In this report, we bring you our full coverage of the 2016 European Obesity Summit (EOS), held this year in beautiful Gothenburg, Sweden (where the sun was shining for 18 hours each day!). This conference represents the first annual merging of the congresses of the European Association for the Study of Obesity (EASO) (who hosted the European Congress of Obesity [ECO] last year – see our coverage here) and the International Federation for the Surgery of Obesity (IFSO) European Chapter (IFSO-EC Annual Congress). The below report presents in-depth coverage and commentary on this year’s most compelling EOS presentations. To guide you, it is organized into the following categories: (i) Obesity Pharmacotherapies; (ii) Surgical Methods for the Treatment of Obesity; (iii) Obesity and the Brain; and (iv) Additional Topics: Basic Science, Public Health, Lifestyle, and Behavior; and (v) Exhibit Hall. We’ve highlighted in yellow any presentations and commentary that we found particularly notable.
- Detailed Discussion and Commentary
- Obesity Pharmacotherapies
- Incretin Conjugates
- Early Weight Loss Responders to Liraglutide 3.0 mg Achieved Greater Weight Loss and Regression to Normoglycaemia, and Reduced Development of T2D At 3 Years, Versus Early Non-Responders in the SCALE Obesity and Prediabetes Trial
- Novel Drug Targets – Lessons from Bariatric Surgery
- Surgical Methods for the Treatment of Obesity
- Lessons from SOS
- Critical Evaluation of Metabolic Surgery in Obese Diabetic Patients
- Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes
- Aspiration Therapy for Obesity: Two Year Results and Quality of Life
- Improvements in NAFLD
- Obesity and the Brain
- Leptin Suppresses the Pleasure of Eating
- The Role of Non-Neuronal Cells in Energy Balance
- A Neural Basis for MC4 Receptor-Regulated Appetite
- Additional Topics: Basic Science, Public Health, Lifestyle, and Behavior
- Using Epigenetics
- Can We Learn Anything from Omics?
- Metabolically Healthy Obesity?
- Obesity is a New Major Cause of Cancer
- Promising Practices to Address Weight Stigma
- The Preview Intervention Study: How Does 8-Weeks Weight Loss and 4 Months Weight Maintenance Phase INfluence T2D Risk Factors?
- Mobile and Wireless Technology (Mhealth) to Combat Child and Youth Obesity: Exploring The Scope For Prevention And Treatment
- Exhibit Hall
- Obesity Pharmacotherapies
Detailed Discussion and Commentary
Timo Müller, MD (Helmholtz Diabetes Center, Germany)
Dr. Timo Müller expressed enthusiasm for unimolecular co-agonist peptides as well as peptide-mediated nuclear hormone delivery as promising novel approaches in obesity and diabetes pharmacotherapies. Specifically, regarding co-agonist peptides, he pointed to the promise of GLP-1/glucagon co-agonism and GLP-1/GIP/glucagon tri-agonism, as he demonstrated the positive findings of these candidates in rodents, primates, and humans. He highlighted that the tri-agonism approach has shown to have superiority compared to dual incretin co-agonism, noting its ability to exclusively reduce fat mass (having no effect on lean mass) and to work on each receptor with greater potency. Dr. Müller then emphasized how peptide-mediated nuclear hormone delivery and its impressive selectivity can help expand the biological toolbox for selected nuclear hormones. Providing specific examples, he shared the promising data around targeted estrogen delivery using GLP-1, noting the positive effects on body weight and blood glucose with no mitogenic effects on the uterus – see our past coverage of this approach at the recent Levine-Riggs meeting. In addition, Dr. Müller touched on glucagon-mediated delivery of thyroid hormone T3: while he noted that this has very little effect on body weight, he explained that this therapy improves cholesterol handling, avoids cardiac hypertrophy, and limits negative feedback on the heart. With the selectivity advantages of this kind of hormone delivery, we can imagine that this therapeutic area may also be potentially appealing on the safety and tolerability front and opens up a new frontier of how to target various mechanisms at one time in a disease as complex as obesity.
- In the Q&A of a Novo Nordisk-supported corporate symposium, Dr. Luc Van Gaal (Antwerp Hospital, Belgium) similarly called attention to the promise of combination therapies. He noted that combination approaches can block the compensatory mechanisms with some drugs. Specifically, he characterized SGLT-2 inhibitors in combination with GLP-1 agonists as a promising option, stating that some trials are already investigating this approach – see commentary from China CODHy expressing similar enthusiasm for this therapy. In addition, Dr. Van Gaal highlighted the dual and triple co-agonism of GIP and glucagon as potentially very positive combinations, stating that, “for the long-term, I think that combined peptide therapy may be the future for our patients with obesity.”
