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5th Canadian Obesity Summit – Four More Days To Submit Your Abstracts!

banff-springs-hotelEvery two years the Canadian Obesity Network holds its National Obesity Summit – the only national obesity meeting in Canada covering all aspects of obesity – from basic and population science to prevention and health promotion to clinical management and health policy.

Anyone who has been to one of the past four Summits has experienced the cross-disciplinary networking and breaking down of silos (the Network takes networking very seriously).

Of all the scientific meetings I go to around the world, none has quite the informal and personal feel of the Canadian Obesity Summit – despite all differences in interests and backgrounds, everyone who attends is part of the same community – working on different pieces of the puzzle that only makes sense when it all fits together in the end.

The 5th Canadian Obesity Summit will be held at the Banff Springs Hotel in Banff National Park, a UNESCO World Heritage Site, located in the heart of the Canadian Rockies (which in itself should make it worth attending the summit), April 25-29, 2017.

Yesterday, the call went out for abstracts and workshops – the latter an opportunity for a wide range of special interest groups to meet and discuss their findings (the last Summit featured over 20 separate workshops – perhaps a tad too many, which is why the program committee will be far more selective this time around).

So here is what the program committee is looking for:

  • Basic science – cellular, molecular, physiological or neuronal related aspects of obesity
  • Epidemiology – epidemiological techniques/methods to address obesity related questions in populations studies
  • Prevention of obesity and health promotion interventions – research targeting different populations, settings, and intervention levels (e.g. community-based, school, workplace, health systems, and policy)
  • Weight bias and weight-based discrimination – including prevalence studies as well as interventions to reduce weight bias and weight-based discrimination; both qualitative and quantitative studies
  • Pregnancy and maternal health – studies across clinical, health services and population health themes
  • Childhood and adolescent obesity – research conducted with children and or adolescents and reports on the correlates, causes and consequences of pediatric obesity as well as interventions for treatment and prevention.
  • Obesity in adults and older adults – prevalence studies and interventions to address obesity in these populations
  • Health services and policy research – reaserch addressing issues related to obesity management services which idenitfy the most effective ways to organize, manage, finance, and deliver high quality are, reduce medical errors or improve patient safety
  • Bariatric surgery – issues that are relevant to metabolic or weight loss surgery
  • Clinical management – clinical management of overweight and obesity across the life span (infants through to older adults) including interventions for prevention and treatment of obesity and weight-related comorbidities
  • Rehabilitation –  investigations that explore opportunities for engagement in meaningful and health-building occupations for people with obesity
  • Diversity – studies that are relevant to diverse or underrepresented populations
  • eHealth/mHealth – research that incorporates social media, internet and/or mobile devices in prevention and treatment
  • Cancer – research relevant to obesity and cancer

…..and of course anything else related to obesity.

Deadline for submission is October 24, 2016

To submit an abstract or workshop – click here

For more information on the 5th Canadian Obesity Summit – click here

For sponsorship opportunities – click here

Looking forward to seeing you in Banff next year!

Edmonton, AB


How Strong Is The Physiological Drive To Regain Lost Weight?

Yo-Yo Rubber Band Feb 2014It is now well established that the almost non-existant rates of long-term weight loss are not because of lack of will power or lack of motivation. Rather, they are firmly embedded in human (and animal) physiology, that is designed to defend body weight at all costs through complex neuroendocrine homeostatic mechanisms that will eventually wear out even the staunchest dieter.

But just how strong is the physiological drive to defend and regain lost body weight? Or even more specifically, how much does an increase in appetite counteract weight loss?

This is the topic of a paper by David Polidori and colleagues, prepublished on bioRxiv*.

The researchers use data from a 52-week trial of canagliflozin, a sodium glucose co-transporter (SGLT2) inhibitor leads to a urinary glucose loss of approximately 90 g/day throughout the duration of treatment.

This amounts to a net daily energy loss of ~360 kcal/day that occurs without directly altering central pathways controlling energy intake and without the patients being directly aware of the energy deficit.

Based on the observed changes in body weight over time, the researchers used a validated mathematical method to calculate changes in daily energy intake using principles from engineering control theory.

The complex mathematical formula takes into account a wide range of parameters including changes in the energy expenditure rate and density of fat and fat-free mass, energy cost of fat and protein turnover, dietary and adaptive thermogenesis as well as changes in physical activity (no change in physical activity was assumed in this study).

