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Weight Change (Not Weight!) Is A Vital Sign

Why do doctors weigh people? Because, very early in medical school, we are taught that body weight is an important indicator of health.

While one may certainly argue about the value of a single weight measurement at any point in time (especially in adults), there is simply no denying that weight trajectories (changes in body weight – up or down) can provide important (often vital) clinical information.

Let’s begin with the easiest (and least arguable) situations of all – unintentional weight loss.

Among all clinical parameters one could possibly measure, perhaps non should be as alarming as someone losing weight without actively trying. In almost every single instance of “unintentional” weight loss, the underlying problem needs to be found, and more often than not, the diagnosis is probably serious (cancer is just one possibility).

As with any serious condition, the earlier you detect it, the sooner you can do something about it, therefore, the more often you weight someone, the more likely you will detect early “non-intentional” weight loss.

The contrary situation (un-intentional weight gain) is as important. When someone is gaining weight for no good reason, one needs to look for the underlying cause, which can include everything from an endocrine problem to heart failure.

On the other hand, weight stability, is generally a sign that things are probably “under control”, as they should be when energy homeostasis works fine and people are in energy balance.

Perhaps my own obsession with weighing people comes from my work in nephrology, where we obsess about people’s “dry weight” and use weight as a general means to monitor fluid status. The same is true for working with patients who have heart failure.

Note for all of the above, that while a single (random) weight measurement tells you very little (almost nothing) about anybody’s health status, unexplained changes in body weight are one of the most useful and important clinical signs in all of medicine. Obviously, to plot a trajectory, one has to start somewhere, which means that every patient needs to have a “baseline” body weight recorded somewhere in their chart. While this value may not provide any valuable information, the next one may.

This is why every single patient needs to be weighed at least once in a clinical setting.

As you will imagine, both the context and interpretation of serial weight measurements becomes most challenging in the setting of obesity management.

For one, there is no greater challenge than to suspect underlying “un-intentional” weight loss in someone who is actively trying to lose weight. When “suddenly” a weight loss strategy that was providing modest results “starts working” – all alarm bells should go off. Also, if weight loss is much better than “predicted” it is time to take a serious second look at what’s happening. Furthermore, you need to watch out for patients who are doing far better than expected (even after bariatric surgery) – it takes a keen clinical  mind to watch out for weight loss that appears “too good to be true” (even if the patient is delighted to see the pounds drop off).

Also, in the obesity management setting, weight stability is an important clinical indicator. In someone at their maximum weight, it tells me that the patient is not actively gaining weight, which by definition means that the patient is in caloric balance – remember, the first sign of “success” in obesity management is when the patient stops gaining weight.

In someone, who has already lost weight (in the context of obesity management), weight stability means that the patient’s efforts are continuing (here weight stability is a means to monitor “control”) – weight regain means that the patient may have to re-engage in weight control efforts or (more often) that something has come up in that person’s life that is “sabotaging” their efforts and may need to be identified and addressed (e.g. lost a job, change in medication, depression, etc.). Again, the earlier you identify a “relapse”, the earlier you can intervene.

Finally, in someone attending an obesity clinic, who continues gaining weight, you can be sure that the underlying cause of weight gain has not yet been fully identified or addressed. In other words, the disease is not “controlled” and continues to “progress”.

Thus, patients must be aware, that asking not to be weighed (usually out of shame or embarrassment) derives their clinician of important and possibly “vital” information about their health status.

Again, while a single weight (or BMI) says very little about a patient’s health, changes in body weight (up or down) is a vital sign that should prompt further clinical investigation and possibly intervention.

None of this has anything to do with the fact that people can very well be healthy over a wide range of body shapes and sizes.

It also does not mean that we should take a “weight-centric” approach to obesity management – all of the usual HAES arguments remain valid, even when you regularly ask your patient to step on the scale.

Recording a weight trajectory should be no more “judgemental” than recording a fever chart in a patient with an infection – everything lies in the context and interpretation of the data.

@DrSharma
Edmonton, AB.

