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Aims To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB). Materials and methods This was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale. Results Mean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP. Conclusion The elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.

Liraglutide is marketed in Europe as Victoza® (1.2 mg/1.8 mg), indicated for glycaemic control in type 2 diabetes, and Saxenda® (3.0 mg), indicated for weight management in adults with obesity. We performed a post-authorization safety study (PASS) to assess the in-market use of Saxenda® and Victoza® according to approved indications and posology.This retrospective, non-interventional study was conducted at 41 sites between December 2016 and May 2019. Via medical record review, physicians at each site identified patients who had been prescribed Saxenda® (Italy) or Victoza® (Italy/Germany) within the 24 months following launch in each country. Pseudonymized data were abstracted on patient and site characteristics, indication for the prescription, posology and duration of usage. Adherence to the approved indications and posology, and to the Saxenda® stopping rule, were assessed. No formal statistical analysis was performed.A total of 440 patients were pre-screened and 225 (51.1%) were enrolled (Saxenda®: N=75, all in Italy; Victoza®: N=75 in Italy; N=75 in Germany). In all, 96% (72/75) of Saxenda® prescriptions, and 98.7% (148/150) of Victoza®, were in accordance with the approved indications. Among the 40 patients treated with Saxenda® for ≥16 weeks, only two (5.0%) were confirmed as non-adherent to the stopping rule. Adherence could not be assessed in 23 (57.5%) patients owing to missing body weight measurements.This retrospective, real-world PASS provides reassurance that Saxenda® and Victoza® are primarily used according to the approved European label, thus their real-world utilization does not raise safety concerns.gov identifier: NCT02967757. This article is protected by copyright. All rights reserved.

Muath Alobaida,1,* Abdullah Alrumayh,1,* Ayodipupo S Oguntade,2 Faez Al-Amodi,3 Mwango Bwalya3 1Department of Basic Sciences, Prince Sultan bin Abdulaziz College for Emergency Medical Services, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Nuffield Department of Population Health, University of Oxford, Oxford, UK; 3Institute of Cardiovascular Science, University College London, London, UK*These authors contributed equally to this workCorrespondence: Muath Alobaida; Abdullah AlrumayhDepartment of Basic Science, Prince Sultan bin Abdulaziz College for Emergency Medical Services, King Saud University, Riyadh, Kingdom of Saudi ArabiaEmail malobaida1@ksu.edu.sa; aalrumayh@ksu.edu.saAbstract: Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.Keywords: anti-obesity medication, cardiovascular diseases, cardiovascular outcome trials, type 2 diabetes mellitus, obesity, obesity therapy

The pandemic spread of obesity and type 2 diabetes is a serious health problem that cannot be contained with common therapies. At present, the most effective therapeutic tool is metabolic surgery, which substantially modifies the gastrointestinal anatomical structure. This review reflects the state of the art research in obesity and type 2 diabetes, describing the probable reason for their spread, how the various brain sectors are involved (with particular emphasis on the role of the vagal system controlling different digestive functions), and the possible mechanisms for the effectiveness of bariatric surgery. According to the writer’s interpretation, the identification of drugs that can modulate the activity of some receptor subunits of the vagal neurons and energy-controlling structures of the central nervous system (CNS), and/or specific physical treatment of cortical areas, could reproduce, non-surgically, the positive effects of metabolic surgery.

Several randomized controlled clinical trials (RCCTs) have shown that the use of Liraglutide (L) in addition to diet and exercise in patients with obesity or overweight (OO), compared to dietary behavioral changes alone, leads to a significantly greater weight loss. This retrospective study aimed at evaluating the effectiveness of L therapy in a real-life setting. 93 consecutive non-diabetic OO, referring to a single Obesity Center, started L therapy from October 2016 to December 2018: 21/93 OO discontinued the treatment within 90 days for various reasons. 72/93 OO (55 females, 17 males), mean ± SD age 49 ± 12.5 years (18–78) and mean body mass index 39.1 ± 5.8 (28.3–55.3) were included for further analysis. 60/72 OO reached the final dose of 3.0 mg/day. Mean weight loss was 7.1% in the OO who reached the dose of 3.0 mg; 68.3%, 20.0% and 10.0% of OO lost ≥ 5%, 10% and 15% of body weight, respectively. A linear correlation between early and final weight loss was found. Moreover, we observed a significant reduction of mean systolic and diastolic blood pressure and a significant increase of mean heart rate. The overall incidence of side effects was 18.3% (17/93). L treatment of OO in a real life setting yielded results comparable to those reported by the major RCCTs. Combining the results of RCCTs with the observations from real life may increase their power and overcome their respective limitations.

Aim To evaluate the safety of efpeglenatide, a long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), and its effects on body weight management in adults without diabetes. Materials and methods In this phase II, randomized, placebo‐controlled, double‐blind trial, participants with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with comorbidity were randomized 1:1:1:1:1 to efpeglenatide (4 mg once weekly, 6 mg once weekly, 6 mg once every 2 wk, or 8 mg once every 2 wk; n = 237) or placebo (n = 60) in combination with a hypocaloric diet. The primary endpoint was body weight change from baseline after 20 wk of treatment, assessed using a mixed‐effect model with repeated measures with an unstructured covariance matrix over all post‐screening visits; treatment comparisons were based on least squares mean estimates. Results Over 20 wk, all doses of efpeglenatide significantly reduced body weight from baseline versus placebo (P < 0.0001), with placebo‐adjusted reductions ranging between −6.3 kg (6 mg once every 2 wk) and −7.2 kg (6 mg once weekly). Greater proportions of efpeglenatide‐treated participants had body weight loss of ≥5% or ≥10% versus placebo (P < 0.01, all comparisons). Efpeglenatide led to significant improvements in glycaemic variables (fasting plasma glucose and glycated haemoglobin) and lipid profiles (cholesterol, triglycerides) versus placebo. Rates of study discontinuations as a result of adverse events ranged from 5% to 19% with efpeglenatide. Gastrointestinal effects were the most common treatment‐emergent adverse events. Conclusions Efpeglenatide once weekly and once every 2 wk led to significant body weight reduction and improved glycaemic and lipid variables versus placebo. It was also well tolerated for weight management in adults without diabetes.