Subjects in the treatment arm showed the typical initial weight loss (of about 5 Kg) followed by the maintenance of a weight-loss plateau throughout the remainder of the study, a pattern which, in light of a continuing daily energy loss of about 360 kcal is consistent with a proportional feedback control system that serves to limit the amount of weight loss and creates a drive towards weight regain (think of this as the tension that counteracts a steady pull  on a rubber band).

Based on their calculations, the amount of daily increase in caloric intake required to maintain the weight loss plateau (rather than continuing to lose weight), was in the order of about 100 Kg/day per Kg weight loss. This is substantially more than the reduction in metabolic rate generally seen with weight loss (of about 10-20% of body weight) is only about 30 kcal/day per Kg weight loss).

When applying these finding to the typical weight-loss curve seen in the usual commercial weight loss programs (an initial weight loss followed by gradual weight regain), the researchers show that the difference between the homeostatic drive to eat and the actual energy intake, a quantitative index of the ongoing effort to sustain the intervention in the face of the continuing biological signals to overeat, requires that subjects have to demonstrate a persistent effort to avoid overeating above baseline during the intervention even when the average energy intake returns to near baseline levels.

Despite the elegant use of real data, the authors caution about limitations of their study, which include the fact that all subjects had type 2 diabetes and the overall degree of weight loss was rather modest. Thus, the model may well look different in subjects without diabetes or more extreme weight loss.
Nevertheless, as the authors discuss,
“…homeostatic feedback control of energy intake is likely a primary reason why it is so difficult to achieve large sustained weight losses in patients with obesity. Rather, weight regain is typical in the absence of heroic and vigilant efforts to maintain behavior changes in the face of an omnipresent obesogenic environment. Unfortunately, there is no evidence that the energy intake feedback control system resets or relaxes with prolonged maintenance of lost weight – an effect similar to the long-term persistent suppression of energy expenditure in weight-reduced humans. Therefore, the effort associated with a weight loss intervention persists until either body weight is fully regained or energy intake increases above baseline to match the homeostatic drive to eat.”
Thus, the key to finding long-term obesity treatments that work, will be to find means of permanently subverting or countering this feedback control system (which is exactly how medications or surgery theoretically work).
No wonder, that will power alone will rarely result in sustainable weight loss and will always require on-going (heroic?) effort in the cases where it does.
Edmonton, AB
*Papers published on bioRxiv are “preprints” before peer review, thus allowing other scientists to see, discuss, and comment on the findings immediately. Readers should therefore be aware that articles on bioRxiv have not been finalized by authors, might contain errors, and report information that has not yet been accepted or endorsed in any way by the scientific or medical community.



Resetting The Setpoint: Is There Something To Learn From Bariatric Surgery?

Yo-Yo Rubber Band Feb 2014I am currently in Rio de Janeiro, speaking at the 21st World Congress of the International Federation for the Surgery of Obesity & Metabolic Disorders – IFSO 2016.

As Lee Kaplan from Harvard University reminded the audience, obesity is a disease of energy homeostasis, where everything seems to be working just fine, except that the “setpoint” of the system is set too high.

Kaplan used the analogy of the temperature in a room, where the thermostat is set too high – say to 30 Centigrade.

Everything else in the room works just fine: nothing wrong with the heater, or the air-conditioning, or the ventilation system, or the isolation. In fact, even the thermostat is working just fine doing its job – except that it is set too high!

Dieting would be like tearing open a window to lower the temperature in the room. Yes, if you open the window, things may cool down, but the thermostat will only make the heating work extra hard trying to heat the room and, once you close the window, the thermostat will rapidly bring the temperature back to 30 Centigrade (or come off your diet).

So how do we reset the set point?

Well, that appears to be exactly what bariatric surgery does to the system – it somehow manages to lower the set point, allowing the body to regulate its weight at a lower level than before (something that does not happen when you lose weight simply with diet and exercise).

How exactly surgery does this, remains unclear, but there is no doubt that this happens and there are a lot of experiments showing that after sugery, the body actively regulates body weight at a lower “setpoint”.

Unfortunately, this “resetting” is not permanent.

If you reverse the surgery, the body goes right back to regulating its weight at the higher level, resulting in the rapid weight regain, which is why I consider obesity surgery a “treatment” rather than a “cure”.

Kaplan went on to talk about the role of the bacteriome and bile acid metabolism (both dramatically changes with bariatric surgery – but very little with diet and exercise).

Figuring out how bariatric surgery changes the setpoint (even temporarily) will hopefully lead to new medical treatments for obesity.

