Arya M. Sharma, MD

Yesterday, I discussed how part of the improvements in type 2 diabetes patients after gastric bypass surgery may be due to increased postprandial release of GLP-1.

However, it is becoming increasingly apparent that GLP-1 also exerts central effects on hunger and satiety, and perhaps even affects the desire for certain foods.

Therefore, not surprisingly, GLP-1 analogues, while already available for treating diabetes, are currently being investigated for the treatment of obesity.

This topic was recently reviewed by Torekov and colleagues from the University of Denmark, in a paper published in Obesity Reviews.

As the authors note, GLP-1 receptors are expressed in many regions of the brain and in particular in the arcuate nucleus and other hypothalamic regions involved in the regulation of food intake. Animal studies have confirmed that GLP-1’s has central effects on hunger and satiety that are independent of its peripheral effects on glucose metabolism.

However, whether peripherally injected GLP-1 actually makes it into the human brain, as suggested by some animal studies, is still a matter of debate. It is also possible that some of the effects of GLP-1 agonists on food intake may be mediated by interaction with sensory afferent neurones of the vagus nerves in the gastrointestinal tract.

The notion that GLP-1 analogues may affect feeding even when they do not enter the brain is supported by studies showing that large molecular size GLP-1 receptor agonists (albumin-conjugated GLP-1 receptor agonists), that cannot cross the blood-brain barrier can inhibit feeding in both humans and mice.

Thus, it appears that GLP-1 analogues may affect feeding behaviour both through central and peripheral effects.

As a side note, it may be of interest that while the ‘hunger hormone’ ghrelin appears to counteract (or rather override) the effects of GLP-1 on satiety, the commonly used anti-diabetic drug metformin appears to increase expression of GLP-1 receptors and enhance GLP-1 secretion and sensitivity in both rodents and humans.

Currently, the long-acting GLP-1 analogues exenatide and liraglutide are being investigated as potential anti-obesity drugs, with early indications that this may indeed be worthwhile.

Thus, for example, as noted by the authors, in one study with liraglutide, obese subjects in the quartile of greatest weight loss had a mean weight loss of 18 kg with 3.0 mg of liraglutide compared with only 9 kg on placebo.

Overall, the authors conclude that:

“The recognition that several gastrointestinal hormones, released in response to nutritional stimuli are important regulators of appetite (PYY, oxyntomodulin, GLP-1 and decreased secretion of ghrelin), offers a strategy for the development of more effective ant-iobesity agents….treatment of obesity could involved a combination of hormones, e.g. GLP-1, PYY, and/or oxyntomodulin to produce a superior appetite suppressing hormone profile that may result in a weight loss far exceeding that seen in single-agent trials. Using several hormones in low doses and incorporating lifestyle interventions might maximize the clinical effect while minimizing the side effects.”

Clearly, many patients would find daily injections of hormones preferable to undergoing bariatric surgery, even if these injections would need to be continued in the long-term to keep the weight off.

Wether or not such injections would in the end also prove cost-effective will remain to be seen.

AMS
London, UK

Disclosure: I am a consultant to Novo-Nordisk and involved in studies with liraglutide.

Torekov SS, Madsbad S, & Holst JJ (2011). Obesity - an indication for GLP-1 treatment? Obesity pathophysiology and GLP-1 treatment potential. Obesity reviews : an official journal of the International Association for the Study of Obesity, 12 (8), 593-601 PMID: 21401851

Yesterday, I posted on the recent Senate Committee call on the FDA to ease the path to approval of new obesity, which it described as “a significant unmet medical need.”

In my commentary, I suggested that one solution to better balancing risk and benefit would be to subcategorize obesity into meaningful subtypes, ideally based on an objective aetiological framework.

In a paper just published in Appetite, Caroline Davis and colleagues from Toronto’s York University provide evidence suggesting that ‘food addiction’ (FA) may be a valid clinical sub-phenotype of obesity.

The researchers examined the validity of the Yale Food Addiction Scale (YFAS) - the first tool developed to identify individuals with addictive tendencies towards food - in a sample of obese adults (aged 25-45 years) and non-obese controls.

The YFAS is available here - the instruction sheet for interpreting the test is available here.

In their analysis, the researchers focused on three domains relevant to the characterization of conventional substance-dependence disorders: clinical co-morbidities, psychological risk factors, and abnormal motivation for the addictive substance.

Not only were their results strongly supportive of the ‘food addiction’ construct demonstrated validity of the YFAS, in addition, those who met the diagnostic criteria for food addiction had a significantly greater co-morbidity with Binge Eating Disorder, depression, and attention-deficit/hyperactivity disorder compared to their age- and weight-equivalent counterparts.

Those with FA were also more impulsive and displayed greater emotional reactivity than non-FA obese controls. They also displayed greater food cravings and the tendency to ’self-soothe’ with food.

As the authors conclude:

“These findings advance the quest to identify clinically relevant subtypes of obesity that may possess different vulnerabilities to environmental risk factors, and thereby could inform more personalized treatment approaches for those who struggle with overeating and weight gain.”

From a treatment perspective, these would be the patients, who would perhaps be most responsive to behavioural and pharmacological treatments aligned with an addiction paradigm.

In contrast, non-food addicted obese individuals will likely be far less responsive to these approaches.

Thus, while it may make sense to expose individuals with food addiction to drugs like buproprion, naltrexone, or rimonabant, non-addictive obese individuals may neither respond well nor warrant the risk of these drugs for treating their obesity.

As long as we continue on the path to developing obesity treatments using an outdated and simplistic ‘let’s-get-anyone-with-a-BMI-higher-than-X-to-lose-weight’ approach, we will never get a good handle on risk benefit ratios, let alone, get any closer to ‘aetiology based’ treatments.

AMS
Lisbon, Portugal

Davis C, Curtis C, Levitan RD, Carter JC, Kaplan AS, & Kennedy JL (2011). Evidence that ‘food addiction’ is a valid phenotype of obesity. Appetite PMID: 21907742

Today’s post is another excerpt from “Best Weight: A Practical Guide to Office-Based Weight Management“, recently published by the Canadian Obesity Network.

This guide is meant for health professionals dealing with obese clients and is NOT a self-management tool or weight-loss program. However, I assume that even general readers may find some of this material of interest.

Mindless Eating

Brian Wansink coined the term “mindless eating” to describe hidden cues that trigger eating behaviours, such as family, friends, packaging, plate size, names and numbers, labels, colours, shapes, smells, distractions, distances, cupboards, and containers. It is possible that response to these cues also has roots in evolutionary biology.

One cue in particular may play a significant role in your patients’ difficulties with weight management: social eating. Put simply, the more people we eat with, the more we tend to eat. This may result from being encouraged by others to eat, or eating to fit in, but sometimes, as Dr. Wansink suggests, it is completely mindless. Consider how this might influence your patient’s weight if he or she has a wine-and-dine sales job, multiple work meetings or a circle of friends or family who centre all of their social interactions on food.

© Copyright 2010 by Dr. Arya M. Sharma and Dr. Yoni Freedhoff. All rights reserved.

The opinions in this book are those of the authors and do not represent those of the Canadian Obesity Network.

Members of the Canadian Obesity Network can download Best Weight for free.

Best Weight is also available at Amazon and Barnes & Nobles (part of the proceeds from all sales go to support the Canadian Obesity Network)

If you have already read Best Weight, please take a few minutes to leave a review on the Amazon or Barnes & Nobles website.

As not everyone may have a chance during the week to read every post, here’s a roundup of last week’s posts:

• Will Losing Weight Make You Fat?
• Is It Time To Abandon The Notion of Personal Choice In Dietary Counseling?
• Bariatric Surgery Reduces Response to Food Cues?
• Gastric Bypass Reduces Appetite for Fat?
• Stretching Beats Walking to Prevent Complictions of Pregnancy?

Have a great Sunday! (or what’s left of it)

AMS
Edmonton, Alberta

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Traditionally, dietary counseling has focused largely on client education and prescriptive approaches to promoting better ‘choices’.

Based on the limited success that such approaches have had on changing long-term dietary habits, a rather provocative article by Bradley Applehaus and colleagues from the Rush University Medical Centre, Chicago, Il, published in a recent issue of the Journal of the American Dietetic Association, argues that it is perhaps now time to discard the notion of ‘choice’ in favor of a strategy based on a deeper understanding of the complex interaction between neurobehavioural processes and environmental determinants of overeating.