 

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The Key To Obesity Management Lies In The Science Of Energy Homeostasis

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]

Clearly,

“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.

@DrSharma
Edmonton, AB

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Alternate Day Fasting Is No Better Than Any Other Fad Diet

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.

@DrSharma
Edmonton, AB

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GLP-1 Analogue Semaglutide Appears Promising in Phase 2 Study

Readers may by now be familiar with the GLP-1 analogue liraglutide, which has now been approved at the 3 mg dose (Saxenda(R)) for long-term obesity treatment in a growing number of countries.

Now, Novo Nordisk, the maker of liraglutide, announced preliminary results from their long-acting GLP-1 analogue semaglutide, suggesting a rather remarkable ~14% weight loss in a one-year double-blind placebo controlled dose-finding study.

According to the company’s press release,

In the trial, 957 people with obesity were randomised to treatment with doses of semaglutide between 0.05 to 0.4 mg/day or placebo. Liraglutide 3.0 mg/day was included for comparison. Approximately 100 people were included in each active treatment arm in combination with diet and exercise. All people in the trial were treated for 52 weeks followed by a 7-week follow-up period.

Furthermore,

From a mean baseline weight of around 111 kg and a body mass index of approximately 39 kg/m2, a weight loss up to 17.8 kg was observed after 52 weeks of treatment with semaglutide. This corresponded to an estimated 13.8% weight loss compared to the weight loss of 2.3% achieved by diet, exercise and placebo alone, with all treatment arms adjusted for people discontinuing treatment in the study. The results from the liraglutide 3.0 mg treatment arm were broadly in line with previously reported data.

Side effects were mainly reported as gastro-intestinal, as expected from this class of hormone analogues.

Clearly, if borne out by the final publication and confirmed in larger and longer studies, semaglutide may well prove to be even more effective than liraglutide.

It may be worth noting, that the ~14% weight loss reported in this trial comes very close to the mean ~15% weight loss seen with adjustable gastric banding, a bariatric surgical technique that is now increasingly seen as obsolete due to long-term complications and loss of effectiveness.

I’m guessing it’s now on to Phase 3 for this promising anti-obesity drug.

@DrSharma
Edmonton, AB

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

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1st International Diabetes Expert Conclave (IDEC) 2017

In front of the Aga Khan Palace, Pune, India

Last week I was an invited plenary speaker at the 1st International Diabetes Expert Conclave (IDEC2017) held in Pune, India.

This 3-day event, organised by Drs. Neeta Deshpande (Belgaum), Sanjay Agrawal (Pune) and colleagues, brought together well over 900 physicians from across India for a jam-packed program that covered everything from diabetic food disease and neuropathy to the latest in insulin pumps and devices – all in a uniquely Indian context.

I, of course, was there to speak on obesity, which featured prominently in the program. Topics on obesity ranged from the potential role of gut bugs to bariatric surgery. While Dr. Allison Goldfine, former Director of Clinical Research at the Joslin Diabetes Center in Boston spoke on the latest developments in anti-obesity pharmacotherapy (delivering her talk via Skype), I spoke about obesity as a chronic disease and the need to redefine obesity based on actual indicators of health rather than BMI.

During my visit in Pune, I also had the opportunity to visit with my friend and colleague Dr. Shashank Shah, whose bariatric surgical center in Pune alone performs about 75 to 100 bariatric operations per month – a remarkable number by any standards.

Of course, the overwhelming number of talks were given by Indian faculty (there being only a handful of select invited international faculty at the meeting), and I did come away most impressed by the breadth and depth of knowledge presented by the local speakers.

Diabetes care certainly appears to be in good hands although the sheer number of patients with diabetes (estimated at about 70 million, which I assume to be a rather conservative assessment), would provide a challenge to any health care system.

On the obesity front, things are a lot less rosy, given that (as everywhere else) obesity has yet to receive the same level of professional attention and expertise afforded to diabetes or other chronic diseases.

Thanks again to the organisers for inviting me to this exciting meeting and congratulations on an excellent event that bodes well for the 2nd Conclave planned for 2018.

@DrSharma
Edmonton, AB

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