Reduction In Total Body Weight Research Articles

Effectiveness of Jena DM® Herbal Formulation as Complementary Therapy to Conventional Oral Hypoglycemic Agents in Type-2 Diabetes Mellitus: A Quasi-experimental Study.

There is vast preclinical evidence that indicates that extracts from several Artemisia plant species have significant antidiabetic benefits. However, clinical evidence is limited to this effect. We sought to evaluate the effectiveness ofJena DM® (anArtemisia annua-based poly-herbal formulation) on glycemic control (Hb A1C) and insulin metabolism (HOMA), when administered as a complementary therapy in type-2 diabetes mellitus (T2DM). This study was supported by a research grant (JRD005) from Jena Herbals (U) Ltd, which is a local herbal medicines manufacturing facility in Uganda. We conducted a 12-week quasi-experimental study, involving 118 patients under routine follow-up at a diabetes and endocrinology clinic. Random assignment to either conventional or experimental study groups was done using a random number generator (Microsoft Excel version 16.0). Participant sociodemographic and clinical data as well as whole blood samples (3-5 mL) were obtained at scheduled clinic visits. Medication adherence was assessed using the Hill-Bone Scale, and adverse drug events (ADEs) using the Naranjo causality and the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) scales. Group differences in glycemic control (HbA1C), fasting serum insulin (FSI) indices (% HOMA2-B, HOMA-IR), and other cardiometabolic parameters were assessed using independent samples t-test, and Pearson chi-square statistical tests were used. A p-value <0.05 was considered statistically significant. Ethical approvals were obtained before the study commencement. 12-week daily complementary therapy withJena DM® showed no significant effect on Hb A1C reduction (0.1 (95% CI: -0.56, 0.80) %;p=0.798); however, we observed a significant reduction in total body weight (2.0 (95% CI: 0.73, 3.28) kg;p=0.002). The overall frequency of self-reported ADEs including dizziness was significantly higher among patients that usedJena DM® (p=0.001).Epigastric pain was the most severe ADE necessitating clinical management. There was no significant difference in the homeostatic model assessment for insulin resistance (HOMA2-IR) between study groups. In contrast to a few studies that previously showed significanthypoglycemic effects ofArtemisia-basedextracts, this study did not show a statistically significant reduction on HbA1C during a 12-week complementary use ofJena DM® in patients withT2DM. Based on the findings of this study, future research should evaluate the long-term effects ofJena DM® on body weight, overall insulin metabolism, and the subsequent effect on glycemic control in T2DM.

RF35 | PSAT268 Reversal of Graves’ Disease Associated Facial Volume Expansion and Eyelid Changes Following Teprotumumab Therapy

Abstract Background Thyroid eye disease (TED) causes orbital soft tissue expansion. Teprotumumab, a monoclonal antibody to the IGF-1R reduces orbital soft tissue swelling in TED. In this study, we quantified the changes to pan facial soft tissue volumes, following treatment with Teprotumumab. Methods In this prospective longitudinal study, all patients presenting at our institution for the treatment of TED were considered for study eligibility. Patients who were currently on any other medical therapy for TED were excluded. Further, patients who had any plans to embark on a weight loss regime, or medications that might cause weight loss were excluded. The primary outcome measure was a change in soft tissue volume of the face from baseline to within 3 weeks of the final infusion. Secondary outcome measures included changes in proptosis, clinical activity score and body weight. All patients had 3D facial imaging using the Vectra H2 (Canfield, USA). The use of this system to quantify volumetric change in facial soft tissue has previously been shown to be reliable and accurate. We also used the Mimics (Materialise) software to build 3D reconstructions of the face from CT scans, allowing us to calculate the volume of muscle and fat tissue pre and post treatment. Relationships between continuous variables were analyzed using bivariate and multivariate analysis. Intraobserver and Interobserver variability was calculated by two observers doing all calculations twice on two separate days. Results Forty-three patients with confirmed euthyroid status at the time of study were included. The mean duration of TED was 30 months (34). Following Teprotumumab therapy, the mean (SD) decrease in volume for each region was 0.74 mL (0.82) in the upper face, 1.9 mL (1.2) in the periorbital region, 0.18 mL (0.6) in the temples, 1.73 mL (2.2) in the midface and 2.84 mL (4.7) in the lower face. The mean (SD) decrease in the volume of the full face was 8.4 mL (8.5) (figure 2). There was a significant correlation between 3D facial imaging and volumetric study using CT scans (p &amp;lt; 0.05). Mean (SD) weight prior to therapy was 75 kg (12) and 69 kg (15) following therapy (p &amp;lt; 0.05). There was no relationship between previous steroid use and total body weight reduction and changes in facial volume. Conclusion The results of this study expand the borders of TED, suggesting its sequelae may reach beyond that of the orbit and periorbital tissues, to include changes across the entire face. Teprotumumab significantly reduces these changes. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.

