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New European Guidelines on Medical Management After Bariatric Surgery

The European Association for the Study of Obesity (EASO) had now released the new OMTF guidelines Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for Post-Bariatric Surgery Medical Management.

The guidelines provide the latest guidance on nutritional management, micronutrient supplementation, managing co-morbidities, pharmacotherapy, psychological management, and prevention and management of weight regain. The guidelines also address the issue of post-bariatric surgery pregnancy.

Not covered are issues related to dealing with excess skin and rehabilitation (e.g. return to work, reintegration in social activities, education, etc.), both of significant importance, especially in people with severe obesity.

As the authors note,

“Bariatric surgery is in general safe and effective, but it can cause new clinical problems and it is associated with specific diagnostic, preventive and therapeutic needs. Special knowledge and skills of the clinicians are required in order to deliver appropriate and effective care to the post-bariatric patient. A post-bariatric multidisciplinary follow-up programme should be an integral part of the clinical pathway at centres delivering bariatric surgery, and it should be offered to patients requiring it”

These guidelines are now available open access in Obesity Facts.

@DrSharma
Edmonton, AB

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Reducing Cardiovascular Risk In Adolescents With Bariatric Surgery

Given the limited effectiveness of “lifestyle” interventions and the lack of access to medical treatments, many adolescents struggling with severe obesity are left with no option but to consider having bariatric surgery.

Now, a paper by Marc Michalsky and colleagues on behalf of the Teens LABS Consortium, in a paper published in Pediatrics, describes the effect of bariatric surgery on cardiovascular risk factors in adolescents undergoing these procedures.

The study includes 242 adolescents (76% girls, 72% white, mean age 17 ± 1.6 y,  median BMI 51) undergoing bariatric surgery (Roux-en-Y gastric bypass (n = 161), vertical sleeve gastrectomy (n = 67), or adjustable gastric banding (n = 14)), at five centers.

At 3 years following surgery, weight was significantly lower in all groups (28%, 26%, and 8% for RYGB, VSG, and AGB, respectively).

Hypertension, observed in 44% of participants, declined to 15% at 3 years.

Dyslipidemia observed in 75% of participants, declining to 27% by 1 year and 29% by 3 years. This improvement was largely due to decrease in triclycerides and increases in HDL cholesterol.

Baseline diabetes was present in 13% of participants with major metabolic improvement (0.5%) by 3 years. Similarly, baseline impaired fasting glucose (26%) and hyperinsulinemia (74%) dramatically improved by year 3 (4% and 20%, respectively).

Improvements in these parameters were related to the degree of weight loss.

Remission rates were negatively correlated to higher age and positively correlated to female sex and white race.

Overall, the authors conclude that this study documents the improvements in cardiovascular risk factors in adolescent bariatric surgery.

Unfortunately, the study does not present any information on surgical complications or reoperation rates, an obvious matter of concern when it comes to surgery in this young population.

While there may well have been no alternative to surgical treatment in these kids, we can only hope that eventually medical treatments will become available for this population, hopefully with similar outcomes. Unfortunately, that may well still be a long way off.

@DrSharma
Edmonton, AB

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Molecular Changes During Weight Gain – Everyone Is Different

As one may well imagine, changes in body weight (up or down) can profoundly affect a vast number of hormonal and metabolic pathways.

Now, a team of researchers led by Brian Piening and colleagues, in a paper published in Cell Systems used a broad “omics” based approach to study what happens when people lose ore gain weight.

Specifically, the goal of this study was to:

(1) assemble a comprehensive map of the molecular changes in humans (in circulating blood as well as the microbiome) that occur over the course of a carefully controlled weight gain and their reversibility with weight loss; and

(2) determine whether inulin sensitive (IS) and insulin resistant (IR) individuals who are matched for degree of obesity demonstrate unique biomolecular signatures and/or pathway activation during similar weight gain.