Aims Enteropeptidase is a serine protease localized on the duodenal brush border that catalyzes the conversion of inactive trypsinogen into active trypsin, thereby regulating protein breakdown in the gut. We evaluated the effects of SCO‐792, a novel enteropeptidase inhibitor, in mice. Materials and methods In vivo inhibition of enteropeptidase was evaluated via an oral protein challenge. Pharmacological effects were evaluated in normal mice, in diet‐induced obese (DIO) mice and in obese and diabetic ob/ob mice. Results A single oral administration of SCO‐792 inhibited plasma branched‐chain amino acids (BCAAs) in an oral protein challenge test in mice, indicating in vivo inhibition of enteropeptidase. Repeated treatment with SCO‐792 induced reduction in food intake and decrease in body weight in DIO and ob/ob mice. Plasma FGF21 levels were increased in SCO‐792‐treated DIO mice, an observation that was probably independent of reduction in food intake. Hyperglycaemia was markedly improved in SCO‐792‐treated ob/ob mice. A hyperinsulinaemic‐euglycaemic clamp study revealed improved muscle insulin sensitivity in SCO‐792‐treated ob/ob mice. SCO‐792 also improved plasma and liver lipid profiles and decreased plasma alanine transaminase, suggesting a potential treatment for liver diseases. Dietary supplementation with essential amino acids attenuated the effect of SCO‐792 on reduction in food intake and decrease in body weight in normal mice, suggesting a pivotal role for enteropeptidase in these biological phenomena. Conclusions SCO‐792 inhibited enteropeptidase in vivo, reduced food intake, decreased body weight, increased insulin sensitivity, improved glucose and lipid control, and ameliorated liver parameters in mouse models with obesity and/or diabetes. SCO‐792 may exhibit similar effects in patients.

(1) Background/aims: Intragastric botulinum toxin A injection (IGBI) combined with diet control is a new and effective weight loss method for grade 2 obese patients. However, the application of IGIB on overweight or obese adults still needs further research to confirm its efficacy. (2) Methods: We retrospectively collected medical data from 1 July 2021 to 1 January 2022 from a total of 71 patients without diabetes who participated in the bariatric clinic with a body mass index (BMI) > 25 kg/m2. Forty-nine participants opted for intragastric botulinum injection (IGBI) using 300 units of botulinum injected into the antrum, body, and fundus, followed with a low-calorie high-protein diet course. Another 22 people participated only in the low-calorie high-protein diet course as a placebo group. This study analyzes the weight loss percentage of the two groups. Adverse events after IGBI are also reported in a safety assessment. (3) Results: In terms of the characteristics of the two groups, the mean BMI was 29.3 kg/m2 in the IGBI group and 28.0 kg/m in the placebo group (p = 0.63 without significant difference). Comparing the percent weight loss from baseline in the two groups after 12 weeks, the IGBI group lost 11.5% of their body weight and the placebo group lost 1.8%. In terms of group analysis, the percentages of participants with a weight reduction of at least 5% for the IGBI and placebo groups were 95% and 4%, respectively. For weight reduction of at least 10%, these values for the IGBI and placebo groups were 63% and 4%, respectively. In terms of adverse events after IGBI for 12 weeks, 12 participants (24.4%) had constipation, which was the main side effect. No serious adverse events were observed during the study period. (4) Conclusion: The combination of a low-calorie high-protein diet and IGBI is an effective and safe procedure in overweight or obese adults for weight reduction, but further larger studies are needed.

Background A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alstrom syndrome. Here, we present the study design of an ongoing, randomized, double-blind, placebo-controlled, phase 3 trial to assess the long-term efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS or Alstrom syndrome ( ClinicalTrials.gov identifier: NCT03746522). Methods It was initially planned that ~30 participants aged ≥6 years with a clinical diagnosis of BBS or Alstrom syndrome would be enrolled. Participants with obesity as defined by a body mass index ≥30 kg/m2 (in those aged ≥16 years) or a weight >97th percentile (in those aged 6–15 years) are included. Participants are initially randomized in a 1:1 ratio to receive setmelanotide or placebo for 14 weeks (period 1). Following period 1, all participants receive 38 weeks of open-label treatment with setmelanotide (period 2). In each treatment period, setmelanotide is administered at 3 mg once a day following completion of dose escalation. The primary endpoint is the proportion of participants aged ≥12 years achieving a clinically meaningful reduction from baseline (≥10%) in body weight after ~52 weeks (eg, following period 2). Safety and tolerability are assessed by frequency of adverse events. Conclusions This pivotal trial is designed to evaluate the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS and Alstrom syndrome. Submission category Study Design, Statistical Design, Study Protocols.

Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.

