Yesterday, 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.
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.
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.
Now, the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), has published a new Position Statement on indications for surgery for obesity and weight-related diseases, published in Obesity Surgery.
Recommendations are graded based on the strength of the current evidence.
Recommendations with the highest strength of evidence include the following:
- Surgery for obesity and weight-related diseases is a codified discipline that has proven to be effective in the treatment of obesity resulting in long-term weight loss, improvement in or resolution of comorbidities, and the lengthening of life expectancy. (Level of evidence 1, grade of recommendation A)
- Surgery for obesity and weight-related diseases is a safe and effective therapeutic option for the management of T2DM in patients with obesity. Along with optimal medical treatment and lifestyle adjustment, it has been demon- strated that surgery for obesity and weight-related diseases can achieve a better glycemic control, lower glyco- sylated hemoglobin, and reduction of diabetes medications than optimal medical and lifestyle treatment alone. (Level of evidence 1, grade of recommendation A)
- Surgery for obesity and weight-related diseases demonstrated an excellent short- and midterm risk/benefit ratio in patients with class I obesity (BMI 30–35 kg/m2) suffering from T2DM and/or other comorbidities.
(Level of evidence 1, grade of recommendation A)
- Obesity, and visceral obesity in particular, is a major modifiable risk factor for cardiovascular diseases (CVD). Weight loss induced by surgery has been shown to reduce CVD risk, with the most relevant reductions in risk ob- served in the group of patients having the higher CVD risk before surgery. These patients obtain the most significant metabolic improvements thereafter. (Level of evidence 1, grade of recommendation A)
- Weight loss induced by surgery for obesity and weight- related diseases is associated to a reduction in the inci- dence of major cardiovascular events in patients with obesity, including myocardial infarction and stroke. Event reductions are more relevant in patients with a high cardiovascular risk before surgery. (Level of evidence 1, grade of recommendation A)
- Surgery for obesity and weight-related diseases may result in resolution/improvement of obstructive sleep apnea syndrome (OSAS). (Level of evidence 1, grade of recommendation A)
- In patients undergoing surgery for obesity and weight- related diseases, weight loss results in a substantial im- provement in pain and a reduction of disability derived from joint disease. (Level of evidence 1, grade of recommendation A)
- Surgery for obesity and weight-related diseases has proven to be effective in determining the overall improvement of the quality of life of patients suffering from obesity. (Level of evidence 1, grade of recommendation A)
- The improvement in the quality of life of the patient with obesity treated by surgery for obesity and weight-related diseases is independent from the type of performed procedure. (Level of evidence 1, grade of recommendation A)
- Surgery for obesity and weight-related diseases is effective in patients with class I obesity (BMI 30–35 kg/m2) and comorbidity. (Level of evidence 1, grade of recommendation A)
In addition, there are numerous recommendations, for which the evidence is perhaps less robust but nevertheless promising.
These recommendations cover a wide range of health issues including gastroesophageal reflux disease (GERD), hepatobiliary diseases, mental health, endocrinopathies and fertility, cancer and organ transplantation, pseudotumor cerebri, chronic inflammation, urinary tract and renal function, functional status, and quality of life.
I was particularly pleased to see the statement include recommendations regarding the limitations of BMI and an extensive discussion of the Edmonton Obesity Staging System as a potential guide to better defining indications for surgery.
Now a study by Peter Nordström and colleagues, published in JAMA Internal Medicine, reports that a higher BMI in identical twins is associated with a greater risk for type 2 diabetes but not myocardial infarction or death.
The researchers looked at data from 4,046 monzygous twin pairs with discordant BMIs (difference >0.01 units) from the nationwide Swedish twin registry.
During a mean follow-up of 12 years, the rate of myocardial infarcts and deaths were similar in the twins with lower BMI compared to their higher BMI co-twin (5.0% vs. 5.2% and 13.6% vs. 15.6%, respectively).
This lack of difference remained true even when the researchers compared the extremes of BMI discordance and only considered twins with BMI greater than 30.
In contrast, both higher BMI and greater increase in BMI since 30 years before baseline was associated with greater risk of incident diabetes.
Given that diabetes is such a powerful risk factor for cardiovascular disease, one can only wonder why this did not translate into a higher cardiovascular risk in the higher weight twins.
One possible explanation, offered by the authors is that cardiovascular risk may have been well managed in these individuals thus minimizing any increased risk due to diabetes (or other BMI associated risk factors such as dyslipidemia or hypertension).
Indeed, it would probably have required a far larger group of twins (or much longer follow-up) to fully rule out higher cardiovascular risk in these twins.
Let us also not forget that BMI is a rather lousy measure of overall cardiovascular risk.
Thus, which the study is certainly compatible with the (genetics-independant?) role of higher BMI in the risk for diabetes, it certainly should not be interpreted as demonstrating that this increased risk in benign in terms of cardiovascular disease.