Follow me on

Why Calories Still Matter

Over the past decade or so, alternative explanations for the rise in obesity rates, that de-emphasize the role of caloric intake vs. the role of specific nutrients, have had a field day.   Leading amongst these, no doubt, is the Carbohydrate-Insulin-Model (CIM) of obesity, whereby, carbs stimulate insulin release, which in turn stimulates expansion of adipose tissue, which in turn leads to insulin resistance, resulting in even higher insulin levels, ultimately resulting in a vicious cycle that can only be interrupted by religious adherence to a low-carb diet.  Although this model has had broad populistic appeal, spawning a whole industry of best-sellers, low-carb products, and even treatment programs built around this paradigm, as pointed out in rather comprehensive article by Kevin Hall and a host of notable obesity experts, published in the American Journal of Nutrition, CIM (which has undergone several modifications since its inception), does not quite concur with all of the pre-clinical and clinical evidence.  In this paper, the authors make a rather compelling argument in favor of the Energy-Balance-Model (EBM), which pretty much aligns with virtually everything we know about the science of body weight regulation.  According to the authors, “The EBM proposes that the brain is the primary organ responsible for body weight regulation via integration of external signals from the food environment along with internal signals from peripheral organs to control food intake. Specific brain regions, such as the hypothalamus, basal ganglia, and the brainstem modulate food intake below our conscious awareness via complex endocrine, metabolic, and nervous system signals acting in response to the body’s dynamic energy needs as well as environmental influences…..whereas day-to-day energy intake and energy balance of an individual can be highly variable, neural regulation of energy balance is generally achieved over prolonged time scales.”   The key term in all of this is “positive energy balance”, without which there can be no accumulation of excess weight. Ergo, as calories are  the currency of energy balance, there can be no excess energy balance without excess calories.  As the authors go on to explain, the physiological processes that determine caloric intake are subject to a host of biological and environmental perturbations, explaining both the differences in individual susceptibility as well as the wide variability in shape and size evident even in populations with similar environmental exposure. Furthermore, this model also explains the wide variation in response  to dietary, pharmacological, or even surgical manipulations that… Read More »

Full Post

Will the Weight-Loss Results for Tirzepatide Shrink the Field for Future Anti-Obesity Treatments?

At the 2022 European Congress on Obesity, which I attended over the last few days, there was much buzz about the rather spectacular 22% average weight loss achieved with the dual GIP-GLP-1 agonist tirzepatide – a degree of weight loss that is not far from matching the weight-loss outcomes of patients undergoing metabolic surgery. Clearly these results  are shifting the benchmark for what we can expect from future anti-obesity medications.  While we await the full publication of these results and the outcomes of the other trials in the SURMOUNT program, it may be prudent to speculate what these results mean for compounds and treatment options for obesity currently in the pipeline.  At last count, there were over twenty different anti-obesity compounds across a range of modes of action at various stages of clinical development.  Some may well have the capacity to match the degree of weight loss seen with tirzepatide, but matching or even exceeding the 20% mark is likely to be a tall order for most.  Thus, no doubt many anti-obesity medication development programs may now be seriously reconsidering or even abandoning current candidates.   This would be unfortunate!  For one, given the heterogeneity of pharmacodynamics responses, there will always be individuals for whom tirzepatide may either not work or not be well tolerated, leaving ample room for less effective medications that may do the job for these patients.  More importantly, it may well be that, although these compounds may not be effective enough when used alone, they may be ideal candidates for add-on or combination treatments.  An example that comes to mind would be the combination of the long-acting amylin analogue cagrilinitide with the long-acting GLP-1 analogue semaglutide, for which we have early data suggesting that it may well match or even exceed the weight loss seen with tirzepatide.  Given that combination treatment is now the most common approach to treating a host of chronic diseases including hypertension, diabetes, heart or kidney disease, there is no reason why this would not be the case for obesity.   While each component of these combinations may only be moderately effective on their own, they may well have synergistic effects that more than add up (as seen for buproprion plus naltrexone) or allow the use of lower doses, thus improving safety and tolerability (as with the combination of low-dose phentermine and low-dose topiramate).  Thus, rather than abandoning compounds currently in the pipelines just because… Read More »

Full Post

Zooming Forward to New Connections

This week I am attending the joint meeting of the European Association for the Study of Obesity (EASO) and the International Federation for the Surgery of Obesity and Metabolic Disorders – European Chapter (IFSO-EC) in Maastricht, held under the timely title ZoomForward2022. Indeed, after two years of virtual meetings on Zoom and other platforms, it is finally time to meet friends and colleagues again in-person.  Given the hiatus, for many young students, postdocs, residents, and other trainees, this may be their first opportunity to meet and connect with their peers in-person.  I therefore thought it would be appropriate to remind everyone of a previous post on how to get the most out of scientific meetings – a guide for early career participants.  The key messages, that I think will be most useful to anyone starting out their careers (and perhaps for some older folks) are summarized in this video on YouTube. Hopefully, these tips, based on my own strategies and tactics, that have helped me throughout my career, will help you get the most out of the next few days (or any other scientific meeting you may attend in the future). See you in Maastricht.DrSharma,Berlin, D

Full Post

Deep Dive Into Obesity Phenotypes

Last week, in my capacity as a Strategic Advisor, I had the pleasure of attending the SOPHIA general assembly in Favrholm, just outside of Copenhagen. SOPHIA stands for the Stratification of Obesity Phenotypes to Optimise Future Therapies, and consists of a large research consortium that includes thirty-one international members from academia, industry, and NGOs. With funding support of around € 16 million from the Innovative Medicines Initiative (IMI), a joint undertaking of the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA), T1D Exchange, JDRF, International Diabetes Federation (IDF), and Obesity Action Coalition, the SOPHIA research consortium aims to find better solutions to address obesity and reduce its consequences.  The eight work packages range over a variety of issues ranging from technical challenges like creating a confederation of large harmonised databases to allow sophisticated analyses of phenotypes, trajectories and outcomes, specific projects on the relationship between obesity and diabetes (both type 1 and 2), exploration of surgical outcomes, to important work on better understanding the patient voice and incorporating their views and needs throughout the various projects.  Now in its 3rd year, the progress in all work packages has been remarkable (despite the complications due to COVID) and one of our strategic recommendations has been to perhaps explore opportunities to identify and incorporate additional data sets, particularly in the areas of mental, cardiovascular, and reproductive health. Researchers working in these areas, who may be interested in contributing datasets to this initiative can contact the SOPHIA office via the project website. Overall, this joint effort, guided by the patient voice, is certainly exciting and innovative and I look forward to several of the work packages presenting their findings during the 28th European Congress on Obesity in Maastricht later this week.  @DrSharmaBerlin, D

Full Post

Is Obesity Best Managed by Generalists?

Obesity is complex and few medical professionals have any formal background or training in obesity management. Furthermore, the range of problems that patients can present with (potentially affecting every organ system and mental health as well as socio-ecomonic aspects), is rather broad, thus requiring expertise across a wide range of disciplines.  These circumstances have of course fostered the notion that obesity is best managed by specialists – ideally working in a multidisciplinary team that includes dietitians, exercise specialists and clinical psychologists. While there is little doubt that health care providers, who have undergone specific training in obesity medicine, will likely do a much better job of managing patients with obesity that a doctor with no such experience or training, it is quite unrealistic to expect that we will ever have enough obesity specialists to address the needs of the millions of patients living with this chronic disease.  Indeed, the vast number of people living with obesity means that it would be entirely unrealistic to expect that any speciality, be it endocrinology or cardiology, will ever have the capacity to handle this vast demand.  Thus, as with other common chronic diseases (such as hypertension or diabetes), the vast majority of patients with obesity will have to be managed by their family doctor in primary care.  As it turns out, this may not be a bad thing. In fact, given the broad nature of medical and psychosocial challenges presented by these patients, the fact that it can occur throughout the lifespan, and the need for life-long management, one may well argue that family medicine is indeed the discipline best suited to managing the vast majority of patients living with obesity.   In contrast to specialists, who by nature tend to focus their care on their respective specialty, family doctors tend to be generalists who are just as comfortable managing hypertension or diabetes as they are managing depression, anxiety, chronic pain, or any of the other multitude of issues that can make obesity management challenging.  Thus, while a cardiologist may primarily focus on controlling hypertension, a diabetologist may focus on optimising glycemic control, a pulmonologist may focus on sleep apnea, a hepatologist may focus on NAFLD, and a psychiatrist may focus on depression or ADHD, a family doctor would probably step back and look at the “big picture” thereby prioritising and integrating the various aspects of care across disciplines, while also taking into consideration… Read More »

Full Post

The Complexities of Nipping Obesity in the Bud

Later today, I will have the pleasure of moderating a live-streamed educational panel (Fokus Adipositas), with my German colleagues Martin Wabitsch, Johannes Hebebrand and Mattias Blueher,  on the issue of managing obesity in kids and adolescents.  Given the topic, I have no doubt that the issue of nipping the obesity epidemic  in the bud by focusing our attention on kids will come up. While in theory, this is certainly a good idea, in reality, this is much easier said than done.  As in adults, the root causes of weight gain in kids is just as complex with a wide range of environmental, socio-economic, psychological, and biological factors often working together to promote excessive weight gain.  As in adults, childhood obesity is associated with clear health risks ranging from the psychological impact of bullying to the cardiometabolic and other pathophysiological consequences of excess weight.  As in adults, by the time the kids get to be seen by an obesity specialist, their condition has generally progressed to a point where there is little doubt for the need of treatment.  However, in contrast to adults, treating obesity in kids is a whole lot more delicate and challenging.  For one, if anyone believes that behavioural modification in an adult is already difficult enough, trying to implement such modifications in kids, especially teens, is a whole order of magnitude harder.  Indeed, trying to change health behaviours without precipitating unhealthy weight-obsession, inducing harmful weight-control behaviours, or reinforcing body-dissatisfaction, is even more challenging in kids than in adults.  Furthermore, while we have now largely accepted that effective obesity treatment in adults will likely require medical or even surgical treatment – both options are limited when it comes to kids.  Although there are now a couple of anti-obesity medications approved for use in kids (such as liraglutide and setmelanotide), and despite the fact that bariatric surgery in adolescents is a lot more common today than ever before, these options are generally reserved for the most severe cases and the vast majority of kids (or their parents and most doctors) would not even remotely consider these as options.  Thus, I certainly do not envy my pediatric colleagues when it comes to their ability to manage childhood obesity.  Clearly, when people talk about nipping the obesity epidemic in the bud by focusing our attention on childhood obesity, they are apparently unaware of just how limited our ability to provide effective… Read More »

Full Post

Are We Moving the Needle on Weight Bias?

Twenty years ago, when I first became aware of the issue of weight bias as an important barrier to effective obesity prevention, treatment and research policies, there wasn’t really much in terms of research, evidence, or advocacy to go on. Back then, my friend and colleague (and fellow Canadian) Rebecca Puhl, then at the Rudd Center for Food Policy, was virtually the lone “she-wolf” in the wilderness trying her best to attract attention to this topic. Reading her papers and speaking to my patients and colleagues, it was clear to me then, that in order to move forward in terms of respectful and meaningful obesity prevention policies, improving access to obesity treatments, and increasing funding allocations towards obesity research, tackling weight-bias and discrimination needed to be a central focus for the newly created Canadian Obesity Network (now Obesity Canada).  Just how far along we have come in terms of broader awareness of this issue is nicely outlined in a paper by Adrian Brown and colleagues in a paper published online in eClincal Medicine as part of The Lancet Discovery Science series.  The paper summarises the current evidence to support the pervasiveness, impact, and implications of weight bias in the context of policy, healthcare, media, workplaces, and education. I was, of course, particularly tickled by the fact that the authors chose to highlight our efforts in Canada (e.g. the EveryBODY Matters Collaborative) to tackle weight bias on multiple fronts using complementary as well as consistent and persistent strategies, which have to date resulted in notable changes within Canada and beyond. At the end, the authors propose short- and medium-term recommendations to address weight stigma in an effort to end weight stigma and discrimination accross society. These include, changing the narrative around obesity and recognising it as a chronic relapsing disease, the need for a non-weight-based definition of obesity that focuses on health rather than size, the importance of using proper language, and reframing health policies to address the wider determinants of health with a focus on health behaviours rather than weight loss.  At a clinical level (not extensively discussed in this paper), I would humbly add, we need policies to ensure that every person living with obesity has the same access to evidence based treatments that must include behavioural modification, medications, and bariatric surgery, in a manner comparable to treatment access for other chronic diseases like diabetes or hypetension.  Although we… Read More »

Full Post

Does the Edmonton Obesity Staging System Hold Up in the Real World?

Back in 2008, when I first proposed what is now widely referred to as the Edmonton Obesity Staging System (EOSS) as a means of classifying the severity of obesity beyond BMI, I could not have imagined how readily this concept would be embraced by those of us interested in clinical obesity management.  A current PubMed search reveals almost 60 published articles on the use of EOSS to determine risk and outcomes in a variety of populations and settings, consistently showing that EOSS does a far better job of predicting morbidity, mortality, surgical complications, fertility rates, occupational function, hospital stay, and even cost than BMI.  But how practical is the application of EOSS to real-world data in primary care? This is now the topic of a paper by Rukia Swaleh and colleagues from the University of Alberta, published in CMAJ open. The paper describes the development of a clinical dashboard that calculates and displays the relation between BMI and EOSS and the prevalence of related comorbidities based on cross-sectional data in over 30,000 patients within the Northern Alberta Primary Care Network and the Canadian Primary Care Sentinal Surveillance Network, who were at least 18 years of age with BMI between 30 and 60 and visited a network clinic between July 2016 and July 2019.  This EOSS dashboard provides an interactive tool that readily identifies and characterizes patients based on EOSS stage within a primary care practice, thus prompting better surveillance, prevention, and management of patients with obesity and related complications.  Applying these analyses to the study population revealed several interesting findings. Firstly, BMI class distribution appeared to be rather similar across EOSS stages, confirming once again that BMI is not a useful or reliable measure of obesity severity.  Secondly, age alone described 31% of the variation in EOSS stages. In contrast, sex and BMI explained very little of the variation in EOSS stages, together accounting for just over 1% of the variation. Thirdly, hypertension, dyslipidemia and diabetes (and their complications) were the leading drivers of higher EOSS stages. The EOSS tool provides several useful features that can be used to further characterize and analyse patients down to seeing tests, medical prescriptions, and last date of visit for individual patients based on EOSS stage.  Thus, this paper not only shows that one can develop electronic EOSS tools based on real-world practice data but also shows how these data can be used to… Read More »

Full Post