2015: Supplement 1

Background: Obesity is characterized by an increased risk of diabetes mellitus, coronary heart disease, arterial hypertension and reproductive system disorders, which makes it necessary to implement multifactorial correction of metabolic disturbances.

Aim: To analyze diet intake structure of patients with obesity, efficacy and safety of sibutramine monotherapy and sibutramine/metformin combination therapy in the formation of adequate nutritional stereotypes and reduction of bodyweight.

Materials and methods: Eighty-two obese women aged 18 to 49 years (mean age 29.7±5.7 years) were included into this observational study. Inclusion criteria: women aged 18 to 49 years, with waist circumference>80 cm, body mass index (BMI)>27 kg/m², triglyceride level>1.7  mmol/L and/or low-density lipoprotein cholesterol>3.8  mmol/L, and/or high-density lipoprotein cholesterol<1.29 mmol/L. Exclusion criteria in this study were presence of severe somatic and endocrine disorders. The control group consisted of 35 healthy women aged 18 to 49 years (mean age 28.7±5.6 years). All patients were recruited within the observational program PrimaVera.

 Results: Analysis of dietary intake in female obese patients showed an excess of daily energy intake of 650±250 kcal compared to that in subjects with normal BMI and normal waist circumference. Seventy one percent of patients had excessive expectations from treatment duration and desired weight loss. For control of their eating behavior, 52 patients were administered Reduxin® (sibutramine+cellulose microcristallic) 10 mg daily. Other 30 patients (24 women with a history of carbohydrate metabolism disturbances during pregnancy and 6 women who had delivered babies with birth weight of above4 kg) were administered Reduxin® 10 mg and metformin 500  mg daily, with weekly dose increase by 500  mg to the final dose of 1500 mg daily. The treatment lasted for 24  weeks. Daily caloric intake decreased by 24±4% from baseline (p<0.05) on monotherapy and by 28±7% from baseline (p<0.05) on combination therapy. Average weight loss comprised -8.9±1.6 kg(p<0.05) under monotherapy and 9.7±1.5 kg(p<0,05) under combination therapy. Reduction in waist circumference amounted to 11.4±1.8 cm(p<0.05) under monotherapy and 14.1±1.5 cm(p<0.05) under combination therapy. Physical activity (data from pedometers) increased by 6.9±1.8 thousand steps (p<0.05) in the monotherapy group and 7.2±2.0 thousand steps (p<0.05) in the combination therapy group. After 24 weeks of treatment 48.3% of females had their libido increased, 35.4% reported an increase in their self-consciousness as a sexual partner. Menstrual cycle was normalized in 83.8% of patients and restoration of ovulation in 75.8%. There were no significant adverse effects with Reduxin® 10 mg monotherapy and its combination with metformin 1500 mg.

Conclusion: Obesity should be considered mostly as a result of imbalanced dietary intake. Treatment with Reduxin® 10 mg and combination therapy with Reduxin® 10 mg and metformin 1500 mg for 6 months resulted in reduction of daily caloric intake, control of eating behavior, target weight loss, reduced abnormalities in reproductive system and sexual problems. The results obtained indicate that 6 months of Reduxin® 10 mg and combination therapy with Reduxin® 10 mg and metformin 1500 mg are effective and safe. 

Background: One of the main pathophysiological features of metabolic syndrome is abdominal obesity which forms the basis of metabolic syndrome associated disorders, such as disorders of carbohydrate metabolism and atherogenic dyslipoproteinemia. Abdominal obesity and metabolic disturbances promote the development of constellation of various disorders, like that of the liver (non-alcoholic fatty disease), biliary tract, heart, as well as pancreas (with formation of steatosis). This makes an obese patient polimorbid and significantly complicates his/hers treatment. Therefore, development of modern and safe approaches to treatment of obesity, with consideration of individual characteristics of metabolic abnormalities, seems to be highly relevant.

