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Scalability of Obesity Treatments: Need To Target

bariatric patient in bedYesterday, I discussed the desperate need for scalable obesity treatments.

I pointed out that neither behavioural nor surgical interventions are readily scalable to provide long-term obesity treatments to the over 7,000,000 Canadians currently considered to have obesity.

I also noted that, like for other chronic diseases, only medical treatments with anti-obesity medications have the potential for scalability in the millions – we do this regularly for the millions of people living with diabetes, hypertension, heart disease, or any of the other common chronic diseases affecting Canadians.

Nevertheless, before we discuss what it would take to scale up medical treatments, let us take a look at whether all 7,000,000 affected Canadians really need obesity treatment.

Let us first note that the number 7,000,000 refers to Canadians with a BMI over 30. This may well overestimate the problem – as not everyone will actually need or likely benefit from anti-obesity treatments (BMI measures size – not health!).

In fact, if we apply the actual WHO definition of obesity, namely the presence of abnormal or excess body fat that impairs health, we can perhaps readily reduce this number by about 5-10% (anyone with Edmonton Obesity Stage 0) obesity, as these individuals are pretty healthy despite their excess weight. As there is no evidence that these rather healthy individuals would experience any long-term benefits from anti-obesity treatments, it would be entirely reasonable to take a “watch and wait” approach.

The 7,000,000 also includes an additional 15-20% of people, who would have rather mild impairments in health (Edmonton Obesity Stage 1), associated with a very low long-term risk – for these there is also no proven long-term benefit of obesity treatment.

Thus, we can readily exclude about 20 to 30% of individuals for whom the risk-benefit ratio (and thus, the cost-benefit relationship) would hardly justify the use of prescription medications.

This would reduce the number needed to treat by as many as 2 million – leaving us with about 5,000,000 left to treat.

Of these (by definition), all would have Edmonton Obesity Stage 2 or higher, meaning that they will all have some obesity related health impairments.

However, many of these individuals will have obesity related health risks (e.g. hypertension, diabetes, sleep apnea) that are currently well managed with other available treatments (e.g. anti-hypertensive or anti-diabetic medications, CPAP, etc.). For these well-managed patients, it is not clear what additional value anti-obesity medications would offer.

Let us assume that this number of well managed patients is about 50% of the remaining 5,000,000 – this leaves us with only 2,500,000 individuals with obesity related health problems that are not well managed with the available treatments for their comorbidities. It is probably only in these individuals that medical obesity treatment would make sense – both in terms of cost and benefit.

Let us further assume that for another 50% of the remaining for various reasons (e.g. too sick, too old, no ready access to medically supervised care, not interested in obesity treatment, etc.) medical treatment for obesity is not feasible.

This would leave us with only about 1,250,000 patients where medical treatment with prescription drugs would be both practical and likely cost-effective.

This is now a much more manageable problem. In fact, this is only about half the number of Canadians currently living with diabetes, a problem that is routinely managed with medical treatments.

So where are the anti-obesity treatments for these patients?

That will be the topic of tomorrow’s post.

@DrSharma
Edmonton, AB

 

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We Desperately Need Scalable Treatments For Obesity

NN Benefits White Paper CoverObesity, defined as the presence of abnormal or excess body fat that impairs health, currently affects 100s of millions of people worldwide.

Although “weight-loss” is a booming global multi-billion dollar business, we desperately lack effective long-term treatments for this chronic disease – the vast majority of people who fall prey to the natural supplement, diet, and fitness industry will on occasion manage to lose weight – but few will keep it off.

Thus, there is little evidence that the majority (or even just a significant proportion) of people trying to lose weight with help of the “commercial weight loss industry” will experience long-term health benefits.

When it comes to evidence-based treatments, there is ample evidence that behavioural interventions can help patients achieve and sustain important health benefits, but the magnitude of sustainable weight loss is modest (3-5% of initial weight at best).

Furthermore, although one may think that “behavioural” or “lifestyle” interventions are cost-effective, this is by no means the case. Successful behaviour change requires significant intervention by trained health professionals, a limited and expensive resource to which most patients will never have access. Moreover, there is ample evidence showing maintenance of long-term behaviour change requires significant on-going resources in terms of follow-up visits – thus adding to the cost.

This severely limits the scalability of behavioural treatments for obesity.

If for example, every Canadian with obesity (around 7,000,000) met with a registered dietitian just twice a year on an ongoing basis (which is probably far less than required to sustain ongoing behaviour change), the Canadian Health Care system would need to provide 14,000,000 dietitian consultations for obesity alone.

Given that there are currently fewer than 10,000 registered dietitians in Canada, each dietitian would need to do 14,000 consultations for obesity annually (~ 70 consultations per day) or look after approximately 7,000 clients living with obesity each year. Even if some of these consultations were not done by dietitians but by less-qualified health professionals, it is easy to see how this approach is simply not scalable to the size of the problem.

