Long-term Weight Loss Research Articles

Sustained weight loss may reduce cancer risk.

Sustained weight loss may reduce cancer risk.

OR10-3 Long-term Weight Loss Maintenance with Obesity Pharmacotherapy: a 5-Year Retrospective Study

Abstract Objective To determine the association of anti-obesity medications (FDA-approved and off-label) with weight loss maintenance over 3-5 years. Methods We performed a retrospective observational study of adults 18-75 years treated for overweight/obesity at a tertiary academic weight management center with an initial visit between April 1st, 2014 and April 1st, 2016. We excluded patients who had a period of follow-up less than 2.5 years or a gap in follow-up of greater than 2 years. Patients who had bariatric surgery, pregnancy, or a medical condition predisposing them to weight loss during the study were also excluded. We extracted key demographic data, medical history, and weight at each visit. Anti-obesity medication (AOM) start date and end date was determined through chart review with attention to patient self-reporting of medication adherence to calculate total exposure to each AOM. We used the weight loss maintenance definition of weight regain ≤ 3% of the nadir weight. Results A total of 428 patients met inclusion criteria for the analysis and were followed for a mean of 4.4 years. The mean age was 50.9 years, 73% were female, and median initial BMI was 34.3 kg/m2. Weight categories were as follows: 19% overweight, 35% class 1, 25% class 2, and 20% class 3 obesity. In addition, 16% had diabetes and 36% had prediabetes. The median nadir BMI was 25.6 with a median maximum weight loss of 14.7%. The median time to achieving nadir weight was 1.9 years. Average weight change from the initial to final visit was -10.6% (-10.9 kg), with a final visit median BMI of 27.4. The proportion of patients who achieved ≥5%, ≥10%, ≥15%, and ≥20% total weight loss was 70.8%, 48.1%, 30.1%, and 16.8%, respectively. During the 4.4 years the patients were followed, weight regain following the nadir weight was 6.3%. At the last observation, 40.2% of all patients had maintained their maximum weight loss. The mean number of AOMs trialed throughout the duration of the study was 4.2. At the final visit, a mean of 2.5 AOMs were being taken. The most common medications observed at the final visit alone or in combination were metformin (76.2% of patients), phentermine (31.1%), topiramate (30.8%), bupropion (29.9%), and semaglutide (24.5%). Conclusion Long-term weight loss of 10.6% was observed over 3-5 years in adults with overweight/obesity who were managed with pharmacotherapy. This study demonstrates clinically significant long-term weight loss maintenance can be achieved with pharmacotherapy and lifestyle interventions. Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.

RF04 | PSUN295 Evolution of Monomeric Multi-Agonists of GLP-1 and NPY Receptors

Abstract Current treatments for type 2 diabetes (T2D) and obesity do not reliably achieve long-term weight-loss and up to 50% of patients experience nausea and vomiting. Thus, there is a critical need for obesity medications that provide glycemic control with enhanced hypophagic response without nausea/emesis. Based on rational design and in silico modelling of the glucagon-like peptide 1-receptor agonist (GLP1RA) exendin-4 (Ex4) and the neuropeptide Y2 receptor (Y2R) agonist peptide YY (PYY) 3-36, we have developed and screeened several new monomeric chimeric peptides that display dual agonism of the anorectic Y2R and the glucoregulatory GLP1R. In addition, we explored a third agonistic behavior at the neuropeptide Y1 receptor (Y1R), which potentially relates to pancreatic beta-cell protection. Our current lead, GEP44, binds the Y2R, Y1R, and GLP1R. We tested effects of daily injections of these chimeric peptides in adult Sprague-Dawley rats on food intake (FI), body weight (BW) changes, blood glucose levels and an indicator of nausea (kaolin intake). GEP44 produced profound reduction in FI (2-d average GEP44 at 20 nmol/kg FI -71%; Ex-4 20 nmol/kg FI -40%). Anorectic doses of GEP44 did not trigger a pica response assessed by kaolin consumption in treated rats, while in Ex-4 treated rats, kaolin consumption accounted for 28% of total daily solid intake, indicating a clear nausea response. In addition, we assayed for emetic response in the musk shrew, with little to no such emesis displayed (n=8) for GEP44 (1/8), but emesis noted across all animals tested for Ex4. During 11 d of treatment with GEP44, FI was consistently reduced resulting in a significantly stronger reduction of BW compared to Ex4 at the end of treatment (GEP44 -7.6%, Ex4 -3.7%, p<0.05). Furthermore, 5-day injections of GEP44 showed greater reduction of glucose levels than for Ex4 in diet induced obese rats receiving ip glucose. In conclusion, simultaneously targeting serial anorectic pathways with single molecule chimeric peptides can address multiple coexisting conditions to more efficaciously reduce FI, BW and blood glucose levels, devoid of side-effects to improve patient patient and quality of life. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study

ObjectiveThe hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight. Summary background dataProspective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery. Methods65 participants were included (HO-surgery: n = 8, HO-control: n = 10, CO-surgery: n = 12, CO-control: n = 12, Lean-control: n = 23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated. ResultsPatients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5 % vs. 26.2 %, p = 0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151 ± 1667 pmol/l/h vs. 8099 ± 1235 pmol/l/h, p = 0.028) and GLP-1 (20,975 ± 2893 pmol/l/h vs. 13,060 ± 2357 pmol/l/h, p = 0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI. ConclusionsHypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.

Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis.

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPACNts neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPACNts neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPACNts neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

The challenge of weight loss maintenance in obesity: a review of the evidence on the best strategies available

Long-term weight loss maintenance represents a big challenge for the management of obesity. This narrative review aims to provide an overview of the main endocrine mechanisms involved in weight regain in subjects with obesity and to review the current evidence on the best lifestyle approaches, including diet and physical activity. Weight regain after weight loss occurs in about 50% of subjects with obesity in the absence of lifestyle changes. The primary endocrine mechanism responsible for weight regain involves the brain-gut axis, which encourages food intake and thus weight regain through the secretion and action of several gastrointestinal hormones, such as ghrelin, leptin and cholecystokinin. Several evidence reported changes of secretion of these hormones during weight loss and weight loss maintenance programs. Endurance training is the most effective physical activity to lose and keep weight loss; the association of endurance with resistance training is recommended for remodelling body shape.

Perceived challenges to implementing childhood obesity prevention strategies in pediatric primary care

Childhood is an opportune time to address issues related to weight management, as children with obesity are more likely to have obesity in adulthood, and few successful long-term weight loss strategies exist. In 2007, an Expert Committee established guidelines for integrating obesity prevention into primary care, yet few studies have examined the extent to which pediatric primary care providers provide education about nutrition and physical activity at preventive (i.e., well-child) visits. This study aimed to identify challenges encountered and strategies used by pediatric primary care providers in South Carolina to address childhood obesity. Two focus group discussions (FGDs) were conducted with pediatric primary care providers (n ​= ​23) from a federally qualified health center (FQHC) in South Carolina. Participants responded to a series of semi-structured, open-ended questions about their experiences integrating obesity prevention and treatment into primary care. Focus groups were audio recorded and transcribed verbatim. Two coders used an iterative coding and consensus-building process to identify themes and subthemes, finalize coding, and extract illustrative quotations. Providers reported that families they served experienced many barriers to healthy eating and physical activity, including lack of community-based programming and social determinants of health. Provider-focused challenges were also identified, including time constraints, lack of focus on prevention, and logistic issues. . Providers described multiple strategies to address childhood obesity in their pediatric practice, including using family-centered approaches and tailoring obesity prevention and treatment approaches to patient demographics (e.g., age, ethnicity, comorbid conditions). A number of tools were also described as helpful in promoting physical activity and healthy eating during well-child visits.

Weight loss and all-cause mortality: A propensity score matching cohort study

BackgroundWeight loss was supposed to help with decreasing risk of premature mortality. However, results on this topic remain debatable and limited by study design. ObjectiveThe present study aimed to investigate the association between weight loss and all-cause mortality among US adults with overweight or obesity in a national cohort study by using propensity score matching (PSM) analysis. MethodsA total of 5486 pairs of participants were matched in the National Health and Nutrition Examination Survey (NHANES, 2003–2015) after PSM. Hazard ratios (95% confidence intervals) (HRs (95% CIs)) were employed to evaluate the association between weight loss indicated by long-term weight loss (LTWL) and all-cause mortality by using Cox proportional hazards regression models. ResultsDuring a median follow-up of 6.8 years, 674 participants died from all-cause mortality. In each PSM match, compared with participants with LTWL < 5%, the HRs (95% CIs) for participants with LTWL of 5–9.9% (2877 pairs), 10–14.9% (1315 pairs), and ≥ 15% (1294 pairs) were 1.18 (0.83–1.68) (P = 0.366), 1.65 (1.17–2.34) (P = 0.005), and 1.91 (1.21–3.00) (P = 0.006), respectively. The significant increased risk of all-cause mortality for LTWL ≥ 15% remained among male, female, participants aged ≥ 65 years, without weight loss intention, with non-communicable diseases, and without exceeding estimated energy requirement. ConclusionWeight loss especially for being ≥ 15% should be cautious for US adults with overweight or obesity.

Comparison of weight loss outcomes between Roux-en-Y gastric bypass and sleeve gastrectomy in a racially mixed urban patient population.

National data show a trend favoring laparoscopic sleeve gastrectomy (SG) over Roux-en-Y gastric bypass (RYGB). Published data demonstrating the differences in weight loss between the two procedures are mixed. In this retrospective study using clinical data from 2010 to 2020, we compared the clinical and demographic characteristics of patients undergoing either SG or RYGB to evaluate their long-term weight loss outcomes. University hospital in the United States. A total of 3329 patients were identified in our institutional Metabolic and Bariatric Surgery Accreditation and Quality Improvement database using Current Procedural Terminology codes for either RYGB or SG. A general linear model was used for baseline characteristics. Logistic regression was used for factors favoring RYGB versus SG. A multivariable linear mixed model was used for weight-trajectory analysis. Cox regression was used for a cumulative hazard ratio of 10% weight regained from nadir. Factors favoring RYGB were diagnoses of type 2 diabetes and gastroesophageal reflux disease, Hispanic ethnicity, and surgeon's preference. SG was favored among Black patients and smokers. RYGB was associated with more weight loss at all time points. The risk of weight regain was significantly higher after SG versus RYGB. The bariatric procedure choice is significantly influenced by race, medical history, and surgeon's experience. RYGB results in a significantly more durable weight loss compared with SG regardless of race or other stratification factors.

Ten-year outcome of one-anastomosis gastric bypass with a biliopancreatic limb of 150 cm versus Roux-en-Y gastric bypass: a single-institution series of 940 patients.

Long-term outcomes of one-anastomosis gastric bypass (OAGB) need to be compared with those of Roux-en-Y gastric bypass (RYGB). The present study evaluates the long-term outcomes at 10-year follow-up of OAGB with a biliopancreatic limb of 150 cm versus RYGB. Private practice, France. Data of patients who underwent OAGB or RYGB as primary or secondary procedures between 2010 and 2011 at a referral center were collected prospectively and analyzed retrospectively. A total of 940 patients underwent OAGB (n = 405) or RYGB (n = 535). Operative time was significantly shorter in the OAGB group. Postoperative morbidity occurred in 17.2% of patients after RYGB versus 8.1% after OAGB (P ≤ .0001). Patients in the RYGB group had a significantly higher rate of kinking of the jejuno-jejunal anastomosis, stenosis of the gastrojejunal anastomosis, and dysphagia for early ulcers. At long term, no differences were found in the rate of severe malnutrition. Cumulated morbidity was significantly higher after RYGB, with higher incidence of internal hernia, anastomotic ulcer, blind-loop syndrome, and hypoglycemia. Conversion to RYGB and laparoscopic exploration for chronic pain were more frequent after OAGB. Surgery for weight regain was significantly more frequent after RYGB. Patients in the OAGB group had significantly lower weight, body mass index, and greater percentage excess, and total weight losses at 120 months. No significant differences were detected in co-morbidity outcomes. After 10 years, both RYGB and OAGB are effective procedures. However, OAGB is associated with shorter operative times and better results in short- and long-term morbidity and weight loss outcomes.

Long-Term Changes in Cardiac Structure and Function Following Bariatric Surgery

BackgroundStudies with short-term follow-up have demonstrated favorable effects of weight loss (WL) on the heart, but little information is available regarding long-term effects or effects of visceral fat reduction. ObjectivesThe purpose of this study was to evaluate the effects of long-term WL following bariatric surgery on cardiac structure, function, ventricular interaction, and body composition, including epicardial adipose thickness and abdominal visceral adipose tissue (VAT). MethodsA total of 213 obese patients underwent echocardiography before and >180 days following bariatric surgery. Abdominal VAT area was measured by computed tomography in 52 of these patients. ResultsAfter 5.3 years (IQR: 2.9-7.9 years), body mass index (BMI) decreased by 22%, with favorable reductions in blood pressure, fasting glucose, and left ventricular (LV) remodeling in the full sample. In the subgroup of patients with abdominal computed tomography, VAT area decreased by 30%. In all subjects, epicardial adipose thickness was reduced by 14% (both P < 0.0001) in tandem with reductions in ventricular interdependence. LV and right ventricular longitudinal strain improved following WL, but left atrial (LA) strain deteriorated, while LA volume and estimated LA pressures increased. In subgroup analysis, LV wall thickness and strain correlated more strongly with VAT than BMI at baseline, and reductions in LV mass following surgery were correlated with decreases in VAT, but not BMI. ConclusionsIn this observational study, weight loss following bariatric surgery was associated with epicardial fat reduction, reduced ventricular interaction, LV reverse remodeling, and improved longitudinal biventricular mechanics, but LA myopathy and hemodynamic congestion still progressed. Reduction in visceral fat was associated with favorable cardiac effects, suggesting this might be a key target of WL interventions.

Contrasts of Initial and Gain Scores in Obesity Treatment-Targeted Psychosocial Variables by Women Participants' Weight Change Patterns Over 2 Years.

The typical pattern of weight change associated with behavioral obesity treatments has been some loss in weight through approximately 6 months, followed by near complete regain. However, patterns vary widely across individuals. The objectives are to determine whether recent prediction model-based indications of relations among changes in psychosocial correlates of the weight loss behaviors of physical activity and controlled eating vary by patterns of weight change. Women with obesity enrolled in a community-based behavioral obesity treatment who failed to lose at least 5% of their baseline weight (Minimal Effect group, n = 44), lost 5% or greater and then regained most during months 6 to 24 (Loss/Regain group, n = 42), or lost 5% or greater and then maintained/continued loss (Loss/Loss group n = 42) were evaluated. Improvements in physical activity- and eating-related self-regulation and self-efficacy, mood, and emotional eating over 6 months were significant overall and generally most favorable in the Loss/Loss group and least favorable in the Minimal Effect group. Expected model-based relationships between 6-month changes in the aforementioned psychosocial variables were significant and generally not significantly affected by weight change group. However, group substantially affected the prediction of self-regulation of eating at month 24-a key correlate of long-term weight loss. Findings suggested community-based obesity treatment targets and emphases.

Addressing Adverse Childhood Experiences and Psychological Symptoms Among Bariatric Patients.

Adverse Childhood Experiences (ACEs) have been shown to be prevalent in bariatric surgery candidates with comorbid psychological symptoms. While bariatric patients who have mental illness or a history of ACEs are less likely to lose weight, presence of a support system has been reported to mitigate ACEs' effects and to maintain long-term weight loss. The current study aims to examine the association between ACEs and psychological symptoms and the effect of potential protective factors on the association among bariatric patients. The study included a total of 199 subjects seeking bariatric surgery who completed a psychological evaluation including ACEs, psychological symptoms, and presence of support system as part of the presurgical multidisciplinary weight management consultations at a large university hospital. Multivariate regression models were used to examine the association between ACEs and psychological symptoms and potential effect of support system on the association. The study found that there is a significant association between ACEs and psychological symptoms. The study also revealed that patients who reported having a childhood supportive person were significantly associated with a lower BMI, while those who reported having adulthood supportive person showed significantly less symptoms of depression, anxiety, and binge eating. The findings have significant implications that addressing ACEs in preoperative surgical process in relation to psychological conditions and therapeutic interventions within their close environmental system will be beneficial for patients to achieve optimal surgical outcomes.

Long-term Weight Loss in a Primary Care-Anchored eHealth Lifestyle Coaching Program: Randomized Controlled Trial.

BackgroundLong-term weight loss in people living with obesity can reduce the risk and progression of noncommunicable diseases. Observational studies suggest that digital coaching can lead to long-term weight loss.ObjectiveWe investigated whether an eHealth lifestyle coaching program for people living with obesity with or without type 2 diabetes led to significant, long-term (12-month) weight loss compared to usual care.MethodsIn a randomized controlled trial that took place in 50 municipalities in Denmark, 340 people living with obesity with or without type 2 diabetes were enrolled from April 16, 2018, to April 1, 2019, and randomized via an automated computer algorithm to an intervention (n=200) or a control (n=140) group. Patients were recruited via their general practitioners, the Danish diabetes organization, and social media. The digital coaching intervention consisted of an initial 1-hour face-to-face motivational interview followed by digital coaching using behavioral change techniques enabled by individual live monitoring. The primary outcome was change in body weight from baseline to 12 months.ResultsData were assessed for 200 participants, including 127 from the intervention group and 73 from the control group, who completed 12 months of follow-up. After 12 months, mean body weight and BMI were significantly reduced in both groups but significantly more so in the intervention group than the control group (–4.5 kg, 95% CI –5.6 to –3.4 vs –1.5 kg, 95% CI –2.7 to –0.2, respectively; P<.001; and –1.5 kg/m2, 95% CI –1.9 to –1.2 vs –0.5 kg/m2, 95% CI –0.9 to –0.1, respectively; P<.001). Hemoglobin A1c was significantly reduced in both the intervention (–6.0 mmol/mol, 95% CI –7.7 to –4.3) and control (–4.9 mmol/mol, 95% CI –7.4 to –2.4) groups, without a significant group difference (all P>.46).ConclusionsCompared to usual care, digital lifestyle coaching can induce significant weight loss for people living with obesity, both with and without type 2 diabetes, after 12 months.Trial RegistrationClinicalTrials.gov NCT03788915; https://clinicaltrials.gov/ct2/show/NCT03788915

Gut microbiome and microbial metabolites in NAFLD and after bariatric surgery: Correlation and causality.

Non-alcoholic fatty liver disease (NAFLD) is currently related to a heavy socioeconomic burden and increased incidence. Since obesity is the most prevalent risk factor for NAFLD, weight loss is an effective therapeutic solution. Bariatric surgery (BS), which can achieve long-term weight loss, improves the overall health of patients with NAFLD. The two most common surgeries are the Roux-en-Y gastric bypass and sleeve gastrectomy. The gut-liver axis is the complex network of cross-talking between the gut, its microbiome, and the liver. The gut microbiome, involved in the homeostasis of the gut-liver axis, is believed to play a significant role in the pathogenesis of NAFLD and the metabolic improvement after BS. Alterations in the gut microbiome in NAFLD have been confirmed compared to that in healthy individuals. The mechanisms linking the gut microbiome to NAFLD have been proposed, including increased intestinal permeability, higher energy intake, and other pathophysiological alterations. Interestingly, several correlation studies suggested that the gut microbial signatures after BS become more similar to those of lean, healthy controls than that of patients with NAFLD. The resolution of NAFLD after BS is related to changes in the gut microbiome and its metabolites. However, confirming a causal link remains challenging. This review summarizes characteristics of the gut microbiome in patients with NAFLD before and after BS and accumulates existing evidence about the underlying mechanisms of the gut microbiome.

Patients successfully lose body weight after primary total knee arthroplasty but not more than a matched general population

IntroductionHigh BMI is associated with increased risk for knee osteoarthritis, ultimately necessitating total knee arthroplasty (TKA). The aim of this retrospective study was to (1) analyse the amount of postoperative long-term weight loss as reflected by BMI change in TKA patients, (2) identify factors associated with increased change in BMI, and to (3) compare changes with BMI trends of a general population.Materials and methodsOverall, 298 TKA patients [198 females; mean age: 65.1 ± 7.9 years, median follow-up 8.8 (interquartile range: 5.9–10.8 years)] were included in the final evaluation and compared with an age group-matched control group from the general population regarding weight trends between 2006 and 2014. Main variable of interest in both cohorts was body mass index (BMI). Linear regression analyses were performed to assess changes in weight and BMI over time between TKA patients and the general population. Furthermore, mixed linear-effects models were constructed to analyse the potential change in BMI independent from age and gender.ResultsIn TKA patients, a significant drop in BMI by 0.8 ± 3.2 points from postoperative to final follow-up was observed (p < 0.001), with reduction being significant independently from age (p = 0.382), gender (p = 0.310), or revision surgery (p = 0.195). In the general population, likewise a significant BMI-decrease by 0.7 ± 6.1 points was observed between 2006 and 2014, with younger people (p = 0.004) and females (p < 0.001) being more likely to reduce BMI. Yet, BMI-decrease between TKA patients and the general population over time was comparable (p = 0.734). Notably, patients with initially higher BMI were significantly more likely to lose weight postoperatively than normal-weight patients (p < 0.001).ConclusionsOur results point against the notion that TKA patients lose a considerable amount of weight in comparison to the general population as soon as improved joint function and pain relief have been achieved. Thus, individualized patient education programmes should be reinforced, promoting a healthy lifestyle.

Weight History Association With Current Cardiorespiratory And Muscular Fitness

High cardiorespiratory and muscular fitness are often associated with lower body fat mass. Age-associated increases in body mass might be attenuated by maintaining a higher level of fitness into middle-age. PURPOSE: This study aimed to compare the cardiorespiratory and muscular fitness of individuals who have maintained body mass during adulthood to those who have had substantial increases and/or decreases in body mass in adulthood. METHODS: Obese, overweight, and non-obese adults were recruited to participate. Long-term health and weight history was collected retrospectively on 79 individuals. Total body composition, maximal oxygen consumption, grip strength, and maximal isometric knee extension strength were measured. Participants were subsequently categorized based on short term and long-term weight loss history, cardiorespiratory fitness, and muscle function for further analysis. RESULTS: Participants (31 Male, 45 female, aged 41.0 ± 12.3 years) were 29.2 ± 10.1% body fat having gained 9.3 ± 11.7 kg since 20 years of age. Current cardiorespiratory fitness as indicated by relative maximal oxygen consumption was 36.6 ± 12.0 ml*kg-1*min-1. No significant relationship existed between weight gain since age 20 and current cardiorespiratory fitness (r = -0.12). No differences in weight history were observed after classification of participants into high vs. low cardiorespiratory fitness nor high vs. low muscular fitness. CONCLUSIONS: Current cardiorespiratory and muscular fitness are independent of past body weight history. Despite the limitations of retrospective analysis of weight history and inability to determine previous levels of fitness, these results imply that high fitness might not be protective against age-associated body mass increases, but also that low fitness might not destine an individual to larger than normal gains in body mass

Comparison of weight loss induced by daily caloric restriction versus intermittent fasting (DRIFT) in individuals with obesity: study protocol for a 52-week randomized clinical trial

BackgroundThe standard of care for treating overweight and obesity is daily caloric restriction (DCR). While this approach produces modest weight loss, adherence to DCR declines over time and weight regain is common. Intermittent fasting (IMF) is an alternative dietary strategy for reducing energy intake (EI) that involves >60% energy restriction on 2–3 days per week, or on alternate days, with habitual intake on fed days. While numerous studies have evaluated IMF as a weight loss strategy, there are several limitations including lack of a standard-of-care DCR control, failure to provide guideline-based behavioral support, and failure to rigorously evaluate dietary and PA adherence using objective measures. To date, only three longer-term (52-week) trials have evaluated IMF as a weight loss strategy. None of these longer-duration studies reported significant differences between IMF and DCR in changes in weight. However, each of these studies has limitations that prohibit drawing generalizable conclusions about the relative long-term efficacy of IMF vs. DCR for obesity treatment.MethodsThe Daily Caloric Restriction vs. Intermittent Fasting Trial (DRIFT) is a two-arm, 52-week block randomized (1:1) clinical weight loss trial. The two intervention arms (DCR and IMF) are designed to prescribe an equivalent average weekly energy deficit from baseline weight maintenance energy requirements. Both DCR and IMF will be provided guideline-based behavioral support and a PA prescription. The primary outcome is change in body weight at 52 weeks. Secondary outcomes include changes in body composition (dual-energy x-ray absorptiometry (DXA)), metabolic parameters, total daily energy expenditure (TDEE, doubly labeled water (DLW)), EI (DLW intake-balance method, 7-day diet diaries), and patterns of physical activity (PA, activPAL device).DiscussionAlthough DCR leads to modest weight loss success in the short-term, there is wide inter-individual variability in weight loss and poor long-term weight loss maintenance. Evidence-based dietary approaches to energy restriction that are effective long-term are needed to provide a range of evidence-based options to individuals seeking weight loss. The DRIFT study will evaluate the long-term effectiveness of IMF vs. DCR on changes in objectively measured weight, EI, and PA, when these approaches are delivered using guideline-based behavioral support and PA prescriptions.

Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation.

The ongoing obesity epidemic represents a global public health crisis that contributes to poor health outcomes, reduced quality of life, and >2.8 million deaths each year. Obesity is relapsing, progressive, and heterogeneous. It is considered a chronic disease by the World Obesity Federation (WOF) and a chronic condition by the World Heart Federation (WHF). People living with overweight/obesity are at greater risk for cardiovascular (CV) morbidity and mortality. Increased adiposity (body fat), particularly visceral/abdominal fat, is linked to CV risk and CV disease (CVD) via multiple direct and indirect pathophysiological mechanisms. The development of CVD is driven, in part, by obesity-related metabolic, endocrinologic, immunologic, structural, humoral, haemodynamic, and functional alterations. The complex multifaceted nature of these mechanisms can be challenging to understand and address in clinical practice. People living with obesity and CVD often have concurrent chronic physical or psychological disorders (multimorbidity) requiring multidisciplinary care pathways and polypharmacy. Evidence indicates that intentional weight loss (particularly when substantial) lowers CVD risk among people with overweight/obesity. Long-term weight loss and maintenance require ongoing commitment from both the individual and those responsible for their care. This position paper, developed by the WOF and the WHF, aims to improve understanding of the direct and indirect links between overweight/obesity and CVD, the key controversies in this area and evidence relating to cardiometabolic outcomes with available weight management options. Finally, an action plan for clinicians provides recommendations to help in identifying and addressing the risks of obesity-related CVD (recognizing resource and support variances between countries).

Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery.

The Circadian Locomotor Output Cycles Kaput (CLOCK) gene has been linked to metabolic dysfunction and obesity. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of CLOCK gene with obesity and with long-term weight response after different bariatric surgery (BS) techniques. The cohort includes 375 patients with morbid obesity (MO) and 230 controls. In the association study of SNPs with weight response we combined several variables as phenotype at 6 years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed by allelic discrimination using Taqman® probes. The genotype association study was performed using the SNPStats program, with comparisons adjusted for sex, age, initial Body Mass Index, type 2 diabetes and hypertension diagnosis, and type of surgery. In the case-control study two of three SNPs were significantly associated with MO. The variant rs1801260 had a protective effect for MO whereas the TT genotype of rs3749474 variant had the strongest association with MO (OR = 2.25 (1.39–3.66); p = 0.0006). In the linear regression analysis both variants showed significant association with long-term weight loss and weight regain after BS, independently of the pre-surgery patient profile.