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.
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.
...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.
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).
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT03611582.
Background
Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and ...well‐being. The international evidence base for strategies to prevent obesity is very large and is accumulating rapidly. This is an update of a previous review.
Objectives
To determine the effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children.
Search methods
We searched CENTRAL, MEDLINE, Embase, PsychINFO and CINAHL in June 2015. We re‐ran the search from June 2015 to January 2018 and included a search of trial registers.
Selection criteria
Randomised controlled trials (RCTs) of diet or physical activity interventions, or combined diet and physical activity interventions, for preventing overweight or obesity in children (0‐17 years) that reported outcomes at a minimum of 12 weeks from baseline.
Data collection and analysis
Two authors independently extracted data, assessed risk‐of‐bias and evaluated overall certainty of the evidence using GRADE. We extracted data on adiposity outcomes, sociodemographic characteristics, adverse events, intervention process and costs. We meta‐analysed data as guided by the Cochrane Handbook for Systematic Reviews of Interventions and presented separate meta‐analyses by age group for child 0 to 5 years, 6 to 12 years, and 13 to 18 years for zBMI and BMI.
Main results
We included 153 RCTs, mostly from the USA or Europe. Thirteen studies were based in upper‐middle‐income countries (UMIC: Brazil, Ecuador, Lebanon, Mexico, Thailand, Turkey, US‐Mexico border), and one was based in a lower middle‐income country (LMIC: Egypt). The majority (85) targeted children aged 6 to 12 years.
Children aged 0‐5 years: There is moderate‐certainty evidence from 16 RCTs (n = 6261) that diet combined with physical activity interventions, compared with control, reduced BMI (mean difference (MD) −0.07 kg/m2, 95% confidence interval (CI) −0.14 to −0.01), and had a similar effect (11 RCTs, n = 5536) on zBMI (MD −0.11, 95% CI −0.21 to 0.01). Neither diet (moderate‐certainty evidence) nor physical activity interventions alone (high‐certainty evidence) compared with control reduced BMI (physical activity alone: MD −0.22 kg/m2, 95% CI −0.44 to 0.01) or zBMI (diet alone: MD −0.14, 95% CI −0.32 to 0.04; physical activity alone: MD 0.01, 95% CI −0.10 to 0.13) in children aged 0‐5 years.
Children aged 6 to 12 years: There is moderate‐certainty evidence from 14 RCTs (n = 16,410) that physical activity interventions, compared with control, reduced BMI (MD −0.10 kg/m2, 95% CI −0.14 to −0.05). However, there is moderate‐certainty evidence that they had little or no effect on zBMI (MD −0.02, 95% CI −0.06 to 0.02). There is low‐certainty evidence from 20 RCTs (n = 24,043) that diet combined with physical activity interventions, compared with control, reduced zBMI (MD −0.05 kg/m2, 95% CI −0.10 to −0.01). There is high‐certainty evidence that diet interventions, compared with control, had little impact on zBMI (MD −0.03, 95% CI −0.06 to 0.01) or BMI (−0.02 kg/m2, 95% CI −0.11 to 0.06).
Children aged 13 to 18 years: There is very low‐certainty evidence that physical activity interventions, compared with control reduced BMI (MD −1.53 kg/m2, 95% CI −2.67 to −0.39; 4 RCTs; n = 720); and low‐certainty evidence for a reduction in zBMI (MD ‐0.2, 95% CI −0.3 to ‐0.1; 1 RCT; n = 100). There is low‐certainty evidence from eight RCTs (n = 16,583) that diet combined with physical activity interventions, compared with control, had no effect on BMI (MD −0.02 kg/m2, 95% CI −0.10 to 0.05); or zBMI (MD 0.01, 95% CI −0.05 to 0.07; 6 RCTs; n = 16,543). Evidence from two RCTs (low‐certainty evidence; n = 294) found no effect of diet interventions on BMI.
Direct comparisons of interventions: Two RCTs reported data directly comparing diet with either physical activity or diet combined with physical activity interventions for children aged 6 to 12 years and reported no differences.
Heterogeneity was apparent in the results from all three age groups, which could not be entirely explained by setting or duration of the interventions. Where reported, interventions did not appear to result in adverse effects (16 RCTs) or increase health inequalities (gender: 30 RCTs; socioeconomic status: 18 RCTs), although relatively few studies examined these factors.
Re‐running the searches in January 2018 identified 315 records with potential relevance to this review, which will be synthesised in the next update.
Authors' conclusions
Interventions that include diet combined with physical activity interventions can reduce the risk of obesity (zBMI and BMI) in young children aged 0 to 5 years. There is weaker evidence from a single study that dietary interventions may be beneficial.
However, interventions that focus only on physical activity do not appear to be effective in children of this age. In contrast, interventions that only focus on physical activity can reduce the risk of obesity (BMI) in children aged 6 to 12 years, and adolescents aged 13 to 18 years. In these age groups, there is no evidence that interventions that only focus on diet are effective, and some evidence that diet combined with physical activity interventions may be effective. Importantly, this updated review also suggests that interventions to prevent childhood obesity do not appear to result in adverse effects or health inequalities.
The review will not be updated in its current form. To manage the growth in RCTs of child obesity prevention interventions, in future, this review will be split into three separate reviews based on child age.
Background
Child and adolescent overweight and obesity has increased globally, and can be associated with significant short‐ and long‐term health consequences. This is an update of a Cochrane review ...published first in 2003, and updated previously in 2009. However, the update has now been split into six reviews addressing different childhood obesity treatments at different ages.
Objectives
To assess the effects of diet, physical activity and behavioural interventions (behaviour‐changing interventions) for the treatment of overweight or obese children aged 6 to 11 years.
Search methods
We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of studies and systematic reviews. We did not apply any language restrictions. The date of the last search was July 2016 for all databases.
Selection criteria
We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions (behaviour‐changing interventions) for treating overweight or obese children aged 6 to 11 years, with a minimum of six months' follow‐up. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity.
Data collection and analysis
Two review authors independently screened references, extracted data, assessed risk of bias, and evaluated the quality of the evidence using the GRADE instrument. We contacted study authors for additional information. We carried out meta‐analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions.
Main results
We included 70 RCTs with a total of 8461 participants randomised to either the intervention or control groups. The number of participants per trial ranged from 16 to 686. Fifty‐five trials compared a behaviour‐changing intervention with no treatment/usual care control and 15 evaluated the effectiveness of adding an additional component to a behaviour‐changing intervention. Sixty‐four trials were parallel RCTs, and four were cluster RCTs. Sixty‐four trials were multicomponent, two were diet only and four were physical activity only interventions. Ten trials had more than two arms. The overall quality of the evidence was low or very low and 62 trials had a high risk of bias for at least one criterion. Total duration of trials ranged from six months to three years. The median age of participants was 10 years old and the median BMI z score was 2.2.
Primary analyses demonstrated that behaviour‐changing interventions compared to no treatment/usual care control at longest follow‐up reduced BMI, BMI z score and weight. Mean difference (MD) in BMI was ‐0.53 kg/m2 (95% confidence interval (CI) ‐0.82 to ‐0.24); P < 0.00001; 24 trials; 2785 participants; low‐quality evidence. MD in BMI z score was ‐0.06 units (95% CI ‐0.10 to ‐0.02); P = 0.001; 37 trials; 4019 participants; low‐quality evidence and MD in weight was ‐1.45 kg (95% CI ‐1.88 to ‐1.02); P < 0.00001; 17 trials; 1774 participants; low‐quality evidence.
Thirty‐one trials reported on serious adverse events, with 29 trials reporting zero occurrences RR 0.57 (95% CI 0.17 to 1.93); P = 0.37; 4/2105 participants in the behaviour‐changing intervention groups compared with 7/1991 participants in the comparator groups). Few trials reported health‐related quality of life or behaviour change outcomes, and none of the analyses demonstrated a substantial difference in these outcomes between intervention and control. In two trials reporting on minutes per day of TV viewing, a small reduction of 6.6 minutes per day (95% CI ‐12.88 to ‐0.31), P = 0.04; 2 trials; 55 participants) was found in favour of the intervention. No trials reported on all‐cause mortality, morbidity or socioeconomic effects, and few trials reported on participant views; none of which could be meta‐analysed.
As the meta‐analyses revealed substantial heterogeneity, we conducted subgroup analyses to examine the impact of type of comparator, type of intervention, risk of attrition bias, setting, duration of post‐intervention follow‐up period, parental involvement and baseline BMI z score. No subgroup effects were shown for any of the subgroups on any of the outcomes. Some data indicated that a reduction in BMI immediately post‐intervention was no longer evident at follow‐up at less than six months, which has to be investigated in further trials.
Authors' conclusions
Multi‐component behaviour‐changing interventions that incorporate diet, physical activity and behaviour change may be beneficial in achieving small, short‐term reductions in BMI, BMI z score and weight in children aged 6 to 11 years. The evidence suggests a very low occurrence of adverse events. The quality of the evidence was low or very low. The heterogeneity observed across all outcomes was not explained by subgrouping. Further research is required of behaviour‐changing interventions in lower income countries and in children from different ethnic groups; also on the impact of behaviour‐changing interventions on health‐related quality of life and comorbidities. The sustainability of reduction in BMI/BMI z score and weight is a key consideration and there is a need for longer‐term follow‐up and further research on the most appropriate forms of post‐intervention maintenance in order to ensure intervention benefits are sustained over the longer term.
Abstract The majority of people with type 2 diabetes are overweight or obese, and weight loss is a recommended treatment strategy. A systematic review and meta-analysis was undertaken to answer the ...following primary question: In overweight or obese adults with type 2 diabetes, what are the outcomes on hemoglobin A1c (HbA1c) from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? Secondary questions are: What are the lipid (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) and blood pressure (systolic and diastolic) outcomes from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? And, what are the weight and metabolic outcomes from differing amounts of macronutrients in weight-loss interventions? Inclusion criteria included randomized clinical trial implementing weight-loss interventions in overweight or obese adults with type 2 diabetes, minimum 12-month study duration, a 70% completion rate, and an HbA1c value reported at 12 months. Eleven trials (eight compared two weight-loss interventions and three compared a weight-loss intervention group with a usual care/control group) with 6,754 participants met study criteria. At 12 months, 17 study groups (8 categories of weight-loss intervention) reported weight loss <5% of initial weight (−3.2 kg 95% CI: −5.9, −0.6). A meta-analysis of the weight-loss interventions reported nonsignificant beneficial effects on HbA1c, lipids, or blood pressure. Two study groups reported a weight loss of ≥5%: a Mediterranean-style diet implemented in newly diagnosed adults with type 2 diabetes and an intensive lifestyle intervention implemented in the Look AHEAD (Action for Health in Diabetes) trial. Both included regular physical activity and frequent contact with health professionals and reported significant beneficial effects on HbA1c, lipids, and blood pressure. Five trials (10 study groups) compared weight-loss interventions of differing amounts of macronutrients and reported nonsignificant differences in weight loss, HbA1c, lipids, and blood pressure. The majority of lifestyle weight-loss interventions in overweight or obese adults with type 2 diabetes resulted in weight loss <5% and did not result in beneficial metabolic outcomes. A weight loss of >5% appears necessary for beneficial effects on HbA1c, lipids, and blood pressure. Achieving this level of weight loss requires intense interventions, including energy restriction, regular physical activity, and frequent contact with health professionals. Weight loss for many overweight or obese individuals with type 2 diabetes might not be a realistic primary treatment strategy for improved glycemic control. Nutrition therapy for individuals with type 2 diabetes should encourage a healthful eating pattern, a reduced energy intake, regular physical activity, education, and support as primary treatment strategies.
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.
The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in ...adults—defined as a body mass index (BMI) ≥ 25 kg/m2—increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6‐fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high‐income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy‐dense, nutrient‐poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low‐income countries to 7% or 8% in some high‐income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high‐income countries and the increasing prevalence in low‐ and middle‐income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight.
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.
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.
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.
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.
Summary
Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut ...microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords ‘overweight’ or ‘obesity’ and ‘microbiota’ and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross‐feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long‐term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.
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