had the highest percentages of asthma compared to men, and had a higher body mass index than men.

Obesity and metabolism. 2018;15(4):44-47
Rational approach to patients treatment with type 2 diabetes and obesity: results of the All-Russian observational program «AURORA»
Dedov I.I., Romantsova T.I., Shestakova M.V.

Background: As in many other developed nations, the problem of obesity and type 2 diabetes is acute in Russia. In Russia, the only combination of sibutramine and metformine (Reduxin®Met) is authorized to reduce body mass and prevention development of type 2 diabetes mellitus or its complication. The article presents the results of the observational program “AVRORA”.

Aim: Evaluation of the effectiveness and safety of Reduxin®Met (sibutramine + microcrystalline cellulose + Metformin) in patients with type 2 diabetes and alimentary obesity in routine clinical practice.

Materials & methods: The observational program “AVRORA” was conducted from September 2016 to October 2017 under the auspices of the Endocrinological Scientific Center and the Russian Association of Endocrinologists. The “AVRORA” program was a multicenter, non-interventional study of patients to whom the attending physicians prescribed Reduxin®Met, a set (tablets + capsules), in accordance with the instruction for medical use as part of routine clinical practice. The treated group included patients of both sexes, aged 18–65 years, with an established diagnosis of obesity in combination with type 2 diabetes. The duration of the drug usage was determined by the attending physician and was up to 6 months. Reduxine®Met was prescribed in addition to the existing glucose-lowering therapy, the dose of metformin was adjusted to the patient's needs.

Results: The “AVRORA” study was attended by 259 doctors and 5,812 patients in 240 medical institutions from 12 cities of the Russian Federation. The average age of patients was 46.6 ± 10.5 years, the ratio of male / female -24% / 76%. The decreasing of BMI during 6 months of the therapy amounted to 5.4 ± 2.3 kg / m2 (on average, 15.1 ± 6.4 kg). After 3 months of the therapy 81.6% of patients achieved clinically significant weight loss of 10.6% or more. The average decrease in waist circumference during 6 months of therapy was 13.8 ± 7.4 cm. A decrease of indicators of glycemic control and lipid metabolism right up to the target values was observed.

Conclusions: In “AVRORA” study it was shown that addition of Reduxine®Met (sibutramine+ microcrystalline cellulose+metformine) to the complex therapy of the diabetes in combination with obesity according to approved indications is safe and effective for long-term treatment in regards to weight loss, regulation of lipemic index, glucose profile and quality of life.

Obesity and metabolism. 2018;15(4):48-58
Hormonal regulation of menstrual function in patients of reproductive age with acromegaly
Vorotnikova S.Y., Dzeranova L.K., Stanoevich I.V., Pigarova E.A., Andreeva E.N., Nikankina L.V., Masenko V.P.

Background: The frequency of menstrual disorders in patients with acromegaly is 40–84% and are caused by three main reasons – the development of normal or hypogonadotropic hypogonadism due to hyperprolactinemia or a mass effect of the tumor and direct effects of GH and IGF-1 on the reproductive system. Nevertheless the exact mechanisms of reproductive dysfunction are not clear now. Hypothalamic structures play significant role in the regulation of hypothalamic-pituitary-ovary axis, so it’s important to study key neuropeptides and evaluate their effects to the pathogenesis of ovarian dysfunction during excessive secretion of growth hormone.

Aim: The aim of the work is to study the hormonal regulation of menstrual function in patients of reproductive age with acromegaly in the active stage of the disease.

Material and methods: The study included patients with a confirmed diagnosis of acromegaly and healthy women, comparable in age and BMI. Blood serum samples were taken in the morning (8–9 hours) on an empty stomach for 3–5 days of the menstrual cycle or on any day with amenorrhea and frozen at -70°C. The hormonal study was carried out by an enzyme immunoassay, in the case of a kisspeptin, with the preliminary extraction of serum samples.

