Weight Loss Response Research Articles

Exercise training enhances muscle mitochondrial metabolism in diet-resistant obesity.

SummaryBackgroundCurrent paradigms for predicting weight loss in response to energy restriction have general validity but a subset of individuals fail to respond adequately despite documented diet adherence. Patients in the bottom 20% for rate of weight loss following a hypocaloric diet (diet-resistant) have been found to have less type I muscle fibres and lower skeletal muscle mitochondrial function, leading to the hypothesis that physical exercise may be an effective treatment when diet alone is inadequate. In this study, we aimed to assess the efficacy of exercise training on mitochondrial function in women with obesity with a documented history of minimal diet-induced weight loss.MethodsFrom over 5000 patient records, 228 files were reviewed to identify baseline characteristics of weight loss response from women with obesity who were previously classified in the top or bottom 20% quintiles based on rate of weight loss in the first 6 weeks during which a 900 kcal/day meal replacement was consumed. A subset of 20 women with obesity were identified based on diet-resistance (n=10) and diet sensitivity (n=10) to undergo a 6-week supervised, progressive, combined aerobic and resistance exercise intervention.FindingsDiet-sensitive women had lower baseline adiposity, higher fasting insulin and triglycerides, and a greater number of ATP-III criteria for metabolic syndrome. Conversely in diet-resistant women, the exercise intervention improved body composition, skeletal muscle mitochondrial content and metabolism, with minimal effects in diet-sensitive women. In-depth analyses of muscle metabolomes revealed distinct group- and intervention- differences, including lower serine-associated sphingolipid synthesis in diet-resistant women following exercise training.InterpretationExercise preferentially enhances skeletal muscle metabolism and improves body composition in women with a history of minimal diet-induced weight loss. These clinical and metabolic mechanism insights move the field towards better personalised approaches for the treatment of distinct obesity phenotypes.FundingCanadian Institutes of Health Research (CIHR-INMD and FDN-143278; CAN-163902; CIHR PJT-148634).

The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery

Although patients generally prefer oral drug delivery to injections, low permeability of the gastrointestinal tract makes this method impossible for most biomacromolecules. One potential solution is codelivery of macromolecules, including therapeutic proteins or nucleic acids, with intestinal permeation enhancers; however, enhancer use has been limited clinically by modest efficacy and toxicity concerns surrounding long-term administration. Here, we hypothesized that plant-based foods, which are well tolerated by the gastrointestinal tract, may contain compounds that enable oral macromolecular absorption without causing adverse effects. Upon testing more than 100 fruits, vegetables, and herbs, we identified strawberry and its red pigment, pelargonidin, as potent, well-tolerated enhancers of intestinal permeability. In mice, an oral capsule formulation comprising pelargonidin and a 1 U/kg dose of insulin reduced blood glucose levels for over 4 h, with bioactivity exceeding 100% relative to subcutaneous injection. Effects were reversible within 2 h and associated with actin and tight junction rearrangement. Furthermore, daily dosing of mice with pelargonidin for 1 mo resulted in no detectable side effects, including weight loss, tissue damage, or inflammatory responses. These data suggest that pelargonidin is an exceptionally effective enhancer of oral protein uptake that may be safe for routine pharmaceutical use.

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation

This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Weight loss and β-cell responses following gastric banding or pharmacotherapy in adults with impaired glucose tolerance or type 2 diabetes: a randomized trial.

