Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: A meta-analysis
In a systematic review, published in Medicine, the authors sought to investigate whether obesity conveyed a benefit to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer. Breast cancer is a complex condition with many different subtypes, which each behave in different ways. Triple negative breast cancer means that there is not enough expression of three receptors, ER, PR and HER-2. It is a rare and often aggressive form of breast cancer, characterised by short recurrence time and greater chance of metastasis via the bloodstream.
The effect of obesity on cancer survival is still contested, and it varies between each type of cancer. The rationale behind it increasing survival is that by having a greater body mass, an obese patient is better able to survive the wasting effects of cancer and its treatment. Conversely, it is argued that many endocrine, metabolic and inflammatory complications that result from a persistent obese state, predispose these patients to cancer and limits there survival ability. This review included data from 9 studies for DFS meta-analysis (4,412 patients) and 8 studies for OS meta-analysis (4,392 patients). It found a number of controversial studies, which suggested obesity conveyed a very significant survival advantage, and others, which concluded that the opposite was true. The result of their analysis is that there was no statistically significant difference between the DFS and OS rates of obese patients compared to normal weight patients in triple negative breast cancer.
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Effects of Physical Activity and Sedentary Behaviour on Brain Response to High‐Calorie Food Cues in Young Adults
Physical activity is known to be an effective method of weight management, due to increased burning of calories. However, this study published in Obesity, found that beyond the calorific effect, there is also a physiological change in the brain in areas associated with reward.
For this study, 22 lean and 18 obese people were selected and their activity levels assessed. Looking at levels of moderate to vigorous physical activity (MVPA), and levels of sedentary behaviour (SB). Next, they ingested some glucose and underwent an fMRI brain scan, and while in the scanner, they were shown images of high-calorie foods, alongside inanimate objects. The researchers looked at 10 regions of the brain known to be responsive to visual food cues. What they found is that those who engaged in MVPA had lower responses to the food cues, and those who engaged in SB, had higher responses. This was true of the healthy weight individuals, and particularly true amongst the obese participants.
The potential mechanism through which physical activity suppresses responses to food cues is still unclear, however what is clear is that reducing SB and increasing MVPA can have positive effects on regions of the brain associated with food perception. Future studies on the underlying mediators of the effects of physical activity on the brain’s response to unhealthy food cues, may provide an interesting new approach to treating obesity.
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Identification of Children’s BMI Trajectories and Prediction from Weight Gain in Infancy
The causes of childhood obesity are not always clear; however, the risk that it poses to adult health outcomes, such as cardiovascular health and premature death, mean that an understanding of common patterns and predictors in infancy are essential. This paper published in Obesity, used data on birthweight and BMI from 1,364 children of ages 24 months to 13 years, to see which patterns are associated with higher risk of becoming overweight or obese.
They found that risk of membership of a high-BMI trajectory could be predicted from as early as 15 months old. Birth weight for gestational age and percent weight increase in the first 15 months are the strongest predictors for following a high-rising trajectory of weight change across childhood. Therefore, high-birth weight should trigger parents and physicians to ensure healthy nutrition. More importantly than that, rapid weight gain in the first 15 months was found to be strongly correlated to high-BMI in later life, meaning that close monitoring of weight-gain in early life, along with intervention, could be a new way of preventing childhood obesity.
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Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk
This study, published in the Journal of the American College of Cardiology, used data from 6,089 participants of the MESA study to see how having a healthy metabolic profile despite obesity, affects your risk of cardiovascular disease.
The debate over the risk of cardiovascular disease (CVD) associated with the three groups, metabolically healthy normal (MHN), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO), stems from the apparent contradiction that an individual can be obese (BMI>30 Kg/m2) and yet be free of metabolic syndrome (MetS). This study found that for the vast majority of people, MHO was a transition state towards MUO, and that there was a dosing effect associated with obesity. With the risk of developing MetS being relative to cumulative obesity exposure. They found that almost one-half of those with MHO at baseline, developed MetS during follow-up. Higher MetS duration was also significantly associated with CVD, supporting the theory that risk from obesity is cumulative.
Very few individuals can stay metabolically healthy when continuously exposed to obesity, and the transition to MetS represents a massive increase in risk of CVD. Clinicians should see MHO as an opportunity for early intervention, to prevent later disease, rather than waiting for an unhealthy metabolic profile to develop, by which point, risk has already massively gone up.
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Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study
Obesity is usually evaluated based on BMI, however more and more research is showing that the distribution of fat within the body is important in determining the harmful metabolic effects of obesity.
In this historical cohort study, conducted in Japan, and published in the international journal of obesity, the authors set out to determine the relationship between different phenotypes of obesity and the onset of type 2 diabetes. The authors used three phenotypes, obesity, visceral fat obesity and ectopic fat obesity; defined as body mass index >25 Kg/m2, waist circumference >90cm in men or >80cm in women, and having fatty liver diagnosed by abdominal ultrasound. Ectopic fat is defined as extra adipose tissue in locations not originally associated with adipose tissue storage. The study included 15,464 participants, who were divided into 8 groups, depending on the absence or presence of each phenotype.
They found that obesity and visceral fat alone had very little effect on the risk of incident type 2 diabetes and that the presence of ectopic fat obesity presented the greatest risk of developing type 2 diabetes. Several studies have shown before that increased adiposity in the liver leads to disrupted metabolic function, including glucose control, however this is the first study to directly compare phenotypes and assess risk. Although there were limitations to this study, the data suggests that body composition analysis should be considered when assessing a patient’s risk of obesity related disease.
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How Physiological Changes Associated with Obesity Affect Drug Metabolism
Obesity is known to have a significant impact on many organ systems that are crucial in drug metabolism. As the prevalence of obesity continues to rise, clinicians are being challenged with the problem of dosing in the extreme overweight population. This review article discusses the different physiological changes associated with obesity and how they affect absorption, distribution, drug metabolism and clearance in morbidly obese patients.
The changes that occur in the organs of the body do not correlate linearly with BMI, but also includes factors such as time and individual body composition. For example, in the kidney of an obese patient, renal clearance is initially enhanced by a compensatory hyperfiltration and hyper-perfusion, though, eventually, this declines as a result of a constantly elevated intra-glomerular pressure which leads to chronic kidney disease. Likewise, cardiac output is increased in obese patients in order to provide oxygen and nutrients to the excess tissue. This should mean that that blood flow to the liver increases, however due to non-alcoholic fatty liver disease resulting in steatosis, together with sinusoidal narrowing, blood flow may actually decrease over time.
Obesity also has an effect on the gastric emptying and gut permeability, meaning that drugs are absorbed at different rates to normal. Drug penetration into tissue is also affected, meaning that a higher dose may be needed in order to reach effective concentrations. For example, with antibiotics to treat a local infection, obese patients may require a much higher dose, which can then introduce issues of drug toxicity.
What is clear from these few examples is that with a growing number of obese patients, there needs to be a quantitative system in place that can derive drug dosing recommendations for obese patients. Currently there is a lack of understanding of how obesity affects the pharmacokinetics and pharmacodynamics of drugs, which leads to improper and potentially dangerous dosing of obese patients.
To learn more about obesity, its prevention, and its treatment please look at CCH’s Postgraduate Academic Courses in Lifestyle Medicine (Obesity Care), and CPD Short Courses in topics such as childhood obesity and behaviour change, designed to up-skill health professionals in this vitally important, and often overlooked, area of care.
Read MoreFamine Exposure During Early Life May Lead to an Increased BMI in Adulthood
It has been previously reported in epidemiologic studies that famine exposure during early life is associated with overweight or obesity in adulthood. In this systematic review and meta-analysis of 20 studies, this paper set out to determine whether exposure to famine in early-life had any association with overweight or obesity in later life.
This study was conducted according to the Cochrane methodology, and included research from a variety of different famines across the world with considerations for gender and age. It found that there was a significant correlation between early life exposure to famine and being overweight in later life, and that this association was stronger in females, individuals less than 50 years of age and individuals who experienced foetal exposure.
The mechanisms for this phenomenon are still not clear, however the author goes on to discuss the different systems that the famine could affect, including a formatting of the HPA neuroendocrine access that controls energy intake and expenditure, epigenetic changes sustained during famine causing behavioural differences, as well as psychological damage to the individual, which will affect their behaviour and attitude towards food.
Read MoreEfficacy, Safety, and Mechanisms Of Herbal Medicines Used In The Treatment Of Obesity: A Protocol For Systematic Review
There is a huge amount of conflicting evidence over the potential efficacy of herbal remedies for the treatment of obesity. Although several systematic reviews have been conducted, the market is saturated with poorly evidenced claims, and a huge number of different remedies. This study sets out a protocol for a comprehensive systematic review into herbal remedies and their efficacy at treating obesity.
Herbal medicines can cause weight loss through 5 different mechanisms, namely appetite control, stimulation of thermogenesis, inhibition of fat absorption as well as decreasing lipogenesis.
Efficacy has been evaluated before, however, the authors feel a new systematic review, focussing on clinical trials data is needed. This systematic review will be seen as an update, with all new data plus any new research on active components and methods of action.
Herbal remedies are defined as raw or refined products derived from plants or parts of plants, in this case used for the treatment of obesity. The primary outcomes expected will be an improvement in BMI, waist circumference, waist-hip ratio, body fat and appetite. Secondary outcomes will focus more on the metabolic features of obesity, meaning improvements to cholesterol, low-density lipoprotein, high-density lipoprotein, blood pressure, triglycerides and blood sugar.
The increasing number of randomised controlled clinical trials means that a new and updated review of the mechanisms of action and efficacy of these treatments is needed. They have the potential to become a cheap new therapy in the treatment of obesity or if proven otherwise, then this systematic review will put to rest the debate over their efficacy.
Read MoreCardiorespiratory fitness as a Determinant Factor for the 30% of Obese Individuals That are Metabolically Healthy
Previous studies have shown that individuals can be obese and metabolically healthy, or of normal weight with an unhealthy metabolic profile. The metabolically healthy obese (MHO) phenotype currently represents 30% of obese individuals. However, major studies have so far failed to consider the possible impact of cardiorespiratory fitness on metabolic health.
MHO individuals are characterised by having low abdominal adiposity, low inflammation level and low risk of developing metabolic comorbidity. This study hypothesised that cardiorespiratory fitness, is a determinant factor for the MHO phenotype. It aimed to investigate the associations between fitness, abdominal adiposity and low-grade inflammation within different BMI categories. Data from 10,976 individuals on waist circumference (a surrogate measurement for abdominal adiposity), cardiorespiratory fitness and C-reactive protein levels (a measure of low-grade inflammation) were analysed.
In both men and women, this study found a strong inverse association between fitness and waist circumference adjusted for age, education, smoking, alcohol and BMI. It also found that fitness reduced levels of inflammation regardless of BMI. Furthermore, a positive association between waist circumference and C-reactive protein, in both men and women in all BMI categories. This study demonstrates that there is a considerable difference in the values for abdominal adiposity, fitness and low-grade inflammation in people with the same BMI. Therefore, in order for clinicians to obtain a more accurate identification of individuals who are healthy despite obesity and individuals who are at metabolic risk despite the normal weight, additional measurements of waist circumference, CRP and fitness should be taken in to account.
Read MoreThe Effectiveness of a School Intervention Program. A Panacea against Obesity?
A large randomised controlled trial was conducted in the West Midlands, looking into the effectiveness of a school and family based healthy lifestyle programme, in comparison to usual practice. 1,467 year 1 pupils aged 5 to 6 years (control, 778 pupils), were randomised into the study, with follow-ups at 15 months and 30 months. The intervention consisted of encouraging healthy eating and physical activity, which included a daily additional 30-minute school time physical activity opportunity and a 6-week interactive skills programme in conjunction with Aston Villa football club. There was also signposting of family physical opportunities and termly workshops looking at healthy eating cooking skills.
The main outcome measured in the study was BMIz score at 15 and 30 months respectively. They also looked at other anthropometric, dietary, physical activity and psychological measurements. Unfortunately, at 15 and 30 months follow up, there was no statistically significant improvement in any of the outcomes measured. Despite this rigorous in-school intervention, the primary analysis suggests that it was in fact, ineffective. Although this study was inconclusive, the authors go on to point out that it highlights the difficulty of the task of reducing weight in children, and that schools alone may not be the answer. A holistic approach that incorporates school, home, environment and policy is one that is most likely to succeed, and the idea that school-based interventions will solve the problem is likely oversimplifying the issue.
Rethinking public mental health: learning from obesity
This commentary piece written in the Lancet Psychiatary, reviews Stanley J Ulijaszek’s new book, Models of Obesity. It argues that the field of mental health could learn a lot from the challenges of obesity and the approaches used to tackle it. It first argues that the obesity debate has been reframed in a way that presents it as a chronic relapsing-remitting condition. This has shifted the approach to the treatment of obesity and would be a useful if implemented in mental health.
Next, it highlights the standard unit of measurement that exists in obesity; BMI. Despite its faults, this practice has meant that it’s far easier to make sense of population obesity through epidemiological studies. Mental health researchers often use confused terminology, meaning that it is difficult to perform population studies and so to grasp the scale and nature of the issue.
Third, the field of obesity considers the complex systems that create public health problems better than that of mental health. This means that considerations for environmental factors and psychopathogenic factors are much better integrated into obesity care than in mental health.
Fourth, there is a polyrational approach in obesity that frames obesity public health in a field of competing interests and behaviours, such as between corporations and governments. This means that there is a better understanding of the rationalities and their relationship to each other.
Finally, “viable clumsy solutions” are used to address obesity; these are “a combination of single rational policies towards a particular problem”. This follows from the polyrational approach of understanding obesogenic environments. It involves bringing individual stakeholders together to find solutions, which combine to advise policy.
Read MoreThe obesity paradox in cancer: clinical insights and perspectives
The obesity paradox refers to the paradoxical relationship between obesity and instances of better long-term survival in cancer, given the huge body of evidence for obesity’s carcinogenic effects. This article, published in Eating and weight disorders- studies on anorexia, bulimia and Obesity, seeks to explore the available studies concerning cancer incidence, survival and obesity in order to offer possible explanations for the paradox and a methodological framework.
The potential mechanisms highlighted for the ‘obesity paradox’ are that obesity provides a nutritional reserve, helping the patient survive surgical interventions and anti-cancer treatments. Also, that obesity is associated with a lower-stage of disease, smaller tumour size and less aggressive subtypes. Finally, that obese patients are likely to be frequent users of healthcare, therefore cancer may be diagnosed sooner.
There are however, methodological issues with these explanations. The issue of BMI, which is a proportional score based on weight and height, gives no information regarding body composition which is important in cancer care. Furthermore, the overall literature that supports this relationship, uses mainly retrospective studies and often fails to include confounding variables such as age and smoking. Rigorous prospective studies need to be conducted to define the impact of obesity in the oncology setting.
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