 Aim: To assess efficacy and safety of a combined product of sibutramine and microcristallic cellulose (Reduxin®) in patients with alimentary constitutional obesity resistant to medical treatment, as well as to identify factors that influence efficacy of sibutramine in this patient category.

 Materials and methods: Forty patients (25 males and 15 females) with grade II–III obesity resistant to medical treatment participated in the study. Mean age of patients was 36.8 ± 10.4 years. Their clinical and laboratory assessment, beyond standard parameters, included measurement of insulin resistance index, leptin levels, assessment of vasomotor endothelial function, type of eating behavior and gut microflora. Weight reduction program was based on hypocaloric diet, regular physical exercise of moderate intensity and treatment with sibutramine (Reduxin®) 15 mg daily for 6 months. Efficacy of treatment was assessed as reduction of body mass by ≥ 5% from baseline within 3 months of treatment.

Results: After 3 months of treatment, effective reduction of body mass by ≥ 10% was seen in 80% of patients. After 6 months from the study start, 100% of patients achieved and maintained effective reduction of body weight by 10.6 to 20.2% from baseline values. Patients with whom treatment was least effective, had higher insulin resistance index (r = 0.32, p < 0.05), higher leptin levels (r = 0.42, p < 0.05), higher degree of liver steatosis on ultrasound examination (r = 0.38, p < 0.05), higher proportion of patients with emotionally triggered eating behavior (r = 0.29, p < 0.05), as well as more advanced dysbiotic abnormalities of gut microflora (r = 0.27, p < 0.05). To decrease dysbiotic abnormalities of the gut, patients with previous lack of treatment efficacy were administered a prebiotic complex Eubicor®. 24-hour ambulatory blood pressure monitoring and electrocardiographic monitoring before the start of the treatment allowed to avoid significant side effects with daily sibutramine dose of 15 mg. During treatment with sibutramine, the following potentially related side effects were reported: dryness of mouth (6 cases in 15% of patients), episode of tachycardia at rest (2 cases, 5% patients), transient sleep disorder (3 cases, 7.5% patients).

Conclusion: Sibutramine can be considered as an effective and safe agent for comprehensive treatment of patients with alimentary constitutional obesity grade II–III, resistant to previous medical therapy. Addition of the prebiotic complex (Eubicor®) to diet allows for improvement of treatment efficacy in patients taking Reduxin®. 

Background: Due to high prevalence of obesity that has turned into enormous economic and social burden, studies aimed at assessment of damages caused by this medico-social problem are seen as very important in the last years.

 Aim: To assess economic burden of obesity in the Russian Federation taking as an example three main socially significant medical conditions: acute cerebrovascular accident (stroke), acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM).

Materials and methods: We analyzed available evidence on assessment of costs of management and treatment of obese patients and its relation to the disorders selected. To measure costs of obesity for the state budget, we used clinical and economic analysis “cost of illness” with consideration of risks of stroke, AMI and T2DM in the population. Taking into account specific features of cost assessment and based on publically available data, we developed separate models to calculate cost of illness for each selected disease type.

Results: Obesity-related expenses incurred by the state for treatment and management of patients amounted to 10.2 billion rubles for stroke, 7.6 billion rubles for AMI and 346.3 billion rubles for T2DM.

Conclusion: Оbesity is a serious problem causing significant economic and social losses that are increasing.

Background: Prevalence of type 2 diabetes mellitus (T2DM) has reached an epidemic level worldwide and continues to increase steadily.

Aim: To assess appropriateness of FINDRISC questionnaire to identify groups with high risk of T2DM in the population of theMoscowregion.

Materials and methods: Four hundred and four subjects aged above 18 years in the Lukhovitsy district of theMoscowregion were screened for disturbances of carbohydrate metabolism. All participants filled in the questionnaire of the Finnish Diabetes Association, FINDRISC (the Finnish Diabetes Risk Score). An oral glucose tolerance test was performed in all subjects.

