Greater Reduction In Body Weight Research Articles

52-OR: Effect of Oral Nonpeptide GLP-1 Receptor Agonist Orforglipron (LY3502970) in Participants with Obesity or Overweight—A Phase 2 Study

Orforglipron (OFG) is a novel once daily oral non-peptide GLP-1 receptor agonist (RA) which can be taken with or without food, in development for chronic weight management. The objective of this Phase 2 study was to assess the efficacy, safety, and tolerability of OFG in patients with obesity or overweight with ≥1 weight-related comorbidity. Participants (N=272) were randomized to placebo or OFG (12, 24, 36, or 45 mg) treatment. OFG doses were increased to target using different dose escalation schemes in each arm. The primary endpoint was to compare percent body weight (BW) change from baseline in OFG vs placebo at Week 26, while the study continued to 36 weeks. Secondary endpoints included change from baseline in waist circumference (WC) and BMI, and the percentage of participants achieving ≥5 or ≥10% weight loss. At baseline, mean BW was 108.7 kg, BMI was 37.9 kg/m2, and 94% of participants had a BMI ≥30 kg/m2. Mean percentage BW loss, mean change in BMI and WC, and the percentage of participants achieving ≥5% or ≥10% weight loss were significantly greater with all OFG doses vs placebo (Figure). The AE profile was similar to other GLP-1 RAs; most were GI-related and mild to moderate in severity. The novel non-peptide GLP-1 RA OFG led to greater reductions in BW, BMI, and WC compared with placebo. These promising data support continued development of OFG as an oral treatment for obesity. Disclosure S.Wharton: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim International GmbH, Bausch Health, Canada, Research Support; Novo Nordisk, Eli Lilly and Company, Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Bausch Health, Canada. C.M.Kazda: Employee; Eli Lilly and Company. M.Konig: None. T.Blevins: Other Relationship; Medtronic, Research Support; Lilly Diabetes, Novo Nordisk, Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Medtronic, Speaker's Bureau; Lilly Diabetes, Novo Nordisk A/S. L.B.Connery: None. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. S.Raha: Employee; Eli Lilly and Company. K.J.Mather: Employee; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. D.A.Robins: None. E.J.Pratt: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

Effectiveness of intermittent fasting for weight loss in individuals with obesity: A meta-analysis of randomized controlled trials

AimTo assess whether intermittent fasting (IF) diets are associated with improvement in weight loss, metabolic parameters, and subjective well-being, in people with obesity. Data synthesisWe performed a Meta-analysis of Randomized Controlled Trials longer than 2 months, retrieved through an extensive search on MedLine, Cochrane CENTRAL Library, and Embase online databases, comparing weight loss with IF diets and control diets in people with Body Mass index (BMI) > 30 kg/m2. We retrieved 9 trials, enrolling 540 patients. IF was not associated with a significantly greater reduction of body weight or BMI at any time point with respect to controls or in respect to continuous restricted diets, with low-to moderate quality of evidence; no significant difference in efficacy between alternate day fasting and time restricted eating was found. Differences in fasting plasma glucose, total or high-density lipoprotein cholesterol or blood pressure at any time point were not statistically significant, whereas a reduction of low-density lipoprotein cholesterol (MD −8.39 [−15.96, −0.81] mg/dl, P = 0.03; I2 = 0%) was observed at 2–4 months, but not in the longer term. Data on psychological parameters and overall well-being were insufficient to perform a formal meta-analysis, whereas a qualitative synthesis did not show any difference between IF and controls. ConclusionsIF is not associated with greater or lesser weight loss than non-intermittent fasting diets. Further data on psychological parameters and overall well-being are needed to properly assess the role of IF diets in the management of obesity.

