Arya M. Sharma, MD

No question - Canada, as many other Western countries is experiencing an unprescedented epidemic of childhood overweight and obesity. Many of these children will need obesity treatment - they are beyond the stage where “prevention” is likely to help.

So do obesity interventions for kids actually work?

This was the topic of a Cochrane review by Oude Luttikhuis and colleagues from the University of Groningen published earlier this year.

The authors analysed all randomised controlled trials (RCTs) of lifestyle (i.e. dietary, physical activity and/or behavioural therapy), drug and surgical interventions for treating obesity in children (mean age under 18 years) with or without the support of family members, with a minimum of six months follow up (three months for actual drug therapy).

The final analysis included 64 RCTs (5230 participants). The studies included varied greatly in intervention design, outcome measurements and methodological quality (the surgical studies were considered to be of too poor quality to include in the analysis).

The authors conclude that although there is not enough data to to recommend one treatment program versus another, there is little doubt that combined behavioural lifestyle interventions are superior to standard care or self-help in producing clinically meaningful reduction in overweight in children and adolescents. In obese adolescents, consideration should also be given to the use of either orlistat or sibutramine, as an adjunct to lifestyle interventions.

As they point out, there is a continuing need for high quality research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care.

It appears to me that obesity management in kids is no different than treatment in adults in that it requires multidisciplinary intervention and ongoing monitoring to assure that lost weight is not regained.

Unfortunately, we are far from having the infrastructure, the resources, or the medical expertise to provide adequate obesity interventions to the over 500,000 Canadian kids (and their parents?), who urgently require obesity treatments.

AMS
Edmonton, Alberta

Yesterday, EnteroMedics announced European approval of their VBLOC system (Maestro) for obesity. As blogged previously, the system reduces food intake by blocking vagal signals from the stomach and gut to the brain. The system is implanted laparoscopically and uses high-frequency, low-energy electrical impulses to intermittently block vagal activity.

On their website, the company reports results of their pivotal study, which showed show excess weight loss, or EWL, of 37.6% in 9 patients at 18 months of VBLOC Therapy and 28.1% in 17 patients at 12 months of therapy. To date, no deaths or unanticipated adverse device events have been reported.

It will be interesting to see how this new treatment for obesity is embraced in Europe and whether or not it will find its niche in obesity management.

AMS
Edmonton, Alberta

The hypothalamus, located deep inside the brain, is a critical centre for the integration and regulation of hunger and satiety signals in humans and animals. A team of New Zealand and US researchers has now reported that transferring a gene to this part of the brain can significantly reduce body weight both in genetically and dietary-induced obese mice.

The paper by Lei Cao, published in yesterday’s issue of Nature Medicine, describes the hypothalamic injection of an adenoviral vector containing brain-derived neurotrophic factor (BDNF) coupled to a physiological responsive regulatory element. This gene transfer resulted in a 20% weight loss within 3 weeks of injection with subsequent weight maintenance over 11 months (several decades in human years).

The researchers also demonstrated that they can “rescue” these mice from the treatment, thereby theoretically increasing the safety of this approach. This may not be a bad idea, because in some experiments where the BDNF gene transfer was not coupled with a regulatory element, the animals showed bizarre behavioural changes with catastrophic weight loss.

Clearly the researchers are pleased with their results and in their paper go as far as stating that this treatment for severe obesity may become available for human treatment in the foreseeable future. Indeed, Matthew During, the senior author on the paper is co-owner of Neurologix, a biotechnological company that is currently conducting a Phase 2 neurosurgical gene treatment study in patients with severe Parkinson’s disease. This demonstrates that first human neurosurgical experiments with BDNF gene transfer may not be too far away.

While these new findings clearly point to the importance of central neuroregulation in energy homeostasis and show that this can be modified to reduce severe obesity, I find it difficult to foresee widespread use of neurosurgical treatment for a disorder as common as obesity. After all, even if this treatment was limited only to people with severe obesity, we’d still be looking at millions of people worldwide.

In the near future, I’d rather place my bets on gastrointestinal than on stereotactic neurosurgery.

AMS
Edmonton, Alberta

Most people who stop smoking gain weight, on average about 7kg in the long term. Indeed, weight control is one of the most common reasons I hear in my practice for people continuing to smoke.

So how can the weight gain associated with smoking cessation be prevented?

This was the topic of an exhaustive literature analysis published in the Cochrane Database of Systematic Reviews by Amanda Parsons and colleagues from the University of Birmingham, UK.

The review looked both at interventions designed specifically to aid smoking cessation and limit post-cessation weight gain and interventions designed to aid smoking cessation that may also plausibly have an effect on weight

Using the rigorous Cochrane methodolgy, the authors found evidence that compared to lifestyle interventions alone, pharmacological interventions aimed at reducing post-cessation weight gain resulted in a significant reduction in weight gain at the end of treatment (dexfenfluramine (-2.50 kg), fluoxetine (-0.80 kg], phenylpropanolamine (-0.50 kg), naltrexone (-0.76 kg). However, there was no evidence of any maintenance of these effects at 6 or 12 months after treatment.

In cases, where the intervention was limited to behavioural advice to control weight, not only was there no reduction in weight gain, there was also a trend towards less abstinence. In contrast, when programmes were individualized, there was reduced weight gain at end of treatment and at 12 months (-2.5 8 kg) without a reduction in abstinence rates. Exercise intervention alone did not limit weight gain at 12 months.

Very low calorie diets (-1.30kg at 12 months) and cognitive behavioural therapy (-5.20 kg at 12 months) were both associated with improved abstinence and reduced weight gain at end of treatment and at long-term follow up.

While both bupropion (-0.76 kg) and fluoxetine (-1.30 kg), when used for smoking cessation, limited post-cessation weight gain at the end of treatment, these effects were not maintained at one year.

Nicotine-replacement treatments resulted in attenuation of post-cessation weight gain (-0.45 kg) at the end of treatment and at 12 months (-0.42 kg).

One study randomized successful quitters to 12 more weeks of varenicline treatment resulting in a weight reduction of 0.71 kg. In three studies, participants taking bupropion gained significantly less weight at the end of treatment than those on varenicline.

Apparently, there were no studies on anti-obesity drugs (sibutramine or orlistat) to prevent post-cessation weight gain.

From this analysis, the authors conclude that general behavioural interventions that fall short of formal CBT are largely ineffective in preventing smoking cessation-related weight gain, and may in fact reduce abstinence.

Individualized interventions, very low calorie diets, and CBT may be effective without reducing abstinence. Bupropion, fluoxetine, nicotine replacement therapy, and probably varenicline all reduced weight gain while being used.

Currently, there does not appear to be any effective way to curtail the long-term weight gain associated with smoking cessation.

Nevertheless, given the substantial risks associated with smoking, the risk/benefit relationship of smoking cessation, i.e. the potential health risks from weight gain vs. the potential health risks from continued smoking are clearly in favor of smoking cessation.

This said, it appears that there is considerable room (and need) for more effective interventions to prevent cessation-associated weight gain.

AMS
Edmonton, Alberta
p.s. interestingly, OBESITY PANACEA also had a post yesterday on the issue of obesity and smoking.

Yesterday, the Public Health Agency of Canada (PHAC) announced funding for its Canadian Heart Health Strategy Action Plan (CHHS-AP), which will involve spending $700 Mill on a wide range of efforts aimed at reducing the incidence and burden of heart disease in Canada.

(ERRATUM (March 9, 2009): It turns out that the above announcement was NOT actually an announcement of funding, but rather only the announcement of a REQUEST FOR funding - thus, whether or not this strategy will actually be funded remains to be seen).

The strategy includes six key recommendations:

• Create heart healthy environments, such as making healthy foods cheaper and building cities where walking is easy;

• Help Canadians lead healthier lives with education programs and screening programs;

• End the “cardiovascular health crisis among aboriginal/indigenous peoples” by improving everything from prevention to treatment for natives;

• Reform the delivery of health care to emphasize integrated, patient-centred care, with particular emphasis on heart disease;

• Build a “knowledge infrastructure” that promotes research on heart disease and stroke;

• Ensure that there are enough health professionals to ensure appropriate care.

While I agree with the need for addressing heart disease as the #1 cause of premature death in Canada, I wonder if this is at all possible without first addressing the #1 cause of heart disease, namely obesity.

I may well be accused of taking a rather “obesocentric” view of this issue, but to my knowledge, obesity is not only the most important or root cause of type 2 diabetes, hypertension, and low-HDL cholesterol, but fear of obesity or weight control is also one of the most important motivators for smoking (especially amongst women).

As the Scientific Director of the Canadian Obesity Network, I can certainly promise that PHAC and the CHHS can count on the full support of the many obesity researchers and health professionals in Canada to help reduce the burden of obesity on Canadians - clearly, a nice “side effect” of any endeavour that helps prevent obesity and provides better access to obesity treatments for the 1 in 5 Canadian, who already have this condition, will likely be a notable reduction in heart disease.

I must admit that I have yet to see the full Action Plan, but am indeed curious to see how much of the $700 Mill are specifically devoted to obesity prevention, increasing public and professional education on obesity, and improving access to obesity treatments for Canadians.

To hear what I had to say about the CHHS on CBC-Newsworld click here

AMS
Edmonton, Alberta