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JAMA Apr 2021Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.
IMPORTANCE
Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.
OBJECTIVE
To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.
DESIGN, SETTING, AND PARTICIPANTS
Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).
INTERVENTIONS
Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.
MAIN OUTCOMES AND MEASURES
The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.
RESULTS
Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.
CONCLUSIONS AND RELEVANCE
Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03611582.
Topics: Adult; Anti-Obesity Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Injections, Subcutaneous; Male; Middle Aged; Obesity; Overweight; Weight Loss
PubMed: 33625476
DOI: 10.1001/jama.2021.1831 -
Nature Medicine Jul 2019Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well... (Randomized Controlled Trial)
Randomized Controlled Trial
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 10 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
Topics: Adult; Aged; Dietary Supplements; Double-Blind Method; Feces; Gastrointestinal Microbiome; Humans; Insulin Resistance; Middle Aged; Obesity; Overweight; Pilot Projects; Verrucomicrobia
PubMed: 31263284
DOI: 10.1038/s41591-019-0495-2 -
International Journal of Environmental... Jun 2021Early childhood is a critical period for obesity prevention. This randomized controlled study evaluated the effectiveness of an educational intervention preventing... (Randomized Controlled Trial)
Randomized Controlled Trial
Early childhood is a critical period for obesity prevention. This randomized controlled study evaluated the effectiveness of an educational intervention preventing obesity in preschool-age children. A nutritional education intervention, with a follow-up session one year later, was conducted with parents of children aged 3 to 4 years of public schools in the province of Málaga. The main outcome variable was the body mass index z-score (zBMI). The prevalence of overweight or obesity was the secondary outcome variable. The sample comprised 261 students (control group = 139). Initial BMI, weight, height-for-age and prevalence of overweight and obesity were similar for both groups. After the first year of the intervention, the zBMI of the intervention group decreased significantly from 0.23 to 0.10 ( = 0.002), and the subgroup of patients with baseline zBMI above the median decreased from 1 to 0.72 ( = 0.001), and in the second year from 1.01 to 0.73 ( = 0.002). The joint prevalence of overweight and obesity increased in the control group (12.2% to 20.1%; = 0.027), while in the intervention group, there were no significant changes. This preschool educational intervention with parents improved their children's BMI, especially those with a higher BMI for their age, and favored the prevention of overweight or obesity.
Topics: Body Mass Index; Child; Child, Preschool; Health Education; Humans; Overweight; Pediatric Obesity; Schools
PubMed: 34207231
DOI: 10.3390/ijerph18126569 -
Lancet (London, England) Jan 2020Malnutrition has historically been researched and addressed within two distinct silos, focusing either on undernutrition, food insecurity, and micronutrient... (Review)
Review
Malnutrition has historically been researched and addressed within two distinct silos, focusing either on undernutrition, food insecurity, and micronutrient deficiencies, or on overweight, obesity, and dietary excess. However, through rapid global nutrition transition, an increasing proportion of individuals are exposed to different forms of malnutrition during the life course and have the double burden of malnutrition (DBM) directly. Long-lasting effects of malnutrition in early life can be attributed to interconnected biological pathways, involving imbalance of the gut microbiome, inflammation, metabolic dysregulation, and impaired insulin signalling. Life-course exposure to early undernutrition followed by later overweight increases the risk of non-communicable disease, by imposing a high metabolic load on a depleted capacity for homoeostasis, and in women increases the risk of childbirth complications. These life-course trajectories are shaped both by societal driving factors-ie, rapidly changing diets, norms of eating, and physical activity patterns-and by broader ecological factors such as pathogen burden and extrinsic mortality risk. Mitigation of the DBM will require major societal shifts regarding nutrition and public health, to implement comprehensive change that is sustained over decades, and scaled up into the entire global food system.
Topics: Africa South of the Sahara; Age of Onset; Exercise; Female; Gastrointestinal Microbiome; Humans; Indonesia; Male; Malnutrition; Metabolic Networks and Pathways; Nutritional Status; Obesity; Overweight; Prevalence
PubMed: 31852605
DOI: 10.1016/S0140-6736(19)32472-9 -
Gut Jul 2020This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects... (Randomized Controlled Trial)
Randomized Controlled Trial
Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.
OBJECTIVES
This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.
DESIGN
Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.
RESULTS
Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.
CONCLUSION
Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
Topics: Adult; Cholesterol; Diet, Mediterranean; Energy Intake; Female; Gastrointestinal Microbiome; Humans; Male; Metabolome; Obesity; Overweight
PubMed: 32075887
DOI: 10.1136/gutjnl-2019-320438 -
Journal of Human Nutrition and... Apr 2022The global prevalence of overweight and obesity in pregnancy is rising and this represents a significant challenge for the management of pregnancy and delivery. Women... (Review)
Review
The global prevalence of overweight and obesity in pregnancy is rising and this represents a significant challenge for the management of pregnancy and delivery. Women who have a pre-pregnancy body mass index greater than 25 kg m are more likely than those with a body mass index in the ideal range (20-24.99 kg m ) to have problems conceiving a child and are at greater risk of miscarriage and stillbirth. All pregnancy complications are more likely with overweight, obesity and excessive gestational weight gain, including those that pose a significant threat to the lives of mothers and babies. Labour complications arise more often when pregnancies are complicated by overweight and obesity. Pregnancy is a stage of life when women have greater openness to messages about their lifestyle and health. It is also a time when they come into greater contact with health professionals. Currently management of pregnancy weight gain and the impact of overweight tends to be poor, although a number of research studies have demonstrated that appropriate interventions based around dietary change can be effective in controlling weight gain and reducing the risk of pregnancy complications. The development of individualised and flexible plans for avoiding adverse outcomes of obesity in pregnancy will require investment in training of health professionals and better integration into normal antenatal care.
Topics: Body Mass Index; Female; Gestational Weight Gain; Humans; Obesity; Obesity, Maternal; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Factors; Weight Gain
PubMed: 35239212
DOI: 10.1111/jhn.12999 -
European Journal of Clinical Nutrition Dec 2021Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically.... (Review)
Review
Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. In addition to genetic mechanisms, mounting evidence demonstrates the induction of epigenetic alterations by maternal obesity, which can affect the offspring's phenotype, thereby influencing the later risk of obesity and cardiometabolic disease. Clear evidence in this regard comes from various animal models of maternal obesity. Evidence derived from clinical studies remains limited. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Furthermore, a short excurse is given on epigenetic mechanisms and emerging data regarding a putative interaction between metabolism and epigenetics. Finally, a summary of important findings of animal and clinical studies investigating maternal obesity-related epigenetic effects is presented also addressing current limitations of clinical studies.
Topics: Animals; Epigenesis, Genetic; Female; Humans; Obesity; Obesity, Maternal; Overweight; Placenta; Pregnancy
PubMed: 34230629
DOI: 10.1038/s41430-021-00905-6 -
JAMA Jun 2023Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics.... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings.
OBJECTIVE
To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021.
INTERVENTIONS
Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress.
MAIN OUTCOMES AND MEASURES
The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents.
RESULTS
Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings).
CONCLUSIONS AND RELEVANCE
Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02873715.
Topics: Child; Female; Humans; Male; Behavior Therapy; Body Mass Index; Overweight; Pediatric Obesity; Primary Health Care; Family Therapy; Pediatrics; Siblings; Parents
PubMed: 37314275
DOI: 10.1001/jama.2023.8061 -
European Journal of Preventive... Oct 2021The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight,...
AIMS
The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight, and risk for early cardiovascular disease (CVD) and mortality.
METHODS AND RESULTS
In this prospective, registry-based study, we used weight data in early pregnancy from women, registered in the Swedish Medical Birth Registry, and who gave birth between 1982 and 2014 (n = 1,495,499; median age 28.3 years). Of the women, 118,212 (7.9%) were obese (BMI ≥ 30 kg/m2) and 29,630 (2.0%) severely obese (BMI ≥ 35 kg/m2). After a follow-up of median 16.3 years, we identified 3295 and 4375 cases of acute myocardial infarction (AMI) and ischemic stroke (IS) corresponding to 13.4 and 17.8 per 100,000 observation years, respectively, occurring at mean ages of 49.8 and 47.3 years. Compared to women with a BMI 20-<22.5 kg/m2, the hazard ratio (HR) of AMI increased with higher BMI from 1.40 (95% confidence interval (CI) 1.27-1.54) among women with BMI 22.5-<25.0 kg/m2 to 4.71 (95% CI 3.88-5.72) among women with severe obesity, with similar findings for IS and CVD death, after adjustment for age, pregnancy year, parity and comorbidities at baseline. Women with BMI 30-<35.0 and ≥35 kg/m2 had increased all-cause mortality with adjusted HR 1.53 (95% CI 1.43-1.63) and 1.83 (95% CI 1.63-2.05), respectively.
CONCLUSION
A significant increase in the risk for early AMI, IS and CVD death was noticeable in overweight young women, with a marked increase in obese women.
Topics: Adult; Body Mass Index; Cardiovascular Diseases; Female; Humans; Obesity; Overweight; Pregnancy; Prospective Studies; Risk Factors
PubMed: 34647583
DOI: 10.1177/2047487320908983 -
Advances in Nutrition (Bethesda, Md.) Oct 2022This WHO-commissioned review contributed to the update of complementary feeding recommendations, synthesizing evidence on effects of unhealthy food and beverage... (Meta-Analysis)
Meta-Analysis
This WHO-commissioned review contributed to the update of complementary feeding recommendations, synthesizing evidence on effects of unhealthy food and beverage consumption in children on overweight and obesity. We searched PubMed (Medline), Cochrane CENTRAL, and Embase for articles, irrespective of language or geography. Inclusion criteria were: 1) randomized controlled trials (RCTs), non-RCTs, cohort studies, and pre/post studies with control; 2) participants aged ≤10.9 y at exposure; 3) studies reporting greater consumption of unhealthy foods/beverages compared with no or low consumption; 4) studies assessing anthropometric and/or body composition; and 5) publication date ≥1971. Unhealthy foods and beverages were defined using nutrient- and food-based approaches. Risk of bias was assessed using the ROBINS-I (risk of bias in nonrandomized studies of interventions version I) and RoB2 [Cochrane RoB (version 2)] tools for nonrandomized and randomized studies, respectively. Narrative synthesis was complemented by meta-analyses where appropriate. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Of 26,542 identified citations, 60 studies from 71 articles were included. Most studies were observational (59/60), and no included studies were from low-income countries. The evidence base was low quality, as assessed by ROBINS-I and RoB2 tools. Evidence synthesis was limited by the different interventions and comparators across studies. Evidence indicated that consumption of sugar-sweetened beverages (SSBs) and unhealthy foods in childhood may increase BMI/BMI z-score, percentage body fat, or odds of overweight/obesity (low certainty of evidence). Artificially sweetened beverages and 100% fruit juice consumption make little/no difference to BMI, percentage body fat, or overweight/obesity outcomes (low certainty of evidence). Meta-analyses of a subset of studies indicated a positive association between SSB intake and percentage body fat, but no association with change in BMI and BMI z-score. High-quality epidemiological studies that are designed to assess the effects of unhealthy food consumption during childhood on risk of overweight/obesity are needed to contribute to a more robust evidence base upon which to design policy recommendations. This protocol was registered at https://www.crd.york.ac.uk/PROSPERO as CRD42020218109.
Topics: Beverages; Child; Food; Humans; Obesity; Overweight; Sugar-Sweetened Beverages
PubMed: 35362512
DOI: 10.1093/advances/nmac032