Effect of Aerobic Training Versus Chair Aerobics on Body Mass Index and Quality of Life in Obese Desk Job Workers

Obesity is defined as an excess accumulation of body fat. A sedentary lifestyle is associated with an increase in BMI over time, thus leading to obesity. Physical activity has been shown to reduce stress and anxiety traits and to improve physical self- perception and mental well-being. In desk job profession, physical activity levels at work are low while sedentary behavior is high. Aerobic exercise training using treadmill has capacity to improve the intrinsic pump capacity of the myocardium. Participation in regular aerobic exercises is now considered an essential component in any long term obesity management. Chair aerobics is a form of aerobic exercise performed while sitting in a chair, which include upper and lower body movements led by an instructor while listening to music and sitting in a straight-back chair. Aim : to study the effect of aerobic versus chair aerobics on body mass index and quality of life in obese desk job workers. Method:The materials that will be used in this study are treadmill and chair with outcome measures as Obesity Related Well-Being Questionnaire (ORWELL-97) and BMI. 38 subjects will be randomly divided into 2 groups. Group 1(aerobic training) will be given aerobic training on treadmill for 30 minutes, 3 times per week for 2 months. Group 2 (chair aerobics) will be given Chair aerobics for 30 minutes 4 times per week for 2 months. Pre & post intervention assessments i.e. body mass index and ORWELL- 97 Questionnaire will give the final result for the given topic. Outcome measures: Prior and after treatment both the outcome measures, Body Mass Index (BMI) and quality of life using Obesity Related Well Being Questionnaire (ORWELL-97) were measured. Result: The result of the present study demonstrates that in group 1there was greater reduction in body weight as compared to group 2 but there was greater improvement in quality of life in group 2 than in group 1. There was no significant effect statistically in BMI in both the groups. Conclusion: Study was done exclusively on desk job workers to compare the effect of aerobic training versus chair aerobics on BMI and quality of life. Aerobic training using treadmill showed greater reduction in body weight as compared to chair aerobics. Chair aerobics showed greater improvement in quality of life as compared to aerobic training using treadmill.

Abstract 65: DNA Methylation at ABCG1 and Long-Term Changes in Adiposity in Response to Diet Interventions: The POUNDS Lost Trial

Introduction: Epigenome-wide association studies identified that DNA methylation (DNAm) at the ABCG1 gene (cg06500161) was associated with obesity. However, little is known about whether DNAm at ABCG1 is associated with long-term changes in adiposity and body fat distribution in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying DNAm at ABCG1 might respond differently to dietary weight-loss interventions on long-term changes in adiposity and body fat distribution. Methods: The current study included 673 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm level was profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at ABCG1 was defined as the average methylation level over CpGs within ± 250 bp of cg06500161. Two-year changes in adiposity and Computed Tomography (CT)-measured body fat distribution were calculated. Results: We found that regional DNAm at ABCG1 significantly interacted with dietary protein intake on long-term changes in body weight and waist circumference (WC) at 6 months and 2 years (P-interaction<0.05 for all, Figure ). Among participants assigned to an average-protein (15%) diet, lower regional DNAm at ABCG1 was associated with greater reductions in body weight and WC at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interactions were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (P-interaction<0.05 for all). Conclusion: Our data indicate that DNAm at ABCG1 interacted with dietary protein intake on long-term changes in adiposity and body fat distribution. Participants with hypomethylation at ABCG1 benefited more in long-term improvement in adiposity and body fat distribution by consuming an average-protein diet.

Continuous Infusion Versus Bolus Injection of Loop Diuretics for Patients With Congestive Heart Failure: A Meta-Analysis.

Loop diuretics continue to be a crucial component of pharmacological treatment, to eliminate extra fluid and enhance symptom control in acute decompensated heart failure (ADHF). Understanding the loop diuretics' more efficient form of administration would be very beneficial in improving the management of people's ADHF, resulting in a quicker resolution of symptoms and a notable decrease inmorbidity. To assess the outcomes of intravenous continuous infusion with bolus injection of loop diuretics for patients with ADHF, this meta-analysis was carried out. The current meta-analysis was conducted as per the Cochrane Collaboration guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension (PRISMA) guidelines. A search was carried out on PubMed and EMBASE databases for studies comparing continuous infusion with intermittent bolus injection of furosemide in patients with congestive heart failure without restriction on the language of publication from 1January 2001 to 31July 2022. The primary outcome of the meta-analysis was all-cause mortality and loss of body weight (kg). Pre-defined secondary outcomes included length of hospital stay (LOS) in days, brain natriuretic peptide(BNP) reduction (pg/ml), number of patients with hypokalemia, and urine output at 24 hours (ml). A total of nine articles were included in this meta-analysis enrolling 713 patients. No significant difference was reported between patients who received intermittent bolus injections and continuous infusion of furosemide in regards to all-cause mortality, LOS, total urine output, the incidence of hypokalemia, and change in BNP. However, the reduction of body weight was greater in the continuous infusion group compared to bolus administration. In conclusion, in the current meta-analysis of nine randomized controlled trials (RCTs), continuous infusion of furosemide seemed to have a greater reduction of body weight. However, no significant difference was there in 24-hrs urine output. However, we cannot conclude that intravenous continuous infusion has a better diuretic effect compared to bolus administration.

Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study

AimTo compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D).MethodsThis was a multicentre retrospective study on patients aged 70–80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015–2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM).ResultsPatients initiating dapagliflozin (n = 445) differed from those initiating DPP-4i (n = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p < 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors.ConclusionsElderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints.

The effects of glucagon-like peptide-1 receptor agonists on adipose tissues in patients with type 2 diabetes: A meta-analysis of randomised controlled trials.

AimsGlucagon‑like peptide 1 receptor agonist (GLP-1RA) treatment can improve adipose distribution. We performed this meta-analysis to investigate whether GLP-1RAs preferentially reduce visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT) in patients with type 2 diabetes.Materials and methodsWe searched MEDLINE and the Cochrane Library for randomised controlled trials explicitly reporting changes in VAT and SAT. A random-effects model was performed to estimate the weighted mean difference (MD) for VAT and SAT. Heterogeneity among the studies was assessed using I2 statistics, and publication bias was assessed using Egger’s tests. Meta-regression was performed to identify the correlation between changes in adipose tissues and changes in body weight and glycated haemoglobin level.ResultsTen trials with 924 patients were enrolled in the meta-analysis. GLP-1RA treatment led to similar absolute area (cm2) reductions in VAT (MD -21.13 cm2, 95% CI [-29.82, -12.44]) and SAT (MD -22.89 cm2, 95% CI [-29.83, -15.95]). No significant publication bias was detected, and this result was stable in the sensitivity and subgroup analyses. Moreover, GLP-1RA treatment resulted in a greater reduction in VAT and SAT in the subgroup with a greater reduction in body weight. The absolute area reduction in VAT was significantly correlated with the reduction in body weight (r = 6.324, p = 0.035).ConclusionsGLP-1RA treatment leads to significant and similar absolute reductions in VAT and SAT, and the reduction in adipose tissues may be correlated with the reduction in body weight.

Intermittent fasting two days versus one day per week, matched for total energy intake and expenditure, increases weight loss in overweight/obese men and women

BackgroundIntermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4–5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown.MethodsThis randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5).ResultsBoth groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10).ConclusionsThese findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men.Trial registrationThis trial was registered March 03, 2020 at www.clinicaltrials.gov as NCT04327141.

Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials.

AimsThe melanocortin 4 receptor (MC4R) plays a central role in appetite regulation, and agonistic activity at this receptor promotes satiety. Results from two randomized controlled clinical trials examine the effects of bremelanotide's agonism at MC4R on caloric intake and body weight.MethodsPremenopausal women with a body mass index >30 kg/m2 were studied in two phase 1, single‐centre, randomized, double‐blind, placebo‐controlled trials. Study A matched subjects 1:1 to receive subcutaneous placebo or bremelanotide three times daily for days 1‐15. Study B was a crossover trial with six distinct treatment sequences consisting of three 4‐day treatment periods, investigating once‐a‐day and twice‐a‐day exposure to bremelanotide versus placebo. Subjects received one of the three treatments twice‐daily during each period: 0 mg/0 mg, 2.5 mg/0 mg or 2.5 mg/2.0 mg bremelanotide. Body weight and food intake were recorded in detail daily. Adverse events were recorded throughout both studies.ResultsIn Study A, 27 of 30 bremelanotide subjects (90.0%) completed the trial and exhibited a significantly greater reduction in body weight after 16 days versus placebo [least squares mean difference (95% CI), −1.3 (−1.9 to −0.8) kg; p < .0001]. Mean caloric intake in bremelanotide subjects was decreased versus placebo, with a magnitude of reduction of approximately 400 kcal/day throughout Study A (p < .01). In Study B, 15 of 27 subjects (55.6%) completed all three phases. Significantly greater reduction of mean body weight occurred in twice‐daily bremelanotide subjects versus placebo (1.7 vs. 0.9 kg, respectively, p < .001). Total caloric intake reduction was significantly greater in the bremelanotide groups versus placebo (mean difference range: 398‐469 kcal; p < .0001).ConclusionsAgonist activity at the MC4R may aid in reducing caloric intake and weight loss in obese women.

