To anyone involved in adult obesity management, harrowing stories of adverse life events that may have significantly contributed to weight gain, are neither uncommon nor surprising.
While retrospective data in adults often implicates adverse events during childhood, longitudinal studies on the role of such events on body weight during childhood are less common.
This is now the topic of a study by Miriam Schiff and colleagues published in Public Health Nutrition.
The researchers looked at the relationship between adverse childhood events (ACEs) and excess weight? in longitudinal data from three waves of the second cohort of the US National Survey of Child and Adolescent Well-Being (NSCAW II), which sampled cases from US Child Protective Services investigations that were closed between February 2008 and April 2009 nationwide. The sample included 3170 kids ranging in age between infancy and 14 at baseline.?
Abusive and neglectful events were measured using the Conflict Tactics Scale – Parent-Child version at each wave, whereby hitting with a fist or kicking, beating, choking, burning and threatening with or using a knife or gun were coded as physical abuse; leaving a child alone when an adult should be present, not being able to provide food, being too drunk or high, or not being able to get to a doctor when a child needed it were coded as neglect; any forced sexual contact was coded as sexual abuse; so caught up with problems that parent did not tell child (s)he were not loved were coded as emotional neglect and shout/yell/scream, swear or curse, called dumb or lazy or threaten to send away were coded as psychological abuse.?
While supporting the hypothesis that ACEs play a role in the development of childhood obesity, both the number and nature of events as well as the sex of the child appear to matter.
Thus, for e.g., while for all youth, neglect as a single event was associated with about 2.5 greater odds of obesity, for girls who experienced neglect, the odds ratio was closer to 5.
Not all ACEs were positively associated with obesity. Thus, girls, experiencing physical abuse or having a parent with mental health problems had decreased odds of obesity (OR = 0.4), while boys who experienced sexual abuse were likewise less likely to develop obesity (OR =0.06).
As the authors point out, several limitations to these data must be considered. For one, the assessment of ACEs was entirely based on parental reports. Furthermore, it is not clear that these data are fully representative of the population at risk due to the way that individuals were ascertained.
If anything, the data highlight the need for more research (including qualitative assessments) into understanding the role of ACEs in childhood obesity.
Back in the days, the answer to how bariatric surgery works was rather simple. Mechanistically, you either caused surgical restriction (e.g. vertical banded gastroplasty, adjustable gastric banding) or malabsorption (e.g. jejuno-ileostomy, bilio-pancreatic diversion).
In the meantime, we know that neither restriction nor malabsorption play a significant role (if any) in why bariatric surgery works.
Rather, we now believe that the remarkable long-term success of these surgical interventions is based on important metabolic changes induced by these procedures, thus prompting the renaming of bariatric to metabolic surgery.
But what exactly are the metabolic changes induced by the various current procedures, and how do they contribute to the weight loss and other metabolic changes seen in these patients?
This is now the topic of an extensive review by Alina Akalestou and colleagues, published in Endocrine Reviews.?
In this paper, the authors discuss what is known about the roles of alterations in the neuroendocrine mechanisms of central appetite control (both wanting and liking), release of gut peptides that change hunger and satiety, as well as change in microbiota and bile acids.
In addition they briefly review the possibility that metabolic surgery impairs adaptive thermogenesis thereby resulting in a greater metabolic rate than to be expected given the magnitude of weight loss.
Overall, the mechanisms are clearly manifold and complex and may vary substantially based on the actual surgical procedure but also on the time course following surgery.
Clearly better understanding these mechanisms should not only inform surgical innovations but also help identify potential pharmacological targets for novel anti-obesity medications.
One of the often repeated wisdoms regarding changes in energy expenditure as we age, is that we lose about 10-15 Cal per year. According to this formula, someone going from age 20 to age 50 would lose about 300-450 Cal in energy requirements.?
But how accurate is this figure and does it really hold true?
This is the topic of perhaps the most comprehensive analysis of human energy expenditure over the lifespan ever to be conducted, by Herman Pontzer and colleagues, published in SCIENCE.
The researchers investigated the effects of age, body composition, and sex on total expenditure using a large (n= 6421 subjects; 64% female), diverse (n = 29 countries) database of doubly labeled water measurements for subjects aged 8 days to 95 years. In addition they looked at published measures of basal expenditure in neonates and doubly labeled water–measured total expenditure in pregnant and postpartum women.
After adjusting for body size to isolate potential effects of age, sex, and other factors, they found four distinct phases of human energy expenditure.
