We returned to the Cleveland Clinic on September 29-30 for its 11th annual Obesity Summit. Consistent with last year’s meeting, the Summit offered a wide-ranging agenda filled with actionable tips for obesity management – a welcome testament to the growing recognition of obesity as an enormous public health problem, though this meeting was aimed more at education than catalyzing new discussion in our view.
Day #1 was packed with insight on the basic science and behavior modification fronts. Notably, we heard from Dr. Sam Klein (University of Washington, St. Louis, MO) on the ever-provocative topic of metabolically normal obesity vs. metabolically abnormal obesity and listened to a fascinating panel on pediatric obesity, a supremely challenging clinical area where few therapies are approved (or even tested!). Day 2 focused on obesity treatments and comorbidities. After getting a literal inside look at two bariatric surgery procedures via a laparoscopic live-feed, we heard a comprehensive overview of the world of obesity pharmacotherapy from the esteemed Dr. Louis Aronne (Weill Cornell Medical Hospital, New York, NY). The summit concluded with intriguing commentary from two Cleveland Clinic faculty members: Dr. Steve Nissen on the relationship between obesity and cardiovascular disease, and Dr. Naim Alkhouri on NASH, a startling prevalent complication of obesity with no treatment currently available.
Below we outline five prominent themes from the meeting, followed by full in-depth coverage of the Summit’s most notable talks and workshops. Sessions we found particularly important are indicated in yellow.
1. Nearly universally, talks emphasized that obesity is more complex than simply eating more calories than you burn. We heard multiple perspectives on the myriad factors contributing to the development of obesity, including environmental chemicals, drug side effects, endocrine abnormalities, and alterations in neural circuitry just to name a few.
2. Consistent with the Cleveland Clinic’s status as one of the leading centers for bariatric surgery, the Summit featured significant positive commentary on these procedures as effective treatments for diabetes and obesity alike. Indeed, a great deal of messaging surrounding other treatment options such as diet, exercise, pharmacotherapy, and activity monitoring were positioned as a complement to bariatric surgery more frequently than as standalone options. Faculty specifically emphasized the benefits of sleeve gastrectomy and roux-en-Y gastric bypass; we witnessed both of these procedures in real-time via a surgery live feed, and heard firsthand from a panel of patients who underwent extreme weight loss thanks to these procedures.
3. Talks on obesity drugs illustrated opportunities for improvement. Obesity pharmacotherapy is vastly underutilized by eligible patients due to cost, lack of insurance coverage, lack of trust of HCPs, and stigma, among other things. At every turn, philosophical disagreements surround these drugs; pharmacology enthusiast Dr. Louis Aronne lamented the small number of available obesity pharmacotherapies (strange from our view since what there is isn’t used), while Dr. Steve Nissen cautioned against the potentially dangerous cardiovascular effects of these agents.
4. This Summit was clearly planned with interactiveness in mind. During breaks in the agenda, attendees were encouraged to step on a scale and determine their BMI (a body composition scanner was also available for the especially curious), and the summit featured an ongoing competition to guess the average BMI of the conference organizers, Drs. Phil Schauer, Bartolome Burguera, and John Kirwan, as well as the average BMI of the audience (this ranged from 17 to 40 kg/m2) Dr. Schauer thoughtfully pointed out that physicians weigh patients every day, and can benefit from being reminded of the bravery it takes to step onto a scale.
5. Given the current lack of consensus on the ideal practices for effective weight loss, another key takeaway from the summit was the importance of simplifying the message that physicians give patients. Weight loss is frustrating in and of itself, and overcomplicated advice only exacerbates this. We heard this in the context of diet (according to Dr. Donna Ryan, the best diet is simply the one that people can stick to) and in the context of exercise (according to Dr. John Jakicic, the best exercise routine is simply 30-60 minutes per day of walking at ‘late to a meeting’ pace).
Detailed Discussion and Commentary
Developmental Origins of Obesity – Hormones and Disrupting Chemicals
Jerry Heindel, PhD (National Institute of Environmental Health Sciences, Durham, NC)
Discussions surrounding environmental factors that contribute to the obesity epidemic have historically focused on over eating and lack of exercise. While these are no doubt crucial considerations, the Obesity Summit kicked off with Dr. Jerry Heindel (National Institute of Environmental Health Sciences, Durham, NC) discussing the role of environmental chemicals as a contributing factor to obesity. Endocrine disrupting compounds (EDCs) with the potential to alter gene expression and hormonal programming are ubiquitously present in agricultural and industrial chemicals, plastics, pharmaceutical products, and cosmetics. Exposure to certain EDCs have been linked to increased incidence of ADHD, asthma, and infection susceptibility, and emerging evidence suggests that the same is true for obesity. After all, metabolic control is an endocrine process, so it follows that it is sensitive to disruption by certain EDCs. So-called “obesogenic” EDCs such as phthalates, BPA, TBT, DDT, and jet fuel, when exposed to pregnant mice, have led to an obese phenotype in not one but four subsequent generations – presumably by influencing the patterning of brain satiety centers to increase food intake. Furthermore, prenatal exposure to TBT may reprogram mesenchymal stem cells to differentiate into fat instead of bone through TBT’s disruption of PPARγ signaling.
- Dr. Heindel outlined a putative mechanism by which obesogens operate, proposing that developmental exposure to these EDCs can alter homeostatic programming such as alterations in the wiring of satiety and reward pathways or changes in the number of fat cells. These mechanisms may leave an individual poised for future weight gain in the event of stress on the metabolic system.
- Although Dr. Heindel forecasted that this unsettling early evidence is likely “only the tip of the iceberg” when it comes to the impact and prevalence of obesogens, he concluded on an optimistic note, remarking that windows of susceptibility to obesogens are also windows of prevention. With attentiveness and conscientiousness, it is possible to reduce EDC exposure – especially during pregnancy, infancy, and toddlerhood – but more impactful preventative measures will require action at the policy level.
Questions and Answers
Q: What should we do as individuals to prevent our exposure to EDCs?
A: We need to reduce the amount of these chemicals in the environment. We put them out there without having any idea what they’re doing. Industry replaced BPA with a different chemical that has the same effects. We are behind the eight ball in terms of reducing EDC exposure via policy and that’s a problem.
Q: Are there any data that reducing the body content of these EDCs will cause weight loss?
A: That’s a terrific experiment. So far this has not been done, but we have been pushing researchers in both the human and animal fields to take on questions like this.
Q: You told us about a number of obesogens. Which one is most important and what should we do to combat it?
A: I don’t know which one is most important. A long list of environmental chemicals is developing, and for each there are different things to do. Our general thought is to reduce exposure to as many as possible, by avoiding canned foods and certain cosmetics. The reason we don’t focus so much on one in particular is because we are all exposed to a mixture; reducing exposure to one obesogen may not have much of an effect since we are exposed to so many.
Obesity in Older Adults
Samuel Klein, MD (Washington University, St. Louis, MO)
The esteemed Dr. Sam Klein (Washington University, St. Louis, MO) provided an overview of the unique challenges faced by older adults who have obesity. Aging involves decreased height and a gradual shift toward higher body fat composition, inevitably leading to increases in BMI. Currently, 35% of adults in the US who are over the age of 65 have obesity (13 million individuals), and this number is expected to more than double to 88.5 million by 2050, making obesity in the elderly an increasingly relevant issue for physicians. The implications of obesity are arguable more debilitating in the elderly population considering muscle mass and strength naturally decrease with age, and when combined with excess weight, movement and independent functioning become increasingly difficult. Likely due to these adverse consequences related to physical functioning, obesity significantly increases the risk of admission to nursing home facilities among the elderly. Dr. Klein underscored the importance of weight loss in this population, noting that even modest weight loss of 10% can produce significant improvements on a variety of subjective quality of life measures, including physical functioning, vitality, bodily pain, and ability to conduct daily activities. From a patient perspective, we would point out that 10% weight loss is no “cakewalk” – that’s very difficult for most patients! Dr. Klein pointed out that in his experience, elderly patients are not inflexible to behavioral change – they are in fact more able to make positive lifestyle changes thanks to fewer distractions and high motivation in group sessions.
Questions and Answers
Q: Although a focus on protein can slightly decrease weight loss-induced muscle mass loss in older adults, it can also increase insulin resistance. Can you give a bit more color on that?
A: High protein diets are associated with diabetes and high protein intake causes insulin resistance. In fact, high protein intake while consuming a calorie-restricted diet to lose weight can blunt the beneficial effect of weight loss on insulin action.
Q: Since there are all these benefits to weight loss, is there hard evidence of reduced mortality when you lose weight?
A: Increased health, physical function, and quality of life, not increasing survival, are the primary goals for weight loss in older adults who are obese. The results from several studies have found that unintended weight loss is associated with increased mortality, but there are no data to show that intentional weight loss is associated with increased mortality.
Session 1: Basic Science – Environmental Factors
Mechanisms for Reducing Lipid Excess in Obesity
Bret Goodpaster, PhD (Stanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL)
Dr. Bret Goodpaster (Stanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL) addressed the complex subject of exercise and fatty acid metabolism. Dr. Goodpaster explained that both individuals with obesity and endurance athletes have high levels of fatty acids present in muscle cells, while sedentary lean individuals do not. Furthermore, both sedentary lean individuals and endurance athletes tend to have low insulin resistance. Lean sedentary individuals are distinguished by having low levels of intramyocellular lipids, while both individuals with obesity and endurance athletes have high intramyocellular lipids. That said, endurance athletes are highly efficient at burning muscle fat, but in individuals with obesity, fat simply accumulates in muscle cells. The takeaway message to the physician audience was that exercise confers a metabolic benefit, i.e. improved fatty acid oxidation, that weight loss alone will not achieve.
Questions and Answers
Q: Could you give us a bit of granularity on physical activity as it relates to non-exercise such as sitting time?
A: We had patients wear activity monitors. It is important that we consider not only structured exercise, but non-exercise sedentary activity. It is the non-exercise physical activity data that is important in the long term in determining outcomes and weight loss maintenance.
Q: If there is a higher-than-expected presence of lipids in the muscle tissue of athletes, what is it in former athletes? Do they have higher propensity to retain lipids in the muscle after they stop training?
A: The short answer is if you don’t use it, you lose it. If you stop exercising, the phenotype will reverse. There have been studies putting athletes on bedrest for 10 days. They lose muscle mass and their oxidative capacity goes down…it’s like aging 8 years in 10 days.
Q: It seems like no matter what we do, there is still an acceptable amount of exercise we need to do.
A: Our studies were designed to show ‘if you exercise, this is what happens.’ How we get people to exercise is a completely different issue.
Metabolically Normal and Abnormal Obesity
Samuel Klein, MD (University of Washington, St. Louis, MO)
Dr. Sam Klein took the stage to address the controversial topic of metabolically normal obesity (MNO) and metabolically abnormal obesity (MAO). “In general, no organ is not adversely affected by having excess body fat,” according to Dr. Klein, but some people with obesity do not develop metabolic complications such as diabetes, dyslipidemia, and cardiovascular disease. Understanding this issue is made difficult by the lack of a clear definition for “metabolic health.” In six separate studies, all involving a different definition of metabolic health, the incidence of MNO ranged from 3-32% in men and 11-39% in women. While the exact prevalence of MNO remains unclear, Dr. Klein reviewed a strong body of evidence that distinct MAO/MNO phenotypes do indeed exist. He clarified that individuals with MNO might still not be entirely “healthy,” and we do not know if they have an increased incidence of arthritis, cancer, and cognitive dysfunction that often accompanies obesity, but explained that differences in metabolic risk between different types of patients has implications for the nature and aggressiveness of the obesity therapy that should be prescribed.
- A popular criticism of the notion of MNO is that it represents an early stage in the progression of obesity before signals of metabolic abnormalities have had time to present, but a 2015 study from Dr. Klein’s laboratory provides convincing evidence for MNO and MAO as distinct phenotypes. People with MNO and MAO were overfed with 1000 extra calories/day of fast food until they gained 6% of their body weight. While percentage body fat remained constant between the two groups, notable differences emerged: (1) MAO led to a higher proportion of fat deposition in the liver; (2) MAO was associated with decreased insulin sensitivity in adipose tissue, liver, and muscle, whereas these factors remained unchanged in the MNO group following weight gain; and (iii) MNO was associated with adipose tissue upregulation of the FADS1, FADS2, and ELOVL6 genes.
- Dr. Klein proposed that the phenotypic differences between MNO and MAO could be mediated by adipose tissue. Accumulating evidence suggests that MAO is associated with several cellular-level abnormalities in adipocytes. In further support of the importance of adipose tissue in differentiating MNO and MAO, rodent studies reveal that adipose transplants from healthy, exercise-trained mice can improve the glucose tolerance and insulin sensitivity of obese mice.
Questions and Answers
Q: How do we take clinical data and define these normal and abnormal phenotypes, since the definitions are variable? How can it be converted into real clinical practice and use?
A: First we should stop using BMI as the only determinant for weight loss and treat the whole patient. If someone has a BMI of 45 kg/m2, and their whole family has had a BMI of 45 kg/m2 and have all lived to 100, that person does not require as aggressive obesity therapy as someone who is at much higher risk of obesity related medical complications. On the flip side, high triglyceride and high liver fat content are signs of MAO, even at lower BMIs.
Q: What is a good, easy way to measure liver fat?
A: Ultrasound can be used in a clinical setting to assess liver fat content, but it is not sensitive enough to detect moderate elevations in liver fat
Q: What about waist circumference?
A: In my opinion measuring waist circumference is not practical in a clinical setting and does not add much to clinical management (editor’s note – it wasn’t said, but we’ve also heard that doctors do not like doing this). It is not easy to do: the person has to strip down, it requires training and standardization, and it is not reimbursed. Moreover, the current criteria used to define high waist circumference are not much better than using BMI to identify people at medical risk.
Session 2: Obesity Treatment – Lifestyle, Diet, and Exercise
Exercise Prescriptions for the Overweight and obese Adult
John Jakicic, PhD (University of Pittsburgh, Pittsburgh, PA)
Dr. John Jakacic (University of Pittsburgh, PA) reviewed the literature on the role of exercise for weight loss and maintenance, offering guidelines that are specific and relatively easy to recommend to patients. The literature suggests that weight loss is primarily dependent upon diet, with exercise functioning as an adjunct that perhaps improves results around 20% in the short term (six months). Moderate intensity physical activity – defined by Dr. Jakacic as “late for a meeting” walking pace – of 150-250 minutes per week contributes around 3% to weight loss, which may be enough to modify disease risk factors, but is not comparable to diet-driven weight loss. Going deeper, Dr. Jakacic presented data suggesting that exercise is more likely to contribute to maintaining weight loss over a medium term period of 24 months. As an adjunct to a behavioral weight control program, those who exercised with moderate to vigorous intensity maintained greater-than-10% weight loss that was achieved over six months for an additional 18 months. Those who achieved greater-than-10% weight loss, but did not exercise, were not able to maintain their weight loss. Dr. Jakacic also presented data indicating that the prescribed 150-250 minutes per week could be broken down into short bouts of say 10-20 minutes 3x per day without loss of effectiveness. He recommended that primary care physicians present this as an alternative to patients, especially those who could not commit to an hour in addition to a trip to the gym.
Questions and Answers
Q: It is difficult to estimate how many calories people burn. I can tell people to exercise to their max heart rate for a certain amount of time, but this does not necessarily translate to calories lost.
A: This is where the balance comes in. There is the research way, the clinical way, and the public health way of prescribing physical activity. People are frustrated because we keep changing the bar and overcomplicating things. My suggestion is to make the message simple: 30-60 min/day of exercise (as vigorous as walking briskly, as if late to a meeting) can improve health parameters in a very positive way. This is easy to understand, and physicians can easily get the message out. What we find when we ask very simple questions about physical activity prescription is that physicians get it wrong. People at the front lines are overcomplicating things.
What is the Best Diet for Weight Loss?
Donna Ryan, MD (Pennington Biomedical Institute, Baton Rouge, LA)
In contrast to other discussions at the Summit on the optimal diet to promote weight loss and metabolic health, Dr. Ryan offered simple advice: adherence, not macronutrient content, is the biggest predictor of weight loss response to a diet. The best diet is the diet to which people can adhere. This recommendation comes on the basis of a recent study that systematically reviewed 17 distinct diets (including the AHA step 1, EASD/ADA diet, low-cal, low-carb, low-fat, vegan, vegetarian, Mediterranean, and Atkins) and found no one diet to be clearly superior for weight loss over at least one year. Of course, it is not the case that all calorie reduced diets will lead to improved health, but Dr. Ryan urged physicians to realize the need to make multiple dietary pathways available to patients, within the boundaries of what we know good nutrition to be – vegetables, fruits, and whole grains with limited sweets. Furthermore, weight loss rarely comes from diet alone and Dr. Ryan explained the importance of encouraging patients to pursue self-monitoring, goal-setting, and social support as crucial supplementary components of their weight loss plan – these are, after all, powerful forces to promote the all-important notion of adherence.
- Dr. Ryan forecasted that the future of weight loss will involve a personalized medicine approach, speculating that genetic information may one day be able to predict an individual’s weight loss response to certain diets and, perhaps more importantly, how well this weight loss will be maintained over the long term. As we hear more about precision medicine, and begin to understand predictors of weight loss, we look forward to seeing what research come out regarding what diet or exercise routine is best for which person.
Questions and Answers
Q: In terms of adherence, macronutrient composition affects hunger and satiety, so are there benefits to different approaches?
A: That is what we are trying to achieve with medications. Hunger and satiety are absolutely key measures. The NIH is doing a large study on variations in weight loss response to determine what the predictors are, whether they are psychological, biological, etc.
Q: You said that adherence is the best predictor of weight loss, so which diet has the best adherence?
A: The thing about adherence is that everyone starts strong, but it degrades over time. Hopefully we would eventually be able to identify, maybe through genetic profile, which would be the one you would best adhere to. That’s coming. It’s not here.
Clinical Strategies for Weight Loss: Preventing and Reversing Heart Disease
Caldwell Esselstyn, MD (Cleveland Clinic Wellness Institute, Lyndhurt, OH)
Dr. Caldwell Esselstyn (Cleveland Clinic, Lyndhurt, OH) has been a strong advocate of a plant-based diet, but especially for patients with coronary artery disease. Former President Bill Clinton has been a public advocate of Dr. Esselstyn’s diet. While it is impossible to do his diet recommendations justice in this space, Dr. Esselstyn maintains an informative website and published a book describing his philosophy in 2007, titled “Prevent and Reverse Heart Disease.” His presentation made it clear that he enjoys a strong following (enough to conduct a 200 patient multiyear clinical study), which includes senior physicians at the Clinic. To complement this clinical data, Dr. Esselstyn himself is a testament to the effectiveness of the plant-based diet. During a break between sessions, a small crowd gathered around as Dr. Esselstyn volunteered to undergo a body composition analysis scan in the small exhibit hall, raving about his outstanding numbers.
Questions and Answers
Q: What percentage of the US population restricts their diet to whole food, plant-based diet, why is it so low, and why hasn’t it increased based on this great evidence you have?
A: Change is challenging. The environment is so different now than it was years ago when I started. We are truly on the cusp of what could be the seismic revolution in health. And this won’t come from another pill, procedure, or medication. It will come when we share with the public what is the lifestyle and nutritional literacy that will empower people from getting these chronic, killing diseases.
Session 3: Pediatric/Adolescent Obesity
Long-Term Durability of Bariatric Surgery vs. Competing Risks of Not Operating on Adolescent Patients
Thomas Inge, MD, PhD (Cincinnati Children’s Hospital, Cincinnati, OH)
Dr. Thomas Inge (Cincinnati Children’s Hospital, Cincinnati, OH) tackled the controversial subject of bariatric surgery in pediatric and adolescent patients. Severe obesity in children is more common than pediatric cancer, congenital heart disease, celiac disease, cystic fibrosis, and autism combined (!) but is a challenging issue to address given the risks and scarcity of clinical data surrounding surgery and pharmacotherapy in pediatric and adolescent patients. Dr. Inge argued that the typical treatment protocol of lifestyle modification recommendations for pediatric patients with obesity are “serially ineffective.” He went on to describe that meaningful weight loss is rare for any treatment option other than bariatric surgery, suggesting that bariatric surgery offers a rare opportunity to reverse severe obesity in adolescents, and may even reduce the risk type 2 diabetes and other obesity-related comorbidities. Although bariatric surgery certainly comes with risks, Dr. Inge argued that these are often outweighed by the risks associated with severe obese from such an early age.
- The TEEN-LABS study, a multi-center prospective outcome study (n=242 adolescents age <19 at the time of surgery; average BMI=53 kg/m2), found that bariatric surgery provides effective weight loss for adolescents with severe obesity. Patients who underwent roux-en-Y gastric bypass (RYGB; n=161), sleeve gastrectomy (n=67), and lap band (n=14) experienced approximately 30% weight reduction that persisted for at least three years. Furthermore, 90% of those with type 2 diabetes and 77% of those with pre-diabetes experienced remission after three years, and the study population as a whole benefitted from a 43% improvement in self-reported quality of life measures. We are under the impression that the study will continue longitudinal assessment into the future, although no specifics on this timeline have been provided. For more information visit ClinicalTrials.gov.
- To complement the TEEN-LABS study, the FABS-5+ study demonstrates a long-term benefit to adolescent bariatric surgery after follow-up of longer than five years. This study followed individuals who underwent RYGB as adolescents in 2001-2007, comparing their long-term outcomes in 2011-2013 to those of individuals of comparably high BMIs but who did not have surgery. While the subjects who did not receive the operation gained 6% in BMI over eight years, RYGB patients maintained a BMI reduction of 33%. In addition, 94% of RYGB patients had fasting plasma glucose levels <100 mg/dl compared to 82% of the non-operated subjects. From baseline to follow-up, diabetes incidence for RYGB patients dropped from 16% to 2%, while incidence for non-operated subjects remained at 10%. For more information visit ClinicalTrials.gov.
Questions and Answers
Q: How do you counsel teens on bariatric surgery: sleeve, band, or bypass?
A: We haven’t seen enough to know what to expect with the band in teens. It is about half as effective as other options in adults, so this is likely similar in teens. Between sleeve and bypass, it’s a toss-up. The studies examining mechanisms of weight loss show that the sleeve involves most of the same mechanisms as the bypass. Hopefully the longer term multicenter data will bear on that as well.
Q: How far could you push this on an age basis?
A: It is probably not appropriate anymore to let teens reach BMIs in the 60 kg/m2 range, but does that mean we should operate on them at BMIs of 40 kg/m2 in preteen years? Comorbidities of the weight should drive the decision-making, and this is a balance. There are risks of surgery and also risks of staying severely obese.
Q: I’m concerned about bariatric surgery before the completion of puberty, since bariatric surgery reduces bone mineral density.
A: As the data become more and more clear about the harms of waiting, we need to consider the risk. There is increasing increasing data to show excellent height evolution for preteen bariatric surgery patients (50 such surgeries were performed in Saudi Arabia). Consider how lousy their health will be later in life if we don’t look at all of the options for weight loss.
Q: Do you have any long term data on the use of alcohol or other substance abuse behaviors after surgery?
A: Right now the signals that we have at two years are that the children are drinking at developmentally-appropriate levels, no different from their counterparts.
Q: It sounds like we’re having the same debate about preteen surgery that we had about teen surgery a few years ago.
A: It’s a complex topic
Q: What do you do when surgery isn’t reimbursed?
A: If the family’s policy offers coverage for the adult, we can usually argue and get coverage for the child. We encourage and help our patients navigate the complexity of reimbursement because a lot of care is necessary, especially in the first year after surgery. We don’t want the family to be responsible for that.
Management of Pediatric Obesity: Moving Beyond Diet and Exercise
Sara Lappé, MD (Cleveland Clinic, Cleveland, OH)
The Cleveland Clinic’s own Dr. Sara Lappé offered insightful and actionable commentary on the management of pediatric obesity, which currently affects 17% of children in the US. To complement the Summit’s earlier session on bariatric surgery in pediatric patients, Dr. Lappé offered perspective on dietary interventions and use of pharmacotherapy – two areas for which data is unfortunately very limited in the adolescent population. On the dietary front, Dr. Lappé highlighted the protein sparing modified fast (PSMF) on the basis of its effectiveness in the adult population in her own study conducted at the Cleveland Clinic. PSMF involves an 800 calorie per day diet that eliminates carbohydrates and added fats, in order to induce ketosis. The addition of high-protein foods ensures that the body does not enter a catabolic state, and aids in appetite suppression. This diet can be used as a standalone approach to weight loss, or a preliminary measure in preparation for bariatric surgery. On the pharmacotherapy front, orlistat, a pancreatic lipase inhibitor, is the only weight loss medication approved for adolescents (age ≥12 with a BMI at least two units above the 95% percentile). While moderately effective, orlistat is associated with severe GI side effects. Given the scarcity of options for the pharmacological management of pediatric obesity, Dr. Lappé detailed some off-label strategies she uses in her practice: Metformin (which is approved for children over 10 with diabetes) can produce modest BMI reductions, as can topiramate (approved in adolescents for seizures and migraines), though a major caveat is the side effects of memory and concentration difficulties. Another major barrier is cost as obesity medications are notoriously difficult to get covered by insurance, and this is exacerbated in the case of off-label use – particularly in the pediatric population. Dr. Lappé emphasized that any pharmacotherapy regimen will be most effective when used in conjunction with lifestyle modification, nutrition support, and behavior modification, ending her presentation with a note of urgency to her fellow providers in the audience: “For severe obesity, don’t wait. They will not grow out of it, and it will get worse.”
Questions and Answers
Q: I’m thinking about this from an eating disorder and obesity perspective. Many patients who are overweight go on to develop eating disorders. What do you think of apps that can help track calories, but may also make patients hyperaware?
A: I try to avoid giving specific numerical calorie or weight goals, and focus on everything else instead. I screen for those hyperaware habits. We really try to bring this up and constantly screen for it.
Session 4: Obesity Treatment – Surgical
Live Surgery Transmission
Stacy Brethauer, MD (Cleveland Clinic, Cleveland, OH) & Matthew Kroh, MD (Cleveland Clinic, Cleveland, OH)
Day 2 began on a fascinating note, with the Summit’s annual live surgery transmission – a live broadcast of bariatric surgery procedures from the operating rooms of the neighboring Cleveland Clinic, described in real-time by the operating surgeons themselves. The demonstration offered an inside look (literally!) at two simultaneously-occurring procedures, a laparoscopic sleeve gastrectomy performed by Dr. Stacy Brethauer (president-elect of the American Society for Metabolic and Bariatric Surgery) and a laparoscopic roux-en-Y gastric bypass performed by Dr. Matthew Kroh. Audience members remained on the edge of their seats throughout the hour long demonstration, fascinated by the step-by-step narration of the procedures, and taking full opportunity of the unique opportunity to ask questions of the operating surgeon while the surgery was ongoing. The session cast bariatric surgery in a decidedly positive light, certainly achieving its goal of demystifying the nature of these procedures. We were surprised to learn that the sleeve gastrectomy is currently the most commonly performed surgical procedure in the United States (although the roux-en-Y gastric bypass is the most popular procedure at the Cleveland Clinic). Clearly, this is an area in which Cleveland Clinic benefits financially though that was not addressed.
New International Guidelines for Metabolic Surgery
Phil Schauer, MD (Cleveland Clinic, Cleveland, OH)
Dr. Phil Schauer, who impressed us as he always does with his organization and management of the Obesity Summit, presented a review session on metabolic surgery guidelines. Referencing the NHANES 2007-2010 data on the success rate of life style plus drug therapy for type 2 diabetes, Dr. Schauer noted that only 19% of subjects were in range for the combination of A1c (< 7%), blood pressure (130/80), and lipids (LDL<100). He suggested that metabolic surgery could help improve that low success rate, referencing the Swedish Obese Subjects (SOS) study, which demonstrated showed improvements for individuals who underwent bariatric surgery group in (i) all-cause mortality; (ii) reduced CV events (both fatal and non-fatal); (iii) cancer mortality; and (iv) microvascular complications. Regarding safety, Dr. Schauer referenced the Cleveland Clinic’s own data showing that laproscopic roux-en-Y gastric bypass has a post-operative complications rate of 3.4%, the lowest among a group of comparable procedures which included four other laparoscopic procedures, as well as three surgical procedures. However, surgery is not without its complications and as shown in a recently published Diabetes Care article, Dr. Schauer and colleagues reported complications of mild anemia (15%-25%), severe hypoglycemia (<1%), increased suicide risk (unquantified) and weight regain (10-15%). Finally, Dr. Schauer reviewed the results of the STAMPEDE study (three year results published in March 2014; five year results presented at ACC in February 2016, currently under review before publication). Over five years, gastric bypass and sleeve procedures were more effective than medical treatment of diabetes in controlling A1c and BMI, including BMIs under 35 kg/m2. These results contributed to a change in the ADA’s Standards of Medical Care in Diabetes treatment guidelines, namely that metabolic surgery be “considered” as a diabetes therapy for individuals with a BMI between 30 and 34.9, and for Asians with BMI as low as 27.5 with inadequately controlled hyperglycemia. Notably, Dr. Schauer forecasted that this joint recommendation by international diabetes organizations will likely be adopted by payers which cover metabolic surgery in 2017.
Endoscopic Therapies for Weight Loss
Stacy Brethauer, MD (Cleveland Clinic, Cleveland, OH)
Freshly returned from the operating room featured in the morning’s live surgery transmission, Dr. Stacy Brethauer took the stage to discuss the emerging class of endoscopic therapies for weight loss. Dr. Brethauser optimistically forecasted that endoscopic devices, though newly-emerging and not yet covered by insurance, may fill the long-standing obesity “treatment gap” between bariatric surgery (effective, but costly and risky) and simple lifestyle modification therapy (low cost and low risk, but less efficacious). Of the multiple endoscopic devices are currently in development, Dr. Brethauser specifically focused on: (i) the intragastric balloon, a saline-filled balloon placed inside the stomach to limit capacity and reduce food intake (approved by the FDA this year); (2) endoluminal gastrectomy, which gastric restriction via a suturing device placed on an endoscope ; and (3) the EndoBarrier, a thin plastic sleeve that seats itself in the duodenal bowl, causing food to be absorbed further down in the small intestine. Interestingly, the EndoBarrier has effectively promoted antidiabetic effects in pilot studies beyond what can be explained by weight loss (de Moura et al., 2012). The majority of other endoscopic therapies currently under development have yet to be assessed for antidiabetic effects, but we would argue that this could be an important point of differentiation in this arena of endoscopic therapies, given the concordance of obesity and type 2 diabetes. We would love to see more emphasis on these antidiabetic mechanisms as the market develops. Dr. Brethauser surmised that these endoscopic therapies are a conceptually promising option, but are “not yet ready for prime time.” Going forward, the prime issue for such devices in obtaining FDA approval and coverage by insurance plans will be their long-term durability and suitability for repeat therapy over many years, given that obesity is a chronic disease.
Questions and Answers
Q: When will guidelines about endoscopic procedures go into effect?
A: It takes about a year for the data from the guidelines to be incorporated into insurance policies. These procedures are widely endorsed and essentially standard of care now; presumably, soon they will be incorporated into insurance policy. With guidelines in place for bariatric surgery at BMIs above 35 kg/m2, we will stand a bigger chance of winning an appeal for a patient with a lower BMI of say 32 kg/m2 if they are a good surgery candidate.
Session 5: Obesity Treatment – Medical
Medications and Treatments that Cause Weight Gain
Donna Ryan, MD (Pennington Biomedical Research Center, Baton Rouge, LA)
Pharmaceutical iatrogenesis is a major and often overlooked factor contributing to obesity, and the esteemed Dr. Donna Ryan shared her expertise on how to prescribe in ways that prevent this. Pointing out the irony that we are reluctant to prescribe medications for weight loss, but have no hesitation in prescribing medications that cause weight gain, Dr. Ryan outlined some common weight gain-associated drug classes and potential alternatives – the Endocrine Society’s 2015 guidance on pharmacotherapy is another excellent resource for wise prescribing:
- Diabetes medications (such as insulin, sulfonylureas, and TZDs); alternatives like metformin, SGLT-2 inhibitors, and GLP-1 agonists are weight-reducing.
- Antidepressants; nefazodone, fluoxetine, and sertraline are weight-neutral alternatives, and bupropion is weight-reducing.
- Hypertension medications (such as α and β blockers); weight-neutral alternatives include ACE inhibitors, calcium channel blockers, and angiotensin-2 receptor agonists.
- Glucocorticoids; a weight neutral alternative for chronic inflammatory disease is non-steroidal anti-inflammatory drugs.
At the center of Dr. Ryan’s philosophy is the notion of a “weight-centric” approach. In the primary care office, it is important for physicians to engage patients on the issue of weight as it relates to health. Beyond using alternatives to drugs that drive weight gain, this requires involving patients in skill-training to help them meet weight management goals.
Questions and Answers
Q: What about venlafaxine, does that contribute to weight gain?
A: I was on the study that examined these associations and venlafaxine didn’t pop out in our analysis. But on the label it is associated with weight gain of 5 lbs.
Q: A lot of our patients are on poly pharmacy. Are the weight effects of these drugs additive? Or multiplicative? How does it stack up?
A: This hasn’t been systematically studied, but certainly the effect would be at least additive. There is a lot of individual variation.
What’s New with Pharmacotherapy in Obesity
Louis Aronne, MD (Weill Cornell Medical Hospital, New York, NY)
The esteemed Dr. Louis Aronne, known for his unique and aggressive pharmacological approach to obesity management, outlined his philosophy of medical intervention techniques. At its core, Dr. Aronne conceptualizes obesity as a disease of the hypothalamic reward and satiety centers in the brain. The prime challenge in this disorder is the plasticity of these systems: initial weight loss causes hormonal adaptations that prevent further weight loss, a phenomenon which explains why people tend not to ‘just lose weight.’ Dr. Aronne has ushered countless patients through these so-called plateaus in weight loss by essentially outmaneuvering this metabolic adaptation phenomenon. As soon as a plateau in weight loss arises, the patient alters their medication regimen to engage a new mechanism that targets a different part of the hypothalamic circuitry related to weight loss. Though this technique has been quite successful in producing lasting weight loss results, Dr. Aronne remarked that it is limited by the scarcity of available obesity medications – see our latest earnings roundup for an overview of the five players available for the treatment of obesity. He issued a call for more drug development in the obesity space, claiming provocatively that greater availability and diversity of obesity medications would result in “a lot less need for treatment of diabetes and hypertension.”
- Dr. Aronne remarked that obesity pharmacotherapy is startlingly underused: nearly half of US adults fit the criteria for the use of these medications according to the 2015 Obesity Pharmacology Guidelines, but only 2% of them receive such treatment. Thus, pharmacotherapy is being utilized by less than 1% of eligible patients who are overweight. This surely reflects a combination of the high cost of the available medications and the lack of conversation surrounding this option at most doctor’s visits; as well, an in-press study by Dr. Aronne suggests that prescribing bias is a major factor, which we don’t find difficult to believe at all. He found that virtually no weight-loss medications (1% of total prescription volume) are prescribed in the exercise-centric Pacific coast, as compared to nearly 45% prescription volume in the South.
- Diet and exercise count as a medication, according to Dr. Aronne. Therefore, in combatting a weight loss plateau, modification of one’s lifestyle is as important as modification of the pharmacological regimen.
- Dr. Aronne made it clear that pharmacotherapy should not be viewed as being in competition with surgery (an important point for this audience, given the Cleveland Clinic’s emphasis on and expertise in bariatric surgery and given that it is part of their profitable business!). Instead, he said, the two are complementary; medication can make additional weight loss possible after surgery, and can be used to stabilize or counteract the weight gain that typically occurs after surgery.
Questions and Answers
Q: You mentioned phentermine with lorcaserine. Is that approved?
A: That is off-label, but we do do it. We look at this the way we look at hypertension: there are many combinations of drugs that work well together but haven’t been particularly investigated in combination.
Drugs Therapies for Type 2 Diabetes and Obesity
Sangeeta Kashyap, MD (Cleveland Clinic, Cleveland, OH)
Type 2 diabetes is highly concordant with obesity, and yet many antihyperglycemic therapies (insulin, sulfonylureas, TZDs, etc.) exacerbate this problem by causing weight gain. Dr. Sangeeta Kashyap eloquently described years of progress in diabetes drug development, culminating in the emergence of glucose-lowering medications that also produce weight loss: SGLT-2 inhibitors and GLP-1 agonists. Dr. Sangeeta outlined the recent results of the EMPA-REG OUTCOME and LEADER trials, demonstrating weight loss benefits of ~2 kg for the SGLT-2 inhibitor empagliflozin and the GLP-1 agonist liraglutide (in addition to their cardiovascular benefits). Additional studies reveal weight loss benefits for other members of these drug classes, including the SGLT-2 inhibitor canagliflozin and the GLP-1 agonists exenatide, lixisenatide, albiglutide, and dulaglutide.
- In further illustration of the weight loss benefits of the GLP-1 agonist class, Novo Nordisk’s recently-approved obesity medication Saxenda is comprised of a high 3.0 mg dose of liraglutide. Because many patients experience difficulty getting insurance coverage for Saxenda, Dr. Kashyap recommends simply prescribing patients a double dose of Victoza (liraglutide). Presumably, however, many payers would also not cover this!
Questions and Answers
Q: What do you say to the patients who won’t take newer agents because of the risk of cancer?
A: The LEADER trial and the SUSTAIN 6 trials showed no sign of medullary thyroid cancer in these GLP-1 agonists. But the black warning labels are scary and I get a lot of questions about it. I counsel my patients that the cancer signal occurred only in rodent studies.
Session 6: Patient-Centered Treatment
In this patient-centric panel, a perennial and highly-anticipated event at the summit, six formerly obese patients took the stage to discuss their unique weight loss experiences overseen by physicians at the Cleveland Clinic. Walter, Daniel, and Kelly achieved weight loss using pharmacotherapy, whereas Terrence, Laura, and Uneeda underwent bariatric surgery. Though extremely diverse, the individual testimonies centered upon common themes of the importance of developing a regular exercise routine and eating healthfully, as well as the notion of weight loss as a very gradual journey with inevitable ups and downs. This fascinating and deeply personal session concluded with an illuminating Q&A session between all six patients and the audience of providers.
- Patient Testimony – Walter (weight: 265→182 lbs; BMI: 39.2→27 kg/m2; pharmacotherapy): What made me decide to lose weight? It’s pretty obvious why I needed to, I had diabetes and a lot of health problems. Exercise plays a huge role; I’m running on the treadmill seven days a week. If I was told a year ago I would wake up at 5:30 to work out I wouldn’t have believed it. Focusing on eating plain has also been key. When we do the shared appointments, you hear a lot of reasons why people can’t exercise. I own a couple of businesses, I have three kids, and I’m restoring a car. I’m busy but I find time to exercise. There’s no excuse; it’s something you have to schedule in, just like anything else in your day.
- Patient Testimony – Daniel (weight: 290→198 lbs; BMI: 37.2→25.4 kg/m2; pharmacotherapy): What caused me to gain weight? I was always big, and I gradually gained weight throughout my entire life. I went to see my primary care doctor because I was feeling particularly horrible, and he of course recommended losing some weight, and told me that I had type 2 diabetes and NASH. I felt like I needed to do something about it. It was my diabetes education classes that caused the wakeup call; that was the best thing for me. Everything that followed the diabetic diet caused weight to fall off. The importance of exercise and managing stress can’t be overstated. I work in IT and I like technology and metrics. I viewed my weight loss like a budget, calories in and calories out. I can be very strategic about that: I used my iPhone to track my steps, going for 10,000 per day, and used My Fitness Pal to log all of my food.
- Patient Testimony – Kelly (weight: 255→173 lbs; BMI: 41.2→27.7 kg/m2; pharmacotherapy): I dieted up and down my whole life. I can tell you that it is a marathon and not a sprint. Losing the weight has been a lifelong change for me, it has improved all of my health conditions. I’ve heard my peers speak about how the weight loss has improved their diabetes; I didn’t have diabetes to begin with but losing the weight has put my lupus under better control.
- Patient Testimony – Terrance (weight: 470→255 lbs; sleeve gastrectomy): I was always a big kid, people called me ‘Big Terry.’ I went to Cleveland Clinic for bariatric surgery and it’s been a blessing, the best decision I ever made. After losing the weight I can get out of a chair without sticking to the rails, and I’ve been ziplining! I realize that I’m not hungry anymore. I had some minor heartburn and constipation, after the surgery, but not really any major complications. The surgery forced me to limit my intake in food. I had done every diet known to man; they all seemed to work until you veered off. But you can’t veer off from bariatric surgery. It’s been one and half years, and I look forward to many, many more years of keeping it off.
- Patient Testimony – Laura (weight: 315→133 lbs; BMI: 52→22.5 kg/m2; gastric bypass): I came out of the oven chunky, and by the time I was 40 I weighed 300 pounds. I pursued gastric bypass surgery 18 years ago. My keys to success have been: (1) surgery done right; (2) continuing to educate myself in diet and nutrition, which has been key in maintaining my weight loss through the years; (3) keeping up with my vitamins after surgery; and (4) reconstructive surgery for my excess skin after surgery. This did wonders for my confidence. It was financially costly, but an investment in myself because I am now more comfortable in my own skin. Have I had ups and downs? Yes. I had a fall and a back injury. It took me out of the gym, and I regained about 35% of my weight. I felt very depressed and I was embarrassed to go back to the gym since I had been such a success at weight loss before and I felt like a failure. But my peers at the gym were good positive reinforcers. I encourage you to ask your patients to join a fitness center, the social support is great.
- Patient Testimony – Uneeda (weight: 204→125 lbs; BMI: 37→23; sleeve gastrectomy): I was randomized to the medication leg of the STAMPEDE trial. I lost some weight but I still wasn’t happy. I decided to do the surgery. And since then I’ve become active, I’m motivated, I walk. It’s been a wonderful thing for me. I had diabetes and was on metformin, Lantus, NovoLog…you name it I was on it. Now I’m in remission and my A1c is 5.7%. Since the surgery I’ve been eating right, and I’ve had no soda!
Q: Is anyone following a special diet?
Daniel: No, just watching what I eat.
Kelly: Restricting calories.
Terrance: Lots of protein.
Laura: I’m not a calorie counter but I’m on a low calorie, low glycemic index diet. I eat lots of nuts, and flaxseed oil. But I still like butter!
Anita: Protein bars, pure protein, premier protein shakes. And I watch my intake.
Q: Did your taste preferences change after surgery?
Walter: Yes! I crave mostly fruits and vegetables now. A Snickers bar isn’t as good as it used to be. The first thing I had that was sweet after surgery was a grape, and a grape never tasted so good before.
Q: How has your weight loss affected your family?
Walter: I’m lucky to have a great family and a great group of friends supporting me, and I’m very blessed on that front. I know a few people who have had this surgery and they didn’t seem to have the support at home that I had, and they experienced a reversal and gained weight.
Kelly: My family was very supportive. They think I’m too skinny! My friends have been phenomenal. I’m very lucky.
Q: How many of you exercise at least 30 minutes per day?
A: (All hands raised)
Q: Kelly, you mentioned that you have continued to lose weight continuously for 2 years. I think that’s very rare for non-surgical patients. What did you do?
Kelly: Once I hit a plateau I would decrease my calorie intake and change up my exercise routine. I go to Curves three times a week and walk the other days.
Q: Did your family adopt your positive habits? Did it improve their health too?
Walter: I do 99.9% of the cooking, so my family had no choice!
Daniel: There’s no way I could have done this without my wife, and she lost 25 lbs too.
Session 7: Obesity and Comorbidities
Cardiovascular Effects of Obesity
Steve Nissen, MD (Cleveland Clinic, Cleveland, OH)
Dr. Steven Nissen, the Cleveland Clinic’s Chairman of Cardiology and one of the most influential cardiologists in the US, gave what can be regarded as the summary talk of the conference. He demonstrated the clear link between BMI and cardiovascular disease risk, and then located obesity within the framework of other CVD risk factors. While as an individual risk factor obesity “only” ranks 4th with an odds ratio of 1.62 (versus smoking at 2.87, diabetes at 2.37, and hypertension at 1.91), obesity dramatically compounds the score of other risk factors: a hypertensive smoker with diabetes has an odds ratio of 13.0, and if obesity is added the odds ratio jumps to 21.0. While landmark studies such as the Diabetes Prevention Program Research Group’s 2002 NJEM paper demonstrate that modest weight loss substantially reduces the risk of diabetes, Dr. Nissen not all studies have been so conclusive. For instance, the Look AHEAD trial demonstrated that weight loss has a long-term positive impact on A1c, the study’s primary endpoint (a composite of CV death, non-fatal MI and stroke, and angina hospitalization) was not met (p=0.51) (NEJM 2013). In that study, of course, A1c was the primary endpoint and CGM wasn’t yet accurate enough so that time in range was also used as a secondary endpoint. On a further cautionary note, Dr. Nissen referenced the FDA approval and subsequent withdrawal of sibutramine, after a clinical study determined that the drug’s weight loss effects came with increased risk of cardiovascular events. The direct message was that weight loss always had to be placed within the context of cardiovascular safety.
- While not referenced in the slides, Dr. Nissen orally stated that he had reservations about bariatric surgery due to the lack of long-term outcomes studies. The Cleveland Clinic has been a pioneer in bariatric surgery and has contributed an enormous amount of data and knowledge about bariatric procedures to research. While there was no indication that Dr. Nissen was critical of current guidelines regarding bariatric surgery, he clearly sounded a note of caution in its further expansion pending better outcome data. This was very welcome from our view, particularly given perceived bias in all the discussion about bariatric surgery.
Questions and Answers
Q: Does bariatric surgery and weight loss objectively change coronary artery disease?
A: We’d love to look at this in bariatric surgery. It would be breakthrough to show in a clinical trial that surgery makes plaques smaller.
Q: There are 11 RCTs each with a five year follow up all showing that every cardiovascular marker gets better after bariatric surgery. Do we really need another costly RCT to end this debate?
A: Yes we do, and do you know why? The payers. If you can demonstrate objectively with a dedicated clinical trial that bariatric surgery has a cardiovascular benefit, everyone will come around. Until then we are fighting an uphill battle.
NASH/NAFLD: Challenging the Status Quo
Naim Alkhouri, MD (Cleveland Clinic, Cleveland, OH)
The Cleveland Clinic’s Dr. Naim Alkhouri spoke on the complicated topic of Non-Alcoholic Fatty Liver Disease (NAFLD). He started his session with an overview of the pathophysiology, epidemiology, and natural history of NAFLD, and followed with a discussion devoted to current challenges in the management of NAFLD. Dr. Alkhouri framed NAFLD as “the hepatic manifestation of obesity and insulin resistance,” with the liver contributing substantially to systemic insulin resistance. The disease progression in the liver begins with simple steatosis (presence of fat), leading to Non-Alcoholic Steatohepatitis (NASH), followed by fibrosis (scarring), which will eventually progress to cirrhosis (loss of function) if not addressed. NAFLD is further complicated by the fact that it tends to be asymptomatic until late stages of progression, which can take decades. NAFLD affects a staggering 30% of the US adult population, but the incidence is much higher in individuals with type 2 diabetes (up to 70%) or severe obesity (85%). According to Dr. Alkhouri, NASH management faces three principal challenges:
- Health care professionals tend to believe that NAFLD is not a serious disease in young patients. Dr. Alkhouri remarked that that “obesity is turning a generation of children into biological adults, ageing them before their time.” NAFLD is a manifestation of this – a 2009 study determined that children with the disease were faced mortality consequences and transplant needs within 20 years of diagnosis. NASH is the most rapidly increasing indication for liver transplant in young adults, with autoimmune/cholestatic indications staying steady and HCV decreasing rapidly. In fact, 10% of all liver transplants are currently due to NASH.
- Screening for NAFLD/NASH is not indicated, even in high-risk populations. Typically, NAFLD first presents as portal hypertension, often discovered in liver transplant evaluation. Dr. Alkhouri outlined a recent study reporting that out of 124 patients undergoing liver transplant evaluation, 85 (69%) had no knowledge of pre-existing NAFLD before presenting with portal hypertension symptoms. The tools for non-invasive quantitative screening are only now developing – FibroScan, a non-invasive device was approved in the US in 2013 (ten years after having been approved in Europe), allows for accurate NAFLD/fibrosis screening with a 10 minute test.
- There is no FDA-approved treatment for NAFLD/NASH. Despite the prevalence of NAFLD/NASH, there are currently no drugs approved for the treatment of this disease. Dr. Alkhouri provided an overview of several drugs in development – the FXR agonist and dual PPAR alpha/gamma agonist classes appear to be especially promising, see our NAFLD/NASH competitive landscape for more – and recommended that bariatric surgery also be considered as an option to treat NASH.
Questions and Answers
Q: Is metformin a therapy for NAFLD? And I’ve heard studies that black coffee helps, is this true?
A: Metformin is a great medication, but in RCTs it did not improve NASH, so I don’t use it for that. Many of my patients have many indications to be on metformin anyway. And yes, coffee is good for the liver! It has to be black coffee.
Brain and Psychiatric Comorbitidy
John Gunstad, PhD (Kent State University, Kent, OH)
An expert in neurocognitive aspects of obesity, Dr. John Gunstad (Kent State University, Kent, OH) took the stage to discuss the strong, but poorly-understood, link between obesity and psychopathology. Interestingly, individuals with various psychiatric conditions experience a greatly increased risk for obesity: 40-80% for depression, 50-90% for bipolar disorder, 60% for PTSD, and 60% for schizophrenia. Likewise, obesity is associated with a 4-fold greater risk of psychopathology. Dr. Gunstad pointed out that this association between obesity and psychopathology is difficult to study, but mounting evidence demonstrates common factors uniting these conditions. For instance, obesity and psychiatric conditions have a number of shared environmental risk factors – including stress, poverty, social isolation, early life trauma, and physical inactivity – as well as shared physiology. Furthermore, obesity and psychopathology involve similar neuroanatomical signatures such as reduced cortical thickness, gray matter volume, and white matter integrity in frontal and fronto-subcortical regions, and functional changes including impaired cognitive control and altered salience and reward networks. While not a surprise, our interest is certainly piqued by this relationship between obesity and psychopathology, especially as it relates to obesity’s status as a disease with a strong underlying neural dimension. These data further underscore the need for great attention to mental health as it relates to obesity, and including mental health professionals in the care of people with obesity.
Endocrine Causes of Obesity
Betul Hatipoglu, MD (Cleveland Clinic, Cleveland, OH)
Using case-based lessons, Dr. Betul Hatipoglu outlined how obesity can develop due to endocrine mechanisms. Notably, she described the crucial role of glucocorticoids in this process. Glucocorticoids, steroid hormones secreted in response to stress, have several effects on adipose tissue including: (i) increasing adipogenesis; (ii) altering adipocyte metabolism by decreasing glucose metabolism and increasing triglyceride synthesis; and (iii) altering adipokine production by increasing leptin produced in adipocytes and decreasing interleukins in stromal cells. By these mechanisms, repeated elevation of cortisol therefore promotes weight gain. In adipose tissue, cortisol is produced from a cortisone precursor in a reaction catalyzed by the enzyme 11β-HSD. Thus a vicious cycle emerges in individuals with excess adipose tissue, whereby increased cortisol levels promote further adipose tissue development (and thus more 11β-HSD-mediated cortisol production), followed by features of metabolic syndrome including glucose intolerance, hypertension, and dyslipidemia.
Shared Medical Appointments
Donna Ryan, MD (Pennington Biomedical Research Center, Baton Rouge, LA), Lauren Sullivan (Cleveland Clinic, Cleveland, OH), and Marianne Sumego, MD (Cleveland Clinic, Cleveland, OH)
An esteemed and entertaining panel featuring Dr. Donna Ryan (Pennington Biomedical Research Center, Baton Rouge, LA) and the Cleveland Clinic’s own Ms. Lauren Sullivan, RN and Dr. Marianne Sumego overviewed a unique facet of the Cleveland Clinic’s approach to obesity care: the shared medical appointment. These appointments are comprised of a 90-minute session moderated by a physician and facilitator, held simultaneously with a group of 10-15 patients with similar health concerns. Given its emphasis on camaraderie and social support, this model has proven to be highly effective. A recent study of shared medical appointments at a clinic in Palo Alto, CA found that over a two year study period, shared medical appointment patients experienced an average of 1% weight loss, as compared to 0.8% weight gain in a group of patients undergoing traditional care. We would be particularly interested in online versions.
Weight Loss Maintenance
Louis Aronne, MD (Weill Cornell Medical Hospital, New York, NY), Bartolome Burguera, MD, PhD (Cleveland Clinic, Cleveland, OH), and Leslie Heinberg, PhD (Cleveland Clinic, Cleveland, OH)
This well-attended and highly-interactive workshop focused on strategies to help patients maintain weight loss. The respected panel, including Dr. Louis Aronne (Weill Cornell Medical Hospital, New York, NY) and the Cleveland Clinic’s own Drs. Bartolome Burguera and Leslie Heinberg, led the audience in an engaging discussion on the challenges surrounding successful weight loss and weight loss maintenance with the following themes emerging:
- There are a range of factors that contribute to obesity, including evolution, environment, physiology, and pharmacotherapies:
- Dr. Heinberg: I try to help my patients understand that years ago our problem was not obesity, it was making it through the winter. We are all hardwired to be exceedingly good at holding onto calories and not losing weight. Unfortunately, tens of thousands of years have set our bodies up to function in one way, and the environment now works against it. Our biology is a mismatch for the current environment.
- Dr. Aronne: What the latest research shows is that the disease of obesity is due to hypothalamic neurons. The neurons get damaged when you eat fattening foods and have calorie overload. The satiety signal is degraded. That’s what makes the set point go up.
- Dr. Heinberg: As much as 15% of the obesity epidemic is due to drug side effects! Psychotropic medications in particular have a correlation.
- It is essential for physicians to work with patients to evaluate barriers to weight loss, and adjust the treatment regimen as needed to ensure successful weight loss and maintenance:
- Dr. Aronne: Physical activity is crucial. It doesn’t help much in the weight loss process, but for long-term maintenance it appears to be critical. With weight loss the muscle becomes more efficient and burns fewer calories. How do you prevent that? Exercise. Anaerobic exercise is best.
- Dr. Heinberg: It is essential to define weight loss goals in medical terms (such getting off medications or reaching a certain cholesterol level) and in terms of quality of life goals rather than milestone weights.
- Dr. Burguera: A lot of people don’t have the mental energy to focus on both diet and exercise, so we ask them to focus on diet first, and as that gets easier, we bring in the exercise.
- Dr. Aronne: If someone can’t adhere to a diet, yelling louder doesn’t work. Medicine is a good option after dietary intervention alone fails.
A Hands-On Approach to Health and Fitness Apps and Devices
Bret Goodpaster, PhD (Stanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL) & John Jakicic, PhD (University of Pittsburgh, Pittsburgh, PA)
Drs. John Jakacic (University of Pittsburgh, PA) and Bret Goodpaster (Stanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL) led a high energy and high participation session on fitness apps. The topic was extremely timely given Dr. Jakacic’s recently-published study in JAMA, which showed that the addition of wearable technology to standard behavioral therapy over 24 months led to worse outcomes than standard behavioral alone. While disappointing, the results added depth to a discussion regarding the advantages and disadvantages of wearable technology as it relates to weight loss. One widely acknowledged disadvantage to fitness apps and devices is the apparent lack of consensus among patients as to which provides the best features, potentially contributing to “technology exhaustion,” which often manifests itself around six months. Some physicians speculated that meeting one’s daily exercise goals (e.g. steps on a Fitbit) might lead to less focus on other goals, like diet.
- Drs. Jakacic and Goodpaster were most optimistic about the ability of technology to enhance information available to physicians, and thus improve physician/patient communication. They presented data showing that shared data potentially could replace weekly office visits with telephone calls, with better effect on weight loss.
--by Abigail Dove, Terry Vance, Sarah Odeh, and Kelly Close