Impact of Laparoscopic Sleeve Gastrectomy on Thrombomodulin Concentration and Early Markers of Atherosclerosis.

Background Thrombomodulin, an integral membrane protein functioning as a cofactor in the anticoagulant pathways, has recently emerged as a marker of endothelial dysfunction. This study aimed to investigate the impact of laparoscopic sleeve gastrectomy (LSG) on thrombomodulin concentration and early markers of atherosclerosis. Methods Forty-four subjects undergoing LSG were prospectively examined. The change in thrombomodulin concentration from baseline (preoperative) to the sixth postoperative month following the LSG and the relationship between the change in thrombomodulin concentration and BMI, CIMT, ABI, and blood lipids were examined. Results The medical records were available for 44 patients (mean age: 37.2 ± 10.9 years, 65.9% male). LSG led to significant reductions in total body weight and body mass index (BMI) at postoperative six months (37.0 ± 5.6 kg/m2 vs. 47.1 ± 5.8 kg/m2, p < 0.001). Markers of early atherosclerotic events, including carotid intima-media thickness (CIMT) and ABI, improved. The change in thrombomodulin concentration (Δ TMD) was significantly correlated with the change in Δ BMI (r = 0.500, p=0.011), Δ LDL (r = 0.389, p=0.032), Δ systolic blood pressure (r = 0.384, p=0.012), and Δ CIMT (r = 0.327, p=0.012) and was negatively correlated with Δ HDL (r = −0.344, p=0.020) and Δ ABI (r = −0.357, p=0.020). Conclusion LSG leads to significant improvements in blood lipids, systolic and diastolic blood pressure, and in surrogate markers of atherosclerotic burden and endothelial function, including thrombomodulin, ABI, and CIMT, at postoperative six months. LSG might prevent or reduce atherogenesis in the early stages by stopping endothelial dysfunction.

Histamine H3 receptor antagonists - Roles in neurological and endocrine diseases and diabetes mellitus.

Human histamine H3 receptor (H3R) was initially described in the brain of rat in 1983 and cloned in 1999. It can be found in the human brain and functions as a regulator of histamine synthesis and release. H3 receptors are predominantly resident in the presynaptic region of neurons containing histamine, where they modulate the synthesis and release of histamine (autoreceptor) or other neurotransmitters such as dopamine, norepinephrine, gamma-aminobutyric acid (GABA), glutamate, acetylcholine and serotonin (all heteroreceptors). The human histamine H3 receptor has twenty isoforms of which eight are functional. H3 receptor expression is seen in the cerebral cortex, neurons of the basal ganglia and hippocampus, which are important for process of cognition, sleep and homoeostatic regulation. In addition, histamine H3R antagonists stimulate insulin release, through inducing the release of acetylcholine and cause significant reduction in total body weight and triglycerides in obese subjects by causing a feeling of satiety in the hypothalamus. The ability of histamine H3R antagonist to reduce diabetes-induced hyperglycaemia is comparable to that of metformin. It is reasonable therefore, to claim that H3 receptor antagonists may play an important role in the therapy of disorders of cognition, the ability to sleep, oxidative stress, inflammation and anomaly of glucose homoeostasis. A large number of H3R antagonists are being developed by pharmaceutical companies and university research centres. As examples of these new drugs, this review will discuss a number of drugs, including the first histamine H3R receptor antagonist produced.

Changes in Food Choice, Taste, Desire, and Enjoyment 1 Year after Sleeve Gastrectomy: A Prospective Study.

Obesity is a well-recognized global health problem, and bariatric surgery (BS)-induced weight reduction has been demonstrated to improve survival and obesity-related conditions. Sleeve gastrectomy (SG) is actually one of the most performed bariatric procedures. The underlying mechanisms of weight loss and its maintenance after SG are not yet fully understood. However, changes to the taste function could be a contributing factor. Data on the extent of the phenomenon are limited. The primary objective was to assess, through validated questionnaires, the percentage of patients who report an altered perception of post-SG taste and compare the frequency of intake of the different food classes before SG and after 1 year follow-up. The secondary objective was to evaluate the total body weight change. Materials and Methods: We prospectively investigated the changes in food choice and gustatory sensitivity of 52 patients (55.8% females) 12 months after SG. The mean initial weight and body mass index (BMI) were 130.9 ± 24.7 kg and 47.4 ± 7.1 kg/m2, respectively. The frequency of food intake was assessed by food-frequency questionnaire, while changes in taste perception were assessed using the taste desire and enjoyment change questionnaire. The change in total body weight was also assessed. Results: A significant decrease in the intake frequency of bread and crackers (p < 0.001), dairy products and fats (p < 0.001), sweets and snacks (p < 0.001) and soft drinks (p < 0.001), and a significant increase in the frequency of vegetable and fruit consumption (p < 0.001) were observed at 12 months after SG in both genders. On the contrary, we found no significant changes in the frequency of meat and fish intake in females (p = 0.204), whereas a significant change was found in males (p = 0.028). Changes in perceived taste intensity of fatty foods (p = 0.021) and tart foods (p = 0.006) for females and taste of bitter foods for females and males (p = 0.002; p = 0.017) were found. Regarding the change in food desire for both genders, there was a decrease in the desire for sweet, fatty, and salty foods, whereas there was an increasing trend in the desire for tart foods, especially for females. Significant reduction in total body weight and BMI was observed in both genders at the time of follow-up. Conclusions: Based on our findings, we are able to support the evidence that changes in taste, desire, and enjoyment of taste are very common after SG, with a reduced preference for food with high sugar and fat content and an increased postoperative preference for low-sugar and -fat foods. However, further investigation is needed to clarify this issue. The molecular, hormonal, and central mechanisms underlying these changes in taste perception need to be further elucidated, as they could identify new targets able to modify obesogenic eating behavior, opening up a novel personalized therapeutic approach to obesity.

Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: Translational difficulties and pitfalls.

During recent years combining GLP-1 and glucagon receptor agonism with the purpose of achieving superior weight loss and metabolic control compared to GLP-1 alone has received much attention. The superior efficacy has been shown by several in preclinical models but has been difficult to reproduce in humans. In this paper, we present the pre-clinical evaluation of NN1177, a long-acting GLP-1/glucagon receptor co-agonist previously tested in clinical trials. To further investigate the contribution from the respective receptors, two other co-agonists (NN1151, NN1359) with different GLP-1-to-glucagon receptor ratios were evaluated in parallel. In the process of characterizing NN1177, species differences and pitfalls in traditional pre-clinical evaluation methods were identified, highlighting the translational challenges in predicting the optimal receptor balance in humans. In diet-induced obese (DIO) mice, NN1177 induced a dose-dependent body weight loss, primarily due to loss of fat mass, and improvement in glucose tolerance. In DIO rats, NN1177 induced a comparable total body weight reduction, which was in contrast mainly caused by loss of lean mass, and glucose tolerance was impaired. Furthermore, despite long half-lives of the three co-agonists, glucose control during steady state was seen to depend on compound exposure at time of evaluation. When evaluated at higher compound exposure, glucose tolerance was similarly improved for all three co-agonists, independent of receptor balance. However, at lower compound exposure, glucose tolerance was gradually impaired with higher glucagon receptor preference. In addition, glucose tolerance was found to depend on study duration where the effect of glucagon on glucose control became more evident with time. To conclude, the pharmacodynamic effects at a given GLP-1-to-glucagon ratio differs between species, depends on compound exposure and study length, complicating the identification of an optimally balanced clinical candidate. The present findings could partly explain the low number of clinical successes for this dual agonism.

First‐year weight loss following gastric band surgery predicts long‐term outcomes

Laparoscopic adjustable gastric banding (LAGB) continues to be a valid surgical treatment option to address severe obesity. However, outcomes are varied and can be difficult to predict. Early prediction of suboptimal weight loss following LAGB may enable adjustments to postoperative care and consequently improve surgical outcomes. Therefore, our aim is to investigate the prognostic utility of using early weight loss following LAGB to predict long-term weight outcomes. Clinical data from patients undergoing LAGB between 2001 and 2007 at a single institution were retrospectively collected and analysed. The data was used to inform a model for predicting long-term weight loss after LAGB surgery. Percent total weight loss (%TWL) greater than 20% 1 year after surgery was considered a measurement of success since it has been associated with the improvement of comorbidities and increased patient satisfaction. The average %TWL 1 year after LAGB surgery was 23.73% (n=1524, SD=8.68%). Weight loss of less than 10% in 1 year was a negative predictor of weight loss >20% in 8-12 years (OR=0.449; p=0.002; 95% CI=0.272-0.742). Moreover, weight loss >20% in 1 year was a strong predictor of weight loss >20% in 8-12 years (OR=5.33; p < 0.001; 95% CI=3.17-8.97). Total body weight reduction of less than 10% 1 year after LAGB surgery suggests a lesser weight loss at 8-12 years. For these patients, targeted interventions would be appropriate to increase the chances of long-term success.

Facial and Eyelid Changes in Thyroid Eye Disease Are Reversed by Teprotumumab.