S Madsbad, F Greenway, D Lau, P O’Neil, J Wilding, P Jacobsen, T Skjøth, and K Fujioka
Novo Nordisk presented a poster with new three-year data from the SCALE Obesity and Prediabetes trial, showing that early responders to Saxenda (liraglutide 3.0 mg) achieved greater improvements in weight loss, glycemic parameters, and cardiometabolic risk factors compared to early non-responders. As background, participants treated with Saxenda who lost 5% or more of their body weight at 16 weeks were classified as “early responders” – at 16 weeks, 68% of the Saxenda group were early responders vs. 22% of the placebo group. This impressive new analysis demonstrated that at week 160, early responders who completed the trial (n=580) achieved an average weight loss of 8.6% vs. 2.9% among early non-responders (n=210). When looking at glycemic measures, somewhat more early responders achieved regression to normoglycemia when compared to early non-responders (70% vs. 55%); early responders also experienced a very significant reduction in the development of type 2 diabetes compared to early non-responders (0.5% vs. 3.2%). In addition, Saxenda early responders experienced greater improvements in systolic blood pressure (-3.7 vs. -3.3 mmHg) and in health-related quality of life measures (IWQoL-Lite score 13.4 vs. 9.5) compared to early non-responders. The new analysis’ safety and tolerability findings were similar to previous analyses, and adverse event rates were similar between early responders and non-responders, with GI-related adverse events being the most common in both groups. Notably, gallbladder disorders were more frequent in early responders (6.3% vs. 2.2%) – potentially a consequence of rapid weight loss, this came as a surprise. This longer-term follow-up of early response further supports the 56-week findings of an early responder analysis presented at ADA 2015 and speaks to how powerful it can be to match the right patient to the right treatment option. As the field continues to seek insight on how to identify best predictors of treatment response, we think it is important to consider early weight loss as a main factor in treatment long-term decisions.
Novel Drug Targets – Lessons from Bariatric Surgery
Carel Le Roux, MD (University College Dublin, Ireland)
Dr. Carel Le Roux commented that it will be challenging to develop a therapy mimicking bariatric surgery, as he discussed the lessons we can apply to novel drug targets. Opening his presentation, Dr. Le Roux highlighted that there is no “silver bullet” to obesity therapy when it comes to mimicking surgery’s impressive benefits, as he reviewed the complexity of bariatric surgery. He first stressed that “all of the effects of surgery are in the brain,” labeling this as the most important learning point from surgery. Delving into more specifics, Dr. Le Roux emphasized that in developing new therapies, it is important to work off of how people feel less hungry and more satisfied regarding food consumption post-surgery. In this realm, he pointed to the changes in hormone levels and the suggestion that surgery is allowing multiple gut responses. In addition, Dr. Le Roux noted the reduced activation in the brain’s reward system in response to high-calorie foods following gastric bypass surgery, stressing that in the search for novel drug targets, reward centers will need to be changed. He concluded by hypothesizing that surgery provides the framework to allow patients to come down to a new set point, as the operation is governed by many physiological factors that ultimately help hold the patient in that new set point after the surgery. We agree that with these many physiological factors, surgery represents a very complex web of changes that will require combination drug approaches and likely multi-modal therapy and more to mimic these effects in a less invasive therapeutic approach. For more on the latest of approaches we are exploring within the brain (featured here again as the star of the show), please see our interview with University of Washington’s Dr. Michael Schwartz.
Surgical Methods for the Treatment of Obesity
Lessons from SOS
Lena Carlsson, MD, PhD (University of Gothenburg, Sweden)
In the joint opening plenary lecture, Dr. Lena Carlsson presented new data from the Swedish Obese Subjects (SOS) study on increased suicide risk after bariatric surgery. At a median follow-up of 18 years, there were nine completed suicides in the surgery group, compared to three in the control group. Expanding these data to number of completed or attempted suicides, Dr. Carlsson reported that the surgery group experienced 87 completed or attempted suicide events vs. 48 in the control group. Due to this difference, Dr. Carlsson then shared that her research group examined suicide in a separate cohort, presenting data from the Scandinavian Obesity Surgery Registry (SOReg) (n=14,113 gastric-bypass patients) and the Itrim cohort (n=14,113 individuals treated with low/very-low-calorie-diets). These two populations were recruited between 2006 and 2013 and were matched on a 1:1 basis on age, sex, history of attempted suicide, psychiatric disorders, substance abuse, psychiatric drug use, and treatment year, with a median follow-up of 2.8 years. According to Dr. Carlsson, in this new cohort, the surgery and diet groups had 14 and 4 completed suicides, respectively; similarly, the surgery group had 140 completed or attempted suicide events vs. 59 in the diet group. In addition, the increased suicide risk reportedly remained when analyzing patients free of baseline psychiatric disorders. As these new data come from one of the longest and largest studies in surgery, they confirm the risk of suicide with bariatric surgery that has recently come to light (see the recent JAMA article on this) and point to a major safety signal that needs to be critically addressed. We would be curious to see a closer analysis on whether there is any correlation between weight loss, weight maintenance, and weight regain, and which patients attempt or complete suicide. While Dr. Carlsson did not provide hypotheses on mechanisms of this increased risk, we would guess that surgery’s effects on the reward system could be at play. As bariatric surgery is recognized in guidelines as a potential treatment for diabetes (see the new consensus statement in Diabetes Care) and gains more attention, it will certainly be important to see how this safety signal will affect discussions on broader use of the surgery in coming years.