The extent to which weight loss contributes to increases in insulin sensitivity (IS) and β-cell function after surgical or medical intervention has not been directly compared in individuals with impaired glucose tolerance or newly diagnosed type 2 diabetes. The Restoring Insulin Secretion (RISE) Study included adults in the Beta-Cell Restoration Through Fat Mitigation Study (n=88 randomized to laparoscopic gastric banding or metformin [MET]) and the Adult Medication Study (n=267 randomized to placebo, MET, insulin glargine/MET, or liraglutide + MET [L + M]). IS and β-cell responses were measured at baseline and after 12 months by modeling of oral glucose tolerance tests and during arginine-stimulated hyperglycemic clamps. Linear regression models assessed differences between and within treatments over time. BMI decreased in all treatment groups, except placebo, at 12 months. IS increased in all arms except placebo and was inversely correlated with changes in BMI. L + M was the only treatment arm that enhanced multiple measures of β-cell function independent of weight loss. Insulin secretion decreased in the laparoscopic gastric banding arm proportional to increases in IS, with no net benefit on β-cell function. Reducing demand on the β-cell by improving IS through weight loss does not reverse β-cell dysfunction. L + M was the only treatment that enhanced β-cell function.

O106 Maximising the benefits of bariatric surgery through targeting ghrelin: a randomised, double-blind, placebo-controlled crossover study in people with suboptimal weight loss after bariatric surgery

Abstract Introduction One in 5 people have a suboptimal weight-loss (WL) response to bariatric surgery. The causes are unclear, but patients report resumed hunger and increased food intake, eating behaviours driven by the orexigenic hormone, ghrelin. This proof-of-concept study aimed to evaluate the impact of reducing circulating acyl-ghrelin, the biologically active isoform, on appetite and energy intake in people with suboptimal WL and aberrant ghrelin profile after bariatric surgery. Methods Thirty-five patients with &amp;lt;20%WL from 12 months after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and aberrant circulating ghrelin profile underwent 10 days of treatment with a novel, highly-selective ghrelin o-acyltransferase inhibitor, GLWL-01, and placebo. The primary endpoint was within-person change in ad libitum energy intake during a test meal on day 10. Secondary endpoints assessed subjective appetite, food cravings, macronutrient intake, gut hormones, cardiometabolic profile and body composition. Ethical approval was obtained. Results Thirty-one participants (26 RYGB, 9 SG) completed both cycles. GLWL-01 produced a 58.9±27.2% decrease in fasting plasma acyl-ghrelin and 29.3±27.1% increase in desacyl-ghrelin after 10 days. Marked reduction in subjective hunger, food cravings and hedonic influence on appetite was observed with GLWL-01, however objective appetite measures – ad libitum and free-living energy intake – did not change. Circulating levels of cardiovascular risk-conferring lipoproteins significantly improved and no adverse impact on glycaemic control was observed. Conclusion Pharmacological modulation of the ghrelin system may be used as part of a personalised therapeutic approach to optimise clinical outcomes in patients with suboptimal WL after bariatric surgery. Take-home message This first-in-human mechanistic study shows that pharmacological modulation of the ghrelin system is a promising therapeutic strategy for maximising weight loss response to bariatric surgery.

EE79 A Cost of Control Analysis of Once-Weekly Subcutaneous Semaglutide Versus Dulaglutide for Bringing Patients to Treatment Targets in China

In the SUSTAIN 7 randomized controlled trial, once-weekly subcutaneous semaglutide (OW) subcutaneous (s.c.) 0.5mg was associated with greater reduction in glycated hemoglobin (HbA1c) and body weight in people with type 2 diabetes mellitus (T2DM) comparing dulaglutide 1.5mg. The present study estimated the annual cost per patient achieving HbA1c treatment targets and weight loss responses with OW s.c. semaglutide and dulaglutide in the Chinese healthcare system setting over a one-year period.

Combined First Month Body Weight Loss and Development of Tolerance as Predictors of 6-Month Efficacy of Mazindol in Mild and Moderate Obese Subjects.

The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, “one size does not fit all”.