Background:Thyroid eye disease (TED) causes orbital soft-tissue expansion. Recent studies have suggested that brow and temple changes may also occur. Teprotumumab, a monoclonal antibody to the insulin-like growth factor 1 receptor reduces soft-tissue swelling in TED. In this study, we quantified the changes to pan facial soft-tissue volumes and eyelid position, following treatment with teprotumumab.Methods:In this prospective study, consecutive patients who were treated with teprotumumab were appraised for study eligibility. All patients had 3D facial imaging using the Vectra H2. Soft-tissue volume changes in the upper face, periorbita, temples, midface, and lower face were quantified before and after teprotumumab therapy. Furthermore, the marginal reflex distance (MRD)1, MRD2, and intercanthal distance were also measured pretreatment and posttreatment.Results:Twenty-three patients were included in the study. The mean duration of TED was 29 months (38). Following teprotumumab therapy, the mean (SD) decrease in volume for each region was 0.75 mL (0.84) in the upper face, 1.8 mL (1.3) in the periorbital region, 0.17 mL (0.5) in the temples, 1.62 mL (3.16) in the midface, and 2.67 mL (4.6) in the lower face. The mean (SD) decrease in the volume of the full face was 8.9 mL (8.7). There was also a significant reduction in MRD1, MRD2, and the intercanthal space following treatment. There was no relationship between previous steroid use and total body weight reduction and changes in facial volume.Conclusion:TED may cause significant tissue expansion across the entire face and this may be reduced following teprotumumab therapy.

Evaluation of the Low Carb Program Digital Intervention for the Self-Management of Type 2 Diabetes and Prediabetes in an NHS England General Practice: Single-Arm Prospective Study.

BackgroundType 2 diabetes mellitus has serious health consequences, including blindness, amputation, and stroke. Researchers and clinicians are increasingly in agreement that type 2 diabetes may be effectively treated with a carbohydrate-reduced diet. Digital apps are increasingly used as an adjunct to traditional health care provisions to support remote self-management of long-term health conditions.ObjectiveOur objective was to evaluate the real-world 12-month outcomes of patients prescribed the Low Carb Program digital health intervention at a primary care National Health Service (NHS) site. The Low Carb Program is a nutritionally focused, 12-session, digitally delivered, educational behavior change intervention for glycemic control and weight loss for adults with prediabetes and type 2 diabetes. The program educates and supports sustainable dietary changes focused on carbohydrate restriction by utilizing behavior change techniques, including goal setting, peer support, and behavioral self-monitoring, as well as personalized downloadable resources, including recipes and meal plans tailored to ethnicity, weekly shopping budget, and dietary preferences.MethodsThis study evaluated the real-world outcomes of patients recruited to the Low Carb Program at an NHS general practice in Southport, United Kingdom. All of the NHS patients recruited to the program were diagnosed with type 2 diabetes or prediabetes and were given access to the program at no cost. A total of 45 participants, with a mean age of 54.8 years (SD 13.2), were included in the study. Women made up 42% (19/45) of the sample. The mean hemoglobin A1c (HbA1c) of the sample was 56.7 mmol/mol (SD 16.95) and the mean body weight was 89.4 kg (SD 13.8).ResultsOf the 45 study participants recruited to the program, all of them (100%) activated their accounts and 37 (82%) individuals reported outcomes at 12 months. All 45 (100%) patients completed at least 40% of the lessons and 32 (71%) individuals completed more than nine out of 12 core lessons of the program. Glycemic control and weight loss improved, particularly for participants who completed more than nine core lessons in the program over 12 months. The mean HbA1c went from 58.8 mmol/mol at baseline to 54.0 mmol/mol, representing a mean reduction of 4.78 mmol/mol (SD 4.60; t31=5.87; P<.001). Results showed an average total body weight reduction of 4.17%, with an average weight reduction of 3.85 kg (SD 2.49; t31=9.27; P<.001) at the 12-month follow-up point.ConclusionsA digital app prescribed to adults with type 2 diabetes and prediabetes in a primary care setting supporting a transition to a low-carbohydrate diet has been shown to be effective in improving glycemic control and enabling weight loss. Further research to understand more about factors affecting engagement with the app and further positive health implications would be valuable.

The effect of an orally-dosed Gynostemma pentaphyllum extract (ActivAMP®) on body composition in overweight, adult men and women: A double-blind, randomised, placebo-controlled study.

BackgroundThe present study examined the effect of a herbal supplement containing a Gynostemma pentaphyllum (Gpp) extract (ActivAMP®) with respect to improving body composition in overweight males and females.MethodsOne‐hundred and seventeen men and women aged over 18 years completed 16 weeks of daily supplementation with either Gpp or a placebo. Participants underwent dual‐energy X‐rays to assess body composition (fat mass, lean mass and mass distribution), as well as anthropometric measures (weight, height, hip and waist circumference), in addition to blood tests to assess inflammatory and safety markers.ResultsFollowing 16 weeks of treatment, the Gpp group had a significant reduction in total body weight, body mass index, total fat mass and gynoid fat mass compared to the placebo group. Blood measures showed plasma triglyceride, alanine aminotransferase and tumour necrosis factor‐α to be statistically different between groups at week 16. Subgroup analysis of gender for fat distribution showed males in the Gpp group had a significant reduction in visceral fat compared to males in the placebo group and females in the Gpp group had a significant reduction in gynoid fat compared to the placebo group.ConclusionsGpp was capable of altering fat mass and fat distribution in overweight and obese males and females compared to a placebo.

