The recently released Canadian Practice Guidelines on the prevention and management of overweight and obesity in children and youth released by the Canadian Task Force on Preventive Health Care (CMAJ 2015), rightly recommended that surgery not be routinely offered to children or youth who are overweight or obese.
Nevertheless, there is increasing evidence that some of these kids, especially those with severe obesity, may well require rather drastic treatments that go well beyond the current clinical practice of doing almost nothing.
Just how ill kids can be before they are generally considered potential candidates for bariatric surgery is evident from a study by Marc Michalsky and colleagues, who just published the baseline characteristics of participants in the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Study, a prospective cohort study following patients undergoing bariatric surgery at five adolescent weight-loss surgery centers in the United States (JAMA Pediatrics).
While the mean age of participants was 17 with a median body mass index of 50, the prevalence of cardiovascular risk factors was remarkable: fasting hyperinsulinemia (74%), elevated hsCRP (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%).
Not reported in this paper are the many non-cardiovascular problems raging from psychiatric issues to sleep apnea and muskuloskeletal problems, that often dramatically affect the life of these kids.
While surgery certainly appears rather drastic, the fact that these kids are undergoing surgery is merely an indicator of the fact that we don’t have effective medical treatments for this patient population, which would likely require a combination of behavioural interventions and polypharmacy to achieve anything close to the current weight-loss success of bariatric surgery.
That this cannot be the ultimate answer to obesity management (whether for kids or adults), is evident from the rising number of kids and adults presenting with ever-higher BMI’s and related comorbidity – not all of these can or will want surgery.
Thus, while current anti-obesity medications cannot compete with the magnitude of weight-loss generally seen with surgery, medications together with behavioural interventions may well play a role in helping prevent progressive weight gain in earlier stages of the disease.
Unfortunately, I am not aware of any studies that have explored the use of medications in kids to stabilize weight in order to avoid surgery. This would, in my opinion, be a very worthwhile use of such medications.
With all of the recent interest in the gut microbiota as a mediator of systemic inflammation and metabolic disease, it was only a matter of time before researchers would begin targeting pro-inflammatory pathways in the gut to change metabolism.
A proof-of-principle, that this is indeed possible, is presented by Helen Luck and colleagues from the University of Toronto in a paper published in Cell Metabolism.
Using mice models, the researchers not only show that a high-fat diet can alter the gut immune system but also that the chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations is reduced in genetically altered mice that lack beta7 integrin-deficient mice (Beta7null), a driver of gut inflammatory response.
Further more, treatment of high-fat-fed normal mice with the local gut anti-inflammatory agent 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters including insulin resistance (although it had no effect on body weight).
These beneficial effects are are associated with reduced gut permeability and endotoxemia as well as decreased visceral adipose tissue inflammation.
Moreover, treatment with ASA also improved antigen-specific tolerance to luminal antigens.
Thus, as the authors conclude,
“…the mucosal immune system affects multiple pathways associated with systemic insulin resistance and represents a novel therapeutic target in this disease.”
Clearly gut inflammation both in relationship to gut microbiota as well as response to dietary factors is likely to be a hot topic in obesity and metabolic research for the foreseeable future.
Warning – this is not an April Fool’s post! Rather, it is a follow up to yesterday’s post warning that even “lifestyle” or behavioural interventions can have adverse effects – at least for some people.
Point in case, is this paper by Claude Bouchard and colleagues, published in PLOS one back in 2008, clearly documenting clinically significant harmful metabolic effects of exercise in some individuals (about 1 in 10).
I would probably have disregarded this paper, except for the fact that the authors include a who-is-who of exercise experts, Steven Blair, Timothy Church, Nathan Jenkins, just to name a few. These are all enthusiastic supporters of increasing physical activity with rock-solid expertise in exercise physiology.
Their findings are based on completers from six exercise studies involving a total of 1,687 men and women.
Although metabolic parameters in general improved (as expected) in most participants, 8.4% had an adverse change in fasting insulin, 12.2% has a clinically significant increase in resting systolic blood pressure, 10.4% had a relevant increase in fasting triglycerides, and 13.3% had a reduction in HDL-Cholesterol. About 7% of participants experienced adverse responses in two or more risk factors.
While the authors note that the explanation for these findings remain unclear,
“…the adverse response traits are not explained by prior health status of subjects, age, amount of exercise imposed by the program, or lack of improvement in cardiorespiratory fitness. No evidence could be found for the hypothesis that adverse responses were the result of drug-exercise interactions.”
Which brings me back to yesterday’s post, that even the best meant behavioural recommendation (in this case “move more”) can carry risks for some individuals and may require personalised and ongoing monitoring.
Funnily enough, I would imagine that if you packed exercise into a pill with these types of “adverse effects”, I wonder if the FDA would actually let you sell it.
Incidentally, Claude Bouchard will be one of the key note speakers at the upcoming 4th Canadian Obesity Summit in Toronto, April 28-May 2. I’m sure he will be presenting some of these data and the fascinating genetic studies that have since been done on this issue.