A similar calculation can be easily made for clinical psychologists or exercise physiologists.

Thus, behavioural interventions for obesity, delivered by trained and licensed  healthcare professionals are simply not a scalable (or cost-effective) option.

At the other extreme, we now have considerable long-term data supporting the morbidity, mortality, and quality of life benefits of bariatric surgery. However, bariatric surgery is also not scalable to the magnitude of the problem

There are currently well over 1,500,000 Canadians living with obesity that is severe enough to warrant the costs and risks of surgery. However, at the current pace of 10,000 surgeries a year (a number that is unlikely to dramatically increase in the near future), it would take over 150 years to operate every Canadian with severe obesity alive today.

This is where we have to look at how Canada has made significant strides in managing the millions of Canadians living with other chronic diseases?

How are we managing the over 5,000,000 Canadians living with hypertension?

How are we managing the over 2.5 million Canadians living with diabetes?

How are we managing the over 1.5 million Canadians living with heart disease?

The answer to all is – with the help of prescription medications.

There are now millions of Canadians who benefit from their daily dose of blood pressure-, glucose-, and cholesterol-lowering medications. The lives saved by the use of these medications in Canada alone is in the 10s of thousands each year.

So, if millions of Canadians take medications for other chronic diseases (clearly a scalable approach), where are the medications for obesity?

Sadly, there are currently only two prescription medications available to Canadians (neither scalable, one due to cost the other due to unacceptable side effects).

So what would it take to find treatments for obesity that are scalable to the magnitude of the problem?

More on that in tomorrow’s post.

@DrSharma
Edmonton, Ab

 

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Does Gastric Bypass Surgery Change Body Weight Set Point?

sharma-obesity-surgery3The Holy Grail of obesity treatment is to find a way to revere the resetting of the body weight set point from the highest achieved body weight to something that is lower.

Unfortunately, all current treatments fail to “cure” obesity, as they fail to reset the set point to what would be considered “normal weight”. This makes ongoing treatment (be it behavioural, medical, or surgical) inevitable.

For all we know, any attempt at creating and sustaining weight loss regularly activates complex neurohormonal responses that serve to promote weight regain.

The only treatment, which may prove to be an exception is bariatric surgery (although this also only works as long as the surgery is in place – reverse the surgery, and the weight comes back).

Now, a paper by Hans Rudi Berthoud and colleagues, published in the International Journal of Obesity takes an in depth look at if and how gastric bypass surgery changes the body weight set point.

The paper reviews the data in support of the notion that surgery physiologically reprograms the body weight defense mechanism.

Thus, behavioural studies in animal models have shown that the defended body weight is indeed lowered after RYGB and sleeve gastrectomy.

For example, after surgeries, rodents return to their preferred lower body weight if over- or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis.

Furthermore, these authors have also demonstrated that the defense of fat mass is less efficient (whereas defense of lean mass remains intact) after surgery.

However, as they point out,

“…the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute.”

Trying to elucidate the exact underlying mechanisms will hopefully not just improve our understanding of how bariatric surgery works, but also hopefully ultimately lead to the development of novel medical treatments that specifically target the body weight set point and its defence.

@DrSharma
Monterrey, Mexico

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Will WHO STOPS Childhood Obesity Promote Weight Bias And Unhealthy Body Image?

sharma-obesity-kids-playing-outsideChildhood obesity is a grave concern and so far community based interventions to prevent it have been rare and far between, with little evidence that any changes (however meagre) are in fact sustainable over time and will actually lead to a reduction in adult obesity.

Thus, the Australian team of Steven Allander and colleagues must be commended on embarking on what I believe will be the first cluster randomized trial in ten communities in the Great South Coast Region of Victoria, Australia to test whether it is possible to: (1) strengthen community action for childhood obesity prevention, and (2) measure the impact of increased action on risk factors for childhood obesity.

According to the trial design published in the International Journal of Environmental Research in Public Health, the WHO STOPS intervention will involve a facilitated community engagement process that: creates an agreed systems map of childhood obesity causes for a community; identifies intervention opportunities through leveraging the dynamic aspects of the system; and, converts these understandings into community-built, systems-oriented action plans.

Ten communities will be randomized (1:1) to intervention or control in year one and all communities will be included by year three.

The primary outcome is childhood obesity prevalence among grade two (ages 7–8 y), grade four (9–10 y) and grade six (11–12 y) students measured using established community-led monitoring system (69% school and 93% student participation rate in government and independent schools).

An additional group of 13 external communities from other regions of Victoria with no specific interventions will provide an external comparison.

All of this makes sense and is highly commendable.