Abstract 2257: Effect ofALDH1L1folate enzyme on hepatocellular carcinoma inachemical carcinogenesismodel

Abstract Background: ALDH1L1 (aldehyde dehydrogenase 1 family member L1, or cytosolic 10-formyltetrahydrofolate dehydrogenase) is an abundant enzyme in folate metabolism representing about 1% of total soluble protein in hepatocytes. Expression of this protein is strongly and ubiquitously downregulated in human cancers through the promoter methylation. Several studies indicate that patients with hepatocellular carcinoma who had low expression of ALDH1L1 had poorer prognosis than those with high expression. Hypothesis: We propose that in the absence of ALDH1L1, liver tumors proliferate faster and grow to a larger size. Methods: The effect of the Aldh1l1 knockout (Aldh1l1−/−) on hepatocellular carcinoma was investigated using DEN (diethyl nitrosamine) model of chemical carcinogenesis. Fifteen-days-old male Aldh1l1−/- mice and their wild-type littermate controls (Aldh1l1+/+) were injected intraperitoneally with DEN at the dose of 15 mg/kg body weight. Mice were sacrificed 10, 20, 28- and 36-weeks post-injection and livers were examined for for histopathology. Results: Significant reduction in total body weight was observed in the DEN-injected knockout compared to wild type animals at 28 and 36 weeks. Immunohistochemical analysis reveals that tumor size was significantly bigger in Aldh1l1−/− compared to Aldh1l1+/+ mice and also indicated fibrosis in livers of knockout vs wild-type mice. Vascular involvement, highlighted by reticulin staining, was present in both Aldh1l1−/− and Aldh1l1+/+ mice as early as 20 weeks after the injection. Tumor multiplicity did not differ significantly between the Aldh1l1−/− and Aldh1l1+/+ animals. Conclusion:. Aldh1l1 knockout promoted aggressiveness of liver tumors without affecting the tumor initiation. Acknowledgement: These studies were supported by the National Institutes of Health grants DK54388 and CA095030 (S.A.K.). Citation Format: Jaspreet Sharma, Natalia I. Krupenko, Peter Pediaditakis, Kristi Helke, Kyle C. Strickland, Sergey A. Krupenko. Effect ofALDH1L1folate enzyme on hepatocellular carcinoma inachemical carcinogenesismodel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2257.

Early Post-operative Weight Change After Roux-en-Y Gastric Bypass Predicts Weight Loss at 12-Month Follow-up.

Sub-optimal weight loss following Roux-en-Y gastric bypass (RYGB) represents an important clinical challenge in a significant number of patients. Early identification of such patients would be advantageous, as it could aid in the selective implementation of targeted adjunct interventions during the first post-operative year. Clinical audit data from 1137 patients undergoing RYGB between 2013 and 2016 at the Instituto Sallet in Brazil were prospectively registered in an online database (BOLD) and analyzed. Forty-eight percent of patients achieving less than 5% total weight loss after the first post-operative month achieved a 20% total weight loss at 1year (n = 626; OR = 0.6 CI = 95%). Eighty-three percent of patients losing between 5 and 10% at 1month and 95% of patients losing greater than 10% at 1month had lost at least 20% of total body weight after the first post-operative year. Forty-four percent of patients achieving less than 10% total weight loss after the third post-operative month achieved 20% total weight loss at 1year (n = 494; OR = 0.3 CI = 95%). Total bodyweight reduction after RYGB of < 5% at 1month and < 10% at 3months is associated with suboptimal weight loss at 1year. These results reinforce findings from other studies reporting that patients tend to follow a common weight loss trajectory. Identifying the patients with weight trajectory requiring adjunct therapies early on is crucial so appropriate adjustments can be made to post-operative care.

2027-P: A Retrospective Study of Weight and Metabolic Changes in Patients with Obesity (BMI≥30 Kg/m2) after Endoscopic Sleeve Gastroplasty (ESG) or Laparoscopic Sleeve Gastrectomy (LSG)

Weight reduction in obese individuals lowers comorbidities. LSG is the most common bariatric procedure in use today, but there is a need for less invasive approach. ESG, a novel incisionless, minimally invasive procedure, involves endoscopic plication of the greater curvature of the stomach reducing its length and width. We compared weight and metabolic changes associated with these procedures. A single center retrospective study was performed of consecutive patients that underwent LSG or ESG. SAS and multivariate mixed model were used to determine percentage change of total body weight (TBW), BMI, BSA (body surface area), HbA1c and total cholesterol level (TC). 25 patients were recruited (11[44%] had LSG and 14[56%] had ESG). The average age of LSG group was 47±3.9 and ESG group was 39±4.2 years. There was no statistical difference in the age, gender, or race between the groups. 29% of LSG patients and 10% of ESG patients had diabetes. Results are in the Table; * indicates significant differences between the groups. Conclusions: In this limited retrospective study, patients who underwent LSG had a higher % reduction in TBW, BMI and BSA than those who underwent ESG. There was no statistical difference between the groups in the HbA1c or TC change. These preliminary data should be confirmed in larger prospective randomized trials. Disclosure P. Benias: Consultant; Self; Apollo EndoSurgery. A.K. Vegesna: None. T. Leung: None. K. Ziskovich: None. D. Inlall: None. L. Poretsky: None. L.S. Miller: None. Funding New York State Department of Health