Abstract MP35: Circulating MicroRNA-21 And Cardiovascular Risk Reduction In Response To Weight-loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial

Introduction: MicroRNA-21 (MiR-21) is one of the most highly expressed microRNAs in the cardiovascular system and plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Hypothesis: We assessed the hypothesis that circulating miR-21 is associated with the change in overall CVD risk and individual cardiovascular risk factors in response to weight-loss diet interventions. Methods: Circulating miR-21 was measured at baseline and 6 months in 511 participants with overweight or obesity from the 2-year weight-loss diet intervention study, the POUNDS LOST trial. MiR-21-5p is a mature sequence derived from the 5' end of the miR-21 stem-loop precursor and another mature sequence, miR-21-3p, is derived from the 3' end of miR-21. The primary outcome was the change in the global Framingham Risk Score (FRS), which estimates the 10-year probability of a CVD event. Secondary outcomes were the change in the FRS components including systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance, gut microbiota metabolites, and adiposity measures. Results: Circulating miR-21-3p levels were positively associated with fasting insulin ( P =0.011), insulin resistance ( P =0.008), and triglycerides ( P =0.003) at baseline. We found that lower pre-intervention expression levels of miR-21-3p and miR-21-5p were related to a greater reduction in FRS (β[SE]=11.020 [5.025], P =0.029 and β[SE]=0.023 [0.008], P =0.005, respectively) over 6 months. The trajectory of the FRS across the 2-year intervention period differed between the patterns of pre-intervention miR-21 ( P time*miR-21-3p =0.002 and P time*miR-21-5p =0.033). Compared to those with a higher level of miR-21, participants with a lower level of miR-21 had a greater decrease in FRS from baseline to 6 months and then increased substantially from 6 months to 2 years. We also found significant interactions between baseline miR-21-5p and dietary fat on change in FRS ( P fat diets* miR-21-5p =0.04). Participants with a lower level of baseline miR-21-5p on the low-fat diet group showed a greater reduction of FRS than those on the high-fat diet at 6 months. In addition, a greater decrease in miR-21-3p rather than miR-21-5p was significantly associated with a greater reduction in body weight (P&lt;0.0001), waist circumference ( P =0.002), and improvement in trimethylamine N-oxide ( P =0.011) at 6 months. These associations were attenuated at 2 years of the intervention. Conclusions: In conclusion, decreased circulating miR-21 levels were related to a significant reduction in overall CVD risk and improvement in individual cardiovascular risk factors in response to dietary weight-loss interventions.

Changes in pedometer-measured physical activity are associated with weight loss and changes in body composition and fat distribution in response to reduced-energy diet interventions: The POUNDS Lost trial.

To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions. This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight-loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual-energy X-ray absorptiometry and computed tomography scans at baseline, 6months and 24 months. From baseline to 6months, when the maximum weight loss was achieved, each 1000-steps/d increment in PA was associated with a greater reduction in body weight (β[SE]=-0.48[0.11]) and waist circumference (β[SE]=-0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rate qvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24-month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P∆PA*diet < 0.05). Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight-loss diets, and such associations were more evident in people on a high-fat or average-protein diet compared with a low-fat or high-protein diet.

Effects of Isolated Soy Protein Supplementation Combined with Aerobic Exercise Training on Improving Body Composition, Anthropometric Characteristics and Cardiopulmonary Endurance in Women: A Pilot Study.