Aims: \ud Models are needed to quantify the economic implications of obesity in relation to health outcomes and health-related quality of life. This report presents the structure of the Core Obesity Model (COM) and compare its predictions with the UK clinical practice data.\ud \ud Materials and methods: \ud The COM is a Markov, closed-cohort model, which expands on earlier obesity models by including prediabetes as a risk factor for type 2 diabetes (T2D), and sleep apnea and cancer as health outcomes. Selected outcomes predicted by the COM were compared with observed event rates from the Clinical Practice Research Datalink-Hospital Episode Statistics (CPRD-HES) study. The importance of baseline prediabetes prevalence, a factor not taken into account in previous economic models of obesity, was tested in a scenario analysis using data from the 2011 Health Survey of England.\ud \ud Results: \ud Cardiovascular (CV) event rates predicted by the COM were well matched with those in the CPRD-HES study (7.8–8.5 per 1000 patient-years across BMI groups) in both base case and scenario analyses (8.0–9.4 and 8.6–9.9, respectively). Rates of T2D were underpredicted in the base case (1.0–7.6 vs. 2.1–22.7) but increased to match those observed in CPRD-HES for some BMI groups when a prospectively collected prediabetes prevalence was used (2.7–13.1). Mortality rates in the CPRD-HES were consistently higher than the COM predictions, especially in higher BMI groups.\ud \ud Conclusions: \ud The COM predicts the occurrence of CV events and T2D with a good degree of accuracy, particularly when prediabetes is included in the model, indicating the importance of considering this risk factor in economic models of obesity.

‘Imperial Satiety Protocol’ (I-SatPro) is a new multifaceted approach to weight loss for people with obesity (PwO), encompassing dietary advice, time-restricted eating, physical activity and coaching to support behaviour change. Participants (n = 84) attended fortnightly I-SatPro group sessions for 30 weeks, with 70% of participants completing. On completion at 30 weeks, the mean weight loss was 15.2 ± 1.1 kg (13.2 ± 0.8% from baseline, P

AIM To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

ubheadings – aims The nasal application of human insulin is frequently used for investigating brain insulin action. It is utilized in studies on the physiological role of insulin in the human brain as well as in therapeutic interventional trials and its effects have been investigated after both acute and long-term administration. This review aimed to assess the safety of intranasal human insulin in human studies and the temporal stability of nasal insulin sprays. Material and Methods The electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were excerpted. Results Thirty-eight studies on 1092 persons with acute application and 18 studies on 832 persons with treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycemia or severe adverse events were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other adverse events were less commonly reported. There are no reports of subjects who were excluded due to adverse events. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks revealed that it had a chemical stability of up to 57 days. Conclusions Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns. There is, however, insufficient data to ensure long-term safety of this modality of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.

Utkarsh Ojha Faculty of Medicine, Imperial College School of Medicine, Imperial College London, London, UK Abstract: Obesity is a major global health issue. High-protein diets have been shown to be associated with weight loss and satiety. The precise mechanism by which protein-rich diets promote weight loss remains unclear. Evidence suggests amino acids, formed as a consequence of protein digestion, are sensed by specific receptors on L-cells in the gastrointestinal (GI) tract. These L-cells respond by secreting gut hormones that subsequently induce satiety. In recent years, the calcium-sensing receptor has been identified in several cells of the GI tract, including L-cells, and suggested to sense specific amino acids. This review evaluates the evidence for protein-rich diets in inducing weight loss and how the calcium-sensing receptor may be implicated in this phenomenon. Commandeering the mechanisms by which elements of a protein-rich diet suppress appetite may provide another successful avenue for developing anti-obesity drugs. Keywords: amino acids, energy regulation, obesity therapy, glucagon-like-peptide-1, peptide YY

Metformin prevents weight gain in patients with type 2 diabetes (T2D). However, the mechanisms involved are still unknown. In this post hoc analysis of the HOME trial, we aimed to determine whether metformin affects energy intake. Patients with T2D were treated with 850 mg metformin or received placebo added to insulin (1-3 times daily) for 4.3 years. Dietary intake was assessed at baseline, after 1 year and after 4.3 years, according to the dietary history method. Among the 310 included participants, 179 (93 placebo, 86 metformin) completed all 3 dietary assessments. We found no significant difference in energy intake after 4.3 years between the groups (metformin vs placebo: -31.0 kcal/d; 95% CI, -107.4 to 45.4; F-value, 1.3; df = 415; P = .27). Body weight in placebo users increased significantly more than in metformin-users during 4.3 years (4.9 ± 4.9 vs 1.1 ± 5.2 kg; t test: P ≤ .001). Linear mixed models did not show a significant effect of energy intake as explanation for the difference in weight gain between the groups (F-value, 0.1; df = 1; P = .82). In conclusion, the prevention of weight gain by metformin cannot be explained by reduced energy intake.

Aim: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. Materials and Methods: This was a randomised, double-blind, placebo-controlled, two-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardised meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. Results: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin versus placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide versus placebo (incremental area under the curve 0–5 hours [iAUC0-5h]; estimated treatment difference: glucose −1.34 mmol*h/L [−2.42, −0.27]; insulin −921 pmol*h/L [−1461, −381]; C-peptide −1.42 nmol*h/L [−2.33, −0.51]). Fasting and postprandial lipid metabolism improved with semaglutide versus placebo. First-hour gastric emptying after the meal was delayed versus placebo (AUC0-1h; estimated treatment ratio: 0.73 [0.61, 0.87]). Fasting and postprandial lipid metabolism improved with semaglutide versus placebo. First-hour gastric emptying after the meal was delayed versus placebo (AUC0-1h; estimated treatment ratio: 0.73 [0.61, 0.87); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide versus placebo (p=0.0397 and p=0.0097, respectively). Conclusion: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.

