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Even Correlations Based On Billions Of Data Points Do Not Prove Causation
Readers may have already heard about a recent study by Tim Althoff and colleagues from Stanford University, published in Nature, that analyses physical activity data collected from smart phones consisting of 68 million days of physical activity for 717,527 people, in 111 countries (only 46 of which were included in the study). As one may expect, not only do activity levels vary widely across countries but also substantially within countries (which in general terms, the authors refer to as “activity inequality”). It turns out that activity inequality and not actual levels of activity predict obesity rates (based on BMI). Furthermore, “By quantifying the relationship between activity and obesity at the individual level, we were able to determine why a country’s activity inequality is a better predictor of obesity than average activity level. We find that the prevalence of obesity increases more rapidly for females than males as activity decreases. And while lower activity is associated with a substantial increase in obesity prevalence for low-activity individuals, there is little change in obesity prevalence among high-activity individuals. So given two countries with identical average activity levels, the country with higher activity inequality will have a greater fraction of low-activity individuals, many of them female, leading to higher obesity than predicted from average activity levels alone. These findings are analogous to the phenomenon revealed in past studies of the effects of income inequality on health, whereby a relatively small change in income (in our case, activity) for an individual at the bottom of the distribution can lead to substantial improvements in health. On the basis of our model relating activity inequality to obesity prevalence, we also performed a simulation experiment which, assuming perfect information (Methods), suggests that interventions focused on reducing activity inequality could result in a reduction in obesity prevalence up to four times greater than in population-wide approaches.” The authors go on to discuss various limitation of their study but fail to mention the biggest limitation of all, the simple fact that correlations, no matter how strong or how large the data set, simply cannot prove causality. Thus, while the data does prove the point that you can do all sorts of interesting analyses when you have large data sets, it simply does not not prove that activity levels (or activity inequality for that matter) actually has much to do with obesity at all. Indeed, one could think of a number of confounders… Read More »
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… Read More »
Congratulations to Canadian Obesity Network Summer School Class of 2017
All of last week (now for the 11th time), I was teaching at the Canadian Obesity Network’s Obesity Summer School (formerly known as “boot camp”). As always, it’s just wonderful to meet such a group of young and enthusiastic trainees, who (as most past “campers” have experienced) have such a bright future ahead of them. Obesity research, prevention, and management will certainly be in good hands. Congratulations to all graduates – you’ve joined a pretty exclusive group of colleagues from around the world. @DrSharma Edmonton, AB
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… Read More »
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… Read More »
Use of Low Calorie Diets in Type 2 Diabetes
Managing weight in patients with type 2 diabetes (most of who have significant overweight or obesity) is always challenging, not least because many medications used to treat diabetes can also promote weight gain. Now, a paper by Judy Shiau and colleagues from the University of Ottawa, in a paper published in the Canadian Journal of Diabetes, present the results of a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes at 6 months on a low-calorie diet program. The program (week 1 to week 26) included mandatory weekly group sessions led by a dietitian, behaviour therapist or exercise therapist. All patients received OPTIFAST ®900 as full meal replacements (MR) starting at week 2. Patients consume 4 MR shakes per day for a total of 900 kcal per day, a regimen that is high in proteins (90g/day) and moderate in carbohydrates (67 g/day). Patients with initial body mass indexes (BMIs) of 33 kg/m2 or higher commited to 12 weeks of full MRs, while patients with initial BMIs below 33 started with 6 weeks of full MRs and the option to increase to up to 12 weeks of full MRs. Once patients completed their full MR regimen, there was a 5-week transition period to regular food, typically followed by a maintenance diet, as determined in a one-on- one dietitian counselling session. As glycemic control improved with weight loss, anti-diabetes medications were adjusted or discontinued, thereby stopping any weight-gain-promoting medications first. As the authors note, “At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92% sulfonureas, 87% insulins, 79% thiazolidinediones, 78% alpha-glucosidase inhibitors, 50% meglitinides, 33% dipeptidyl peptidase-4 (DPP-4) inhibitors and 33% metformin. At 6 months, compared with baseline, A1C levels improved significantly and at 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002).” Thus, this paper shows that, a low-calorie meal replacement program can substantially improve glycemic control and reduce the need for anti-diabetes medications. Unfortunately, as participants were transitioned to community care at 6 months, little is know about how long these effects last. Nevertheless, with the increasing availability and use of weight-neutral or even weight-reducing anti-diabetes medications, one may expect that some of these effects can be… Read More »
What Do Health Professionals Need To Know About Obesity?
Achieving and maintaining competencies is an ongoing challenge for all health professionals. But in an area like obesity, where most will have received rather rudimentary training (if any), most health professionals will likely be starting from scratch. So what exactly must you expect of a health professional involved in the care of individuals living with obesity. This is the subject of a white paper on “Provider Competencies for the Prevention and Management of Obesity“, developed with support from the Robert Wood Johnson Foundation. The panel of authors led by Don Bradley (Duke) and William Dietz (George Washington) included representatives from over 20 national (US) professional organisations. The competencies expected cover the following 10 topics: Competencies for Core Obesity Knowledge 1.0 Demonstrate a working knowledge of obesity as a disease 2.0 Demonstrate a working knowledge of the epidemiology of the obesity epidemic 3.0 Describe the disparate burden of obesity and approaches to mitigate it Competencies for Interprofessional Obesity Care 4.0 Describe the benefits of working interprofessionally to address obesity to achieve results that cannot be achieved by a single health professional 5.0 Apply the skills necessary for effective interprofessional collaboration and integration of clinical and community care for obesity Competencies for Patient Interactions Related to Obesity 6.0 Use patient-centered communication when working with individuals with obesity and others 7.0 Employ strategies to minimize bias towards and discrimination against people with obesity, including weight, body habitus, and the causes of obesity 8.0 Implement a range of accommodations and safety measures specific to people with obesity 9.0 Utilize evidence-based care/services for people with obesity or at risk for obesity 10.0 Provide evidence-based care/services for people with obesity comorbidities Some of the topics include further subtopics that are deemed especially relevant. Thus, for e.g., topic 6.o, regarding communication, includes the following sub-competencies: 6.1 Discuss obesity in a non-judgmental manner using person-first language in all communications 6.2 Incorporate the environmental, social, emotional, and cultural context of obesity into conversations with people with obesity 6.3 Use person- and family-centered communication (e.g., using active listening, empathy, autonomy support/shared decision making) to engage the patient and others Similarly, topic 7.0, regarding the issue of weight bias and discrimination, includes the following sub-competencies: 7.1 Describe the ways in which weight bias and stigma impact health and wellbeing 7.2 Recognize and mitigate personal biases 7.3 Recognize and mitigate the weight biases of others This is clearly a forward-thinking outline of competencies that we will… Read More »
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