The first phase applied to neonates, up to 1 year of age. While during their first month neonates had a size-adjusted energy expenditures similar to that of adults, this increased rapidly in the first year so that between 9 and 15 months of age, adjusted total and basal expenditures were nearly ~50% elevated compared with that of adults.
The second phase applied to juveniles, 1 to 20 years of age. While total and basal expenditure continued to increase with age throughout childhood and adolescence along with fat-free mass, size-adjusted expenditures steadily declined at a rate of about 3% per year till about age 20, after which it plateaued at adult levels. In contrast to what one might expect, there was no indication of a?pubertal increases in adjusted total or basal expenditure. Although men tended to have a higher energy expenditure, the rate of decline was the same for men and women.?
Over the third phase, from 20 to 60 years of age, total and basal expenditure and fat-free mass remained stable from ages 20 to 60 years in both sexes. During pregnancy, adjusted total and basal expenditures remained stable with the elevation in unadjusted expenditures matching those expected from the gain in mothers’ fat-free mass and fat mass.
Finally, during the fourth phase, starting at about age 60, total and basal expenditure declined at a rate that exceeded the loss attributable to the steady reduction in fat-free mass and fat mass. Thus, adjusted total expenditure declined by –0.7 per year, and adjusted basal expenditure fell at a similar rate. For subjects 90+ years of age, adjusted total expenditure was ~26% below that of middle-aged adults.
In additional analyses, the researchers also found that both physical activity and tissue-specific metabolism contribute to total expenditure and its components across the life span. Elevated tissue-specific metabolism in early life may be related to growth or development, whereas reduced expenditures in later life may reflect a decline in organ-level metabolism.
These observations have several important implications. Firstly, these data contradict the notion that energy requirements change in a continuous fashion over time; rather, each of these phases are distinct, with energy expenditure remaining rather stable over long periods of adult life, with significant changes occurring in childhood and old age.?
Secondly, the researchers note that there are considerable interindividual variations in expenditure even when controlling for fat-free mass, fat mass, sex, and age – meaning that some individuals require fewer calories that others.?
Clearly, understanding the complex biology that underlies these metabolic changes over the life course as well as the variation among individuals will likely help reveal the roles of metabolic variation in health and disease.
Body weight is a highly heritable trait and a host of genes have now been identified as playing a role in its regulation. Furthermore, there is evidence that changes in body weight in response to caloric restriction may also be in part determined by genetic factors.?
This naturally leads to the question whether or not weight loss after metabolic surgery?may be predicted by genetic screening.?
This is the topic of a recent systematic review by Sapana Gupta and colleagues, published in Obesity Surgery.
In their analyses of fifty-seven studies that looked at single genes or genetic risk scores in relationship to weight loss after metabolic surgery, they found some (albeit weak) evidence that certain genetic variants (e.g. UCP, FTO, MC4-R) may predict greater or lesser weight loss. However, results were inconsistent and, where stated, of rather modest magnitude (1.5-4.5 kg).
Given the host of factors that can potentially influence post-surgical weight loss, this should not be surprising. It is indeed extremely unlikely that a genetic score is likely to reliably predict weight loss in a given individual with sufficient sensitivity and specificity to meaningfully guide clinical decision making.
For this, one would need to not only link genetic markers to weight loss but also to the overall potential clinical benefit including prediction of hard outcomes.
Thus, the clinical utility of a genetic score that predicts a higher probability of a given patient perhaps achieving a 2 kg less weight loss than the average, is rather limited.
At this time, I do not see any value of adding genetic screening to assessing patients’ suitability for metabolic surgery.
Obesity is now well recognised as an important risk factor for cancers of the GI tract including oesophagus, stomach, colon, gall-bladder, liver, and pancreas. Furthermore, weight-loss interventions, particularly bariatric surgery, have been shown to reduce cancer morbidity and mortality in people living with obesity.
Traditionally, obesity related cancer risk has been attributed partly to dietary patterns associated with obesity, as well as insulin resistance (with hyperinsulinemia), increased production of pro-inflammatory cytokines, and changes in sex hormones.
Now, a review paper by Maria Angela Guzzardi and colleagues, published in the International Journal of Obesity, discusses the possibility that obesity related alterations in gut hormones may play a hitherto unrecognised role in the etiology of these cancers.?
Gut hormones play a vital role in a wide range of processes ranging from local influences on GI motility, exocrine function and the bacteriome to systemic influences on appetite, glucose homeostasis, and immune response.
As an example, the authors discuss the role of GLP-1:
“Recent studies have shown that GLP-1 receptor (GLP-1R) agonists might have a beneficial anti-inflammatory role independent from the glycemic regulatory actions. In fact, GLP-1R agonists modulate enteric immune response by activating intestinal intraepithelial lymphocytes GLP1R, which may influence microbiota composition and intestinal inflammation. Therefore, the blunted GLP-1 secretion in obesity contributes to the obesity-related pro-inflammatory condition.”
Similarly, vasoactive intestinal peptide (VIP),
“…is a regulator of both innate and adaptive immunity, with an anti-inflammatory role. In fact, in innate immune cells, VIP can inhibit the production of pro-inflammatory factors (e.g., TNF-alpha, IL-6, IL1beta, IL12, iNOS) and promote the production of anti-inflammatory factors (e.g., IL-10 and TGF-beta). In the adaptive immune system, VIP shifts the Th1/Th2 balance during CD4 T cell differentiation in favor of Th2 cells, both in vitro and in vivo, primarily through the vasoactive intestinal peptide receptor-2 (VPAC2).”
Based on the observation that neoplastic samples have been shown to express receptors for many gut hormones, the authors also discuss at length the evidence that gut hormones could modulate the proliferation and perhaps invasiveness of a wide range of cancers.
However, they also note that,
“Overall, existing data are controversial, which might be due to differences between local and systemic effects of the hormone, and among cancer types.”
Hopefully this review will prompt further studies exploring the potential role of obesity-related alteration of gut hormones in the pathogenesis of specific tumors, which will open the perspective of new strategies in the prevention and treatment of cancer in patients with obesity.
Although I have spent the last 25 years helping patients manage their obesity, I have never had obesity myself (at least not based on BMI). Everything I know about what it must be like living with this chronic disease, I have learnt from what my patients have told me.?
Obviously, this is a biased sample, as I have mainly seen patients with more severe obesity and those fortunate enough to have access to an obesity clinic.
So, what is it really like to live with obesity?
This is the topic of a systematic review by Emma Farrell and colleagues published in Obesity Reviews.
The study included findings from 32 peer-reviewed studies relating to the lived experience of patients with obesity.
Overall, fiive “third-order constructs” or themes emerged from their ethnographic analysis related to 1) the development of obesity, 2) a life limited, 3) stigma, judgment, shame, and blame, 4) treatment and 4) experiences of specific or minority groups.
Interestingly, the researchers actually involved people living with obesity to inform and validate their synthesis. Thus, once the third-order constructs had been identified and described, the researchers met with the study’s Patient Advisory Board (PAB) to discuss the findings and to provide a “phenomenological nod” if advisory board members could relate to the synthesis, recognizing it as an experience that they have or could have had.
With regard to the development of obesity, people living with obesity had a wide range of individual experiences to share. While some reported having been heavy since earliest memory, others reported a steady progression, often in response to a major life event. Other reported contributors ranged from negative emotional states and adverse life experiences to genetic predisposition, social pressures, physical environments and sometimes medications. Virtually all experienced weight cycling, often attributable to dieting.?
Obesity clearly was a major limiting factor in many people’s lives, leading to social disconnection as well as restrictions in movement, activities, and opportunities. Many participants described a sense of having to put life on hold. Complications of obesity such as diabetes, high blood pressure, and musculoskeletal pain curtailed many participant’s ability to be active and participate in aspects daily life. Judgment, by self and others, was identified as a major contributor to social isolation and the life-limiting effects of obesity.
Indeed, experiencing stigma, judgment, shame, and blame was one of the most pervasive and consistent themes to emerge from the analyses. Thus, living under the critical gaze of others and being judged as not being good enough, not trying hard enough,being lazy, and/or undeserving of respect was a common issue.
With regard to treatment, sub-themes including difficulties accessing appropriate obesity care, but also negative treatment by healthcare providers—ranging from a lack of respect and compassion to examples of verbal insults, inappropriate humor, unmet healthcare needs, and breaches of dignity.
Finally, virtually all of these issues were amplified in ethnic or other minorities. A particular issue was the failing alignment of “Western” medicine to the cultural sensitivities of these populations.
Overall, the synthesis not only provides important insights into the often negative experiences of people living with obesity, but also, as the authors point out,
“…reveals the dearth of studies that focus solely on the experience of the patient and highlights the tendency for participant-informed, rather than participatory, methods in obesity research.”
Clearly, the call, “Nothing about us, without us”, needs to be more widely heeded in our approach to better understanding and addressing the obesity epidemic.
Clinical trials have consistently documented the weight-loss effect of treatment with the GLP-1 analogue liraglutide. These studies have also generally reported a significant reduction in waist circumference, a simple surrogate measure for visceral obesity.
But, does this finding hold up with more precise measures of ectopic fat?
That is apparently the case, based on a study by Ian Neeland and colleagues published in The Lancet Diabetes and Endocrinology.
The researchers randomised 185 volunteers with a BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling.
At the end of the trial, visceral adipose tissue, assessed with MRI, was reduced by 12.5 % with liraglutide compared to 1.6% with placebo. Interestingly, this difference was substantially underestimated by changes in waist circumference, which only reduced by 7% with lirgalutide vs. 4% with placebo.
Perhaps, even more remarkably, while liver fat reduced by 12% with liraglutide, it actually increased by 21% in the placebo group.
Adverse effects were typical of those expected with liraglutide (largely transient GI-related).
Thus, the authors note that,
“The relative effects of liraglutide on fat reduction were two-times greater in the abdominal viscera and six times greater in the liver than seen on overall bodyweight. The treatment effect seemed consistent across race–ethnicity and baseline BMI categories, and among those with or without baseline prediabetes”
“Although individual body fat depot reductions were highly correlated with overall bodyweight loss, VAT, and to a greater degree liver fat, were less well correlated with weight loss. This could suggest a partially weight-independent effect of GLP-1 receptor agonism on body fat distribution.”
In summary, it certainly appears reassuring that treatment with liraglutide indeed results in a marked reduction in visceral and ectopic fat, as these fat depots have been associated with increased metabolic and cardiovascular risk.
Disclaimer: I have received honoraria as a consultant and speaker from Novo Nordisk, the maker of liraglutide.
Obesity is a heterogeneous complex chronic disease that generally requires patients to make changes to their lifestyles and perhaps deal with various psychological aspects of their mental health.
But so is diabetes, hypertension, coronary artery disease, chronic lung disease, or, for that matter, almost any chronic disease that is routinely managed in clinical practice.?
Obviously, if you have a team of allied health specialists including dietitians, exercise physiologists, behavioural psychologists, occupational therapists, health educators, etc. you could probably do a much better job of managing patients with any of these diseases, than if your were sitting in your office by yourself with no more than 5-8 minutes to dedicate to each patient.
And yet, that is exactly how doctors routinely manage the vast majority of patients presenting with these diseases in their real-world practices.
And to be fair, most docs do a fairly reasonable job of managing these diseases without having the luxury of working in extended multidisciplinary health teams with support from an army of allied health practitioners.?
So, why when it comes to obesity, do we suddenly expect them to harness all these resources in order to provide even the most basic obesity care?
Why, for example, do we think that it is more important to have a dietitian on my team for managing obesity, than say for managing a patient with diabetes or hypertension or dyslipidemia? Why is it more important to have an exercise specialist on my obesity team, than for my patients with coronary artery disease or heart failure? In fact, why is it more important to have a psychologist on my team for managing obesity, than it is for managing my patients with depression or anxiety disorder?
Obviously, patients with any of these conditions would likely benefit from being managed by a multidisciplinary team of experts, but somehow, we manage to provide acceptable care even without all this support.
Why, in obesity care, do we often take the “all or nothing” approach? Frankly, I cannot recall the number of times I have heard colleagues tell me that the most important reason they cannot offer obesity treatments, is because they simply do not have the allied health resources they need.?
And they justify this attitude towards managing obesity, by highlighting the importance that is generally given to multidisciplinary management in obesity guidelines.
In fact, reading these guidelines with their emphasis on lifestyle and behavioral interventions, it is easy to see why most doctors would simply conclude that treating this condition without extensive allied health support would just be a waste of time.
Allow me to go on the record that I firmly believe that any doctor who can do a decent job of managing diabetes, or hypertension, or heart failure, or rheumatoid arthritis, or chronic kidney disease, without the luxury of extensive allied health support, can probably also do a pretty decent job of helping their patients with obesity better manage their disease – if only they knew what they were doing!
Because, in contrast to having learnt all about managing patients with diabetes, or hypertension, or heart failure, or rheumatoid arthritis, or chronic kidney disease in medical school and residency, most doctors have never learnt to manage patients with obesity (beyond telling them to go lose weight).
Naturally, this makes them wish for an allied health team that they hope knows more about managing obesity than they do (which, sadly, they often don’t).
As long as we keep pretending that obesity is so complex that it takes an army of allied health practitioners with hours and hours of time on their hands to manage obesity, we should not expect to see doctors take much interest in obesity management.
Rather, we need to make obesity management as manageable as managing any other chronic disease, if we truly hope to insert obesity management into routine family practice.