Critical Evaluation of Metabolic Surgery in Obese Diabetic Patients
Guntram Schernthaner, MD (Rudolfstiftung Hospital, Vienna, Austria)
Dr. Guntram Schernthaner provided a critical evaluation of metabolic surgery in patients with obesity and type 2 diabetes, concluding that due its associated risks, surgery is only an option when patients are properly selected. He noted that while remission of diabetes tends to occur following bariatric surgery, patients often relapse over time. According to Dr. Schernthaner, in the Swedish Obese Subjects (SOS) study, 72% of the surgery group achieved type 2 diabetes remission at two years post-surgery; however, this declined to 39% after 10 years and 30% after 15 years. Although 30% may sound fairly low, on a population level, a 30% reduction is still very meaningful. Furthermore, Dr. Schernthaner shared that patients tend to experience weight regain, malnutrition, deficiencies in Vitamin D, and increased risk of bone fractures, anemia, and hypoglycemia following bariatric surgery. He discussed the increased risk of suicide, referring to a recent population-based cohort study demonstrating that self-harm emergencies significantly increase after bariatric surgery (3.63 per 1,000 patient-years) compared to before surgery (2.33 per 1000 patient-years). This is extremely concerning. The findings showed that the most common form of attempted suicide was self-poisoning of medications (73%) and importantly, over 90% of all self-harm emergencies occurred in patients diagnosed as having a mental health disorder during the five years pre-surgery, making it clear that there need to be psychological screening prior to the procedure. As bariatric surgery continues to be discussed in the context of type 2 diabetes treatment, (see the new consensus statement in Diabetes Care), it is certainly important to consider which patients are most appropriate for surgery and to not make sweeping generalizations on the procedure’s benefits.
Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes
David Cummings, MD (University of Washington, Seattle, WA)
Dr. David Cummings presented new snapshots of brief topline results of the COSMID (Comparison of Surgery vs. Medicines for Indian Diabetes) trial, demonstrating similar positive efficacy of bariatric/metabolic surgery in the South Asian population. After stressing surgery’s benefits across BMI levels, Dr. Cummings highlighted that South Asians are known to have increased diabetes risk at lower BMI levels, explaining his rationale for conducting the COSMID trial – a randomized controlled trial comparing surgery vs. medical/lifestyle intervention, specifically in the Asian Indian population. He presented topline results from the trial, showing that at two years after gastric bypass, the surgery group achieved significantly greater reductions in A1c (~3% vs. ~1.5% from baseline A1c of ~9.5%), and in the percentage of participants remaining on diabetes medications (45% of surgery group on medication vs. ~85% of medical therapy group on medication). In addition, at two years, 60% of the surgery group achieved diabetes remission whereas only 2.5% of the medical therapy group did. These findings are promising in showing that bariatric/metabolic surgery is applicable to a broader population with regards to racial/ethnic groups. We applaud Dr. Cummings for increasing the diversity of patients involved in these very important clinical trials, as obesity and diabetes are becoming global epidemics. In particular, the largest populations of people with diabetes are in South and East Asia, yet bariatric/metabolic surgery, which powerfully ameliorates this disease, is in its infancy there. For more on Dr. Cummings’ insights on surgery and this specific study, check out our comprehensive interview with him from 2013. And see the full results from ADA of this trial for more details.
Aspiration Therapy for Obesity: Two Year Results and Quality of Life
Erik Norén, MD (Blekinge County Hospital, Karlskrona, Sweden)
Dr. Erik Norén presented positive two-year weight loss and quality of life data with the AspireAssist Aspiration Therapy System. Results from a prospective, observational study of people with obesity (baseline BMI 39.8 kg/m2) demonstrated that after one year, patients (n=20) lost an average 54% of their excess weight and after two years, patients (n=15) achieved an average of 62% excess weight loss. Quality of life was evaluated using the EuroQoL five-dimension questionnaire (EQ-5D) and after one year, improvements in quality of life were observed despite the presence of a gastrostoma and the need to perform drainage of stomach contents three times daily. Importantly, there were no serious adverse events and no potassium disorders. Dr. Norén also shared that his team is conducting an ongoing five-year study comparing weight loss in patients receiving Aspiration Therapy to those receiving gastric bypass surgery. We look forward to seeing these results to see if patients are able to maintain weight loss through five years with the AspireAssist, considering that weight maintenance has been shown to be one of the most challenging aspects of weight management. While not yet approved in the US, the AspireAssist may prove to be a promising addition to the armamentarium for obesity, as we hope to see a greater number of devices on board to fuel collaborations across treatment modalities. The FDA recently approved the AspireAssist – see our coverage of the news from June for more.