As the authors discuss, both counselors and clients frequently attribute obesity largely to poor ‘personal choices’ and studies have shown that dietitians rank ‘lack of willpower’ as far more important to the development of obesity than genetic or other biological factors. This is not only contrary to our current understanding of the complex neurobiology of ingestive behaviour but also only serves to stigmatise and frustrate patients, who in turn blame their own ‘failures’ on lack of motivation or personal ‘failings’.

“The term personal choice implies that human behavior derives from conscious, volitional decisions, and connotes that human beings have free will to decide between alternative courses of action independent of biological and environmental forces. An implication of this definition of personal choice is that individuals can be considered causally, financially, and morally responsible for their behavior”

“In contrast to the notion of personal choice, some argue that human behavior is explained by neurobiological processes and their interaction with environmental stimuli. Supporting this deterministic model of personal choice are studies demonstrating that future actions can be predicted by brain activation patterns up to 10 seconds before individuals become aware of having made a decision, behavior is strongly influenced by processes outside of conscious awareness, and individuals can be led to believe that they have caused actions outside of their control.”

Thus, the authors propose that rather than making adoption of a ‘healthy’ diet a matter of choice, dietetic practitioners may better serve their clients by basing their counseling strategies on the emerging understanding of neurobehavioural drivers of eating behaviours, particularly, on the issues of food reward, inhibitory control, and time discounting.

Whereas the concept of ‘food reward’ involving the brain’s complex mesolimbic reward circuitry (as in addictions) is readily evident, as is the complex neurobiology of the prefrontal cortex that determines motivation, impulsivity and inhibitory self-regulation, time discounting refers to the increased value of immediate (short-term) rewards compared to deferred (long-term) benefits routinely demonstrated in psychological testing and deeply ingrained in human behaviour.

Recognising and fully acknowledging how the brain’s neural circuitry that underlies these behaviours interacts with (and is thus ultimately responsive to) environmental situations and cues can perhaps provide a far more realistic and effective counseling strategy.

In their paper, the authors provide several specific examples of how such an approach may work.

For e.g., the tendency for the brain’s reward circuitry to drive the intake of highly palatable foods can be thwarted by eliminating such foods from the personal foodscape and avoiding temptation and exposure to such foods by sticking to grocery lists or online grocery shopping.

Similarly, inhibitory control can be made easier by avoiding situations that challenge (e.g. buffets) or weaken (e.g. stress) inhibitory control.

The tendency to discount time can be countered by focussing on short-term (immediate) rather than long-term (health) goals.

Many of these strategies may seem familiar to present recommendations, however, the context and manner in which these strategies are presented to and discussed with the client would be vastly different.

Thus, rather than making these behaviours a matter of ‘personal choice’ the counseling goal would be to have clients fully understand how their own genetic predispostiion and neurobiology drives them to these behaviours and how they have to adopt these ‘unnatural’ and ‘difficult’ strategies to overcome their ‘nature’.

As the authors point out:

“the model explains eating behaviors that promote obesity without invoking character flaws (eg, lack of willpower). By emphasizing genetically-influenced neurobiological processes that confer vulnerability to overeating in a toxic food environment, the model enables dietetics practitioners to more effectively address obesity without promoting stigma.”

In terms of the counseling process, the authors suggest that this approach

“…acknowledges that patients are working against potent genetic vulnerabilities and a toxic food environment, and normalizes patients’ (and dietetics practitioners’) frustration with failed attempts at weight control.”

and that

“…patients can better control their weight through strategies focused on the interaction between the brain and the environment. For the majority of dietetics practitioners, this second message constitutes a shift in strategy from urging patients to make the tough choices required for weight control to helping patients minimize the number of tough choices they encounter.”

While it remains to be seen whether or not such a shift in strategy will indeed produce better outcomes, I do appreciate the fact that this paper makes a serious attempt at recognising just how effectively biology drives eating behaviour and that the simplistic concepts of ‘personal choice’ and ‘will power’ are clearly not the most effective strategies to counter the toxic food environment that most of us are exposed to.

To use an analogy that I have used before, recognising that someone has a hypersensitive bronchial system that predisposes them to asthma should lead them to avoiding and eliminating air-borne pollutants in their immediate environment rather than simply trying to breathe less.

AMS
Edmonton, Alberta

Hat tip to Annette for pointing me to this article.

Appelhans BM, Whited MC, Schneider KL, & Pagoto SL (2011). Time to abandon the notion of personal choice in dietary counseling for obesity? Journal of the American Dietetic Association, 111 (8), 1130-6 PMID: 21802557