1410-P: Changes in Circulating MicroRNA-193b and Long-Term Successful Weight Loss in Response to Dietary and Lifestyle Interventions: The POUNDS Lost and CENTRAL Trials

Circulating microRNAs (miRNAs) have been implicated in controlling whole-body metabolism through intercellular communications. MicroRNA-193b (miR-193b) plays essential roles in white and brown adipocyte adipogenesis and regulating adipokine secretion. We tested whether changes in circulating miR-193b were associated with reductions of adiposity and various fat depots in response to weight-loss dietary and lifestyle interventions in two independent trials. This study included participants of a 2-year weight-loss diet intervention trial (POUNDS Lost) with data on changes in circulating miR-193b-5p from baseline to 6 months after interventions (n=509) . We also assessed changes in circulating miR-193b-5p over 18 months in the CENTRAL weight-loss lifestyle intervention trial (n=111) . At baseline, higher miR-193b was associated with greater adiposity, energy expenditure, ectopic fat depots, and lower adiponectin levels. In response to the interventions, decreases in miR-193b were associated with larger reductions of weight (p &amp;lt;.0001) , waist circumference (p &amp;lt;.0001) , and whole-body total % fat mass (p=0.03) at 6 months in the POUNDS Lost trial. In the CENTRAL trial, decreases in miR-193b were associated with larger reductions of weight (p=0.03) , total (p=0.002) and visceral adipose tissue (p=0.004) , and different fat depots (deep and superficial subcutaneous, and hepatic fat; p &amp;lt;0.for all) . In both trials, every 1 SD decrease of miR-193b was associated with an increased probability for the achievement of successful weight loss (-5% or more weight loss) at the end of interventions (odds ratio [OR]: 1.4; p=0.0in POUNDS Lost; OR 1.9; p=0.02 in CENTRAL) . In conclusion, changes in circulating miR-193b in response to weight-loss diet/lifestyle interventions were significantly associated with the long-term successful weight loss and reductions of fat depots closely related to the risk of diabetes. Disclosure Y.Heianza: None. F.Sacks: None. L.Qi: None. Q.Xue: None. J.Rood: None. K.K.Krohn: None. A.Yaskolka meir: None. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. P.Kovacs: None. I.Shai: None. G.Bray: None. Funding NIH (DK091718, DK100383, DK115679)

Adherence to Healthy Lifestyle Habits Is a Determinant of the Effectiveness of Weight Loss among Patients Undergoing Endoscopic Bariatric Therapies.

Endoscopic bariatric therapies (EBTs) are promising strategies for the treatment of obesity. However, there is still great variability in its effectiveness in weight loss. Thus, we investigated whether adherence to healthy lifestyle habits is a significant determinant of weight loss effectiveness among patients undergoing EBTs. Additionally, the role of eating behaviors and psychological traits in the effectiveness of weight loss was studied. A cohort of 361 participants (81.4% women; age 41.8 ± 9.5 years; BMI 37.8 ± 4.3 kg/m2) was followed for 1 year after EBT. Anthropometric parameters, adherence to healthy lifestyle habits, emotional eating, and psychological traits (anxiety and depression) were evaluated. General linear models were used to compare outcome variables according to weight loss effectiveness groups (poor vs. good weight-loss-responders). Additionally, a hierarchical linear regression model was used to determine whether adherence to healthy lifestyle habits, emotional eating, or psychological traits were significant predictors of excess weight loss (%EWL). One year after EBT, weight loss differed significantly between good and poor weight-loss-responders (67.5% EWL [95% CI: 64.2, 70.8] vs. 28.2% EWL [95% CI: 25.5, 30.9], p < 0.001). Participants who adhered to good lifestyle habits had 4.37 more odds [95% CI: 2.19, 8.88] of being good weight-loss-responders. We also observed that eating four to five meals/day and practicing muscle-strengthening activities >2 times/week were the two lifestyle habits that most significantly determined weight loss response. Furthermore, our results revealed that while adherence to healthy lifestyle habits was a significant determinant of %EWL 3, 6, and 12 months after EBT (p < 0.001), emotional eating was a significant determinant of %EWL only 3 and 6 months after the intervention (p < 0.01 and p < 0.05, respectively). Regarding psychological traits, we observed that neither anxiety nor depression were significant determinants of %EWL. Our results revealed that adherence to healthy lifestyle habits is a significant determinant for weight loss effectiveness among patients with obesity undergoing EBT. These findings highlight the importance of implementing an adequate nutritional intervention program, especially since patients who adhere to good lifestyle habits are able to achieve a weight loss that would be comparable with bariatric surgery.