Improvements in NAFLD
Francois Pattou, MD (University of Lille, France)
In a closing session on bariatric surgery, Dr. Francois Pattou discussed the impressive remission of non-alcoholic fatty liver disease (NAFLD) following surgery. Dr. Pattou opened by stressing that as the prevalence of obesity has increased, so has the prevalence of NAFLD, which he estimated at 20%. According to him, while the pathogenesis is not understood, we do know that NAFLD will eventually progress to non-alcoholic steatohepatitis (NASH) and finally cirrhosis, if not addressed. With this background, Dr. Pattou presented data from a one-year histological study (n=109) of patients with NASH who underwent bariatric surgery; at baseline, two-thirds of these patients also had diabetes. Following bariatric surgery, 85% of the patients had remission of NASH and in some cases, improvements in fibrosis were also shown. While he noted that Roux-en-Y gastric bypass (RYGB) led to greater improvements than gastric banding did, he emphasized that the improvements in NASH were primarily driven by the subsequent weight loss. It is certainly encouraging to see bariatric surgeons focusing on NASH/NAFLD, but as surgery remains a limited treatment option for patients, we hope to ultimately see more options on the pharmacotherapy front. As no pharmacotherapies are currently approved for NAFLD/NASH, we are excited by the work of companies like NuSirt. As NAFLD/NASH remains an increasingly significant unmet need with the obesity epidemic, we are encouraged by emerging data in the pipeline demonstrating that weight loss can lead to improvements in liver disease – see our full competitive landscape of this potential market for more.
Obesity and the Brain
Paul Smeets, MD (University Medical Center Utrecht, The Netherlands)
Dr. Paul Smeets highlighted fMRI research as a promising area to help predict weight loss success in the movement toward personalized treatment. In a session on appetite and pleasure, Dr. Smeets reviewed a slew of data showing differences in brain activity between people with and without obesity regarding reward processing, food choice, and more. Notably, he pointed to leveraging the potential predictive value of brain activity in identifying which patients will have greater success with weight loss. Providing a snapshot of this research, Dr. Smeets shared data showing that individuals who show less activation in response to high-calorie food pictures are more likely to lose greater weight 12 weeks after an intervention. In addition, he presented findings demonstrating that upon receipt of milkshakes, low-risk (no parental obesity) individuals have a positive correlation with fat percentage and caudate activity while high-risk (with parental obesity) individuals have a negative correlation. Although this research remains at the tip of the iceberg, these results point to the potential of analyzing various types of neural activity in identifying appropriate patients for treatment – an issue that we see as one of the biggest challenges in obesity management today. We certainly find this work exciting, but note that it will be important in the long run to think about how this can be scaled, given the significant time and cost investments required for brain imaging. Thus, a movement toward eventually linking neural activity to more easily measured psychological markers may be on the horizon. For an example of this potential use of psychological markers, please see our coverage of recent research showing how hunger and restraint can predict weight loss success with phentermine treatment.
Leptin Suppresses the Pleasure of Eating
Roger Adan, MD (Brain Center Rudolf Magnus, Utrecht, The Netherlands)
In a workshop on new aspects of metabolic control, Dr. Roger Adan focused on the role of leptin in the neurobiology of reduced thermogenesis during dieting. As it is well known that many physiological factors can fight against weight loss, Dr. Adan’s discussion provided an insightful look into the phenomenon of reduced thermogenesis (production of heat) that occurs during dieting, counteracting weight loss attempts. Taking a deep dive into this specific trend, Dr. Adan demonstrated through rodent model data that a high-fat, high-sugar (HFHS) diet leads to hyperleptinemia and leptin resistance. According to him, withdrawal from this diet then leads to a significant reduction in body temperature along with a drop in leptin, although leptin resistance notably remains the same. Regarding localization within the brain, he explored the dorsal medial hypothalamus (DMH), the area known to be involved in regulation of brown adipose tissue; here, Dr. Adan presented data (examining the effects of leptin antagonists in rats) showing that leptin signaling within the DMH is essential for thermogenesis. Additionally, rats with decreased DMH leptin signaling were found to store more fat, regardless of food intake. Dr. Adan concluded with the framework that a drop in leptin upon dieting results in a reduction in thermogenesis due to a lack of leptin signaling in DMH neurons projecting to premotor sympathetic neurons in periaqueductal grey area (PAG). Interestingly, during Q&A, when asked if leptin therapy could be beneficial for dieting individuals, Dr. Adan cautioned the approach, pointing out that leptin’s connection to the sympathetic system has been shown to increase heart rate. However, he highlighted that with strong selectivity of another receptor on these leptin-expressing neurons, thermogenesis could potentially be restored. In our eyes, while leptin has been gaining greater attention within obesity research as the hormone has been linked to an array of phenotypes within obesity, the understanding around its specific therapeutic potential and approaches remains somewhat limited.
