Involuntary weight loss Wong, Christopher J
The Medical clinics of North America,
05/2014, Letnik:
98, Številka:
3
Journal Article
Recenzirano
Involuntary weight loss remains an important and challenging clinical problem, with a high degree of morbidity and mortality. Because of the frequency of finding a serious underlying diagnosis, ...clinicians must be thorough in assessment, keeping in mind a broad range of possible causes. Although prediction scores exist, they have not been broadly validated; therefore, clinical judgment remains ever essential.
Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, ...durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.
Summary
Weight loss maintenance is a major challenge for obesity treatment. Weight control registries can be useful in identifying psychological and behavioural factors that could contribute to ...better long‐term success. The objective of this study is to describe the existing weight control registries and their participants and identify correlates of weight loss maintenance. A comprehensive search of peer‐reviewed articles published until November 2018 was conducted in PubMed, Web of Science, and Scopus. Studies that reported results from weight control registries were considered. Fifty‐two articles, corresponding to five registries (the United States, Portugal, Germany, Finland, and Greece), were included. Registries differed in inclusion criteria and procedures. Of 51 identified weight loss and maintenance strategies, grouped in 14 domains of the Oxford Food and Activity Behaviors taxonomy, the following were the most frequently reported: having healthy foods available at home, regular breakfast intake, increasing vegetable consumption, decreasing sugary and fatty foods, limiting certain foods, and reducing fat in meals. Increased physical activity was the most consistent positive correlate of weight loss maintenance. To our knowledge, this is the first systematic review of information about successful weight loss maintenance obtained from weight control registries. Key common influential characteristics of success were identified, which can inform future prospective studies and weight management initiatives.
Introduction
The Diabetes REmission Clinical Trial (DiRECT) has shown that sustained remission of type 2 diabetes in primary care is achievable through weight loss using total diet replacement (TDR) ...with continued behavioural support. Understanding participants’ experiences can help optimise the intervention, support implementation into healthcare, and understand the process of behaviour change.
Methods
Thirty‐four DiRECT participants were recruited into this embedded qualitative evaluation study. In‐person and telephone interviews were conducted before the TDR; at week 6–8 of the TDR; 2 weeks into food reintroduction (FR); and at 1 year, to learn about participant experiences with the programme. Transcribed narratives were analysed thematically, and we used interpretation to develop overarching themes.
Results
Initiation of the TDR and transition to FR were challenging and required increased behavioural support. In general, adhering to TDR proved easier than the participants had anticipated. Some participants chose the optional extension of TDR. Rapid weight loss and changes in diabetes markers provided ongoing motivation. Further weight loss, behavioural support and occasional use of TDR facilitated weight loss maintenance (WLM). A process of behaviour adaptation to change following regime disruption was identified in three stages: (1) expectations of the new, (2) overcoming difficulties with adherence, and (3) acceptance of continuous effort and establishment of routines.
Conclusions
The DiRECT intervention was acceptable and regularity, continuity, and tailoring of behavioural support was instrumental in its implementation in primary care. The adaptation process accounts for some of the individual variability of experiences with the intervention and highlights the need for programme flexibility.
trans-10,cis-12 Conjugated linoleic acid (t10,c12-CLA) is a dietary supplement that promotes weight loss by increasing fat oxidation and energy expenditure. We previously reported that in the absence ...of t10,c12-CLA, mice forced to lose equivalent body weight by food restriction (FR) do not exhibit increases in fat oxidation or energy expenditure but have improved glucose metabolism, consistent with FR as a metabolically healthy weight-loss method.
Because diet is a primary determinant of gut bacterial populations, we hypothesized that the disparate metabolic effects accompanying weight loss from t10,c12-CLA or FR could be related to altered intestinal microbiota.
Ten-week-old male LDL receptor–deficient (Ldlr−/−) mice were fed a high-fat, high-sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1% c9,t11-CLA (obese fatty acid control), HFHS + 1% t10,c12-CLA (weight-loss–inducing fatty acid), or HFHS + FR (weight-loss control group with 75–85% ad libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short-chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal nutrient transporter expression were quantified.
Mice fed t10,c12-CLA or assigned to FR lost 14.5% of baseline body weight. t10,c12-CLA–fed mice had elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold) compared with HFHS-fed controls. Fecal α diversity decreased by 7.6–14% in all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were enriched over time by t10,c12-CLA. By comparing with each control group, we also identified bacterial genera significantly enriched in the t10,c12-CLA recipients, including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium valens of the Allobaculum genus, whereas other taxa were enriched by FR, including Clostridiales and Bacteroides.
Modalities resulting in equivalent weight loss but with divergent metabolic effects are associated with compositional differences in the mouse intestinal microbiota.
Scope
A limited number of human studies have characterized fecal microbiota and metabolome in extreme obesity and after diet‐induced weight loss.
Methods and results
Fecal samples from normal‐weight ...and extremely obese adults and from obese participants before and after moderate diet‐induced weight loss are evaluated for their interaction with the intestinal adenocarcinoma cell line HT29 using an impedance‐based in vitro model, which reveals variations in the interaction between the gut microbiota and host linked to obesity status. Microbiota composition, short chain fatty acids, and other intestinal metabolites are further analyzed to assess the interplay among diet, gut microbiota, and host in extreme obesity. Microbiota profiles are distinct between normal‐weight and obese participants and are accompanied by fecal signatures in the metabolism of biliary compounds and catecholamines. Moderate diet‐induced weight loss promotes shifts in the gut microbiota, and the primary fecal metabolomics features are associated with diet and the gut–liver and gut–brain axes.
Conclusions
Analyses of the fecal microbiota and metabolome enable assessment of the impact of diet on gut microbiota composition and activity, supporting the potential use of certain fecal metabolites or members of the gut microbiota as biomarkers for the efficacy of weight loss in extreme obesity.
Shifts in gut microbiota and fecal metabolome features associated with the metabolism of biliary compounds and catecholamines are observed between normal weight (NW) and extremely obese (OB) individuals. Moderate weight loss after diet (OB.2) promotes changes in the gut microbiota whereas the fecal metabolomic profile is mainly associated with dietary changes and with the gut‐liver and gut‐brain axes.
IMPORTANCE: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. OBJECTIVE: To assess the effect of tirzepatide, with diet and physical activity, on ...the maintenance of weight reduction. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. INTERVENTIONS: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. RESULTS: Participants (n = 670; mean age, 48 years; 473 71% women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was −5.5% with tirzepatide vs 14.0% with placebo (difference, −19.4% 95% CI, −21.2% to −17.7%; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. CONCLUSIONS AND RELEVANCE: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04660643
IMPORTANCE: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and ...prevent relapse. OBJECTIVE: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. DESIGN, SETTING, AND PARTICIPANTS: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. INTERVENTIONS: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). MAIN OUTCOMES AND MEASURES: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. RESULTS: Of the 66 female participants (mean SD age, 32.0 7.8 years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −6.0 1.8 cm cerebrospinal fluid CSF; 95% CI, −9.5 to −2.4 cm CSF; P = .001) and at 24 months (adjusted mean SE difference, −8.2 2.0 cm CSF; 95% CI, −12.2 to −4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −7.2 1.8 cm CSF; 95% CI, −10.6 to −3.7 cm CSF; P < .001) and at 24 months (adjusted mean SE difference, −8.7 2.0 cm CSF; 95% CI, −12.7 to −4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −21.4 5.4 kg; 95% CI, −32.1 to −10.7 kg; P < .001) and at 24 months (adjusted mean SE difference, −26.6 5.6 kg; 95% CI, −37.5 to −15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean SE difference, 7.3 3.6; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean SE difference, 10.4 3.8; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02124486
High body mass index (BMI) is known to be associated with various conditions, including type 2 diabetes (T2D), osteoarthritis, cardiovascular disease (CVD) and sleep apnoea; however, the impact of ...intentional weight loss on the risk of these and other outcomes is not well quantified. We examined the effect of weight loss on ten selected outcomes in a population from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Included individuals were >18 years old at the index date (first BMI value between January 2001 and December 2010). They were categorised by their weight pattern between year 1 post-index and year 4 post-index (baseline period) as having stable weight (-5% to +5%) or weight loss (-25% to -10%, plus evidence of intervention or dietary advice to confirm intention to lose weight). For inclusion, individuals also required a BMI of 25.0-50.0 kg/m
at the start of the follow-up period, during which the occurrence of ten obesity-related outcomes was recorded. Cox proportional hazard models adjusted for BMI, comorbidities, age, sex and smoking status were used to estimate relative risks for weight loss compared with stable weight. Individuals in the weight-loss cohort had median 13% weight loss. Assuming a BMI of 40 kg/m
before weight loss, this resulted in risk reductions for T2D (41%), sleep apnoea (40%), hypertension (22%), dyslipidaemia (19%) and asthma (18%). Furthermore, weight loss was associated with additional benefits, with lower risk of T2D, chronic kidney disease, hypertension and dyslipidaemia compared with maintaining the corresponding stable lower BMI throughout the study. This study provides objective, real-world quantification of the effects of weight loss on selected outcomes, with the greatest benefits observed for the established CVD risk factors T2D, hypertension and dyslipidaemia.
In this study, the levels of circulating mediators of appetite that change after weight loss and promote weight regain did not revert to the values recorded before weight loss. Long-term strategies ...to counteract these changes may be needed to prevent obesity relapse.
Worldwide, there are more than 1.5 billion overweight adults, including 400 million who are obese.
1
Although dietary restriction often results in initial weight loss, the majority of obese dieters fail to maintain their reduced weight.
2
Understanding the barriers to maintenance of weight loss is crucial for the prevention of relapse.
Body weight is centrally regulated, with peripheral hormonal signals released from the gastrointestinal tract, pancreas, and adipose tissue integrated, primarily in the hypothalamus, to regulate food intake and energy expenditure.
3
The number of identified peripheral modulators of appetite is expanding rapidly and includes leptin, ghrelin, cholecystokinin, peptide YY, insulin, pancreatic . . .
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