SUN-650 Body Composition Assessment in Clinical Practice: Use in Rheumatoid Arthritis and Hypogonadism

BACKGROUND: DXA is an accessible, non-invasive method, also used for body composition assessment, standing out for regional composition analysis. In clinical practice, the analysis of body composition is relevant by differentiating lean (fat-free) mass from fat mass. The higher the fat to lean mass ratio, the greater the obesity-related comorbidities.CLINICAL CASE: Case 1: A 22-year-old male, BMI 21kg/m2, with rheumatoid arthritis (RA) and on chronic glucocorticoid (GC) performed a DXA to evaluated body composition. The first analysis, during GC use, showed 26.1% fat (14.6kg) despite the low BMI. The patient, evolved stable from RA, and was able to stay out of GC for 2 years, with no other interventions. A new DXA showed a decrease in fat percentage to 12.6% (6.2kg), a reduction in total body weight (-7kg) and an increase in lean mass (+1.2kg). Within 16 months of GC reintroduction, the fat percentage increased up to 36.8% (23.8kg), the total weight increased by 15.6kg and the lean mass decreased by 2.1kg. Case 2: A 40-year-old male with hypogonadism showed 37% fat (33.8kg) on ​​first DXA evaluation. Testosterone replacement was started, and a new DXA was performed after 10 weeks, and although the total weight increased by 3.1kg, there was a decrease in fat mass to 33.5% (31.6kg) and an increase of 5.3kg in lean mass. After 3 years, there was a reduction to 27.1% of fat (24.5kg) and, after 4 years of therapy initiation, the percentage of fat was 26.9% (24.5kg). There was no change in diet or exercise.CONCLUSION:The exposed cases highlight the importance of body composition assessment in patients with conditions that interferes with energy metabolism. The patient on chronic GC use, after medication withdrawal, presented a significant decrease in fat mass, more pronounced in the android percentage. The reintroduction of the CG showed an increase in fat percentage, with android predominance. The patient with hypogonadism, in the second evaluation performed with only 10 weeks of treatment with testosterone, evolved with a reduction in fat mass associated with an increase in lean mass, besides a reduction in the android percentage.The reported cases illustrate everyday clinical situations in which disease vs. treatment significantly changes body composition. Assessment of body composition is essential in patients exposed to conditions that interfere with energy metabolism since obesity is associated with chronic comorbidities and cardiovascular outcomes.

Changes in Resting Energy Expenditure following Gastric Bypass Surgery: Impact on Total Body Weight.

AbstractBariatric surgery, including Gastric Bypass (GBP) Surgery, is the most efficient modality to manage severe obesity. Resting Energy Expenditure (REE) is an area of interest in the context of weight loss (WL) as it has been postulated to be an independent predictor of WL success following GBP. As such, the aim of this study is to investigate the impact of REE on WL following GBP. 31 GBP patients (77.4% females BMI 45.5 ± 7.0kg/m2 ; 47.3 ± 11.6y) and 32 weight-stable controls (46.9% females; BMI 27.0 ± 4.6kg/m2 ; 41.1 ± 13.5y) were assessed at one-month pre-surgery and at 3 and 12-months post-surgery. Fat mass (FM) and fat-free mass (FFM) were measured using dual energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). REE was measured under standardised conditions using indirect calorimetry (ECAL, Metabolic Health Solutions). Statistical analyses were performed with SPSS v24.0, Armonk, NY. Multiple regression analysis showed that FM (P = 0.001), FFM (P &lt; 0.0001) and gender (P = 0.012) significantly predicted the interindividual variability in REE. Total body weight (TBW) was removed from the model due to collinearity. Adjusted-REE values were then generated using the above predictor variables. Low-REE and high-REE groups were created using within-group adjusted-REE split. At both follow-ups (3- and 12-months post-surgery), patients had a greater reduction in TBW, FM, FFM, measured-REE and adjusted-REE values compared with controls (P &lt; 0.0001). There was also no significant difference between measured and adjusted-REE values at all time-points (P &gt; 0.05). Patients with high REEs at baseline lost more TBW than those in the low-REE group at 3-months post-surgery (-24.9 ± 6.5 kg vs. -16.6 ± 7.0 kg; P = 0.005) and 12-months post-surgery (-41.3 ± 12.5 kg vs. -25.8 ± 10.4.0 kg; P = 0.003). There was no significant difference in mean TBW changes for controls in the low-and high-REE groups at both follow-ups. Patients with high REEs at 3-months post-surgery did not lose more TBW than those in the low-REE group at 12-months post-surgery (-30.1 ± 12.8 kg vs. -38.6 ± 14.4 kg; P = 0.155). Similarly, there was no difference in mean TBW reduction between controls in the low- and high-REE groups (P = 0.115). Thus while patients with a high adjusted-REE value at baseline (&gt; 9746.6kJ/day) lost more weight at 3- and 12-months post-GBP, it is plausible that from the third to the 12th month post-surgery, other key drivers of weight loss, particularly the reduction in energy intake are more important in predicting WL. Further research with a larger sample size is required to increase the chances of detecting a true effect.