The Role of Non-Neuronal Cells in Energy Balance
Julie Chowen, MD (Hospital Infantil Universitario Niño Jesús, Madrid, Spain)
Dr. Julie Chowen discussed the role of glial cells within obesity, touching on gliosis as well as these cells’ interactions with leptin and ghrelin. She illustrated the significance of glial cells within the brain, noting that they are in close contact with neurons and can affect what neurons seek and how they respond. As background, glial cells are a type of support cell within the brain, with subtypes including astrocytes and microglia. Dr. Chowen discussed the role glial cells play in obesity, specifically the inflammation and insulin resistance induced in the hypothalamus in response to a high-fat diet, and pointed to gliosis (the reactive change of glial cells in the brain) that appears in obesity. Notably, she shared research on how leptin is involved in these phenomena, stating that while a high-fat diet activates microglia in the hypothalamus, leptin can return this microglial activation to wild-type levels. In addition, astrogliosis has been shown to increase leptin receptors in hypothalamic astrocytes and studies have shown that leptin can lead to rapid changes in the number of synaptic inputs in the hypothalamus. Similarly, Dr. Chowen illustrated that ghrelin can also modulate hypothalamic astrocytes, noting that ghrelin can bring about significant activation of tanycytes (another type of glial cells involved in the modulation of entry into the hypothalamus) and may affect levels of GLUT transporters and GABA expression. Indeed, these hormones can very much modify the architecture of the glial structure within the brain and as neural circuits become a greater focus within obesity research, the impact of these non-neuronal cells on weight management and energy balance cannot be underestimated. Dr. Michael Schwartz’ team (University of Washington, Seattle, WA) has been known to focus on how gliosis and leptin lead to obesity – see our interview with him this past year as well as his presentation on his work at ENDO.
A Neural Basis for MC4 Receptor-Regulated Appetite
Lora Heisler, MD (University of Aberdeen, Scotland)
Dr. Lora Heisler highlighted POMC and MC4 receptor neurons as “key gatekeepers to energy homeostasis,” pointing to CCK’s activity in the central nervous system as a promising new target. Dr. Heisler began by introducing the role of melanocortin and POMC in energy balance, stressing that the melanocortin-4 receptor (MC4R) is critical for this homeostatic system. She presented data demonstrating that the restoration of ARC POMC neurons specifically expressing 5-HT2C receptors is sufficient to control appetite in male and female mice, as shown by activation of this neuron subpopulation restoring the appetite suppression effects of Arena/Eisai’s Belviq (lorcaserin). Most notably, Dr. Heisler explored if this MC4R system can be a gateway to other circuits for feeding and shared how CCK recruits MC4R neurons of the paraventricular nucleus of the hypothalamus (PVH), suppressing appetite. Additionally, she noted that ~27% of these MC4R neurons express CCK A receptors, thus emphasizing that modulation of this subset of PVH MC4R/CCK A receptor co-expressing neurons may yield a more effective obesity pharmacotherapy. This discussion ultimately brings the future of obesity therapy again to the central nervous system, as the field builds greater understanding of the various circuits in the brain. As a reminder, Motus Pharmaceuticals (formerly Rhythm Pharmaceuticals) is developing MC4R agonist setmelanotide for specific genetic obesity disorders – an approach that we find promising given Dr. Heisler’s work in exploring how this MC4R circuitry can have potential for general obesity indications.
Additional Topics: Basic Science, Public Health, Lifestyle, and Behavior
Ruth Loos, MD (Icahn School of Medicine at Mount Sinai, New York, NY)
Dr. Ruth Loos provided an overview of the basis behind using epigenetics in obesity, concluding that there is not yet enough information on this approach to personalize obesity treatment. Providing background on epigenetics, Dr. Loos introduced it as the dynamic process through which alterations such as histone modification and DNA methylation switch genes on or off, determining the fate of each cell. She noted that these alterations are reversible and can be inherited and passed on from generation to generation, but are also influenced by external factors such as smoking, diet, exercise, medications, and stress. According to Dr. Loos, it is believed that epigenetics can be passed on from parents to offspring for several generations, and while women are usually studied, men may also be able to pass on these traits. Taking a look at specific data related to obesity, Dr. Loos pointed to a study of individuals in the Netherlands who were prenatally exposed to the famine during World War II and the correlation to development of obesity later on in life. Findings of this research showed that offspring exposed to the famine early in gestation were at a higher risk for obesity than those exposed late in gestation, suggesting that environmental factors impacting maternal health have a greater impact on development during early development. Ultimately, Dr. Loos stressed that there is currently not enough information to use epigenetics to personalize obesity treatment, as most studies tend to be small and lack replication. That said, we see this as a very important area of focus within obesity research, as we seek to understand which patients will respond to what treatment and hope to develop a greater evidence-based understanding of how to prevent obesity early on in life. For more on obesity predictors that can be identified as early as in utero, please see Dr. Hans Ulrich-Haring’s (University of Tubingen, Germany) lecture from EASD.
