Any form of rapid weight loss is well known to promote the formation of gall stones. Thus, given the rapid rate of weight loss post bariatric surgery, patients are at particularly high risk of developing gall stones (and related complications).
Now, a study by Lindsay Adams and colleagues, published in Obesity Surgery reports on a trial that examined whether or not administration of ursodeoxycholic acid (UDCA) could reduce the incidence of galls stones following sleeve gastrectomy.
75 eligible patients (57 of who completed the study) were randomized to receiving 300 mg UDCA twice daily for 6 months post-surgery or no treatment. Gallbladder ultrasounds were performed preoperatively and at 6 and 12 months postoperatively.
At 6 months, 2 of the 19 treated patients who had ultrasounds had gall stones compared to 10 of 25 patients in the control group.
However, at 12 months (6 months after discontinuation of therapy), 2 of 22 treated patients had galls stones compared to 3 out of 14 in the control group.
Of the 17 patients who developed gallstones, 7 patients underwent cholecystectomy.
Whether or not patients developed sludge or stones with treatment was highly dependent on compliance to treatment. Thus, from those patients who completed the 6-month ultrasounds, neither gallstones nor sludge were reported in any of 11 patients who reported good compliance. Two out of three patients who reported moderate compliance developed gallstones or sludge, and two out of five who reported poor compliance developed gallstones or sludge.
Overall, the authors note that the incidence of gallstones with about 30% was as high as has been reported for patients with gastric bypass surgery.
Clearly this study (as acknowledged by the authors) has important limitations due to the considerable number of participants that were lost to follow-up.
Nevertheless, for what it’s worth, the study certainly suggests that USCA treatment can markedly reduced the incidence of sludge and gallstones at 6 months in patients undergoing sleeve gastrectomy.
As to whether or not this would justify the routine use of USCA in all patients following bariatric surgery is certainly debatable.
According to a report in JAMA, A bipartisan group of US lawmakers has introduced House and Senate versions of the same bill, the Treat and Reduce Obesity Act of 2015, intended to help reduce health care costs and decrease the incidence of chronic disease associated with obesity, including high blood pressure, heart disease, and type 2 diabetes.
The bill calls for not only giving Medicare beneficiaries access to obesity treatments provided by health care practitioners other than primary care physicians, including nurse practitioners, clinical psychologists, and registered dietitians (if referred by a primary care physician) but also to expand drug coverage for obesity treatment under Medicare.
Meanwhile in Canada, accessing evidence-based treatment for obesity, including services offered by dietitians or psychologists as well as access to anti-obesity medications or surgery remains largely elusive to most Canadians living with obesity.
With upcoming federal elections in Canada, I wonder if any political party would step up to declare that continued discrimination against Canadians living with obesity with denial of access to evidence-based treatments is unacceptable (for e.g. obesity treatments are specifically excluded in most third party drug plans in Canada).
Now a small study by Mojca Jensterle and colleagues from Ljubljana, published in the European Journal of Clinical Pharmacology, reports that genetic variability in the GLP-1 receptor gene may predict the variability to the human GLP-1 analogue liraglutide, now approved for obesity treatment in the US, Canada and Europe.
In their study, Jensterle and colleagues examine the realationship between two common alleles (variants) of the GLP-1 receptor in 57 women with obesity and polycystic ovary syndrome.
All women were treated with liraglutide 1.2 mg QD s.c (well under the 3.0 mg QD dose approved for obesity treatment) for 12 weeks.
Twenty of the participants were classified as strong responders (>5% weight loss), who lost about 7.4 Kg, whereas 37 were considered poor responders losing only 2.2 Kg.
Carriers of at least one rs10305420 allele were about 70% less likely to be a high responder than individuals with two wild-type alleles. Similarly, carriers of at least one rs6923761 allele were about three times as likely to high responders compared to homozygous carriers of the wild type.
Although my previous work in these type of genetic studies have made me highly critical (not to say sceptical) of these types of small studies, the notion that genetic variability in the GLP-1 receptor (the molecular target of liraglutide) may well lead to differences in response is not all that far fetched.
Thus, whether true or not, I have little doubt that indeed much of the variability in pharmacological response to liraglutide (or for that matter any other drug for anything) may well be determined by genetics.
Whether testing people for genetic markers before starting a specific treatment will ever become reality for obesity and whether or not, the genetic variability seen in this study will still be seen when lirglutide is used at the actual dose approved for obesity treatment remains to be seen.
In the meantime, the easiest way to see who responds and who does not is to try it. This why the regulatory approval of liraglutide for obesity comes with a simple stopping rule – if it doesn’t work for you – stop taking it!
Disclaimer: I have received consulting and speaking honoraria from Novo Nordisk, the maker of liraglutide.
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.
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.