 Results: Prevalence of carbohydrate metabolism disorders in the study sample was 36.1%. Among them, newly diagnosed T2DM was found in 6.1%, impaired glucose tolerance, in 14.4%, impaired fasting glycaemia, in 18.5%, both impaired glucose tolerance and fasting glycaemia, in 5.7%. Detection of T2DM and early disorders of carbohydrate metabolism was higher in subjects with higher FINDRISC scores. The screening model that includes diagnostic assessment of subjects with a score of≥12 of this questionnaire has adequate sensitivity and specificity to detect T2DM. This model allows for reduction of the necessary sample to 37.5%. Prevalence of cardiovascular risk factors is higher in the subjects with a high FINDRISC score, compared to those with the minimal score.

Conclusion: Active implementation of FINDRISC questionnaire among the population of theMoscowregion would allow for timely detection of those with T2DM risk for further screening for disorders of carbohydrate metabolism and introduction of activities to prevent T2DM. 

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disorder associated with obesity and metabolic syndrome. The main pathophysiological factor of liver steatosis is insulin resistance that may lead to development of type 2 diabetes mellitus. Overcoming of insulin resistance by means of body weight reduction and administration of insulin sensitizers is considered to be a promising approach to NAFLD treatment. In accordance with the Russian guidelines on diagnostics and treatment of NAFLD, sibutramine is the drug of choice for medical treatment of obesity. As for insulin sensitizers, metformin (biguanide class) is widely used for treatment of NAFLD in everyday clinical practice. Treatment of NAFLD as a component of metabolic syndrome should be multifactorial and aimed at different aspects of the disease pathophysiology. 

Obesity is a risk factor for the development of cardiovascular disease and type 2 diabetes; nevertheless, in many obese patients no cardiometabolic complications are present. For this group of patients the term “metabolically healthy obesity” (MHO) has been established in 1982. Currently, there is no standardized definition of MHO, and there are large variations in its prevalence rate. The underlying mechanisms of this phenotype are not clear. It has been suggested that preserved insulin sensitivity, as well as high levels of physical activity and genetic predisposition may differentiate metabolically healthy from unhealthy obese adults. Low grade inflammation in the adipose tissue is considered to be a crucial factor for the pathogenesis of metabolic diseases. Compared to the metabolically unhealthy obese phenotype, MHO is characterized by a more favorable inflammatory profile in adipose tissue, less visceral fat, less macrophagal infiltration of adipose tissue, smaller adipocyte cell size. The question remains of stability of the MHO phenotype. The aim of this review is to discuss the current literature data concerning characteristics of MHO phenotype, definitions, prevalence and potential protective mechanisms underlying MHO. We also discuss clinical implications of MHO phenotype.

Aim: To assess interim results of the Russian observational program PrimaVera on efficacy and safety sibutramine (Reduxin®) for treatment of obesity within routine medical practice.

 Materials and methods: This multicenter observational program included patients with obesity aged below 65  years, excluding those with uncontrolled arterial hypertension, coronary heart disease, heart failure and cerebrovascular disease. All patients were administered sibutramine for treatment of their obesity. During out-patient follow-up visits, physicians assessed changes in patients’ body mass, blood pressure and heart rate, as well as registered adverse events. Maximal treatment duration was 12 months. In this report, the results from 16  515  patients are analyzed, 82% of whom (n=13 192) were females.

Results: After 3  months of treatment body mass index (BMI) decreased by 2.81±1.0  kg/m², after 6 months, by 5.17±2.15 kg/m². At 12 months decrease in BMI was 1.3-fold higher compared to 6  months’ results and amounted to 6.76±2.93  kg/m². Reduction of body mass with longterm (above 6  months) treatment with sibutramine under supervision of a physician was associated with a decrease in systolic and diastolic blood pressure levels (by 4.1 mm Hg, in both cases) and did not lead to an increase in heart rate (Δ=-1.02  bpm). Based on data from 16  515  medical records processed up to now, 397  episodes of adverse events were registered, with none of them being serious.

Conclusion: This interim results of the program PrimaVera confirmed favorable safety profile of Reduxin® and its high efficacy in the treatment of obesity.