Till then, anyone losing weight (no matter what diet, exercise, or medication) needs to remember that they stand to regain the weight, the minute they stop the “treatment”.

Rio de Janiero


How Far Are We From Once-Weekly Medications For Obesity?

Anyone who follows these pages is aware of the fact that we desperately lack better medical treatments for obesity.

Last year, Health Canada approved the glucagon-like peptide 1 (GLP-1) analogue liraglutide (Saxenda(R)) for obesity treatment, which although effective and generally well-tolerated, has to be administered by daily injections.

Now, the results of the SUSTAIN-6 trial, published in the New England Journal of Medicine, show that the once weekly injection of the GLP-1 analogue semaglutide, not only decreases cardiovascular events, but also significantly lowers body weight, a promising finding for future obesity treatment with this drug.

The SUSTAIN 6 trial randomised 3297 patients with type 2 diabetes to once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks.

At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both.

The primary outcome (MACE) occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74).

Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74); nonfatal stroke occurred in 1.6% and 2.7%, (hazard ratio, 0.61).

While average body weight at week 104 remained stable in the placebo group, it decreased by 3.6 kg in the semaglutide 0.5 mg group and and 4.9 kg in the semaglutide 1.0 mg group.

While this may not seem spectacular, it is important to remember that weight loss is notoriously difficult in patients with type 2 diabetes and that this was a diabetes and not an obesity trial, in which case participants would have also been counselled to change their diet and activity levels to achieve weight loss.

Thus, one can only speculate on what the differences in body weight would have been had the participants been actually trying to lose weight.

That said, it was perhaps surprising to note that fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal.

It will be interesting to see how well semaglutide fares in studies in which this treatment is assessed for the obesity indication, which will hopefully bring us closer to a once-weekly medication for obesity.

In the meantime, once-daily liraglutide 3.0 mg is certainly a welcome addition to medical management of obesity, but clearly there is more to come in terms of harnessing GLP-1 for obesity management.

Edmonton, AB

Disclaimer: I have received consulting and speaking honoraria from Novo Nordisk, the makers of liraglutide and semaglutide


POMC Mutation Obesity Responds To Melanocortin-4 Receptor Agonist

sharma-obesity-hypothalamusMelanocyte-stimulating hormone (a-MSH), which is produced from the hormone precursor proopiomelanocortin (POMC) and acts on the hypothalamic melanocortin-4 receptor, plays a key role in the regulation of satiety and energy expenditure.

In very rare instances, mutations of the gene coding for POMC can cause severe early onset obesity characterised by increased appetite. Due to other effects of POMC deficiency, patients will present with pale skin, red hair and clinical signs of hypocortisolism.

Now, a paper by Peter Kühnen and colleagues published in the New England Journal of Medicine, shows that treating patients with the melanocortin-4 receptor agonist, setmelanotide, can result in significant reduction in appetite and body weight.

The open-label study was performed in two adult patients with POMC deficiency, in cooperation with Rhythm Pharmaceuticals, which provided the study medication and regulatory support.

Both patients weighed around 150 Kg with marked hyperphagia and both responded to treatment with a substantial reduction in appetite and dramatic weight loss of over 20 Kg over 12-13 weeks.

After a brief interruption, one patient was again treated for 42 weeks, ultimately losing 51 kg (32.9% of her initial body weight).

As the authors note,

“Setmelanotide appeared to completely reverse hyperphagia, leading to impressive weight loss and normalization of insulin resistance. More important, both patients reported a dramatic improvement in their quality of life after the initiation of setmelanotide therapy. Moreover, the substantial and ongoing reduction in body weight was similar to the changes observed after leptin administration in patients with leptin deficiency.”

Over all the treatment was well tolerated with no major adverse effects.

While these observations were made in very rare patients with documented POMC deficiency, these findings may have broader implications for individuals with more common “garden-variety” obesity.

“Both patients described here had very high leptin levels before treatment, suggesting leptin resistance. In patients with proopiomelanocortin deficiency, the leptin signal is probably not properly transduced into anorexigenic responses, given the lack of melanocyte-stimulating hormone. Setmelanotide substitutes for melanocyte-stimulating hormone and binds at its receptor, thus overcoming leptin resistance. On the basis of the observation that obese patients without known genetic abnormalities have severe leptin resistance and regain weight owing to a post-dieting increase in appetite, we speculate that setmelanotide may also be effective in nongenetic forms of obesity.”

Appropriate studies in patients with non-POMC deficient obesity are currently underway.

Atlanta, GA