Today, women are concerned with health promotion but also with improvements in body weight and shape. The purpose of this study was to investigate the effects of aerobic exercise training (AET) combined with isolated soy protein (ISP) supplementation on the body composition, anthropometric characteristics, and cardiopulmonary endurance of women. The qualified subjects were randomly assigned to AET or AET + ISP groups. Women in the AET + ISP group were given an ISP-rich supplement (40 g/day) 5 days a week for 8 weeks; those in the AET group were given the same amount of water in an identical manner. All women received 60 min of AET twice a week for 8 weeks at an intensity of 40–65% heart rate reserve (HRR) and their body composition, anthropometric characteristics, and physical fitness were measured one week before and after the 8-week AET class. A total of 16 subjects (age: 36.13 ± 5.76 years) completed the study and were included in the dataset. The results of this study show that the AET + ISP group obtained greater reductions in body weight (effect size = 0.99), body mass index (BMI, effect size = 1.04), percentage body fat (PBF, effect size = 1.18), circumferences (waist and hip, all effect sizes > 0.8), and greater gains in the percentage lean body mass (PLBM, effect size = 0.89), compared with the AET group, without significant differences in 20 m multi-stage shuttle run test (20 m MST). We conclude that there is a trend for the consumption of ISP following AET to improve the body composition and anthropometric characteristics in women, compared with those who received the same AET without ISP supplementation.

Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial.

Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs.Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures.Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity.Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.

Should we really avoid fat in diet? The beneficial effects of low carbohydrate diet versus low fat diet on cardiovascular health: a systematic review and meta-analysis

Abstract Background European Society of Cardiology and the American College of cardiology recommend a diet that is considerably low in fat (&amp;lt;35%) and high in carbohydrates (45–55%) for cardiovascular disease (CVD) prevention. However, recent evidence suggests that low-carbohydrate diets (LCD) can provide similar, if not, better CVD protection. Design Systematic review and meta-analysis Methods 3 databases were screened until 17th of August 2020 for randomized controlled trials (RCTs). Two investigators selected studies, extracted data, and assessed risk of bias. Certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Weighted mean differences and 95% confidence intervals were calculated. Results 25 trials with a total of 2438 patients were included. LCD resulted in greater reductions in body weight (WMD −1.93 (95% CI −2.69, −1.16) kg; p&amp;lt;0.0001), triglycerides (WMD −26.13 (95% CI −23.45, −14.29) mg/dL; p&amp;lt;0.0001), TNF-alpha (WMD −0.5 (95% CI −0.82, −0.17) pg/mL; p=0.003) and IL-6 (95% CI −2.29, −0.59) pg/mL; p=0.0009) with a greater increase in HDL-C (WMD 3.73 (95% CI 2.92, 4.54) mg/dL; p&amp;lt;0.ehab724.24271) and LDL-C (WMD 5.07 (95% 1.9, 8.23) mg/dL; p=0.002) compared to low fat diet (LFD). There was no statistical difference in systolic (WMD 0.5 (95% CI −1.06, 2.05) mmHg; p=0.53) and diastolic blood pressure reduction (WMD −0.22 (95% CI −1.35, 0.91) mmHg; p=0.70). Conclusions Obese patients with other cardiovascular risk factors assigned to an LCD achieved greater reductions in weight loss and triglycerides levels with a greater increase in HDL-C levels and a more pronounced anti-inflammatory state than patients assigned to an LFD. Hence, low carbohydrate diets could be an alternative tool for cardiovascular protection in selected patients. Funding Acknowledgement Type of funding sources: None.

A hypocaloric diet rich in high fiber rye foods causes greater reduction in body weight and body fat than a diet rich in refined wheat: A parallel randomized controlled trial in adults with overweight and obesity (the RyeWeight study).

A high intake of whole grain foods is inversely associated with body mass index (BMI) and body fat in observational studies, but mixed results have been found in interventional studies. Among whole grains, rye is the richest source of dietary fiber and meals containing high-fiber rye foods have shown increased satiety up to 8h, compared to meals containing refined wheat products. The aim of the study was to determine the effect of consuming high fiber rye products, compared to refined wheat products, on body weight and body fat loss in the context of an energy restricted diet. After a 2-week run-in period, 242 males and females with overweight or obesity (BMI 27-35kg/m2), aged 30-70 years, were randomized (1:1) to consume high fiber rye products or refined wheat products for 12 weeks, while adhering to a hypocaloric diet. At week 0, week 6 and week 12 body weight and body composition (dual energy x-ray absorptiometry) was measured and fasting blood samples were collected. Subjective appetite was evaluated for 14h at week 0, 6 and 12. After 12 weeks the participants in the rye group had lost 1.08kg body weight and 0.54% body fat more than the wheat group (95% confidence interval (CI): 0.36; 1.80, p<0.01 and 0.05; 1.03, p=0.03, respectively). C-reactive protein was 28% lower in the rye vs wheat group after 12 weeks of intervention (CI: 7; 53, p<0.01). There were no consistent group differences on subjective appetite or on other cardiometabolic risk markers. Consumption of high fiber rye products as part of a hypocaloric diet for 12 weeks caused a greater weight loss and body fat loss, as well as reduction in C-reactive protein, compared to refined wheat. The difference in weight loss could not be linked to differences in appetite response. www.clinicaltrials.gov, Identifier: NCT03097237.

Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity: Comparison of Gastric Bypass, Sleeve Gastrectomy, and Usual Care.

To determine which one of the two most common metabolic surgical procedures is associated with greater reduction in risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and obesity. A total of 13,490 patients including 1,362 Roux-en-Y gastric bypass (RYGB), 693 sleeve gastrectomy (SG), and 11,435 matched nonsurgical patients with T2DM and obesity who received their care at the Cleveland Clinic (1998-2017) were analyzed, with follow-up through December 2018. With multivariable Cox regression analysis we estimated time to incident extended MACE, defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality. The cumulative incidence of the primary end point at 5 years was 13.7% (95% CI 11.4-15.9) in the RYGB groups and 24.7% (95% CI 19.0-30.0) in the SG group, with an adjusted hazard ratio (HR) of 0.77 (95% CI 0.60-0.98, P = 0.04). Of the six individual end points, RYGB was associated with a significantly lower cumulative incidence of nephropathy at 5 years compared with SG (2.8% vs. 8.3%, respectively; HR 0.47 [95% CI 0.28-0.79], P = 0.005). Furthermore, RYGB was associated with a greater reduction in body weight, glycated hemoglobin, and use of medications to treat diabetes and cardiovascular diseases. Five years after RYGB, patients required more upper endoscopy (45.8% vs. 35.6%, P < 0.001) and abdominal surgical procedures (10.8% vs. 5.4%, P = 0.001) compared with SG. In patients with obesity and T2DM, RYGB may be associated with greater weight loss, better diabetes control, and lower risk of MACE and nephropathy compared with SG.

Changes in Circulating Metabolites During Weight Loss are Associated with Adiposity Improvement, and Body Weight and Adiposity Regain During Weight Loss Maintenance: The SATIN Study.

To examine the relationship between changes in circulating metabolites during diet-induced weight loss and changes of adiposity. This study also investigates changes in these metabolites in relation to body weight and adiposity regain during a weight loss maintenance period. This cohort study is nested within the Satiety Innovation (SATIN) study. Participants (n = 162) achieving ≥8% weight loss during an initial 8-week low-calorie formula diet (LCD) are included in a 12-week weight loss maintenance period. A targeted metabolite profiling (123metabolites) approach is applied using three different platforms (proton nuclear magnetic resonance, liquid chromatography mass spectrometry, gas chromatography mass spectrometry). Changes in several lipid species and citric acid are significantly associated with greater reduction of body weight, total fat, and abdominal adiposity distribution during the LCD. Decreases in the concentrations of lysophosphatidylcholines (LPCs) 14:0, LPC 20:3, phosphatidylcholine (PC) 32:2, PC 38:3, sphingomyelin (SM) 32:2, and increases in citric acid concentrations during the LCD are associated with adiposity regain and loss, respectively, during the weight loss maintenance period. The results show that weight loss is associated with changes in lipid species and citric acid. These changes are related to subsequent weight and adiposity regain identifying the adipose lipid metabolism as an important factor for the maintenance of lost weight and adiposity.

Baseline drinking water consumption and changes in body weight and waist circumference at 2-years of follow-up in a senior Mediterranean population

The association between drinking water consumption and adiposity has been poorly explored. Therefore, we aimed to analyse the associations between the frequency of drinking water consumption and body weight and waist circumference changes in an elderly Mediterranean cohort. A total of 1832 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study with baseline data on drinking water and other beverages assessed by a validated 32-item Spanish fluid-intake questionnaire and with data on body weight (BW) and waist circumference (WC) at 1-year and 2-year were included in these prospective analyses. Multivariable linear regression models were fitted to assess the β-coefficients and 95% confidence interval (CI) for BW and WC changes in terms of categories of baseline drinking water consumption (tap water and bottled water). The theoretical effect on BW and WC of replacing several beverages with drinking water was assessed using mathematical models. The baseline frequency of drinking water consumption was inversely associated with 1-year and 2-year changes in BW. β-coefficients (95%CI) across categories of water consumption (<2.5, 2.5 to <5, 5 to<7.5, ≥7.5 servings/d) expressed in % of weight changes at 2 years of follow-up were 0.0,-0.80 (-1.48,-0.12),-1.36 (-2.18,-0.54), and-1.97 (-3.09,-0.86), respectively. Individuals in the two highest categories of drinking water consumption (5 to<7, and ≥7.5 servings/d) also showed a higher decrease in WC (expressed as % of change) after 2 years of follow-up:-1.11 (-1.96,-0.25) and-1.45 (-2.66,-0.24) compared to the reference intake (<2.5 servings/day), after adjustment for potential confounding factors. The theoretical replacement of soups, beers, spirits, hot beverages, dairy beverages, and other beverages group with drinking water was associated with greater reductions in BW at one- and two-years of follow-up. Drinking water consumption was inversely associated with 2-year adiposity changes in an elderly Mediterranean cohort at high cardiovascular risk. Our results also suggest that the consumption of drinking water instead of energy-containing beverages is associated with lower weight gain. ISRCTN89898870.

Design and Evaluation of Peptide Dual-Agonists of GLP-1 and NPY2 Receptors for Glucoregulation and Weight Loss with Mitigated Nausea and Emesis.

There is a critical unmet need for therapeutics to treat the epidemic of comorbidities associated with obesity and type 2 diabetes, ideally devoid of nausea/emesis. This study developed monomeric peptide agonists of glucagon-like peptide 1 receptor (GLP-1R) and neuropeptide Y2 receptor (Y2-R) based on exendin-4 (Ex-4) and PYY3–36. A novel peptide, GEP44, was obtained via in vitro receptor screens, insulin secretion in islets, stability assays, and in vivo rat and shrew studies of glucoregulation, weight loss, nausea, and emesis. GEP44 in lean and diet-induced obese rats produced greater reduction in body weight compared to Ex-4 without triggering nausea associated behavior. Studies in the shrew demonstrated a near absence of emesis for GEP44 in contrast to Ex-4. Collectively, these data demonstrate that targeting GLP-1R and Y2-R with chimeric single peptides offers a route to new glucoregulatory treatments that are well-tolerated and have improved weight loss when compared directly to Ex-4.

Complementary and Alternative Therapies for Weight Loss: A Narrative Review.

Despite various strategies, overweight and obesity problems are still increasingly prevalent worldwide with serious health outcomes. Consequently, the continuous demand for more effective, safe and acceptable therapies for reducing body weight is also escalating—including complementary and alternative therapies (CATs). The aim of this review is to provide a summary of the most commonly- and recently-used CATs, with evaluation of their safety and efficacy for weight loss. Electronic scientific databases such as Scopus, PubMed and EBSCO Host were explored for articles that reported CATs for overweight and obesity treatment from 2015 to December 2019. Only systematic reviews, meta-analysis and randomized controlled trials (RCTs) published in English were included. Studies whereby CATs were not utilized for reducing body weight were excluded. Eight systematic reviews and meta-analyses and 11 additional RCTs with 765 participants (50.2% overweight and 49.8% obese) related to hypnotherapy, acupuncture and dietary supplements met the inclusion criteria. Their results suggested that spirulina, chitosan, probiotic, EPA + DHA, vitamin D, fiber, and herbal extract supplementation may all provide small reductions in body weight (ranging from 1-10 kg). Interestingly, hypnotherapy and acupuncture reported significantly greater reduction in body weight compared with placebo (p < 0.001 and p < 0.0001, respectively). Nonetheless, the evidence is still relatively limited and not encouraging to provide a definitive conclusion due to the methodological shortcomings and the presence of adverse events in chitosan and fiber supplementation. Hence, studies of this nature need to be further replicated and improved to corroborate the efficacy and safety of the CATs to combat weight issues.