A recent CMAJ article, by Ian Mosby and Tracey Galloway from the University of Toronto argues that one of the key reasons why we see obesity and diabetes so rampant in Canada’s indigenous populations, is the fact that widespread and persistent exposure to hunger during the notorious residential school system may have metabolically “programmed” who generations toward a greater propensity for obesity and type 2 diabetes.
There is indeed a very plausible biological hypothesis for this,
“Hunger itself has profound consequences for childhood development. Children experiencing hunger have an activated hypothalamic–pituitary–adrenal stress response. This causes increased cortisol secretion which, over the long term, blunts insulin response, inhibits the function of insulin-like growth factor and produces long-term changes in lipid metabolism. Through this process, the child’s physiology is essentially “programmed” by hunger to continue the cycle of worsening effects, with their bodies displaying a rapid tendency for fat-mass accumulation when nutritional resources become available.”
While the impact of hunger may well have been one of the key drivers or metabolic changes, the authors failed to acknowledge another (even more?) important consequence of residential schools – the impact on mental health.
Oddly enough, in a blog post I wrote back in 2008, I discussed the notion that the significant (and widespread) physical, emotional, and sexual abuse experienced by the generations of indigenous kids exposed to the residential school system would readily explain much of the rampant psychological problems (addictions, depression, PTSD, etc.) present in the indigenous populations across Canada today.
The following is an excerpt from this previous post:
This disastrous and cruel [residential school] policy resulted in much pain and despair in the First Nations’, Inuit and Metis people that lasts to this day (known as the “generational effect”). Sexual, physical and mental abuse was widespread; students were broken in heart and spirit; culture and identities were destroyed.
Much (if not all) of what ails the Aboriginal peoples of Canada can be traced back to this policy – including possibly issues that affect Aboriginal health to this day.
It is no secret that obesity and its consequences (e.g. diabetes) are rampant amongst the Aboriginal peoples of Canada. While poverty, breakdown of traditional lifestyle and culture and even genetic factors (thrifty genotype) have all been implicated in this, I wonder how much the misery caused by the residential school program had to contribute.
Early traumatic life experiences including sexual, mental and physical abuse as well as neglect and grief have all been implicated in binge eating disorder (BED) – in its purest form – the uncontrollable urge to devour large quantities of highly palatable high-caloric foods in response to emotional hunger. This behaviour has been interpreted as an emotional coping strategy, “filling the inner void”, building a physical protective barrier, etc., the ultimate result being excessive weight gain with all its consequences (the typical binger does not compensate by purging or excessive exercise).
In “treatment-seeking” patients with obesity, the prevalence of BED is estimated at 20-40%. Although I was unable to find a study that has applied the DSM-IV criteria for BED to an Aboriginal population – my guess is: the rates are probably high!
Given its distinct psychopathology, BED is highly responsive to psychotherapeutic approaches. In contrast, educational initiatives based on simply providing information on healthy lifestyles are useless.
Obesity is never an issue of “choice”. I have yet to meet anyone who “chooses” to be obese. This is most certainly also true for Canada’s Aboriginal population.”
If there is one thing we know for sure about obesity management, it is the sad fact, that no diet, exercise, medication, not even bariatric surgery, will permanently reset the body’s tendency to defend and regain its body weight to its set point – this generally being the highest weight that has been achieved and maintained for a notable length of time.
Thus, any effective long-term treatment has to offset the complex neurobiology that will eventually doom every weight-loss attempt to “failure” (no, anecdotes don’t count!).
Just how complex and overpowering this biological system that regulates body weight is, is described in a comprehensive review by the undisputed leaders in this field (Michael Schwartz, Randy Seeley, Eric Ravussin, Rudolph Leibel and colleagues) published in Endocrine Reviews. Indeed the paper is nothing less than a “Scientific Statement” from the venerable Endocrine Society, or, in other words, these folks know what they’re talking about when it comes to the science of energy balance.
As the authors remind us,
“In its third year of existence, the Endocrine Society elected Sir Harvey Cushing as President. In his presidential address, he advocated strongly in favor of adopting the scientific method and abandoning empiricism to better inform the diagnosis and treatment of endocrine disease. In doing so, Cushing helped to usher in the modern era of endocrinology and with it, the end of organo-therapy. (In an interesting historical footnote, Cushing’s Energy Homeostasis and the Physiological Control of Body-Fat Stores presidential address was given in , the same year that insulin was discovered.)”
Over 30 pages, backed by almost 350 scientific citations, the authors outline in excruciating detail just how complex the biological system that regulates, defends, and restores body weight actually is. Moreover, this system is not static but rather, is strongly influenced and modulated by environmental and societal factors.