Obesity is a complex disease influenced by many neurohormonal pathways that regulate body weight towards homeostasis. Presently, the disease of obesity effects over a billion individuals worldwide, and scalable treatment options are desperately needed. Pharmacologic interventions for obesity have been developed to help promote weight loss in individuals with obesity. This area is rapidly developing, and will only exponentially increase to serve the demand for persons with obesity seeking biologically orientated solutions to treat their disease. Understanding the cardiovascular risks and benefits of these weight loss medications is of particular importance due to obesity’s strong association with cardiovascular (CV) disease risk. Moreover, past experiences with pharmacotherapy agents with weight loss properties have demonstrated an association with adverse CV outcomes, leading to market removal in most cases and concerns over the use of similar medications. To better understand the CV risks and benefits pharmacotherapy agents used for weight loss, this review will discuss medication which are FDA-approved for weight loss, as well as medications commonly used off-label for this indication. The goal is to provide an overview of the risks and benefits many of these medications can offer to help guide clinical decision making and patient education.

In the recent decades, obesity has become one of the major public health issues and is associated with severe other diseases. Although current multidisciplinary therapy approaches already include behavioral therapy techniques, the oftentimes remaining lack of psychotherapeutic support after surgery leads to relapses and renewed weight gain. This paper presents an overview of the project ViTraS - Virtual Reality Therapy by Stimulation of Modulated Body Image - that addresses these challenges by: (i) Developing an integrative model predicting the influential paths of immersive media for an effective behavioral change; (ii) Developing an augmented reality (AR)-mirror system enabling an effective therapy on body self-perception of patients, and (iii) Developing a multi-user virtual reality (VR)-system supplying social support from therapists and other patients. The three components of the ViTraS projects are briefly introduced, as well as a first prototype of the AR-mirror system.

Background The aim of this study was to evaluate the effect of sleeve gastrectomy (SG) and Roux-en-Y-bypass (RYGB) on anthropometric and biochemical parameters, including changes in glucose levels, lipid profile and liver function. Drastic decrease in all lipid fractions a few weeks or months after the surgery could be regarded as favourable, but low level of HDL is an independent risk factor for heart diseases. Extreme load on the liver without preparation of the patient to the surgery can have negative consequences. Methods The test group comprised of 40 female patients at the age of 42.96 with average body weight of 131.56 kg and BMI 46.49. Biochemical analyses were performed using calorimetric method. Results No statistically significant differences were observed in glucose levels between the two types of procedures. The highest differences were noted for triglycerides levels, which decreased, as well as all cholesterol fractions, after RYGB, but were increasing during the first months after SG procedure. Changes in lipid profile, caused by the reduction of all lipid fractions, were more visible after RYGB. The decrease in total cholesterol directly and activity of liver enzymes after the procedure was as higher after RYGB as after SG. Increased activity of transaminases indicates significant liver overload. Conclusions With the selection of groups of patients with similar initial parameters, it is not clear whether the differences between the two procedures when assessing the improvement of glycaemia are significant. However, due to invasive character of RYGB, liver overload lasting several months and lifelong limited absorption of nutrients, the possibility of SG procedure should be considered as a first option.

The efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to diet and exercise, was evaluated in racial subgroups. This post hoc analysis of pooled data from five double-blind randomized, placebo-controlled trials was conducted in 5325 adults with either a body mass index (BMI) ≥27 kg/m(2) plus ≥1 comorbidity or a BMI ≥30 kg/m(2). Statistical interaction tests evaluated possible treatment effect differences between racial subgroups: white (4496, 84.4%), black/African-American (550, 10.3%), Asian (168, 3.2%) and other (111, 2.1%). Effects of liraglutide 3.0 mg on weight loss, associated metabolic effects and safety profile were generally consistent across racial subgroups. All achieved statistically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: white 7.7% versus 2.3%, black/African-American 6.3% versus 1.4%, Asian 6.3% versus 2.5%, other 7.3% versus 0.49%. Treatment effects on weight and cardiovascular risk markers generally showed no dependence on race (interaction test p > 0.05). Adverse events were similar across racial subgroups.

The aim of the study is to assess the weight loss programme with regards to the long-term effectiveness of weight reduction and weight maintenance, using completion rate and BMI, blood sugar, cholesterol and blood pressure levels as outcomes. The aim of the study also includes identifying the factors associated with adherence to the programme.The programme was developed by a multidisciplinary team. It included 6 months of introduction and another 18 months of maintenance. The data for 397 participants was collected after 24 months.346 participants have completed the introduction and 123 have completed the programme. In the introduction, the average weight loss was 12% of the initial weight. The participants, who completed the full programme, lost 9.4% of their initial weight. The participants also significantly (p0.05) reduced their blood sugar and cholesterol levels, as well as their blood pressure. The factors associated with adherence to the programme are: age over 50, lower educational levels, lower initial weight and higher weight loss in the introduction.The multi-disciplinary approach to obesity treatment was effective for a selected group of people. The proportion of dropouts was relatively high, but still low compared to similar programmes. Group treatment and mutual support are of a great importance in bringing about and maintaining the changes.Namen raziskave je bil opredeliti kratkoročno in dolgoročno uspešnost programa glede na vztrajanje v njem, ITM, vrednost krvnega sladkorja, holesterola in krvnega tlaka pri udeležencih, ki so program zaključili. Želeli smo tudi opredeliti dejavnike, ki napovedujejo vztrajanje v programu.V programu sodeluje multidisciplinarni tim strokovnjakov: zdravnik, diplomirana medicinska sestra, fizioterapevt in profesor telesne vadbe. Program ima dva dela: 6-mesečni shujševalni del in 18-mesečni vzdrževalni del. V program se je vključilo 397 udeležencev po nasvetu osebnega zdravnika. Podatke smo ocenili po 24 mesecih.Prvi, shujševalni del programa je zaključilo 346 udeležencev, od tega jih je 123 zaključilo celotni program. V shujševalnem delu je bilo povprečno znižanje teže za 12% začetne teže, pri tistih, ki so zaključili vzdrževalni program, pa za 9,4% začetne teže. Udeležencem se je po dveh letih statistično pomembno (p0,05) znižala vrednost krvnega sladkorja in holesterola, prav tako sta se znižala tudi sistolični in diastolični krvni tlak. Dejavniki, ki so vplivali na daljše vztrajanje v programu, so bili starost nad 50 let, nižja izobrazba, nižja vstopna teža in večja izguba kilogramov v prvem delu programa.Z raziskavo smo želeli dokazati, da je multidisciplinarni pristop zdravljenja debelosti za tiste, ki zaključijo program v celoti, učinkovit. Delež tistih, ki so program zaključili predčasno, je relativno visok, vendar v primerjavi z ostalimi podobnimi programi še vedno nizek. Izkazalo se je, da so pogost stik s strokovnjakom, skupinska obravnava ter podpora ljudem z enakimi težavami izrednega pomena pri spreminjanju in vzdrževanju sprememb.

Adipose tissue (AT) dysfunction contributes to the pathophysiology of insulin resistance and type 2 diabetes. Previous studies have shown that altered AT oxygenation affects adipocyte functionality, but it remains to be elucidated whether altered AT oxygenation is more strongly related to obesity or insulin sensitivity. In the present study, we tested the hypothesis that AT oxygenation is associated with insulin sensitivity rather than adiposity in humans. Thirty-five lean and obese individuals (21 men and 14 women, aged 40-65 years) with either normal or impaired glucose metabolism participated in a cross-sectional single-centre study. We measured abdominal subcutaneous AT oxygenation, body composition and insulin sensitivity. AT oxygenation was higher in obese insulin resistant as compared to obese insulin sensitive (IS) individuals with similar age, body mass index and body fat percentage, both in men and women. No significant differences in AT oxygenation were found between obese IS and lean IS men. Moreover, AT oxygenation was positively associated with insulin resistance (r = 0.465; P = .005), even after adjustment for age, sex and body fat percentage (standardized = 0.479; P = .005). In conclusion, abdominal subcutaneous AT oxygenation is associated with insulin sensitivity both in men and women, independently of adiposity. AT oxygenation may therefore be a promising target to improve insulin sensitivity.

Obesity is a major global health issue. High-protein diets have been shown to be associated with weight loss and satiety. The precise mechanism by which protein-rich diets promote weight loss remains unclear. Evidence suggests amino acids, formed as a consequence of protein digestion, are sensed by specific receptors on L-cells in the gastrointestinal (GI) tract. These L-cells respond by secreting gut hormones that subsequently induce satiety. In recent years, the calcium-sensing receptor has been identified in several cells of the GI tract, including L-cells, and suggested to sense specific amino acids. This review evaluates the evidence for protein-rich diets in inducing weight loss and how the calcium-sensing receptor may be implicated in this phenomenon. Commandeering the mechanisms by which elements of a protein-rich diet suppress appetite may provide another successful avenue for developing anti-obesity drugs.

Resumen: Introducción: El objetivo del estudio es conocer si tener padres obesos influye en la adherencia y el éxito del tratamiento frente a la obesidad en la consulta de endocrinología infantil de un hospital. Material y métodos: Estudio analítico, prospectivo y longitudinal en obesos de 4-14 años. En ellos se determinó el IMC inicial y 6 meses después de que recibieran pautas higiénico-dietéticas saludables. Se consideró éxito significativo la disminución de 0,5 DE del IMC y adherencia que los pacientes acudieran a la revisión semestral. Se calculó el IMC de los padres para identificar a los obesos. Se utilizó el test de la χ2 para comparar las variables cualitativas y el test de la t de Student para las variables cuantitativas (significativo: p 3). Eran obesos 41 padres y 38 madres (el 59% tenía uno o los 2 padres obesos). No se adhirieron al tratamiento 25. La adherencia era peor si los 2 padres eran obesos, OR 3,65 (1,3-10,5) (p = 0,01) y era mejor si la madre no era obesa, aunque el padre lo fuera (p = 0,01). El tratamiento tuvo éxito significativo en 40 pacientes. Si la madre era la única obesa en la familia la posibilidad de no tener éxito era mayor, OR 5,6 (1,4-22,4) (p 3). More than half (59%) of the children had one or both parents obese (41 fathers and 37 mothers were obese). Treatment was not adhered to by 25 children. Adherence was worse if both parents were obese OR 3.65 (1.3 to 10.5) (P

AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood.METHODS: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming. Mice were subsequently challenged with high-fat Western-style diet (WSD) for eight weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of six target tissues were determined in adulthood (PN98).RESULTS: Early life synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in two independent European animal facilities. Adult insulin sensitivity and dyslipidemia were improved and most pronounced gene expression changes were observed in the ileum. We observed subtle changes in fecal microbiota composition, both in early life and in adulthood, including increased Bifidobacterium abundance. Microbiota transplantation using samples collected from synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free recipients did not transfer the beneficial phenotype, indicating that synbiotics-modified microbiota at PN42 is not sufficient to transfer the long-lasting protection of the metabolic health status.CONCLUSION: Together, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as preventive measure to ameliorate obesity risk and improve metabolic health throughout life.

AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Due to concerns over the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc.METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/day deficit diet plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered.RESULTS: In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 versus 2.1 events/100 person-years) and anxiety (1.9 versus 1.7 events/100 person-years) through adverse event reporting were similarly low in the liraglutide group and the placebo group. Nine (0.3%) individuals on liraglutide and two (0.1%) on placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 versus 2.9 ± 3.1 for liraglutide versus placebo improved to 1.8 ± 2.7 versus 1.9 ± 2.7 at treatment end; 34/3291 individuals (1.0%) on liraglutide 3.0 mg versus 19/1843 (1.0%) on placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale.CONCLUSIONS: The results of this exploratory pooled analysis do not provide any cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those individuals included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments.

Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs.

Having good intentions to engage in healthy behaviours, to change our lives in a positive direction and make substantial, lasting changes may not always translate into actions or behaviour that is maintained. Motivational Interviewing is a directive person-centred approach designed to explore ambivalence and activate motivation for change [Miller WR, Rollnick S. Motivational Interviewing: Preparing People to Change Addictive Behaviour. London: Guilford Press, 1991]. A key component of a motivational interviewing conversation is to acknowledge that clients have every right to make no change. It uses a guiding communication style which invites people to consider their own situation and find their own solutions to situations that they identify as problematic that are preventing change. Motivational Interviewing was first introduced in adult health addiction services in the early 1980s. It has developed in the physical health specialties, and in the last 20 years or so attention has turned to the potential of Motivational Interviewing in the paediatric setting and the challenges of using it in families with children at differing ages and developmental stages. This article summarizes studies published from 2006 to 2011 of Motivational Interviewing in individuals across the lifespan with type 1 and type 2 diabetes and obesity.

Background: The recommended total dietary energy intake prescribed medical nutrition therapy for obese or overweight patients with type 2 diabetes in Japan is often set at 25 kcal/kg ideal body weight (IBW)/day. This study was conducted to determine the impact of the total dietary energy intake (25 or 30 kcal/kg IBW/day) on the glycemic control, lipid profile, and satisfaction level in overweight patients with type 2 diabetes. M ethods : We performed interview and a designed prospective, randomized, controlled, multicenter study trial. Recruitment for interview for doctors and hospitalization of the obese or overweight patients with type 2 diabetes began from September 2008 and continued until June 2010. The subjects were randomly assigned to 25 kcal/kg IBW/day group (25 kcal group) or 30 kcal/kg IBW/day group (30 kcal group). The primary endpoint was the body weight of the subjects at the time of hospitalization, at the time of discharge from the hospital, and at 3, 6 and 12 months after discharge from the hospital. Results: The glycemic control, lipid control and body weight were similar between the 25 and 30 kcal groups during the 12-month follow-up, and the degree of satisfaction in respect of the medical treatment was significantly higher in the 30 kcal group than in the 25 kcal group at 1 year after discharge. Conclusions: It is considered to be preferable for the caloric intake to be set at 30kcal/kg IBW/day rather than at 25 kcal/kg IBW/day for obese or overweight patients with type 2 diabetes. doi: http://dx.doi.org/10.4021/jocmr1488w

Aims: A multinational, randomized, double-blind, two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus, subcutaneously administered insulin glulisine (glulisine) and insulin aspart (aspart) in insulin-naIve, obese subjects with type 2 diabetes. Methods: Thirty subjects [9/21 females/males; mean ± SD age: 60.7 ± 7.7 years; body mass index (BMI): 33.5 ± 3.3 kg/m2; duration of diabetes: 6.8 ± 4.6 years; HbA1c: 7.1 ± 0.8%] were included in the analysis. They fasted overnight and then received a 0.2 U/kg subcutaneous dose of glulisine or aspart 2 min before starting a standardized test meal, 7 days apart, according to a randomization schedule. Blood samples were taken every 15 min, starting 20 min before the meal and ending 6 h postprandially. Results: The area under the absolute glucose concentration–time curve between 0 and 1 h after insulin injection and maximal glucose concentration was significantly lower with glulisine than with aspart (p = 0.0455 and 0.0337, respectively). However, for the total study period, plasma glucose concentration was similar for glulisine and aspart. Peak insulin concentration was significantly higher for glulisine than for insulin aspart (p < 0.0001). Hypoglycaemic events (≤ 70 mg/dl with or without symptoms) occurred in 13 and 16 subjects treated with glulisine and aspart, respectively, but there were no cases of severe hypoglycaemia requiring intervention. Conclusions: Glulisine was associated with lower glucose levels during the first hour after a standard meal; the remaining glucose profiles were otherwise equivalent, with higher insulin levels observed throughout the study period.

Резюме. Статья посвящена проблеме терапии ожирения в современных условиях. Особое внимание уделяется выбору препаратов для медикаментозной коррекции массы тела с учетом индивидуальных особенностей пациента. Приведены данные о наиболее эффективных режимах терапии ожирения с применением сибутрамина. В клинической практике сибутрамин может оказывать благоприятное влияние на показатели метаболизма, артериального давления, а также на качество жизни и психоэмоциональное состояние пациентов. Представлены результаты российских и зарубежных клинических исследований по оценке эффективности и безопасности применения сибутрамина для снижения массы тела у различных категорий больных, имеющих нарушения менструальной и репродуктивной функции, сахарный диабет 2 типа и артериальную гипертензию. Resume. The article covers the problems of obesity treatment in contemporary conditions. Particular attention is given to choice of dugs for medical correction of body mass with regard to individual peculiarities of the patient. Given data concerning the most effective regimens of obesity treatment with the use of sibutramine. In clinical practice sibutramine can have a favorable influence on metabolic parameters, blood pressure, as well as on quality of life and psychoemotional well being of the patients. We represent the results of Russian and foreign clinical trials accessing the effectiveness and safety of sibutramine use for body mass reduction in different groups of patients, with disordered menstrual and reproductive functions, diabetes mellitus type 2 and arterial hypertension.

Globesity is referred to a global epidemic of obesity, affecting millions of individuals. Molecules released by the enlarged adipose tissue, most of which are pro-inflammatory, have been named adipokines. The present review deals with function, molecular targets and the potential clinical relevance of adipokines. Currently, more than 600 adipokines have been identified, many of them, including leptin, visfatin, resistin as well as Retinol Binding Protein4 may serve as informative markers for metabolic and cardiovascular diseases and play important roles in glucose homeostasis, insulin sensitivity as well as metabolic regulation of energy expenditure. Adiponectin on the contrary exerts anti-inflammatory and insulin sensitizing activity. Adiponectin has additional anti-atherogenic effects and low adiponectin serum concentrations are associated with increased risk for cardiovascular diseases. The understanding of the role of adipokines has provided a wealth of information that has opened great opportunities for new therapeutic advances. Adiponectin may be the most prominent example for the potential use of an adipokine in the treatment of obesity and obesity-associated metabolic diseases. In many studies, administration of recombinant adiponectin results in improved insulin sensitivity, increased insulin secretion and beneficial effects on body weight and hyperglycemia. Up-regulation of adiponectin/adiponectin receptors or enhancing adiponectin receptor function may be an interesting therapeutic strategy for obesity-linked insulin resistance. Moreover, the therapeutic use of combined amylin/leptin agonism (with pramlintide and metreleptin) demonstrated a significant weight-lowering effect in obese subjects. Therefore, adipokines may be clinically relevant either as therapeutic tools or as target in the treatment of obesity related diseases.

My bachelor´s thesis deal with obesity of adolescents and problems with overweight. These problems are described in details, and after that divided into specific parts. The main goal of my bachelor´s thesis is to chart problems with obesity and overweight in age group from 15 to 18 (adolescents) and primary describe their eating habits and physical activity. Theoretical part is focused on occurrence of overweight and obesity in the Czech Republic and in the world, causes of its origin, risk factors, classification and diagnosis, types, therapy and prevention. This bachelor´s work dealing with rational diet, describing basic principles of healthy catering and explaining right or wrong foodstuffs. I point mainly on prevention of overweight and obesity by healthy eating and physical activity. Methodical part is processed thanks to quantitative research. Data were gained by questionnaires, which were given to high school students (1st - 3rd grade). The research group contains 150 respondents from different schools in České Budějovice and close neighborhood. Final results are written down primary in graphs with commentary and data charts. In case of right use of qualitative research, there were determined two hypotheses. First hypothesis: Overweight and obesity is more occurred at adolescents with wrong eating habits. Second hypothesis: Overweight and obesity is more occurred at adolescents with low physical activity. For developing exploratory part, there was used quantitative research, which was provided by questionnaires given to students of age from 15 to 18. Entire data were processed by the use of program Microsoft Excel, and its calculations and functions. The answers of respondents were registered into database, and, by using specific excel functions, I was able to report data in determined categories. The research was mainly concentrated on physical activity and eating habits. Final results are put into well-arranged graphs, which are always enriched by comments, eventually completed by data tables, and, subsequently, statistically evaluated. In results, there might be seen two main differences between adolescents with standard weight and adolescents with overweight or obesity problems. One of those is irregularity in eating and wrong eating habits; big difference is also proved in physical activity. Adolescents with obesity or overweight have often irregular food intake, they drink a lot of high caloric beverages such as Coca-Cola, Sprite, Fanta etc., deficient income of fruit, vegetables, legumes, fish, or low physical activity. Only few of obese adolescents is different, because their problem is caused genetically. Adolescents with standard weight eat more regularly, but there are also some special cases, who have similarly wrong eating habits as obese people; however, all of these adolescents have one typical quality regular physical activity. Both hypotheses are confirmed. The results show that obesity is mainly caused by genetic predispositions, but these factors can be positively affected by periodic physical activity or appropriate eating habits. At the end of the thesis, it should be mentioned that it is necessary to be focused on right eating habits and regular physical from the very young age, when the basic customs and habits are assumed. That should include parents' action around their children, as they are usually the first example and they have the biggest influence.It is important to develop knowledge about all kinds of prevention, which are in most cases major in defending against formation of overweight and obesity.

Background and aims: Exercise training can improve health of patients with metabolic syndrome(MetS).However,whichMetS factors aremost responsive to exercise training remains unclear. We studied the time-course of changes in MetS factors in response to training and detraining. Methods and results: Forty eightMetS patients (52 8.8 yrs old; 33 4 BMI) underwent 4months (3 days/week) of supervised aerobic interval training (AIT) program. After 1 month of training, there were progressive increases in high density lipoprotein cholesterol (HDL-c) and reductions in waist circumference and blood pressure (12 3, 3.9 0.4, and 12 1%, respectively after 4 months; all P < 0.05). However, fasting plasma concentration of triglycerides and glucose were not reduced by training. Insulin sensitivity (HOMA), cardiorespiratory fitness (VO2peak) and exercisemaximal fat oxidation (FOMAx) also progressively improved with training ( 17 5; 21 2 and 31 8%, respectively, after 4months; all P < 0.05). Vastus lateralis samples fromseven subjects revealed that mitochondrial O2 flux was markedly increased with training (71 11%) due to increased mitochondrial content. After 1 month of detraining, the training-induced improvements in waist circumference and blood pressure were maintained. HDL-c and VO2peak returned to the values found after 1e2 months of training while HOMA and FOMAx returned to pre-training values. Conclusions: The health related variables most responsive to aerobic interval training in MetS patients arewaist circumference, blood pressure and the muscle and systemic adaptations to consume oxygen and fat. However, the latter reverse with detraining while blood pressure andwaist circumference are persistent to one month of detraining.

Central obesity have an important impact on the development of risk factors for coronary heart disease, including dislipidemia, glucose intolerance, insulin resistance and hypertension. These factors contribute to building cardiovascular (CV) disease as a major cause of death. The approach to obesity therapy should be designed to reduce CV risk and mortality. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but the resultant weight loss is often small and long-term success is uncommon and disappointing. Drug therapy is considered for individuals with a body mass index greater than 30 kg/m² or ranging from 25 to 30 kg/m² if they have comorbid conditions. Antiobesity agents can be helpful to some patients in achieving and maintaining meaningful weight loss, but yet our pharmaceutical tools are of limited effectiveness considering the magnitude of the problem. At the present, only two drugs, orlistat and sibutramine, are approved for long-term treatment of obesity and promote no more than 5 to 10% of weight loss. Rimonabant, a cannabinoid-1 receptor antagonist, was withdrawn from the market because of concerns about its safety, including risk of suicidal and seizures, although very effective in promoting clinically meaningful weight loss, reduction in waist circumference, and improvements in several metabolic risk factors, rimonabant, a cannabinoid-1 receptor antagonist was withdrawn from the market because it concerns about its safety, including risk of suicidal and seizures. Fortunately, recent fundamental insights into the neuroendocrine mechanisms regulating body weight provide an expanding list of molecular targets for novel, rationally designed antiobesity drugs. In this review, the therapeutic potential of some antiobesity molecules in the development will be analyzed based on an understanding of energy homeostasis. Obesidade e, particularmente, a obesidade central têm influência importante na predisposição a fatores de risco para doença coronariana, incluindo dislipidemia, intolerância à glicose, resistência à insulina e hipertensão. Tais fatores contribuem para tornar as doenças cardiovasculares (DC) causas frequentes de morte. Os métodos de tratamento da obesidade deveriam ser voltados à redução do risco e da mortalidade devido às doenças cardiovasculares. Dietas e mudanças no estilo de vida continuam sendo fatores-chave no tratamento à obesidade, mas a perda de peso resultante é geralmente pequena e o sucesso em longo prazo costuma ser incomum e frustrante. O tratamento com medicamentos é indicado para indivíduos com índice de massa corpórea superior a 30 kg/m² ou entre 25 e 30 kg/m², se apresentarem comorbidades. Agentes antiobesidade podem ajudar alguns pacientes a alcançar e manter uma perda de peso significativa, mas, ainda assim, os agentes farmacológicos são pouco efetivos considerando-se a magnitude do problema. Atualmente, apenas duas drogas, orlistat e sibutramina, são consideradas efetivas para tratamentos em longo prazo, promovendo não mais do que 5% a 10% de perda de peso. Embora seja muito eficaz ao promover perda de peso significativa do ponto de vista clínico, redução da circunferência da cintura e melhora no perfil metabólico, o rimonabanto, um antagonista do receptor canabinoide 1, foi retirado do mercado por fatores relacionados à segurança, incluindo a ocorrência de suicídios e convulsões. Felizmente, conhecimentos fundamentais recentes sobre mecanismos neuroendócrinos que regulam o peso corporal forneceram uma lista considerável de alvos moleculares para novas drogas antiobesidade produzidas racionalmente. Nesta revisão de literatura, a eficácia terapêutica de algumas moléculas antiobesidade será analisada com base no entendimento da homeostase energética.

AimsExamine the association between obesity and glycemic control among patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM).MethodsData from US physician electronic health records (Humedica®) from 2009–2011 were utilized. Patients were defined as having above–target glycemic control if they had an HbA1c ≥7% at any time during the study period. Multinomial logistic regressions were conducted separately for T1DM and T2DM patients, and examined associations between BMI categories and probability of having above–target glycemic control (≥7% and

Aims Treatment with liraglutide 3.0 mg has been associated with gallbladder-related adverse events. To conduct a single-centre, double-blind, 12-week trial comparing the effect of 0.6 mg liraglutide and steady-state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes. Methods Participants were randomized 1:1 to once-daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6-mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600-kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12-week maximum postprandial gallbladder ejection fraction (GBEFmax ), measured over 240 minutes after starting the meal. Results Baseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2 , 50% women). Mean 12-week GBEFmax (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% × min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11-240) minutes with liraglutide 3.0 mg and 77 (22-212) minutes with placebo. Similar findings were noted after the first 0.6-mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events. Conclusions Treatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax .