Thursday, September 18, 2014

Efficacy of Vagal Blockade For Obesity Treatment Remains Vague

VBLOC

VBLOC

Regular readers may recall past posts on the use of intermittent electrical blockade of the vagus nerves (VBLOC) as a means of reducing food intake to promote weight loss.

Now a large randomised controlled study of vagal blocakade, published by Sayeed Ikramuddin and colleagues, published in JAMA, reports on rather disappointing outcomes with this treatment.

In this study (ReCharge), conducted  at one of 10 sites in the United States and Australia between May and December 2011, 239 participants with a BMI greater than 40 (or greater than 35 with at least one comorbidity), were randomised to receiving an active vagal nerve block device (EnteroMedics’ Maestro® Rechargeable (RC) System, n=162) or a sham device (n=77).

Over the 12-month blinded portion of the 5-year study (completed in January 2013), the vagal nerve block group lost about 9% or their initial body weight compared to only 6% in the sham group.

In addition to this rather modest difference in weight loss between the groups (about 3%), participants in the active treatment group also experienced a number of clinically relevant adverse effects (heartburn or dyspepsia and abdominal pain).

Thus, overall these rather disappointing results are in line with the previously disappointing observations in the smaller MAESTRO trial.

Based on these findings, it seems that intermittent electrical blockade of the vagal nerve may not hold its promise of a safe and effective long-term treatment for severe obesity after all.

@DrSharma
Edmonton, AB

ResearchBlogging.orgIkramuddin S, Blackstone RP, Brancatisano A, Toouli J, Shah SN, Wolfe BM, Fujioka K, Maher JW, Swain J, Que FG, Morton JM, Leslie DB, Brancatisano R, Kow L, O’Rourke RW, Deveney C, Takata M, Miller CJ, Knudson MB, Tweden KS, Shikora SA, Sarr MG, & Billington CJ (2014). Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA, 312 (9), 915-22 PMID: 25182100

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Wednesday, September 3, 2014

Can Targeting Estrogen Receptors Alleviate Binge Eating Disorder?

sharma-obesity-mouse-eatingBinge eating disorder, a loss of control of food intake accompanied by dysphoric mood alterations, is more common in women than in men and may account for as much as 40% of severe obesity seen at bariatric centres.

Strangely enough, a new study by Xuehong Cao and colleagues from Baylor College of Medicine, Houston, Texas, published in the Journal of Clinical Investigation, shows that targeting estrogen receptors in the serotonergic neurons of brain centres involved in appetite regulation may alleviate this behaviour, at least in mice.

Previous observations in humans that women with binge eating often suffer from menstrual irregularity, presumably due to impaired functions of ovarian hormones (e.g. estrogens) and that circulating 17β-estradiol levels are inversely associated with binge eating, prompted these investigators to study the role of estrogen in binge eating behaviours in ovarectomised mice.

While estrogen administration resulted in markedly reduced binge eating behaviour in these mice, this effect was absent in genetically modified mice that lacked the estrogen receptor-α (ERα) in the dorsal raphe nuclei (DRN), an area particularly rich in serotonin (5-HT) neurons known to be important in appetite regulation (and sleep).

The researchers also showed that a conjugate that combines GLP-1 and estrogen into one molecule is far more effective in reducing binge eating behaviour than GLP-1 alone (again, this effect was much reduced in ERα KO mice) suggesting that such a conjugate may be used to specifically target GLP-1 receptor neurons, thereby perhaps avoiding any potential adverse effects of estrogen administration.

Obviously, there is a long way from such initial observations in mice to safe and effective treatments in humans.

Nevertheless, these observations should open a new field of interest in finding more effective pharmacological treatments for binge eating disorders or perhaps even more “common-garden-variety” obesity in humans.

@DrSharma
Gambach, Germany

ResearchBlogging.orgCao X, Xu P, Oyola MG, Xia Y, Yan X, Saito K, Zou F, Wang C, Yang Y, Hinton A Jr, Yan C, Ding H, Zhu L, Yu L, Yang B, Feng Y, Clegg DJ, Khan S, DiMarchi R, Mani SK, Tong Q, & Xu Y (2014). Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. The Journal of clinical investigation PMID: 25157819

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Monday, September 1, 2014

Guest Post: Emotional Distress And Weight Gain

Erik Hemmiingsson, PhD, Obesity Research Centre, Karolinska Institute, Stockholm, Sweden

Erik Hemmiingsson, PhD, Obesity Research Centre, Karolinska Institute, Stockholm, Sweden

Today’s guest post comes from Erik Hemmingsson, PhD,  a Group Leader at the Obesity Center, Department of Medicine, Karolinska Institute, Stockholm, Sweden. His group studies the role of psychological and emotional distress in weight gain and obesity by mapping life events that influence stress, metabolism and body weight. Erik has a PhD in Exercise and Health Sciences from the University of Bristol (2004) and a PhD in Medicine from Karolinska Institutet.

I work as a researcher in a specialized obesity treatment center at a university hospital in Sweden. My job is to develop new and more effective treatment and prevention methods so that we can hopefully confine obesity to the history books some day.

For many years I mostly did studies on behaviour therapy combined with low energy diets. Since this did not result in any major breakthroughs, I decided to try something a little different.

I had been aware of that many of our patients had experienced difficult childhoods. There were so many sad stories, but I didn’t fancy doing any research on the topic, it was too painful. But then my attitude gradually started to change about a year ago. It was clear that our current treatment methods were woefully ineffective, but I also became more receptive to all those troublesome stories from the patients. Enough was enough, it was time act. So, like Neo in the Matrix movies, I decided to take the red pill, and delve deeper into the very uncomfortable subject of childhood abuse and adult obesity.

I searched the literature and quickly saw that there were more than enough studies for a systematic review and meta-analysis. I enlisted the help of Dr Kari Johansson and Dr Signy Reynisdottir, and got to work.

What we found very much confirmed all those clinical observations, i.e. there was a very robust association between childhood abuse and adult obesity. The association was also very consistent across difference types of abuse, with an increased risk of about 30-40%. There was also a dose-response association, i.e. the more abuse, the greater the risk of obesity.

While this study confirmed something very important, it was also clear that not everyone who suffers childhood abuse develops obesity, or that all obese individuals have suffered childhood abuse, or the effects would have been even more pronounced. But for me, the study proved that stressful childhood experiences can easily manifest as obesity many years later. This led me even deeper down the rabbit hole. I wanted to know why.

I decided to try and piece together different ideas about how obesity develops in relation to stressful life events. This resulted in a new conceptual causal model consisting of six different developmental stages. Like many diseases, obesity development is more likely when there is socioeconomic disadvantage (applies mainly to Europe and North America). Socioeconomic disadvantage can very easily trigger a chain of events that include adult distress, a disharmonious family environment, offspring distress, psychological and emotional overload, and finally disruption of homeostasis through such mechanisms as maladaptive coping responses, stress, mental health problems, reduced metabolism, appetite up-regulation and inflammation.

Much more research is needed to validate the model, but if there is some truth to this theory, which the childhood abuse meta-analysis clearly suggests that there is, then my hope is that we can use this information to develop more effective treatment and prevention methods.

My other hope is that some of the truly horrendous stigma, shame and discrimination that the obese experience can gradually be alleviated, since there is clearly a lot more to obesity etiology than the commonly held preconception that obese individuals are merely lazy and overindulgent.

After having done all this work on obesity etiology, I would say that my top-3 reasons we have an obesity epidemic (in no particular order) are socioeconomic inequality, the junk food invasion, and psychological and emotional distress patterns (usually established at an early age). And when you combine all three you have the perfect storm for weight gain.

You can find more information at my blog at www.holisticobesity.com

Erik Hemmingsson,
Stockholm, Sweden

References:

Hemmingsson E, Johansson K, Reynisdottir S. Effects of childhood abuse on adult obesity: a systematic review and meta-analysis. Obesity Reviews (epub 15 August 2014).

Hemmingsson E. A new model of the role of psychological and emotional distress in promoting obesity: conceptual review with implications for treatment and prevention. Obesity Reviews 2014, 15:769-779.

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Thursday, August 28, 2014

Call For Abstracts: Canadian Obesity Summit, Toronto, April 28-May 2, 2015

COS2015 toronto callBuilding on the resounding success of Kananaskis, Montreal and Vancouver, the biennial Canadian Obesity Summit is now setting its sights on Toronto.

If you have a professional interest in obesity, it’s your #1 destination for learning, sharing and networking with experts from across Canada around the world.

In 2015, the Canadian Obesity Network (CON-RCO) and the Canadian Association of Bariatric Physicians and Surgeons (CABPS) are combining resources to hold their scientific meetings under one roof.

The 4th Canadian Obesity Summit (#COS2015) will provide the latest information on obesity research, prevention and management to scientists, health care practitioners, policy makers, partner organizations and industry stakeholders working to reduce the social, mental and physical burden of obesity on Canadians.

The COS 2015 program will include plenary presentations, original scientific oral and poster presentations, interactive workshops and a large exhibit hall. Most importantly, COS 2015 will provide ample opportunity for networking and knowledge exchange for anyone with a professional interest in this field.

Abstract submission is now open – click here

Key Dates

  • Abstract submission deadline: October 23, 2014
  • Notification of abstract review: January 8, 2014
  • Early registration deadline: March 5, 2015

For exhibitor and sponsorship information – click here

To join the Canadian Obesity Network – click here

I look forward to seeing you in Toronto next year!

@DrSharma
Montreal, QC

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Wednesday, June 18, 2014

4th Canadian Obesity student Meeting (COSM 2014)

Uwaterloo_sealOver the next three days, I will be in Waterloo, Ontario, attending the 4th biennial Canadian Obesity Student Meeting (COSM 2014), a rather unique capacity building event organised by the Canadian Obesity Network’s Students and New Professionals (CON-SNP).

CON-SNP consist of an extensive network within CON, comprising of over 1000 trainees organised in about 30 chapters at universities and colleges across Canada.

Students and trainees in this network come from a wide range of backgrounds and span faculties and research interests as diverse as molecular genetics and public health, kinesiology and bariatric surgery, education and marketing, or energy metabolism and ingestive behaviour.

Over the past eight years, since the 1st COSM was hosted by laval university in Quebec, these meetings have been attended by over 600 students, most presenting their original research work, often for the first time to an audience of peers.

Indeed, it is the peer-led nature of this meeting that makes it so unique. COSM is entirely organised by CON-SNP – the students select the site, book the venues, review the abstracts, design the program, chair the sessions, and lead the discussions.

Although a few senior faculty are invited, they are largely observers, at best participating in discussions and giving the odd plenary lecture. But 85% of the program is delivered by the trainees themselves.

Apart from the sheer pleasure of sharing in the excitement of the participants, it has been particularly rewarding to follow the careers of many of the trainees who attended the first COSMs – many now themselves hold faculty positions and have trainees of their own.

As my readers are well aware, I regularly attend professional meetings around the world – none match the excitement and intensity of COSM.

I look forward to another succesful meeting as we continue to build the next generation of Canadian obesity researchers, health professionals and policy makers.

You can follow live tweets from this meeting at #COSM2014

@DrSharma
Waterloo, Ontario

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In The News

Diabetics in most need of bariatric surgery, university study finds

Oct. 18, 2013 – Ottawa Citizen: "Encouraging more men to consider bariatric surgery is also important, since it's the best treatment and can stop diabetic patients from needing insulin, said Dr. Arya Sharma, chair in obesity research and management at the University of Alberta." Read article

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