The study included 23 carefully selected healthy participants with BMI 25–35 kg/m2, were studied. Samples were collected at baseline. They then underwent a 30-day weight gain period (average 2.8 kg), followed by an eucaloric diet for 7 days, at which point a second fasted sample of blood and stool was collected. Each participant then underwent a caloric-restricted diet under nutritionist supervision for a subsequent 60-day period designed to return each participant back to his/her initial baseline weight, at which point a third set of fasted samples of blood and stool were collected. A subset of participants returned for a follow-up sampling approximately 3 months after the end of the perturbation.Insulin resistance was assessed at baseline using a modified insulin suppression test.

The large-scale multi-omics assays performed at all time points on each participant included genomics, proteomics, metabolomics and microbiomics.

Despite some differences between the IS and IR group (particularly in differential regulation of inflammatory/immune response pathways), overall, molecular changes were dominated by inter-personal variation (i.e. changes within the same individual), which accounted for more than 90% of the observed variance in some cases (e.g., cytokines). The most striking changes with weight gain were in inflammation response pathways (despite the rather modest weight gain) and were (fortunately) reversed by weight loss.

As the authors note,

“Comparing the variation in cytokine levels between multiple baselines in a single individual versus across individuals, we observed a striking difference: for almost all cytokines, the within-individual coefficient of variation was under 20%, whereas the variation across individuals was 40%–60%. This shows that our baseline cytokine profiles are unique to the individual, a point that has significant implications for one-size-fits-all clinical cytokine assays for the detection and/or monitoring of disease.”

On the opposite side of the spectrum, proteomics and metabolomics measurements had a substantial unexplained component (30% and 35%, respectively), highlighting the presence of unaccounted factors (e.g., food, exercise, and other changing environmental factors) or a subject-specific reaction to the perturbation.

Notably, not all of the responses we observed were consistent across IR and IS participants.

“In particular, for the microbiome, we observed that the microbe A. muciniphila was weight gain responsive only in insulin-sensitive participants. The abundance of this particular microbe in IR individuals did not change across perturbations and was barely or not detectable in most IR individuals.”

Clearly, these findings highlight the fact that each individual is biochemically unique, which the authors note, makes a strong case for personalized analysis in medicine.

Perhaps more importantly for researchers, nearly all of the data are publicly available, enabling exploration of inter-omic relationships and alterations across a longitudinal perturbation, thus providing a valuable resource for the development and validation of bioinformatic tools and pipelines integrating disparate data types.

@DrSharms
Edmonton, AB

 

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How Precise Can Obesity Medicine Get?

Another article in the 2018 JAMA special issue on obesity is one by Susan and Jack Yanovski and deals with the issue of using a precision or “personalised” approach to obesity prevention and management.

As we know, there are myriad factors that can lead to obesity (environmental, genetic, psychological, medical, etc., etc., etc.), with each patient having their own story and set of drivers and barriers.

Furthermore, we know that for any given treatment (whether behavioural, medical, or surgical) there is wide variation in individual outcomes.

So, being able to match the right treatment to the right patient, or even better, reliably predict a given patient’s response to a specific treatment could potentially improve outcomes and reduce patient burden and costs.

However, as the authors note, currently the only real predictor to treatment response is how well patients respond during the early part of treatment. Thus, we know that patient who lose a significant amount of weight during the first few weeks of medical treatment, tend to have the best long-term success in terms of weight loss.

However, this approach is also rather limited. In my own practice, I regularly see patients, who initially do well with behavioural, medical or surgical treatments, but eventually struggle, as well as patients who take longer to respond to a treatment before ultimately doing fine in the long term.

We are of course a long way off from having any kind of genetic or other testing that would reliably predict patient responses to treatment.

While this may become possible in the future, I am not holding my breath.

Not only is every patient’s story different, but the many factors that can determine response (societal, behavioural, psychological, biological, etc.) are almost endless and, moreover, can even vary over time in a given individual.

In fact, for most complex chronic diseases (e.g. diabetes, hypertension, depression, etc.), finding the best treatment for a given patient continues to be “trial and error”, or in other words, “empirical”.

Despite all the progress in genetic research, this has not really changed for most other complex chronic diseases like hypertension, type 2 diabetes, or dyslipidemia (despite a few rare but notable exceptions).

Moveover, as the authors point out, there are many other factors that will determine whether or not a given patient even has access to certain treatments, irrespective of whether or not that treatment is indeed the best treatment for them.

Currently, the best we can do, is to try to understand the drivers and barriers that each of our patients face and discuss with them the best treatment options available to them given their situation and circumstances.

Whether a more precise approach is ever likely (as the authors hope), clearly remains to be seen, but based on the progress made in for other complex chronic conditions, for which similar approaches have been tried, I am perhaps far less optimistic than the authors.

But, then again, I am happy to be proven wrong.

@DrSharma
Edmonton, AB

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Counting Calories For Weight Loss – More of The Same

If there is one article in the 2018 special issue of JAMA on obesity that we could have well done without, it is surely the one by Eve Guth promoting the age-old notion that simply counting calories is a viable and effective means to manage body weight.

As the author suggests:

“It is better for physicians to advise patients to assess and then modify their current eating habits and then reduce their caloric ingestion by counting calories. Counseling patients to do this involves provision of simple handouts detailing the calorie content of common foods, suggested meal plan options, an explanation of a nutrition label, and a list of websites with more detailed information. Patients should be advised that eating about 3500 calories a week in excess of the amount of calories expended results in gaining 1 lb (0.45 kg) of body weight. If a patient reduces caloric ingestion by 500 calories per day for 7 days, she or he would lose about 1 lb of body weight per week, depending on a number of other factors. This is a reasonable and realistic place to start because this approach is easily understood and does not ask a patient to radically change behavior.”

There is so much wrong with this approach, that it is hard to know exactly where to start.

For one, this advise is based on the simplistic assumption that obesity is simply a matter of managing calories to achieve and sustain long-term weight loss.

Not only, do we have ample evidence that these type of approaches rarely result in long-term sustained weight-loss but, more importantly this type of advice comfortably ignores the vast body of scientific literature that tells us that body weight is a tightly regulated physiological variable and that there are a host of complex neuroendocrine responses that will defend our bodies against long-term weight loss – mechanisms that most people (irrespective of whether they have obesity or not) will find it exceedingly hard to overcome with “will-power” alone.

No doubt, caloric “awareness” can be an eye-opener for many patients and there is good evidence that keeping a food journal can positively influence dietary patterns and even reduce “emotional” eating. But the idea that cognitively harnessing “will-power” to count calories (a very “unnatural” behaviour indeed), thereby creating and sustaining a long-term state of caloric deficit is rather optimistic at best.

In fact, legions of people who have been battling obesity all their lives can attest to the fact that encouragement to simply “eat less and move more” (ELMM) as a viable strategy to achieve and sustain significant weight loss is about as effective as reminding people with depression to focus on the brighter side of things and cheer up.

Not to mention the debunked 3500 calorie deficit a week = 1 lb weight loss (week after week after week till a so called  “healthy” weight is achieved) myth, which is simply not how bodies work.

Continuing to propagate this antiquated and simplistic idea of what it takes to manage a complex chronic disease like obesity, is exactly what is holding the field back.

There is no reason to assume why more of the same should produce results that are any different from those in the past.

It is time we recognise that restricting caloric intake by willpower alone (irrespective of the dietary strategy) simply does not change the biology of the underlying physiology that effectively defends our bodies against long-term weight loss.

Reading an article like this in 2018 in a reputable journal that promises to “reimagine” obesity is both disappointing and a stark reminder of just how far we have to go to change widely held beliefs that obesity is simply a matter of calories in and calories out – if only life (and human biology) was that simple!

@DrSharma
Edmonton, AB

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