- According to Dr. Loos, several forms of methylation have been studied in association with obesity but none have provided convincing associations with adiposity traits. She discussed that global methylation has been extensively studied but there is no consistent evidence of association with obesity. Dr. Loos shared that gene-specific methylation in the retinoid X receptor-a (RXRA) has been shown to be associated with increased fat mass, but its predictive value remains unknown and epigenome-wide methylation in the hypoxia inducible factor 3 (HIF3) has been shown to be associated with higher BMI, although she noted that it is also possible that BMI affects methylation.
Can We Learn Anything from Omics?
Ben Van Ommen, MD (Netherlands Metabolomics Center, Utrecht, The Netherlands) and Dominique Langin, MD (Inserm-Paul Sabatier University, France)
In a staged debate on the utility of “omics” in obesity, both Drs. Ben Van Ommen and Dominique Langin ultimately expressed enthusiasm for the approach, noting its potential for integrating various data types and providing insights into personalized therapy. Dr. Van Ommen first highlighted omics’ ability to quantify the expansive complexity of obesity, as it can help classify the many different parameters of the condition. He stressed that omics allows for “super meta-analyses” of raw data, due to the standardization and shareable nature of the omics world. From these opportunities, Dr. Van Ommen shared that “omics gets me out of my comfort zone,” helping to expand existing schemes and allowing for greater forms of systems biology. Similarly, Dr. Langin pointed to the approach’s ability to integrate data of various technologies and bring about network-based analyses, providing links between clinical factors to adipose tissue profiling to gene expression. In addition, both speakers noted how this big data can help the field better understand personalization, as Dr. Van Ommen illustrated findings of how different type 2 diabetes patient subgroups react differently to different diets while Dr. Langin highlighted recent work of personalizing nutrition interventions based on microbiome-diet interactions (see our coverage from China CODHy for a more in-depth presentation on these efforts). Indeed, as various different research disciplines advance in their own ways, we see the work in omics as very important as it provides the opportunity to bring these various systems together to identify new relationships and patterns that can be utilized in the clinical setting.
- Yet, Dr. Langin emphasized that greater standardization and reproducibility along with lower costs will be important for the field to move forward. Providing his assigned counter-argument, Dr. Langin acknowledged that omics efforts have not yet provided actionable interventions for the clinic. He specifically noted that we have yet to identify a genetic variant that has the potential to be quantified in the clinical setting nor has the field found novel validated biomarkers for risk. To make these translational advances, Dr. Langin highlighted the need for “cheap, simple, robust, and reproducible methods” and for greater cross-validation among labs, with certification to standardized requirements. We agree that this field can become so much more powerful if we are able to make its efforts easier to collaborate and share – efforts in which professional societies or large research institutions such as the NIH may be able to play a leading role.
Metabolically Healthy Obesity?
Matthias Bluher, MD (University of Leipzig, Germany), Tommy Visscher, PhD (Windesheim University, Zwolle, The Netherlands), and Jens-Christian Holm, MD, PhD (Danish Obesity Research Center, Frederiksberg, Denmark)
Dr. Matthias Bluher highlighted adipose tissue function differences as the physiological basis of metabolically healthy vs. unhealthy obesity, noting that markers of adipose tissue function can predict the insulin sensitivity of people with obesity. Dr. Bluher shared his framework of “size, sites, and cytes” in different obesity phenotypes, explaining that differences in the size/expandability, distribution, and macrophage infiltration of adipocytes contribute to the insulin resistant state in obesity – see his award lecture from EASD on this for more. Notably, he highlighted a study showing that only two parameters of adipose tissue function – the percentage of immune cells and serum adiponectin levels – can accurately predict the insulin sensitivity of someone with obesity, as these measures were shown to positively correlate with glucose infusion rate (r2=0.98, p<0.0001). As we frequently hear of efforts to personalize therapy, this commentary highlighted another potential area to examine guidelines on treatment individualization or to identify the highest at-risk patients.