Results: The study included 31 patients with acromegaly and 15 healthy women. Between groups there was a statistically significant decrease in levels of LH (p = 0.001), FSH (p = 0.09), inhibin B (p = 0.003), and kisspeptin (p = 0.00005). The frequency of hyperprolactinemia in the cohort of patients was 51.6%. During the correlation analysis, a negative dependence of kisspeptin on the levels of GH and IGF-1 was detected (r = -0.54, p = 0.002 and r = -0.63, p = 0.0002).

Conclusions: The severity of the central depression of regulation of menstrual function in patients with acromegaly may be due to the degree of disease activity.

Obesity and metabolism. 2018;15(4):59-64
Cognitive function and metabolic features in male Sprague-Dawley rats receiving high-fat and low-calorie diets
Shestakova E.A., Stavrovskaya A.V., Gushchina A.S., Yamshikova N.G., Olshansky A.S.

Background: Obesity is a risk factor for cognitive disorders. However, it is still unknown whether low-calorie diet will improve cognitive function in obese patients.

Aim: To evaluate cognitive function and metabolic features in male Sprague-Dawley rats receiving high-fat and low-calorie diets.

Materials and methods: The work was carried out on Sprague Dawley male rats (n = 32), which were divided into 2 groups with 16 animals in each group: Control (normal / low-calorie diet) and Obesity (high-fat diet). In 90 days the rats of the Control group were transferred to a low-calorie diet, the rats of the Obesity group continued to receive high-fat diet. To assess motor activity and cognitive functions at the end of the study (180 days), following behavioral tests were conducted: "open field", "tapering beam", "elevated plus-maze" (EPM) and "passive avoidance reaction". During the study glucose tolerance test were performed: at baseline (GTT 1) and in 30 days (GTT 2).

Results: Obesity group rats gained weight significantly faster than the control animals (547.69 ± 11.32 g against 442.8 ± 19.8 g at study end, p = 0.0001). GTT 2 showed normal carbohydrate metabolism in control group, postprandial hyperglycemia in obesity group. Testing in the open field showed that the rats of the obesity group moved more actively across the installation area than the control ones: the total distance covered was 9.352 ± 0.932 m against 6.781 ± 0.951 m, p = 0.046.

The results of a tapering beam test showed that the number of hind limb extrusions in obese rats significantly exceeded this parameter in control group (33.7 ± 3 vs. 15.7 ± 2.7, p = 0.0001), test time in both groups did not differ.

When testing in EPM, there was no significant difference in any of the key test parameters between the groups. However, the number of looking out from the closed arms in animals of the obesity group was significantly higher than in the control group (4.19 ± 0.6 vs. 2.30 ± 0.58, p = 0.044). When testing the reproduction of conditional reactions of passive avoidance it was shown that after day 1 of the pain stimulation application the latent period of transition to the dark compartment in the obesity group was significantly higher than that of the control group (180.0 ± 0.0 vs. 128 86 ± 21.45, p = 0.008). This indicates a better preservation of the memorial trail compared to the "control" rats. By the end of the study 30% of animals in the control group died.

Conclusions: Rats on high-fat diet were more active, less anxious and showed better results in training tests comparing to animals on low-calorie diet. Adherence to low-calorie diet may be harmful for cognitive functions.

Obesity and metabolism. 2018;15(4):65-73
Chronic hypoparathyroidism in adults: clinical features, diagnosis, management and treatment
Mokrysheva N.G., Eremkina A.K., Kovaleva E.V.

Hypoparathyroidism is a rare сalcium and phosphate metabolic disorder. Most often it develops after neck surgery. The recent studies show increased morbidity in thyroid and parathyroid pathology wich are the most common causes of hypoparathyroidism. Thus makes this problem more relevant and urgent. Management of a patient with chronic hypoparathyroidism is based on personalized treatment regimen, disease monitoring and prevention of therapy adverse events.

Obesity and metabolism. 2018;15(4):74-82

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