In-Vivo Anti-Hyperlipidemic Activity and Preliminary Phytochemical Screening of Canephora robusta

The main aim of this study is to determine the anti-hyerlipidemic and anti-obesity activity of Canephora robusta in hyperlipidemia induced rats. Prepared coffee bean extract (GCE) was procured from the market which is unroasted and contains more quantity of caffeine and chlorogenic acid when compared to roasted coffee. Male albino Wister rats are fed with high fat diet (HFD) for weeks to induce hyperlipidemia in rats, which are divided into 4 groups with 4 animals in each group. Test GCBE was given in doses of 200 mg/kg and 400 mg/kg to III and IV groups which are fed with HFD for 30 days. Then blood samples were collected through retro-orbital sinus by capillaries and serum is separated for analysis. The result obtained from lipid profile which includes total cholesterol, triglycerides, very low density lipoproteins, and low density lipoproteins shows the decreased level when compared to the hyperlipidemic control. This shows the significant reduction of total body weight (p < 0.05) when given with dose of 200 mg/kg and 400 mg/kg. The present study suggests that GCBE has anti-obesity and anti-hyperlipidemic activity, where 400 mg/kg is more effective to reduce the total body weight and lipid levels when compared to 200 mg/kg. Further studies on this extract may lead to identify the possible mechanism of action and isolation of active principle from the same.

Hepatotoxicity and Toxicology of In Vivo Lentiviral Vector Administration in Healthy and Liver-Injury Mouse Models.

General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development are sparse. We have previously demonstrated the efficacy of a lentiviral vector expressing fumarylacetoacetate hydrolase (LV-FAH) to cure animal models of hereditary tyrosinemia type 1. Therefore, we performed a complete preclinical toxicological evaluation of LV-FAH, in a large cohort (n = 20/group) of wildtype mice and included matched groups of N-nitrosodiethylamine/carbon tetrachloride (DEN/CCl4)-induced liver injury mice to assess specific toxicity in fibrotic liver tissue. Mice receiving LV-FAH alone (109 TU/mouse) or in combination with DEN/CCl4 presented clinically similar to control animals, with only slight reductions in total body weight gains over the study period (3.2- to 3.7-fold vs. 4.2-fold). There were no indications of toxicity attributed to administration of LV-FAH alone over the duration of this study. The known hepatotoxic combination of DEN/CCl4 induced fibrotic liver injury, and co-administration with LV-FAH was associated with exaggeration of some findings such as an increased liver:body weight ratio and progression to focal hepatocyte necrosis in some animals. Hepatocellular degeneration/regeneration was present in DEN/CCl4-dosed animals regardless of LV-FAH as evaluated by Ki-67 immunohistochemistry and circulating alpha fetoprotein levels, but there were no tumors identified in any tissue in any dose group. These data demonstrate the inherent safety of LV-FAH and support broader clinical development of lentiviral vectors for in vivo administration.

Usefulness of the ReShape intragastric balloon for obesity

Intragastric balloon (IGB) is approved for weight reduction in obesity patients who have a body mass index (BMI) of 30 to 40 kg/m2. The effectiveness of IGB in various degrees of obesity is not well established. We aimed to study the effect and safety of IGB in different groups of obese patients. A retrospective study was performed. All patients who underwent placement of the ReShape™ gastric balloon and completed a 6-month follow-up were included. There were 35 gastric balloons in 34 patients who had a baseline body weight of 106.5 ± 23.5 kg and a BMI of 37.1 ± 5.5 kg/m2. After IGB removal, total body weight was reduced 6.8 ± 7.3% (P < 0.001) and the BMI reduction was 2.7 ± 2.9 kg/m2 (P < 0.001). Subgroup analysis showed that patients with BMI >40 kg/m2 also had significant reduction of total body weight and BMI. The diastolic blood pressure was reduced by 4.7 ± 12.3 mm Hg (P = 0.03) after balloon removal. The most common complication was nausea in 22.9%. One patient had balloon migration leading to small bowel obstruction. One patient had a bleeding gastric ulcer. In summary, IGBs are an effective method to assist in weight loss in patients with various degrees of obesity, even with a BMI >40 kg/m2, with minor adverse effects.

Effect of Valsartan and Folic Acid on Vascular Reactivity, Leptin Hormone and Some Biochemical Parameters in Fat Diet-Induced Obese Male Rats

AbstractBackground: The development of a chronic low-grade inflammatory state has been shown to play a central role in the development of metabolic complications associated with obesity.Aim of Study: The aim was to determine the impact of oral administration of valsartan and folic acid to fat diet-induced obese male rats on the vascular reactivity & on the serum levels of leptin and some inflammatory and oxidative stress markers.Material and Methods: Fifty male albino rats of local strain were randomized into five equal groups: Control, obese, valsartan-treated obese, folic acid-treated obese and combined valsartan and folic acid-treated obese groups. Obesity was induced by feeding high fat diet and treatment was done for indicated groups for 16 weeks. Thereafter, weight and length were measured, and rats were subjected for rat tail-measurement of Systolic Blood Pressure (SBP). Then, fasting retro-orbital blood samples were collected for measuring serum Total Cholesterol (TC), Triglycerides (TGs), Low Density Lipoprotein-Cholesterol (LDL-C), High Density Lipoprotein-Cholesterol (HDL-C), Malondialdehyde (MDA), C-Reactive Protein (CRP) and leptin levels, as well as serum Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD) activities, andurinary nitrite/nitrate (NOx) level. Rats were tested for Vascular Reactivity to Acetylcholine (VRACh) and sodium nitroprusside (VRSNP) by Doppler flowmeter. Lastly, rats were sacrificed and abdominal visceral fats were resected and weighed.Results: High fat diet resulted in marked impairment of all the measured parameters, except VRSNP. Treatment of obese rats with valsartan resulted in improvement of BMI, adipose tissue mass, TC, LDL, CRP, leptin, NOx, MDA, SBP and VRACh; however, total body weight, TGs, HDL-C and antioxidant enzyme activities were not affected. Folic acid administration to obese rats improves all serum lipid param-eters, increased GPx and SOD activities, and showed a better effect than valsartan on NOx, leptin andVRACh, but less effect on CRP. On the other hand, folic acid had no effect on the anthropometric parameters and SBP of obese rats. Com-bined treatment showed a reduction in total body weight, and a significant better improvement of all the measured parame-ters, except MDA, than those of isolated valsartan or folic acid treatment, with normalization of MBI, TGs, LDL-C, NOx and VRACh.Conclusion: Both valsartan and folic acid, when admin-istered separately, ameliorate the detrimental effects of fat diet-induced obesity in rats. Combined valsartan and folic acid prophylactic treatment of fat diet-induced obese rats has an additive beneficial effect on the associated dyslipidemia, inflammatory state, oxidative stress, leptin hormone level, and endothelial dysfunction that is possibly achieved by different mechanisms of action.

The Effects of Pedometers on Body Weight and Metabolic Factors in Patients with Prediabetes

: Sedentary behavior, increased total body weight, elevated blood glucose levels and hyperlipidemia increase the risk of prediabetes. Individuals diagnosed with prediabetes (fasting blood glucose (FBG) between 100-125mg/dL) are recommended to perform a minimum of 150 minutes of physical activity (PA) per week and decrease total body weight by 7% to reduce the likelihood of developing type 2 diabetes. However, there is little known about the role of pedometers with regards to a Diabetes Prevention Program (DPP) PURPOSE: To determine if pedometer use could aid in the reduction of total body weight, cholesterol, and blood glucose levels as a part of the Centers for Disease Control National DPP. METHODS: Body weight, FBG and lipids (total cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL)) were measured prior to the start of the DPP and 16 weeks following the intervention. All participants were either diagnosed as prediabetic or at risk for prediabetes based on the CDC screening tool. The pedometer group (PG) (n=9) received pedometers and the control group (CG) (n=8) did not. All participants received the same educational sessions that explained dietary changes and strategies to increase PA. The PG was asked to wear a pedometer on their belt for all waking hours of the day, seven days a week, for sixteen weeks. At each weekly DPP meeting, step counts from pedometers were recorded and pedometers were reset and returned to the participants. A 2x2 ANOVA was performed to examine differences. RESULTS: The PG experienced significant (p<0.05) weight loss from pre to post-test (186.2lbs + 9.7 to 180.7 + 8.9) while the control group did not (191.3lbs + 16.8l to 190.1 + 17.0). Interestingly, HDL significantly decreased from pre to post-test (p>0.05) in the PD group (58.1mg/dL + 4.0 to 54.1mg/dL + 3.6) while the CG remained unchanged (50.9mg/dL + 5.1 to 50.5mg/dL + 4.8). There were no differences between any other variables. CONCLUSION: It appears that the addition of pedometers into the DPP can contribute positively to weight loss. It is possible participants experienced a sense of greater accountability due to the added tracking tool. Further research and a larger participation population is needed to elucidate the mechanisms that contribute to the changes in body weight and lipid profile.