Association between clinical and genetic factors and glycemic and weight loss response to liraglutide in patients with type 2 diabetes

Association between clinical and genetic factors and glycemic and weight loss response to liraglutide in patients with type 2 diabetes

Metabolic Profile and Metabolite Analyses in Extreme Weight Responders to Gastric Bypass Surgery.

Background: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut microbiota composition and systemically released metabolites were analyzed in a cohort of extreme weight responders after RYGB. Methods: Patients (n = 23) were categorized based on excess weight loss (EWL) at a minimum of two years after RYGB in a good responder (EWL 93 ± 4.3%) or a bad responder group (EWL 19.5 ± 13.3%) for evaluation of differences in metabolic outcome, eating behavior and gut microbiota taxonomy and metabolic activity. Results: Mean BMI was 47.2 ± 6.4 kg/m2 in the bad vs. 26.6 ± 1.2 kg/m2 in the good responder group (p = 0.0001). We found no difference in hunger and satiety sensation, in fasting or postprandial gut hormone release, or in gut microbiota composition between both groups. Differences in weight loss did not reflect in metabolic outcome after RYGB. While fecal and circulating metabolite analyses showed higher levels of propionate (p = 0.0001) in good and valerate (p = 0.04) in bad responders, respectively, conjugated primary and secondary bile acids were higher in good responders in the fasted (p = 0.03) and postprandial state (GCA, p = 0.02; GCDCA, p = 0.02; TCA, p = 0.01; TCDCA, p = 0.02; GDCA, p = 0.05; GUDCA, p = 0.04; TLCA, p = 0.04). Conclusions: Heterogenous weight loss response to RYGB surgery separates from patients’ metabolic outcome, and is linked to unique serum metabolite signatures post intervention. These findings suggest that the level of adiposity reduction alone is insufficient to assess the metabolic success of RYGB surgery, and that longitudinal metabolite profiling may eventually help us to identify markers that could predict individual adiposity response to surgery and guide patient selection and counseling.

Early Weight Loss

Background: Bariatric surgery is the most effective weight loss intervention for patients with severe obesity. Several studies have shown wide variability in weight loss response between patients. The aim of the study is to identify comparative poor responders based on weight loss in the early postoperative period. Methods: A retrospective analysis of 125 patients who underwent primary bariatric surgery by a single surgeon and completed 1 year of follow-up was performed. Patients were divided into two groups based on % Total Weight loss (%TWL) at 1 month after surgery: Group 1-who lost &lt;10% TWL and Group 2-who lost &gt;10% TWL. The comparison of factors in both groups at different time points was executed using paired t-tests or analysis of variance. The relationships between Group 1 and Group 2 after 1 year follow-up period were assessed through linear regression analyses. Results: Seventy (56%) patients lost &lt;10% TWL and 55 (44%) patients lost more than 10% TWL in 1 month after surgery. Mean weight loss at 1 month and 1 year after surgery was 9 ± 5.5 kg and 37 ± 13.3 kg in Group 1 compared to 16 ± 5.2 and 46 ± 16.4 kg in Group 2, respectively. Patients with &gt;10%TWL at 1 month had significantly greater %TWL at 1 year (P = 0.001). Linear regression analysis showed a positive correlation between patients who lost &gt;10%TWL 1 month after surgery and weight loss at 1 year. Conclusion: Postoperative percentage TWL of &lt;10% at 1 month can be used as an early determinant of comparatively poor weight loss at 1 year. Early initiation of aggressive and multimodal treatment strategies is likely to improve overall weight loss outcomes after surgery.

Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes.

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Amyloid Beta Pathology Exacerbates Weight Loss and Brain Cytokine Responses following Low-Dose Lipopolysaccharide in Aged Female Tg2576 Mice.

Systemic inflammation has been implicated in the progression of Alzheimer’s disease (AD); however, less is understood about how existing AD pathology contributes to adverse outcomes following acute inflammatory insults. In the present study, our goal was to determine how AD-associated amyloid beta (Aβ) pathology influences the acute neuroinflammatory and behavioral responses to a moderate systemic inflammatory insult. We treated 16–18-month-old female Tg2576 (Tg) mice, which overproduce human Aβ and develop plaques, and age-matched wild-type (WT) littermate mice with an intraperitoneal injection of 0.33 mg/kg lipopolysaccharide (LPS) or saline. Mice were then evaluated over the next 28 h for sickness/depressive-like behaviors (food intake, weight loss, locomotion, and sucrose preference), systemic inflammation (serum amyloid A, SAA), blood-brain barrier (BBB) disruption, astrogliosis (glial fibrillary acidic protein/GFAP), Aβ, and cytokine levels in the brain. We found that LPS caused a larger reduction in body weight in Tg vs. WT mice, but that other behavioral responses to LPS did not differ by genotype. BBB disruption was not apparent in either genotype following LPS. Concentrations of the systemic inflammatory marker, SAA, in the blood and brain were significantly increased with LPS but did not significantly differ by genotype. GFAP was increased in Tg mice vs. WT but was not significantly affected by LPS in either genotype. Finally, LPS-induced increases of eight cytokines (IL-1β, IL-6, IL-12 (p40), IL-10, IL-17A, MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5) were found to be significantly higher in Tg mice vs. WT. In summary, our data show that Aβ pathology exacerbates the neuroinflammatory response to LPS and identifies cytokines that are selectively regulated by Aβ. The association of worse neuroinflammation with greater weight loss in Tg mice suggests that Aβ pathology could contribute to poor outcomes following a systemic inflammatory insult.

Developing anemone aquaculture for the marine aquarium trade: A case study using the bubble‐tip anemone Entacmaea quadricolor

Anemones are important aquaculture targets for the marine aquarium trade. We explore survival and growth of whole (W) and half (H) bubble-tip anemones (Entacmaea quadricolor) under: no food (−F−N), directed feeding (+F−N) and/or providing dissolved nutrients (−F+N, +F+N). Treatment effects were assessed using multiple endpoints including: survivorship, weight loss, behaviour and symbiotic-community responses. Survival analysis confirms highly significant differences among treatments. All treatments resulted in weight loss, but only +F−N resulted in significantly lower weight loss than -F+N. All anemones were highly mobile; however, no significant differences for days active, upside down and detached were recorded and the vast majority of anemones did not expel zooxanthellae. Zooxanthellae and chlorophyll pigment concentrations varied over time indicating host-symbiont plasticity. Cutting does not affect zooxanthellae number or pigment concentrations, but dissolved nutrient delivery significantly reduces zooxanthellae numbers and the chlorophyll C concentration per zooxanthellae cell compared with controls. Cutting is a simple culture method that should be routinely used, but more precise regulation of nutrient delivery and feeding is required before they can be incorporated. Finally, for hobbyists to make informed decisions about choosing an anemone, we recommend a review of E. quadricolor's and other species’ suitability for long-term aquarium captivity.

Prediction scale of response to liraglutide therapy as the method for increase of treatment efficacy in type 2 diabetes.

Background:The effects of liraglutide on body weight and hemoglobin A1C (HbA1c) level vary greatly. The cost of this drug negatively affects treatment adherence.Aim:To reveal the baseline patient characteristics, associated with a better response to liraglutide.Materials and methods:A total of 41 patients with BMI of 39.63 ± 7.59 kg/m2 who received liraglutide injection up to 1.8 or 3.0 mg/day for 6 months were enrolled. Demographic and anthropometric data, parameters of glycemic control, food intake, hormones and responses to the eating behavior questionnaire were collected.Results:Weight reduction was dose-dependent (p = 0.007). Liraglutide was not effective in patients with BMI >45 kg/m2. The baseline HbA1c level was a significant factor for HbA1c reduction. Lower leptin and higher glucagon-like-peptide 1 concentrations might predict better weight loss response to liraglutide.Conclusion:Drug-specific efficacy predictors were assumed; thus, further studies are needed to prove their significance.

How to evaluate the potential toxicity of therapeutic carbon nanomaterials? A comprehensive study of carbonized nanogels with multiple animal toxicity test models

Carbon-based nanomaterials have great potential in medical applications, especially in the treatment of infectious diseases and even tumors. However, to safely execute the application of carbon nanomaterials in human treatments, conducting safety assessments and establishing suitable evaluation criteria are necessary. In this study, lysine-carbonized nanogels (Lys-CNGs) that display antibacterial and antiviral abilities were employed in a comprehensive evaluation of their toxicity profiles through assessments in different animal models and growth stages. It was observed that zebrafish at the embryo and eleutheroembryo stages experienced significant toxic effects at a concentration of 15-fold the recommended dosage (0.5 ppm), whereas adult zebrafish following long-term consumption of fodder containing Lys-CNGs presented no adverse effects. Further microbiota analysis indicated that Lys-CNGs did not cause significant changes in the composition of the intestinal bacteria. In contrast, in the toxicity assessments with mammalian animal models, the Lys-CNGs showed no adverse effects, such as weight loss, dermal irritation, and skin sensitization responses in rabbits and guinea pigs, even at a high dose of 2000 mg/kg body weight. Our study revealed that Lys-CNGs have different toxic effects on different growth stages of zebrafish. Researchers in this field should carefully consider the implications of these toxicity profiles during the development of therapeutic carbon-based nanomaterials and for comparison of studies.

Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention: The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

Fluid-filled intragastric balloons are an effective and safe weight loss option across BMI and age ranges.

Obesity is an expanding public health problem, resulting in more than half a billion adults worldwide. Intragastric balloon (IGB) placement is a weight loss alternative for obese patients with an inadequate weight loss response to diet and exercise. The aim of this study is to examine the efficacy and safety of the single-chamber fluid-filled IGB for weight loss and compare its results across different age groups. We performed a database review of 239 consecutive patients from two outpatient GI clinics who underwent placement of an IGB. Our final analysis composed of 239 IGB placements in 232 patients (mean age, 44.5 ± 10.3years; 67% female; baseline BMI 42.0 ± 9.0). Efficacy outcomes included the percentage of the total (%TWL) and excess weight loss (%EWL). Safety outcomes were measured as the number of patients who required early IGB removal (before 6months). %TWL at 3months was 10.1% and 14.4% at 6months. Overall, 92%, 74%, and 47% of patients lost 5%, 10%, and 15% of total weight at 6months, respectively. %EWL was 22.1% and 30.7% at 3 and 6months post-IGB placement, respectively. The balloon was safely removed at six months after placement in most patients, whereas in 13.0% of cases early removal was performed at an average of 12.0weeks after placement (range, 2days-23weeks). The use of a single-chamber fluid-filled IGB is successful in inducing a significant amount of weight loss in almost three-fourths of patients six months after its placement. This beneficial effect is seen across different BMI ranges and age groups at a similar level. IGBs should be considered an effective and safe alternative for obese patients who fail lifestyle interventions and conservative measures, fulfilling the unmet needs of many who are unwilling or unable to undergo bariatric surgery.

Effectiveness of anti-obesity medications approved for long-term use in a multidisciplinary weight management program: a multi-center clinical experience.

Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings. We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020. We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation. The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects. AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials.