In this paper, published in The Lancet, the authors sought to assess efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide, in comparison with a similar drug liraglutide, and placebo. The study was done in 8 countries, involving 71 clinical sites, with the primary endpoint being weight loss at week 52.
GLP-1 analogues mimic the function of human GLP-1, which regulates insulin secretion and glucagon secretion. These processes are linked with appetite, satiety and energy intake. This study found that these drugs, which were initially licensed for diabetes treatment, resulted in weight reductions which were significantly greater than the placebo group at 52 weeks. This weight loss is primarily due to the individuals consuming less energy, because of a combination of appetite suppression and enhanced satiety. Semaglutide was found to be the most effective, with weight loss of 11-14%, compared to Liraglutide’s 7-8%. In terms of side-effects, the most common complaint was of nausea. This was found to be dose dependent, so higher doses made side-effects more likely. Overall however, semaglutide was well tolerated, with no unanticipated safety or tolerability outcomes. Semaglutide has been shown to have a good benefit-risk profile which further supports its use as a weight management drug in its own right, instead of just being licensed for diabetes. Phase-3 studies are ongoing.
Cellular metabolism is a chain reaction of steps, controlled and aided by enzymes, which leads to the production of molecules that the cell requires. An important family of metabolites, called ceramides, are known to have an important role in cell signalling and apoptosis, as well as other physiological functions
In this study published in Nature, the researchers tested a new selective enzyme inhibitor called CerS1 on mice being fed a variety of different diets. They discovered that it has an important role in fat metabolism, specifically on fat deposition in mice. When they used the enzyme to inhibit metabolism, they significantly lowered fat deposition in mice, even if they were on a high-fat diet. They also found that it did not impact on glucose disposal nor insulin stimulated glucose uptake.
Although a lot more research is needed to go from mice studies to human trials, by directly affecting the cellular metabolism to prevent fat deposition, this research has demonstrated a potentially exciting new therapeutic avenue for treating obesity.
Obesity is simply caused by an imbalance in energy consumed and calories burned, however what causes this imbalance is complex and multifactorial. If enough calories are burned through physical activity, then an individual should not gain weight. Following this rationale, if an environment is more conducive to exercise then an individual is less likely to be overweight. This argument is the basis of this paper, which explores the relationship between environment and children’s BMI.
The study included 6001 children in England, between the ages of 3 and 11. The environmental measures used looked at levels of green space, gardens, crime or multiple deprivation of a neighbourhood. Crime rates were derived from police force data, on four criminal offences; burglary, theft, criminal damage and violence. The study found that there was a moderate relationship between environment and a child’s BMI, however it is unlikely that this relationship was causal. The results instead suggest that environmental variables, such as amount of parks or recreational facilities, may be driven by selection. So those families that are less likely to have overweight children, are more likely to choose to live in greener areas. This research goes against many previous studies which suggests a strong causal link between exercise promoting environments and obesity. In light of this, future research and health policy should consider the assumption that these two are linked and that managing the environment will invariably lead to lower levels of obesity.Read More
In some patients, weight-loss guidelines recommend the use of pharmacological agents as adjuncts to lifestyle modification. Although not many are licensed, they have been shown to be effective for long-term weight management. One of the serious downsides of these drugs is the side-effects. Depending on their sight of action, they have been known to precipitate severe complications in the cardiovascular or neuropsychiatric systems, leading to their removal by regulatory agencies over safety concerns.
Lorcaserin is a selective serotonin 2c receptor agonist that modulates appetite. It has proven efficacy for weight management in overweight or obese patients. This paper published in the New England Journal of Medicine sought to determine the cardiovascular risk associated with its use as an obesity treatment. From the study of 12,000 patients, it found no increased risk of cardiovascular complications. It also found that alongside significant weight loss there were also reductions in triglyceride levels and in dysglycaemia. In addition, it was found that there was an improvement in heart rate and blood pressure, which is in contrast to most other weight loss agents. Overall, this drug is an effective adjunct to lifestyle interventions in patients with obesity and cardiovascular disease, and doesn’t increase the risk of cardiovascular events.
Obesity is known to be associated with an increased risk of several major non-communicable diseases including type-2 diabetes, coronary heart disease, stroke, asthma and several cancers. It was previously thought that metabolically healthy obese (MHO) individuals were at no increased risk of these conditions. MHO is characterised by a healthy blood pressure, low cholesterol, normal insulin regulation and reasonable levels of physical fitness. However, more recent longitudinal studies have found that these individuals show a strong tendency to progress to an unhealthy obese state. What has been relatively understudied is the degree to which obesity is associated with the development of these major non-communicable conditions.
In this large study, published in The Lancet, the health data from 120,181 participants was analysed in order to determine how many disease-free years were lost to obesity. The participants were of a range of BMIs, but free of other comorbidities. They found that overweight patients lost 1 disease free-year, mildly obese patients 3-4 years and the severely obese 7-8 years compared with normal weight participants. Severe obesity was associated with the loss of 7-10 disease-free years in active and inactive individuals; current, past and never-smokers; and those of high and low socioeconomic position. The paper suggests that obesity, even in those with a healthy metabolic profile, leads to a substantial loss of disease-free years, across the social hierarchy and irrespective of lifestyle factors such as physical activity and smoking.
Epidemiological studies have previously demonstrated the contribution of a genetic background of diabetes to the development of obesity. The goal of this study was to explore the contribution of parental family history of diabetes to visceral fat area. Diabetes and obesity share many overlapping risk factors and genetic architecture, with visceral fat being responsible for many of the comorbidities associated with obesity. This large study, conducted in China, recruited 1875 people, aged 20-78, with normal glucose tolerance. The recruited individuals then had an assessment of their visceral fat accumulation using MRI.
The study found that a maternal family history of diabetes was associated with visceral fat accumulation, independently in both genders. Maternal transmission had a pronounced effect on obesity and related cardiovascular risk factors, however this study does not elucidate the underlying mechanism of this visceral fat accumulation. Despite the lack of understanding of the mechanism, this data can be used to inform public health policies when trying to predict which groups will be most at risk of obesity and its related comorbidities.
The number of bariatric operations performed globally is increasing every year. It is a very effective treatment, resulting in rapid sustained weight loss and reduction in obesity related comorbidities. However, very little is known about its impact on cancer risk. Obesity is the second biggest preventable cause of cancer after smoking. This study set out to see what effect bariatric operations had on cancer risk.
In order to assess cancer risk, peripheral blood mononuclear cells were collected from 45 obese subjects before, and at two time point after, surgery (6 and 12 months) to assess spontaneous micro-nucleus activity. Population studies have found that micronucleus frequency is correlated to cancer risk and indicates genetic damage.
The study found that micronucleus frequency was significantly reduced in patients who had undergone bariatric surgery, which suggests that alongside it’s other key benefits, bariatric surgery has the potential to reduce the incidence of cancer.
Interactive effects of parenting behaviour and regulatory skills in toddlerhood on child weight outcomes
A known potential risk factor for childhood obesity is a low capacity for self-regulation, which is the ability to control or modulate behaviours, emotions and cognition across situations. Toddlerhood is critical period for this trait, as it is characterised by the rapid development and differentiation in regulatory capacity. In this study, the researchers investigate the relationship between inherent self-regulation and maternal behaviour.
Two aspects of maternal behaviour were assessed.These were positive responsiveness, which involves willingness to endorse the child’s choices, and gentle control, which involves attempts to change, redirect or elicit child behaviour. Toddler regulation was assessed using a variety of task based activities, questionnaires and experimenter ratings. These were then compared with BMI z scores at 4.5 years old.
This study found two significant interactions between maternal behaviours and toddler regulation in predicting BMI z score. Firstly, greater positive responsiveness during free play was significantly related to lower BMI z for toddlers with poor regulation. Secondly, that greater gentle control was associated with lower BMI z for toddlers with low self-regulation, but higher BMI z in toddlers with high self-regulation. The results suggest both parenting and toddler regulation may have important implications for child obesity.
Our gut microbiota is essential to human health. However, unravelling the ways in which this microbial community correlates to health is not straightforward, due to the diversity and complexity of the organisms and the individual. Westernisation, characterised by changes in diet, reduced physical activity and increased prevalence of non-communicable disease, is associated with changes in gut microbiota.
Previous studies looking to understand gut microbiota focus on extremely different populations; usually hunter-gatherers versus urban inhabitants of industrialised countries. This study, published in Nature, instead focuses on a population of 441 Colombian adults, who are in the midst of westernisation. They found that the gut microbiota of these non-western, non-traditional Colombians forms a complex enterogradient, on which features of hunter-gatherers and citizens of industrialized nations can be identified.
In order to investigate the relationships, this paper distinguished groups based on variation in microbiota, then mapped variables relating to host health afterwards. This allowed the discovery of well-defined consortia, associated with obesity, cardiometabolic risk and metabolic pathways through which microbiota could have an impact on health. Their findings illustrate the multiple ways in which the microbiota can affect health and disease. Furthermore, it suggests that strategies to promote a healthy microbiome might be an effective means of alleviating conditions contributing to the burden of disease in Western societies.
Currently one in five american children are suffering obesity. With these figures growing each year, it has become a public health priority to identify modifiable risk factors for the prevention of childhood obesity. The causes of obesity are complex, however can be divided into genetic causes and lifestyle causes. These lifestyle causes often lead to rapid weight gain, suggesting that “nurture” carries more weight than “nature” in driving the current pandemic.
This paper, published in the BMJ, sought to examine the association between a healthy maternal lifestyle and the risk of developing obesity in offspring. A healthy lifestyle was characterised by healthy BMI, high quality diet, regular exercise, no smoking and light to moderate alcohol intake. Overall, it was found that a healthy lifestyle in the mother was associated with substantially lower risk of obesity in their children. If they adhered to the five low risk lifestyle factors, the children had a 75% lower risk of developing incident obesity than children of mothers who did not adhere to any of the low risk lifestyle factors.
Although this paper cannot draw any conclusions as to the mechanism of this relationship, their findings highlight maternal lifestyle choices as a potentially crucial factor in the aetiology of childhood obesity, adding weight to the argument that parent and family based interventions for reducing childhood obesity are a crucial and important target.Read More
The debate on the importance of different macronutrient configurations on body composition has driven many debates and fad-diets. In this new study in mice, published in Cell Metabolism, high dietary fat has been found to be the one diet that was associated with higher energy intake and adiposity.
The study, which involved the controlled feeding of mice 29 different diets varying from 8.3% to 80% fat, 10% to 80% carbohydrate, 5% to 30% protein, and 5% to 30% sucrose, also found an association with increased gene expression of different receptors in the brain. There was increased expression of 5-HT receptors, as well as the dopamine and opioid signalling pathways in the hypothalamus.
It has been documented that mice regulate their energy needs, and thus food consumption, based on caloric, as opposed to protein requirement. However, this study seems to suggest that this system can be compromised by hedonic factors linked to fat, but not carbohydrates. Although this is a long way from proving anything in humans, the shared similarities in energy regulation centres between the two species means that it is possible to speculate that humans share this hedonic factor override of energy regulation systems, which may provide an explanation to unhealthy eating behaviours such as binge eating.
According to the Proceedings of the Nutrition Society, after tobacco, unhealthy diets are the leading behavioural risk factor for all-cause morbidity and mortality in the UK. A poor diet can cause disease both directly via mediating factors such as weight-gain and hypertension, as well as potentially leading to CVD and T2DM through consumption of high-levels of saturated fat and highly refined sugar products.
Among children, 20% of 4-5 years and 33% of 10-11 year olds are either overweight or obese, with poorer children more than twice as likely to suffer obesity compared with children from affluent areas. It is clear, a new strategy is desperately needed if we want to protect the next generation from a whole variety of complex preventable diseases. Obesity is estimated to cost £6 billion per year in direct healthcare costs and a further £27 billion per year when losses in productivity are included. A key strategy for reducing the burden of disease involves trying to reduce overall consumption of unhealthy food, with taxation a primary component of the government’s plan.
There is a growing body of evidence from simulation studies, and other countries’ natural experiments, that sugar taxes can be effective at driving recipe modulation by industry, as well as behaviour changes amongst consumers. The indication is that fiscal measures are able to bring about desired price and purchasing changes to sugary drinks, while the weight of published data on sugary drinks taxes suggests that they will improve population health. However, the evidence is less clear on what the unforeseen outcomes of these taxes are; such as unhealthy recipe substitutions, or price equalisation between taxed unhealthy and untaxed healthy products by the manufacturers.
What is clear from the taxation strategies of other countries around the world is that the taxes need to be broad, intelligently designed, constantly evaluated to minimise unintended consequences, and overseen as to ensure that any loopholes for industry are discovered and managed. The economic costs of obesity are growing year on year and funding strategies must be developed in order to fund the treatment and care of overweight and obese individuals. In April 2018 the UK introduced an SDIL (Soft drinks industry levy). It involves taxing industry based on the concentration of sugar in their drinks using a 3 -tier system. The explicit aim of the tax is to change industry behaviour with regards to manufacture and reformulation, as opposed to trying to change individual behaviours.
This study, published in Obesity Surgery, aimed to generate real-world evidence of the socio-economic impact of bariatric surgery through evaluation of both its indirect and direct costs. Most studies focus on the direct healthcare costs only. However, this study used data collected over a period of 7 years from national registries, social transfer payments and income data, for surgically treated individuals, and compared them to that of a non-surgically treated individual, 3 years before and after surgery. The non-surgical group was defined as being eligible for bariatric surgery but not undertaking it.
The study found that there was a marginal increase in health-care costs in patients who underwent surgery, primarily because of the increased usage of in-patient services. It also found that there was a significant decrease in the costs of drugs, particularly anti-diabetic medication. Furthermore the study found that there a was notable positive effect of the surgery on social transfer payments; the costs of unemployment benefits were reduced and there were significantly higher social security payments.
Although this study was not able to identify net savings, it does not mean that bariatric surgery should be considered ineffective. The increase in health care-costs, mainly due to to complications and adverse effects of the surgery, should be weighted against the positive clinical effects that the patient will receive, namely reductions in prevalence of T2D and circulatory disease and medication to treat these, as well as considerable and sustained weight-loss which will enhance their quality of life and can also lead to a small decrease in total social transfer payments. Increased hospital care is a small price to pay for the sizeable benefits to the individual and society in the medium to long-term.
This study, published in the Journal of Medical Economics, assesses the potential cost-savings of using the OPTIFAST program in a population of US subjects, in comparison to “No intervention” and pharmacotherapy (liraglutide and naltrexone-bupropion).
OPTIFAST is a scientifically proven and medically supervised low-calorie diet program, for individuals with overweight and obesity. It has been shown to achieve acute and sustained weight loss, and reduction of clinical complications of obesity in studies since the 1980s. It involves providing obese patients with a 12 week diet of total meal replacement, with 2 subsequent phases of transition to a food based diet for 12 weeks each, and then another phase of 24 weeks. The total costs of the program is USD 4,500, which consists of USD 1,500 for the meals, and USD 3,000 for the weight management programme.
In the US at the moment, the threshold of willingness to pay for a new medicinal product per QALY is ~USD 50,000. A QALY is equal to one year of life lived in perfect health, and is calculated on numerous factors that assess quality-of-life systematically. This study has found that the cost of a QALY using OPTIFAST is USD 6,475, which is far below the threshold and represents great value for money. One of the reasons for this is the significantly lower incidence of complications, as compared with “no-intervention” and liraglutide or naltrexone-bupropion, in patients with class I or II obesity. This benefit is even more meaningful in class III obese patients with T2DM, and further increases with more time on the programme.
OPTIFAST has been demonstrated to lower healthcare costs, even when compared with bariatric surgery. Furthermore is has additional clinical and socio-economic advantages, due to few and mild adverse events when compared to other treatment regimes.
In this systematic review published in Paediatric Obesity, the authors sought to establish the costs of childhood and adolescent obesity in terms of direct healthcare costs as well as indirect productivity costs. Direct costs include drug costs, hospital in-patient costs, hospital outpatient costs and primary care costs. Indirect costs are divided into costs to society because of workdays lost and income penalty. Lost workdays accumulates the days lost to morbidity, early-retirement and mortality, whereas income penalty tries to assess how being overweight or obese may result in lower salary level.
Using 13 published research articles, they were able to work out that the average total cost was €149,206 for boys and €148,196 for girls. When this number was further broken down, it was found that lifetime cost was proportional to BMI, with lifetime costs increasing in proportion with excess weight during childhood or adolescence. It also found that productivity costs are significantly greater than healthcare costs, with girls being more likely to suffer increased healthcare costs and income penalties, and boys more likely to have increased work days lost.
An erroneous picture of the true cost obesity is created by studies which only focus on the direct costs of obesity. This study admits that the average figure, in the region of €150,000, is probably an underestimate due to the numerous costs which cannot be captured. This indicates a need for further research into the total excess lifetime costs of childhood and adolescent overweight and obesity, as only when this is properly evaluated can public health officials begin to allocate adequate resources.
A growing body of evidence is suggesting that self-perception of overweight/obese status is associated with poor cardiometabolic outcomes, above and beyond actual body weight. This study, conducted in Korea, used survey data from 21,629 people to determine whether there was a correlation between self-perceived obesity and metabolic syndrome (MetS) and cardiometabolic risk factors (CMRs).
In South Korea there has been a worsening of metabolic health indicators over the past decade, with obesity increasing as well as the prevalence of MetS and CMRs. This study found that individuals who identified their weight status as being slightly/very obese (vs. normal weight), were 18-54% more likely to meet MetS criteria. This was greater in men compared with women.
The findings were also in line with previous evidence showing a protective association of perception of normal weight with weight change and depressive symptoms among adolescents and young adults with overweight and obesity.
Recent studies have focussed on emotional responses related with perception of size when trying to understand the link between weight perception, cardiometabolic and emotional responses. They suggest that due to negative societal values towards obesity, self-evaluation of being obese could be associated with weight bias internalization, low self esteem and body dissatisfaction. Weight stigma is prevalent across diverse social groups and weight discrimination can induce sustained psychological distress and maladaptive coping behaviours, which can lead to biological alterations, such as prolonged activation of the hypothalamic-pituitary-adrenal axis and cortisol secretion.
Although this data can not infer any reverse causality between weight perception and metabolic outcomes, it does add to the growing body of evidence that these two are related and it is also the first to demonstrate this in a solely Asian study population. Their findings raise concerns regarding awareness orientated weight management approaches, such as BMI cards, as these may have the unintended consequence of “accurate” perception among individuals with obesity, leading to side-effects on the psychological and metabolic health of the patient. The implication of these findings on clinical practice, could be that clinicians should now take information on patients weight perception, when assessing risk of cardiometabolic dysregulation. Furthermore at policy level, intervention strategies could place the emphasis on lifestyle adjustments, such as healthy eating and increased physical activity, rather than just on the weight aspect.Read More