What is shockingly lacking however – at least I see no mention of this in the published study design – is the inclusion of an explicit focus on what such community interventions aimed at reducing childhood obesity, will do to self-esteem and body image of the kids involved and weight bias in the communities overall.

Indeed, I see no mention of anyone with an explicit expertise in weight bias or kids mental health on the panel of researchers involved in this study.

This is concerning, as we now understand well that body image concerns and both implicit and explicit weight bias begin in kindergarten-age kids and must acknowledge that the “moral panic” created around childhood obesity has been accused of further promoting eating disorders, body image issues and weight bias.

Thus, we have here the unique opportunity to study the potential harm that could be done by school “surveillance” programs that assess body weight in kids or by the well-meant education on “healthy activity and healthy eating” that may teach kids that obesity is simply a result of making poor choices and not moving enough (rather than a complex biopsychosocial chronic disease, that is highly resistant to lasting effects of time-limited interventions).

I would sincerely appeal to the researchers involved to amend their study protocol to include changes in weight bias, unhealthy weight obsessions, body image issues, and eating disorders both at the level of the kids and the community overall, to ensure that the well-meant interventions do not inadvertently replace one problem with another – as always, the Devil of public health interventions lies in the unintended consequences.

In fact, if I was on the ethics committee tasked with approving this study, I would insist that an in-depth assessment plan for the potential harm of this intervention be in place before commencement of any study related activities in the relevant communities.

If the overall goal of the WHO STOPS intervention is to have a healthier generation of kids, nothing is more important than fully understanding the potential impact of this intervention on mental health and social attitudes towards kids and adults living with obesity.

@DrSharma
Copenhagen, DK

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Does CPAP Treatment Affect Body Weight?

sleep-apneaYesterday, I posted on a study suggesting that people at high risk of obstructive sleep apnea may have a harder time losing weight that people without sleep apnea.

This prompted a reader to send me a link to a study by Luciano Drager and colleagues, published in Thorax, that presents a meta-analysis of randomised controlled trials on the effect of CPAP treatment on body weight.

The authors found 25 randomised controlled trials (RCTs) enrolling over 3000 patients with OSA ranging from 1 to 48 months in duration.

Paradoxically, they report that overall CPAP is associated with a 0.5 kg weight gain compared with control therapy.

Whether this weight gain is clinically relevant or not, the key finding is that (perhaps contrary to popular belief – including my own), the data does not support the idea that commencement of CPAP treatment for sleep apnea leads to weight loss.

As for the reasons for weight gain, an accompanying editorial by Sanjay Patel has this to offer,

“The reduction in leptin levels associated with CPAP therapy may result in increased hunger if the degree of leptin resistance does not change. Another explanation is that CPAP leads to reduced energy expenditure during sleep, as work of breathing is reduced due both to a patent upper airway as well as lung volumes rising to a more efficient point on the pressure–volume curve. Removal of the anorectic effects of hypoxia also may play an important role.”

It is also not exactly clear where the additional weight goes.

“A number of trials have demonstrated no substantial impact of CPAP on visceral fat volume, although the imaging methods used may not be sensitive enough to exclude the small magnitude of weight gain observed. Improvements in growth hormone and insulin-like growth factor 1 signalling with CPAP might result in increased muscle mass.13 Further studies are clearly needed to determine whether CPAP-induced weight gain represents increases in fat, lean body or water compartments.”

As for the potential health effects of the weight gain,

“The impact of 0.5 kg weight gain on health outcomes is fairly minimal and so should not change decision making regarding the use of CPAP in symptomatic OSA. However, it does give one pause regarding the use of CPAP in asymptomatic OSA where a cardiovascular benefit of CPAP has yet to be definitively established and makes more urgent the need for RCTs adequately powered to assess meaningful outcomes in this population.”

Clearly, the relationship between sleep apnea and body weight is a fair bit more complex than I would have thought.

Also, whether or not treating sleep apnea actually makes it easier for patients to lose weight (if they get adequate obesity treatment) remains to be seen.

@DrSharma
Copenhagen, DK

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Is Obstructive Sleep Apnea A Barrier to Weight Loss?

sleep-apneaObstructive sleep apnea is a common issue in individuals with excess weight.

Given that untreated sleep apnea negatively affects restorative sleep, which in turn affects both metabolism and appetite, it may well be that sleep apnea is an important barrier to weight loss.

This is exactly what is suggested in a recent study by Whited and colleagues, published in Health Psychology.

The researchers conducted a secondary analysis of a 12 month randomized trial comparing 2 weight loss interventions consisting of dietary counseling for adults with obesity and metabolic syndrome.

Subjects who screened positive for high risk of sleep apnea using the STOP questionnaire (about 50% of the 175 participants), lost less weight (1.2% vs. 4.2%) and were less likely to lose 5% or greater (24% vs. 75%) than participants without risk for sleep apnea.

Thus, the authors conclude that,

“…an OSA screening indicating high risk identifies individuals who will struggle to lose weight when participating in a weight loss intervention, despite equal attendance at treatment sessions and study assessments. Findings of this study suggest that OSA is a significant barrier to weight loss.”

Whether or not treating sleep apnea makes weight loss any easier, the authors have this to offer:

“Although we found that participants reporting current OSA treatment had greater weight loss (6.5% vs. 0.6%), the small sample of individuals receiving OSA treatment (n = 24) precluded statistical comparison.”

Clearly,

“OSA screening as a standard component of weight loss interventions has a high potential for usefulness, as identified individuals can be targeted for more intense or comprehensive treatment. The benefits of OSA treatment as a standard part of weight loss interventions among individuals with obesity and metabolic syndrome has yet to be determined, and future research must include examination of adherence to both OSA and weight loss intervention components.”

@DrSharma
Copenhagen, DK

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Are There Biomarkers For Physical Fitness?

sharma-obesity-african-athlete1Physical fitness is perhaps the most powerful negative predictor of cardiovascular health risk (a rather complicated way of saying “fitness” is good for you).

However, there is no easy way to measure fitness short of standardized exercise testing, both cumbersome and unpractical in a clinical setting.

Now, a paper by Joshua Denham and Priscilla Prestes, published in Frontiers in Genetics, suggests that muscle-enriched microRNAs (miRNAs) measured in whole blood may provide a sensitive blood test for physical fitness.

MiRNAs are genetically conserved, small (18–25 nucleotides), non-coding RNA molecules that post-transcriptionally control gene expression by either promoting mRNA degradation or down-regulating translation. There are over 2,500 known human mature miRNAs and each one can have hundreds of mRNA targets, making them powerful regulators of gene expression.

miRNAs are sensitive to the internal and external environments and it is therefore likely that circulating miRNAs isolated from the peripheral vasculature could serve as biomarkers of disease (and health).

In their study, the researchers examined the effect of long-term strenuous aerobic exercise training and a single bout of maximal aerobic exercise on five muscle-enriched miRNAs implicated in exercise adaptations (miR-1, miR-133a, miR-181a, miR-486, and miR-494).

They also determined linear correlations between miRNAs, resting heart rate, and maximum oxygen uptake in endurance athletes compared to non athletes.

Specific miRNAs were increased in athletes compared to non-athletes and there was a positive correlations between miRNA abundance and O2 max and resting heart rate.

Thus, the authors suggest that muscle-enriched miRNAs isolated from whole blood are regulated by acute and long-term aerobic exercise training and could serve as biomarkers of cardiorespiratory fitness.

Whether this would ever make it into a simple blood test for fitness remains to be seen.

@DrSharma
Copenhagen, DK

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Can Treating Sleep Apnea Reduce Energy Intake?

sharma-obesity-sleepapnea1Obstructive sleep apnea is a common and significant complication of obesity and individuals with untreated sleep apnea are at considerable risk for progressive weight gain.

Now, a paper by Ari Schechter and colleagues from Columbia University, NY, published in Physiology and Behaviour, publish data from a small ‘pilot study’ suggesting that treating obesity with CPAP may reduce calorie intake, at least in some individuals.

The researchers examined ad libitum energy intake in four adult males with overweight or obesity, who had been diagnosed with sleep apnea but had not yet initiated CPAP.

After participants began using CPAP at their titrated setting (active) at home each night for 2 mo, they were invited to participate in this study for two days in an in patient setting.

On the first inpatient day, participants were fed a controlled weight maintenance diet with fixed meal times and participants were asked to use CPAP at their prescribed setting during the scheduled in-lab sleep episode (23:00–7:00).

Ad libitum energy intake was measured throughout the waking period on laboratory day 2, whereby all meals were presented in excess. Participants were instructed to eat until they felt comfortably full.

After a 1-mo washout, participants crossed over into the sham phase. Participants were provided with the sham CPAP devices, and instructed to use the CPAP at the titrated level for 2 mo. This was followed by the second laboratory period (repeat of first phase). After the second phase, participants were debriefed and instructed to return to active CPAP.

Mean total ad libitum EI including fixed meals and free snacks was 3744 ± 511 kcal in the active and 4030 ± 228 kcal in the sham CPAP setting. Three of the four participants increased their total daily EI during sham vs. active, whereas one participant showed a decrease.

While these findings are far from conclusive, they do point to the possibility that ongoing treatment of sleep apnea may influence appetite in a way that serves to reduce energy intake.

This is perhaps not all that surprising given that there is increasing recognition of the importance of restorative sleep on appetite and food intake.

I look forward to seeing more definitive studies exploring this interesting issue.

I would also be interested in hearing is anyone else has experience changes in appetite with starting CPAP treatment for sleep apnea.

@DrSharma
Edmonton, AB

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