- In the same session, Dr. Tommy Visscher (Windesheim University, Zwolle, The Netherlands) and Dr. Jens-Christian Holm (Danish Obesity Research Center, Frederiksberg, Denmark) warned of the public health dangers of spreading the idea of a “healthy” obesity. Both speakers heavily emphasized the rationale of classifying obesity as a disease and stressed that while some people with obesity may be metabolically healthy, these individuals are at high risk of other non-metabolic-related comorbidities as well as the mental health consequences of stigma. Dr. Holm specifically argued that calling attention to metabolically healthy obesity tends to neglect the underlying cause of the condition and its burden. Meanwhile, Dr. Visscher stressed that it is important to not let the press translate messages on metabolically healthy obesity, as this can downplay the greater problem of obesity and the high risks of developing type 2 diabetes. In our eyes, this is certainly a controversial issue within public health communication (see our coverage of a WSJ article on benefits of obesity), but we would hope that the scientific field does not disregard the phenomenon in light of these concerns, as it can provide unique insights into new targets and individualization for obesity treatment.
Obesity is a New Major Cause of Cancer
Andrew Renehan, MD (Institute of Cancer Sciences, University of Manchester, UK)
Dr. Andrew Renehan presented data demonstrating that globally, obesity is the third greatest risk factor for cancer, behind only smoking and viral infections. According to Dr. Renehan, excess adiposity has long been known to be associated with an increased risk of many forms of cancer including esophageal, liver, kidney, colorectal, pancreatic, gallbladder, advanced prostate, post-menopausal breast, ovarian, and endometrial. Dr. Renehan presented data showing that the estimated population attributable fraction (PAF) (which takes into account disease incidence based on a risk factor) for Europe’s excess cases of cancer attributable to increased BMI was 8.6% in women and 3.8% in men in 2008, accounting for more than 130,000 new cases of cancer. Globally, the PAF for excess cases of cancer attributable to increased BMI was 5.4% for women and 1.9% for men, averaging out to 3.6% for both genders and accounting for over 480,000 new cases of cancer – a troubling number, indeed. To put this in perspective, Dr. Renehan highlighted that only the global estimated PAFs for smoking and viral infections are greater than the PAF for elevated BMI, at 21% and 16%, respectively. He noted that while the PAF for obesity is currently lower than that of smoking, data show that the prevalence of smoking is decreasing and as such, smoking-related cancers are going down. However, obesity rates continue to rise, and he speculated that obesity-related cancers are likely to increase as well. Looking at the UK specifically, Dr. Renehan commented that predictions suggest in 2035, nearly 40% of adults will have obesity and over 70% will have overweight or obesity. Following through on these data’s implications on cancer, he emphasized that if we are able to reduce the overweight/obesity prevalence by 1% every year, we could avoid 64,000 cases of cancer over the next 20 years and save 40 million GBP in the annual cost of the nation’s cancer care. These data are staggering and a reminder that obesity is a major public health crisis with major associated health risks and comorbidities. The nearly 500,000 new cases of cancer each year that are attributable to increased BMI are, in our opinion, reason enough to treat obesity as a serious chronic disease.
Promising Practices to Address Weight Stigma
Ximena Ramos-Salas, PhD Candidate (University of Alberta, Edmonton, Canada) and Angela Alberga, PhD (University of Calgary, Alberta, Canada)
In this session, we heard from members of the EveryBODY Matters Collaborative Initiative, highlighting the high prevalence of weight biases among providers and the potential of ongoing physician education efforts. This initiative is run by the Canadian Obesity Network and aims to bring together different disciplines to promote behavior, practice, and policy change in weight bias and obesity stigma. Dr. Ximena Ramos-Salas opened the session by speaking of weight biases, which lead to negative attitudes and views about obesity, and thus drives stigma and discrimination toward individuals with obesity. She discussed the high prevalence of this bias among healthcare professionals, noting that these ideas come from the belief that obesity is controllable by behavioral factors. Importantly, she addressed the many serious consequences of weight-based stigma, including depression, poor body image, suicidal acts, and loneliness, which can ultimately lead to maladaptive eating patterns, avoidance of physical activity, and avoidance of medical care. To work on these issues, Dr. Angela Alberga discussed promising practices in public health to address weight-based stigma, focusing on the training of healthcare professionals in obesity care. Specifically, she discussed methods on educating clinicians about the uncontrollable and non-modified causes of obesity (genetics, biology, sociocultural influences), evoking empathy by repeated positive encounters with patients living with obesity, and peer modeling (shadowing empathetic experts). The session also featured the patient perspective, as an individual spoke of her experience growing up as a child with obesity: she shared the isolation she felt and the lack of support she received from the healthcare community, urging audience members to “look at the person as a whole.” In our eyes, it is not only essential for physicians to understand obesity on a biological level, but to also possess the tools to speak and interact with people with obesity in an effective and empathetic manner. We were pleased to see sessions focused on the stigma surrounding obesity and hope to see more structured training in this area that begin as early as in medical school. The field is moving in the right direction, with the opportunity to now have a certification in obesity medicine, but more needs to be done, particularly given broader societal stigma.
- In a separate media session, members of the EASO patient council spoke of weight-based stigma and the responsibility of the media to portray people with obesity in a positive light. Noting the stigma that comes with obesity, panelists highlighted that that people with obesity are often portrayed by media as lazy and unintelligent. Specifically, they are often portrayed with negative imaging, usually shown as isolated, not moving, and not fully clothed. According to the speakers, these negative images perpetuate negative attitudes toward people with obesity and reinforce prejudices, and discrimination. Indeed, with this point, we stress the importance of multidisciplinary efforts in this work, as collaborations with marketing and media will be a critical part of this movement – public attitudes need to change and we’re very far from that point.
Mikael Fogelholm, PhD (University of Helsinki, Finland)
We heard initial results from the PREVIEW project, which demonstrated successful weight loss and A1c reductions for up to six months, with diet and physical activity interventions. Investigators from the project, including Dr. Mikael Fogelholm, provided an overview of the PREVIEW project, a three-year, randomized-controlled, multicenter study, which aims to evaluate the effect of various lifestyle interventions on the prevention of type 2 diabetes in patients with prediabetes and overweight or obesity. The first two months of the study involved a low-calorie diet (n=2,326), and patients who achieved at least 8% weight loss (n=1,842) at two months were randomized into one of four treatment arms: high-protein, low-glycemic index diet or moderate-protein, moderate GI diet in combination with either moderate-intensity (75 mins/week) or high-intensity (150 mins/week) physical activity. Patients were also enrolled in group counseling led by nutritionists, with the intent of helping participants with goal setting, improving self-efficacy, providing social support and feedback, and preventing relapse. Currently, the data has not been unblinded but investigators shared that the overall findings show reductions in weight, BMI, A1c, and blood pressure, which have been maintained up to six months following the two-month, low-calorie diet period. Specific data on these measures were not shared but the investigators noted that they expect the final participant to finish the study in April 2018, with final results available by the end of 2018. As we continue to understand the importance of individualized care for the treatment of obesity, we will be curious to see if there are any differences correlated between various baseline parameters and success in specific treatment arms. We would speculate that a high-protein, low-glycemic index will produce the greatest weight loss, and therefore the greatest prevention of type 2 diabetes, but imagine that all four treatment arms will produce positive results.
Laura Condon, MD (University of Nottingham, UK)
In a symposium focused on mobile and wireless technology in youth, Dr. Laura Condon raised concerns of possible overstimulation, disengagement, and peer pressure with these health approaches. Dr. Condon noted that while mHealth efforts bring about great benefits, it is important to express some caution around the potential consequences of further dividing teenagers’ attention, constantly exposing them to technology, and providing opportunities for such immediate and instant data sharing. Specifically, she pointed to concerns of possible overstimulation or disengagement due to the pervasiveness of mobile technology. Additionally, Dr. Condon cautioned that while instant feedback can be a powerful motivational technique, it can also bring about performance anxiety or feelings of excess pressure and that social networking can provide further opportunities of peer pressure and cyber bulling if a degree of regulation is not applied to the content shared. As digital health has generally been received with significant enthusiasm from a wide range of sectors, we found this commentary notable in the context of a world that is becoming increasingly reliant on technology. While the benefits may ultimately outweigh the risks on this front, we would agree that this area warrants greater research, given the impressionability of adolescents’ development and the relative novelty and limited research around this mHealth work.
The modest exhibit hall featured booths from Novo Nordisk and Orexigen, both featuring promotion for pharmacotherapies Saxenda (liraglutide 3.0 mg) and Mysimba (naltrexone/bupropion extended-release), respectively. As for other obesity drugs, Vivus and Arena/Eisai were not present on the exhibit floor, which matched our expectations, given the stalled progress of European approvals for Qsymia (phentermine/topiramate extended-release) and Belviq (lorcaserin).
Similar to many recent conferences, Novo Nordisk’s booth focused on Saxenda, featuring key messaging surrounding weight loss and improvement in cardiovascular risk factors, and an image of a woman holding up a large pair of jeans with comorbidities written over them. A flat screen was running an advertisement for Saxenda with the empowering message that weight loss is not simply having willpower but having the proper tools to be successful.
Orexigen was also present with a substantial booth, the first we have seen in quite some time, focused on Mysimba. Messaging at this booth revolved around helping patients who feel “trapped” by their desire to eat and who “cannot see past” their hunger. The booth’s promotional material emphasized that with the help of Mysimba (which has not yet launched in Europe), healthcare providers can help patients overcome their cravings. A flat screen was running an advertisement focused on the brain’s defense against weight loss, the involvement of the reward system in influencing behavior, and the mechanisms by which Mysimba counteracts these systems – another sign of the appeal of the brain’s role within obesity.
-- by Melissa An, Sarah Odeh, and Kelly Close