Indeed, after reading this article, it seems that the very notion, that average Jane or Joe could somehow learn to permanently overcome this intricately fine-tuned system (or the societal drivers) with will power alone is almost laughable (hats off to the very few brave and determined individuals, who can actually do this – you have climbed to the top of Mount Everest and decided to camp out there for the foreseeable future – I wish you all the best!).
Thus, the authors are confident that,
“The identification of neuromolecular mechanisms that integrate short-term and long-term control of feeding behavior, such that calorie intake precisely matches energy expenditure over long time intervals, will almost certainly enable better preventive and therapeutic approaches to obesity.”
Sadly, despite all we have learnt about this system, we are still far from fully understanding it. Thus, the canonical molecular/ cellular signaling pathway: LEP → LEPR → POMC, AgRP → PC → MC4R is just one pathway in a complex network of multiple interacting and sometimes redundant pathways that involve virtually every part of the brain.
Also, the effect of environmental factors appears to be far more complex than most people think. Thus,
“During sensitive periods of development, ontogenic processes in both brain and peripheral organs can be modified so as to match anticipated environmental conditions. Although many exposures during development could potentially predispose to obesity in adulthood, we focus here on two that some researchers think contribute to the secular trends in obesity: parental obesity and exposure to endocrine disrupting chemicals (EDCs).”
Throw in the role of gut bugs, infections, and societal factors, and it is easy to see why no simple solution to the obesity epidemic are in sight (let alone a range of effective long-term treatments like we have for most other common chronic diseases).
As for solutions,
“To be viable, theories of obesity pathogenesis must account not only for how excess body fat is acquired, but also for how excess body fat comes to be biologically defended. To date, the preponderance of research has focused on the former. However, we must consider the possibility that some (perhaps even most) mechanisms underlying weight gain are distinct from those responsible for the biological defense of excess fat mass. A key question, therefore, is how the energy homeostasis system comes to defend an elevated level of fat mass (analogous to the defense of elevated blood pressure in patients with hypertension). Answering this question requires an improved understanding of the neuro-molecular elements that underlie a “defended” level of body fat. What are the molecular/neuroanatomic predicates that help establish and defend a “set point” for adiposity? How do these elements regulate feeding behavior and/or energy expenditure, so as to achieve long-term energy balance? By what mechanisms is an apparently higher set point established and defended in individuals who are obese?” [sic]
“Given that recovery of lost weight (the normal, physiological response to weight loss irrespective of one’s starting weight) is the largest single obstacle to effective long-term weight loss, we cannot overstate the importance of a coherent understanding of obesity-associated alterations of the energy homeostasis system.”
There is much work to be done. Whether or not, in this climate of anti- and pseudo-science, funding for such fundamental work will actually be made available, is anyone’s guess.
It seems that every year someone else comes up with a diet that can supposedly conquer obesity and all others health problems of civilization.
In almost every case, the diet is based on some “new” insight into how our bodies function, or how our ancestors (read – hunters gatherers (never mind that they only lived to be 35) ate, or how modern foods are killing us (never mind that the average person has never lived longer than ever before), or how (insert remote population here) lives today with no chronic disease.
Throw in some scientific terms like “ketogenic”, “guten”, “anti-oxidant”, “fructose”, or “insulin”, add some level of restriction and unusual foods, and (most importantly) get celebrity endorsement and “testemonials” and you have a best-seller (and a successful speaking career) ready to go.
The problem is that, no matter what the “scientific” (sounding) theories suggest, there is little evidence that the enthusiastic promises of any of these hold up under the cold light of scientific study.
Therefore, I am not the least surprised that the same holds true for the much hyped “alternative-day fasting diet”, which supposedly is best for us, because it mimics how our pre-historic ancestors apparently made it to the ripe age of 35 without obesity and heart attacks.
Thus, a year-long randomised controlled study by John Trepanowski and colleagues, published in JAMA Internal Medicine, shows that alternate day fasting is evidently no better in producing superior adherence, weight loss, weight maintenance, or cardioprotection compared to good old daily calorie restriction (which also produces modest long-term results at best).
In fact, the alternate day fasting group had significantly more dropouts than both the daily calorie restriction and control group (38% vs. 29% and 26% respectively). Mean weight loss was virtually identical between both intervention groups (~6 Kg).
Purists of course will instantly critisize that the study did not actually test alternative-day fasting, as more people dropped out and most of the participants who stayed in that group actually ate more than prescribed on fast days, and less than prescribed on feast days – but that is exactly the point of this kind of study – to test whether the proposed diet works in “real life”, because no one in “real life” can ever be expected to be perfectly compliant with any diet. In fact, again, as this study shows, the more “restrictive” the diet (and, yes, starving yourself every other day is “restrictive”), the greater the dropout rate.
