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Fit-Fat Paradox Holds For People With Severe Obesity

Regular readers will be quite familiar with the findings that cardiometabolic health appears to be far more related to “fitness” than to “fatness” – in other words, it is quite possible to mitigate the metabolic risks commonly associated with excess body fat by improving cardiorespiratory fitness.

Now, a study by Kathy Do and colleagues from York University, Toronto, published in BMC Obesity, shows that this relationship also holds for people with quite severe obesity.

The researcher studied 853 patients from the Wharton Medical Clinics in the Greater Toronto Area, who  completed a clinical examination and maximal treadmill test. Patients were then categorized into fit and unfit based on age- and sex-categories and in terms of fatness based on BMI class.

Within the sample, 41% of participants with mild obesity (BMI<35) had high fitness whereas only 25% and 11% of the participants with moderate (BMI 35-40) and severe obesity (BMI>40), respectively, had high fitness.

Individuals with higher fitness tended to be younger and more likely to be female.

While overall fitness did not appear to be independently associated with most of the metabolic risk factors (except systolic blood pressure and triglycerides), the effect of fitness in patients with severe obesity was more pronounced. Thus, the prevalent relative risk for pre-clinical hypertension, hypertriglyceridemia and hypoalphalipoproteinemia and pre-diabetes was only elevated in the unfit moderate and severe obesity groups, and fitness groups were only significantly different in their relative risk for prevalent pre-clinical hypertension within the severe obesity group.

Similarly, high fitness was associated with smaller waist circumferences, with differences between high and low fitness being larger in those with severe obesity than with mild obesity.

Based on these findings, the researchers conclude that the favourable associations of having high fitness on health may be similar if not augmented in individuals with severe compared to mild obesity.

However, it is also apparent based on the rather low number of “fit” individuals in the severe obesity category (only about 1 in 10), that maintaining a high level of fitness proves to be more challenging the higher the BMI.

@DrSharma
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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Taxing Sugar-Sweetened Beverages To Prevent Obesity

In addition to the series of article on long-term outcomes in bariatric surgery, the 2018 special issue of JAMA on obesity, also features several articles discussing the potential role of taxing or otherwise regulating the use of sugar-sweetened beverages (SSB) as a policy measure to address obesity.

In a first article, Jennifer Pomeranz and colleagues discuss whether or not governments can in fact require health warnings on advertisements for sugar-sweetend beverages. The discussion focuses on an injunction issued by the Ninth Circuit Court on the enforcement of San Francisco’s requirement that sugar-sweetened beverage (SSB) advertisements display a health warning statement, finding that this law likely violated the First Amendment rights of advertisers of SSBs.

The background for this court decision was the fact that San Francisco passed a law requiring SSB advertisers to display: “WARNING: Drinking beverages with added sugar(s) contributes to obesity, diabetes, and tooth decay. This is a message from the City and County of San Francisco.

In its decision, the court felt that the proposed warning label was not scientifically accurate, as it focussed exclusively on “added sugar(s)” rather than sugars overall. It appears that there is no scientific evidence suggesting that “added sugars” are any more (or less) harmful than the “natural” sugar occurring in any other foods or beverages).

However, as the authors argue, warning on SSB may well be warranted as

“In addition to being a major source of added sugar in the US diet, the liquid form of SSBs could enable rapid consumption and digestion without the same satiety cues as solid foods. SSBs also contain no relevant ingredients to provide offsetting health benefits, in comparison with sweetened whole grain cereals, nut bars, yogurt, or other foods with added sugars, which can have healthful components. Furthermore, the associations of SSBs with weight gain, obesity, type 2 diabetes, and heart disease are each stronger and more consistent than for added sugars in solid foods. In addition, compared with other foods containing added sugars, SSBs are the only source for which randomized controlled trials have confirmed the observational link to weight gain.”

Another point of contention identified by the court was related to the fact that the warning stated harm irrespective of quantity and would have been more accurate had it included the term “overconsumption” or at leas the qualifier “may”.

Here, the authors argue that,

“health risks of SSBs increase monotonically. Thus, use of the word “overconsumption” would not be scientifically accurate because there is no clear threshold effect between SSB consumption and harm. Yet, due to potential individual variation in responses, incorporating the word “may” or “can” would be scientifically accurate and are used in alcohol and smokeless tobacco warnings.”