Hat tip to Morgan Downey for reminding me of this study.
To preregister for the Canadian Obesity Summit click here
Following the recent release of the Canadian Task Force on Preventive Health Care guidelines for prevention and management of adult obesity in primary care, the Task Force yesterday issued guidelines on the prevention and management of childhood obesity in the Canadian Medical Association Journal (CMAJ).
Key recommendations include:
- For children and youth of all ages the Task Force recommends growth monitoring at appropriate primary care visits using the World Health Organization Growth Charts for Canada.
- For children and youth who are overweight or obese, the Task Force recommends that primary health care practitioners offer or refer to formal, structured behavioural interventions aimed at weight loss.
- For children who are overweight or obese, the Task Force recommends that primary health care practitioners not routinely offer Orlistat or refer to surgical interventions aimed at weight loss.
The lack of enthusiasm for the prevention of childhood obesity is perhaps understandable as the authors note that,
“The quality of evidence for obesity prevention in primary care settings is weak, with interventions showing only modest benefits to BMI in studies of mixed-weight populations, with no evidence of long-term effectiveness.”
leading the Task Force to the following statement,
“We recommend that primary care practitioners not routinely offer structured interventions aimed at preventing overweight and obesity in healthy-weight children and youth aged 17 years and younger. (Weak recommendation; very low-quality evidence)”
Be that as it may, the Task Force does recommend structured behavioural interventions for kids who already carry excess weight based on the finding that,
“Behavioural interventions have shown short-term effectiveness in reducing BMI in overweight or obese children and youth, and are the preferred option, because the benefit-to-harm ratio appears more favourable than for pharmacologic interventions.”
What caught my eye however, was the statement in the accompanying press release which says that,
“Unlike pharmacological treatments that can have adverse effects, such as gastrointestinal problems, behavioural interventions carry no identifiable risks.” (emphasis mine)
While I would certainly not argue for the routine use of orlistat (the only currently available prescription drug for obesity in Canada) in children (or anyone else), I do take exception to the notion that behavioural interventions carry no identifiable risks – they very much do.
As readers may be well aware, a large proportion of the adverse effects of medications is attributable to the wrong use of these medications – problems often occur when they are taken for the wrong indication, at the wrong dose (too high or too low), the wrong frequency (too often or too seldom), and/or when patients are not regularly monitored. In a perfect world, many medications that often lead to problems would be far less problematic than they are in the real world.
Interestingly, the same applies to behavioural interventions.
Take for example diets – simply asking a patient to “eat less” can potentially lead to all kinds of health problems from patients drastically reducing protein, vitamin and mineral intake as a result of going on the next “fad” or “do-it-yourself” diet. Without ensuring that the patient actually follows a prudent diet and does not “overdo” it, which may well require ongoing monitoring, there is very real potential of patients harming themselves. There is also the real danger of promoting an eating disorder or having patients face the negative psychological consequences of yet another “failed” weight-loss diet. Exactly how many patients are harmed by well-meant dietary recommendations is unknown, as I am not aware of any studies that have actually looked at this.
The same can be said for exercise – simply asking a patient to “move more” can result in injury (both short and long-term) and coronary events (in high-risk patients). Again, ongoing guidance and monitoring can do much to reduce this potential harm.
In short when patient apply behavioural recommendations at the wrong dose (too much or too less), wrong frequency (too often or too seldom), and/or are not regularly monitored, there is indeed potential for harm – I would imagine that this potential for harm is of particular concern in kids.
This is not to say that we should not use behavioural interventions – we should – but we must always consider the potential for harm, which is never zero.
I’d certainly be interested in hearing from anyone who has seen harm resulting from a behavioural intervention.
Last week at the 8th Annual Obesity Symposium hosted by the European Surgery Institute in Norderstedt, one of the case presentations included an individual with type 1 diabetes (no insulin production), who had gained weight and subsequently also developed increasing insulin resistance, the hallmark of type 2 diabetes.
In my discussion, I referred to this as 1+2 diabetes, or in other words, type 3 diabetes.
Unfortunately, it turns out that the term type 3 diabetes has already been proposed for the type of neuronal insulin resistance found in patients with Alzheimer’s disease.
As discussed in a paper by Suzanne de la Monte and Jack Wands published in the Journal of Diabetes Science and Technology,
“Referring to Alzheimer’s disease as Type 3 diabetes (T3DM) is justified, because the fundamental molecular and biochemical abnormalities overlap with T1DM and T2DM rather than mimic the effects of either one.”
These findings have considerable implications for our understanding of Alzheimer’s disease as a largely neuroendocrine disorder, which may in part be amenable to treatment with drugs normally used to treat type 1 and/or type 2 diabetes.
In retrospect, I believe, whoever came up with the term type 3 diabetes for Alzheimer’s disease, should perhaps have called it type 4 diabetes, given that the 1+2 diabetes is now increasingly common (and well studied) in patients with type 1 diabetes, who go on to develop type 2 diabetes (which, as discussed at the symposium responds quite well to bariatric or “metabolic” surgery).