Unfortunately, what counts in real life is not what people should be doing, but what people actually do. The question really is not whether or not alternate-day fasting is better for someone trying to lose weight but rather, whether or not “recommending” someone follows an alternate-day fasting plan (and them trying to follow it the best they can) is better for them. The clear answer from this study is “no”.
So why are all diets the same (in that virtually all of them provide a rather modest degree of long-term weight loss)?
My guess is that no diet (or behaviour for that matter) has the capability of fundamentally changing the body’s biology that acts to protect and restore body fat in the long-term. Irrespective of whether a diet leads to weight loss in the short term and irrespective of how it does so (or how slow or fast), ultimately no diet manages to “reset” the body-weight set point to a lower level, that would biologically “stabilize” weight loss in the long-term.
Thus, the amount of long-term weight loss that can be achieved by dieting is always in the same (rather modest) ballpark and it is often only a matter of time before the biology wins out and put all the weight back on.
Clearly, I am not holding my breath for the next diet that comes along that promises to be better than everything we’ve had before.
My advice to patients is, do what works for you, but do not expect miracles – just find the diet you can happily live on and stick to it.
Wow, what a week!
Just back from the 5th Canadian Obesity Summit, there is no doubt that this summit will live long in the minds (and hearts) of the over 500 attendees from across Canada and beyond.
As anyone would have appreciated, the future of obesity research, prevention and practice is alive and kicking in Canada. The over 50 plenary review lectures as well as the over 200 original presentations spanning basic cellular and animal research to health policy and obesity management displayed the gamut and extent of cutting-edge obesity research in Canada.
But, the conference also saw the release of the 2017 Report Card on Access to Obesity Treatment for Adults, which paints a dire picture of treatment access for the over 6,000,000 Canadians living with this chronic disease. The Report Card highlights the virtually non-existant access to multidisciplinary obesity care, medically supervised diets, or prescription drugs for the vast majority of Canadians.
Moreover, the Report Card reveals the shocking inequalities in access to bariatric surgery between provinces. Merely crossing the border from Alberta to Saskatchewan and your chances of bariatric surgery drops from 1 in 300 to 1 in 800 per year (for eligible patients). Sadly, numbers in both provinces are a far cry from access in Quebec (1 in 90), the only province to not get an F in the access to bariatric surgery category.
The presence of patient champions representing the Canadian Obesity Network’s Public Engagement Committee, who bravely told their stories to a spell-bound audience (often moved to tears) at the beginning of each plenary session provided a wake up call to all involved that we are talking about the real lives of real people, who are as deserving of respectful and effective medical care for their chronic disease as Canadians living with any other chronic disease.
Indeed, the clear and virtually unanimous acceptance of obesity as a chronic medical disease at the Summit likely bodes well for Canadians, who can now perhaps hope for better access to obesity care in the foreseeable future.
Thanks again to the Canadian Obesity Network for hosting such a spectacular event (in spectacular settings).
More on some of the topics discussed at the Summit in coming posts.
For an overview of the Summit Program click here
Since the introduction of SGLT-2 inhibitors (“gliflozins” or “glucoretics), as an insulin-independent treatment for type 2 diabetes, that works by blocking glucose reabsorbtion in the kidney resulting in loss of glucose (and calories) through the kidney, much has been written about the (albeit modest) weight loss associated with this treatment.
Several studies have documented that the weight loss leads to a change in body composition with an often significant reduction in fat mass.
Now, Giuseppe Daniele and colleagues, in a paper published in Diabetes Care, show that treatment with these compounds may enhance fat oxidation and increase ketone production in patients with type 2 diabetes.
The researchers randomized 18 individuals with type 2 diabetes to dapagliflozin or placebo for two weeks.
As expected, dapagliflozin reduced fasting plasma glucose significantly (from 167 to 128 mg/dL).
It also increased insulin-stimulated glucose disposal (measured by insulin clamp) by 36%, indicating a significant increase in insulin sensitivity.
Compared to baseline, glucose oxidation decreased by about 20%, whereas nonoxidative glucose disposal (glycogen synthesis) increased by almost 50%.
Moreover, dapagliflozin increased lipid oxidation resulting in a four-fold increase in plasma ketone concentration and and a 30% increase in fasting plasma glucagon.
Thus, the authors note that treatment with dapagliflozine improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production.
While this may explain the recent observation of a greater (albeit still rather rare) incidence of ketoacidosis with the use of these compounds, these findings may also explain part of the change in body composition previously noted with SGLT-2 treatment.
While this still does not make SGLT-2 inhibitors “weight-loss drugs”, there appears to be more to the fat loss seen with these compounds than just the urinary excretion of glucose.