The third objection by the court was related to the proposed size and rectangular border requirements of the warning, which was considered to be “unduly burdensome” – a point that the authors concede could be dealt with by modify formatting requirements by slightly reducing size, permitting “hairline” borders, or using other methods to ensure prominence and conspicuousness.

.In a second article on the issue of SSBs, Lisa Powell and Matthew Maciejewski discuss the case for taxing SSBs, noting they are the largest contributor of added sugar in the US diet, accounting for approximately 6.5% of total daily calories among adults and 7.3% among youth (ages 2-19 years) and approached 8% to 9% of daily calories among minority populations and 9% to 10% among low-income households. In addition consumption of SSBs have been associated with obesity as well as type 2 diabetes, cardiovascular disease, dental caries, and osteoporosis.

As the authors point out, for SSB taxes to be effective, the increased cost of SSBs has to be passed on to the consumer (“pass-through) and the consumer has to respond by decreasing their consumption (“price elasticity”). In places where SSB taxes have been implemented (e.g. Mexico), both effects have been seen, suggesting that an SSB tax can indeed change consumer behaviours.

However, as the authors also note, so far there is little evidence directly demonstrating that such changes have translated into actual health outcomes (for obesity or otherwise).

Nevertheless, the authors feel that an SSB tax can effectively decrease the overall consumption of these beverages and should perhaps be extended even further to include all forms of sugary drinks including 100% fruit juice. For this approach to be broadly acceptable, it would also be important to dedicate any revenue from these taxes to specific educational or public health purposes.

Finally, a third article on this issue by John Cawley deals with an interesting “quasi experimental” pass-through effect of SSB taxes at the Philadelphia International Airport, which happens to straddle the city border, with some terminals in Philadelphia that are subject to the beverage tax (1.5 cents per ounce), and other terminals in Tinicum that are not.

The study included 31 stores: 21 on the taxed side of the airport (Philadelphia) and 10 on the untaxed side (Tinicum).

As the authors found, following the implementation of the SSB tax in Philadelphia, the average price of SSBs increased on both the taxed and untaxed side of the airport (albeit more so on the taxed side). Using only data for taxed stores, the percentage of the tax passed on to consumers was 93%. Overall, however, the price difference between the taxed and untaxed stores was about 0.83 cents per ounce (a 55% relative pass-through rate).

Thus, while the tax did have a significant effect on SSB pricing in Philadelphia, it appears that the non-taxed stores simply went along to increase their profit margins accordingly.

Whether or not these changes in pricing had any impact on actual SSB sales or consumption was not reported.

Together, these studies certainly support the statement by Powell and Maciejewski that

“SSB taxes are likely to remain controversial for some time and policy makers will have a number of issues to consider as they formulate and implement fiscal policies.”

Moreover,

“SSB taxation can only be one approach to what must be a multipronged public health strategy to reduce obesity via improved diets and increased activity. The fact that intake of SSBs has declined over the past decade and the obesity epidemic has continued unabated suggests that reducing SSBs alone is not the sole solution. Adults and youth who frequently consume SSBs are more likely to engage in other unhealthy behaviors (eg, inactivity, greater fast-food consumption), so population-based policies specifically targeting these behaviors need to be designed in concert with SSB taxes. Although SSB consumption remains high in the United States, particularly among vulnerable populations, and taxation is a viable tool for curbing its consumption, the long-run intended and unintended effects of SSB tax policy are yet to be determined. The debate on its merits as an effective tool to improve health outcomes will be greatly informed by rigorous evidence on consumption, sugar intake, and body weight both on average and within vulnerable populations (children, minorities, low-income individuals).”

@DrSharma
Edmonton, AB

 

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Obesity Reimagined: 2018 JAMA Theme Issue On Obesity

This week, JAMA revisits obesity with a dedicated theme issue, which includes a range of articles on obesity prevention and management (including several on the impact of taxing sugar-sweetened beverages and five original long-term studies on bariatric surgery).

In an accompanying editorial, Edward Livingston notes that,

“The approach to the prevention and treatment of obesity needs to be reimagined. The relentless increase in the rate of obesity suggests that the strategies used to date for prevention are simply not working.”

Also,

“From a population perspective, the increase in obesity over the past 4 decades has coincided with reductions in home cooking, greater reliance on preparing meals from packaged foods, the rise of fast foods and eating in restaurants, and a reduction in physical activity. There are excess calories in almost everything people eat in the modern era. Because of this, selecting one particular food type, like SSBs, for targeted reductions is not likely to influence obesity at the population level. Rather, there is a need to consider the entire food supply and gradually encourage people to be more aware of how many calories they ingest from all sources and encourage them to select foods resulting in fewer calories eaten on a daily basis. Perhaps tax policy could be used to encourage these behaviors, with taxes based on the calorie content of foods. Revenue generated from these taxes could be used to subsidize healthy foods to make them more affordable.”

Over the next few days, I will be reviewing about the individual articles and viewpoints included in this special issue.

In the meantime, the entire issue is available here.

@DrSharma
Edmonton, AB

 

 

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How The Body Weighs Itself – Evidence For A Bone “Gravitostat”

In my talks, I have often joked about how to best keep weight off – just carry around a backpack that contains the lost pounds to fool the body into thinking the weight is still there.

It turns out that what was intended as a joke, may in fact not be all too far from how the body actually regulates body weight.

As readers of these posts are well aware, body weight is tightly controlled by a complex neuroendocrine feedback system that effectively defends the body against weight loss (and somewhat, albeit less efficiently, protects against excessive weight gain).

Countless animal experiments (and human observations) show that following weight loss, more often than not, body weight is regained, generally precisely to the level of initial weight.

With the discovery of leptin in the early 90s, an important afferent part of this feedback system became clear. Loss of fat mass leads to a substantial decrease in leptin levels, which in turn results in increased appetite and decreased metabolic rate, both favouring weight regain and thus, restoration of body weight to initial levels.

Now, an international team of researchers led by John-Olov Jansson from the University of Gothenburg, Sweden, in a paper published in the Proceeding of the National Academy of Science (PNAS), provides compelling evidence for the existence of another afferent signal involved in body weight regulation – one derived from weight-bearing bones.

Prompted by observations that prolonged sedentariness can promote weight gain, independent of physical activity, the researchers hypothesised that,

“…there is a homeostat in the lower extremities regulating body weight with an impact on fat mass. Such a homeostat would (together with leptin) ensure sufficient whole body energy depots but still protect land-living animals from becoming too heavy. A prerequisite for such homeostatic regulation of body weight is that the integration center, which may be in the brain, receives afferent information from a body weight sensor. Thereafter, the integration center may adjust the body weight by acting on an effector.”

In a first series of experiments, the researchers observed that implanting a weight corresponding to about 15% of body weight into rodents (rats and mice), resulted in a rapid “spontaneous” adjustment in body weight so that the combined weight of the animal plus the weight implant corresponded more-or-less to that of control animals.

Within two weeks of implanting the weights, ∼80% of the increased loading was counteracted by reduced biological weight, largely due to reduced white adipose tissue (WAT), accompanied by a corresponding decrease in serum leptin levels. (Interestingly, this weight loss was also accompanied by a substantial improvement in insulin resistance and glucose homeostasis).

The decrease in “biological” body weight was mainly attributable to a reduction in caloric intake with no changes in fat oxidation, energy expenditure or physical activity.

Removal of the implanted weights resulted in rapid weight regain to initial levels, showing that the “weight sensor” was active in both directions.

Experiments showed that this “weight sensing” mechanism was largely independent of the leptin pathway and did not appear to involve grehlin, GLP-1, a-MSH, estrogen receptor-a, or the sympathetic nervous system.

Now for the interesting part: the observed effect of weight loading was not seen in mice depleted specifically of DMP1 osteocytes, demonstrating that the suppression of body weight by loading is dependent on osteocytes.

As the authors note, these findings are consistent with a growing body of data indicating that the skeleton is an endocrine organ that regulates energy and glucose metabolism. Indeed, it is well known that osteocytes can sense dynamic short term high-impact bone loading for local bone adaptation – now it appears, that osteocytes may also play a vital role in sensing overall body weight and signalling this to the brain centres that regulate energy balance and body weight.

Thus, in summary, not only have the authors provided compelling evidence for a “weight-sensing” role for bone osteocytes (presumably through their presence in the long weight-bearing bones of our lower extremities) but also provide a plausible biological explanation for the weight gain and change in fat mass seen with prolonged sedentariness (which literally takes the weight off the bone).

These findings may also finally explain why rats held at increased gravity for extended periods of time (simulated G2) become lean even when their energy intake matches their expenditure.

Perhaps, carrying around a heavy backpack may indeed help with long-term weight loss maintenance after all – who knew?

@DrSharma
Berlin, D

Hat tip to Jean-Philippe Chaput for alerting me to this article

 

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