February 27-March 2, 2013; Paris, France – Full Report – Draft

Executive Highlights

This sub-section of the report contains our coverage of type 2 diabetes, obesity, and bariatric surgery. We include our theme below, followed by our full commentary. Talk titles highlighted in blue were not previously published in our daily reports, while talks titles highlighted in yellow represent just a small sample of some of the most memorable presentations we heard.

• This year’s ATTD brought a smattering of talks specifically addressing type 2 diabetes and obesity. A session on regional differences in type 2 diabetes treatment brought perspectives from China (Dr. Linong Ji), Europe (Dr. Cees Tack), India (Dr. Shashank Joshi), and the US (Dr. Irl Hirsch). Dr. Richard Bergenstal (International Diabetes Center, Minneapolis, MN) also discussed type 2 therapies in a session entitled “Treatment or Cure T2D” – GLP-1 receptor agonists were his clear favorite for optimizing A1c without weight gain or hypoglycemia. The session also included presentations by Drs. Dimitri Pournaras (Imperial College London, UK) and Dr. David Flum (University of Washington, Seattle, WA) on endoscopic alternatives to traditional metabolic surgery and the cost/benefits of metabolic surgery, respectively. Dr. Walter Pories (East Carolina University, Greenville, NC) also addressed metabolic surgery in one of our favorite presentations of the entire conference. He explored factors contributing to the under utilization of bariatric surgery in type 2 diabetes and obesity. Zeroing in on obesity therapies, we also heard from Aspire Bariatrics CEO Dr. Katherine Crothall who described the company’s minimally invasive AspireAssist approach. Albeit small, we’re glad to see some focus on type 2 diabetes and obesity at ATTD – the need is certainly huge, and we believe technology can help pave the way towards better outcomes.

Type 2 Diabetes, Obesity, and Bariatric Surgery

Session: ATTD Yearbook

BARIATRIC SURGERY AND DIABETES: ACCESS DENIED

Walter Pories, MD (East Carolina University, Greenville, NC)

“Medical treatment of type 2 diabetes has not been as successful as we had hoped,” said Dr. Pories. In spite of the broad armamentarium and recent advancements in drugs, type 2 diabetes remains a primary or major cause of myriad comorbidities and a major cost to healthcare systems. He explained that bariatric surgery can induce full and durable remission of type 2 diabetes in 80-95% and results in a reduction of mortality from type 2 diabetes of 82%; however, the use of bariatric surgery has plateaued in the US (Livingston, Am J Surg 2010). Dr. Pories attributed the failure to use this therapy to three factors: 1) excessive requirements by insurance carriers; 2) failure to educate the public; and 3) a lack of communication between endocrinologists and “metabolic” surgeons. He believes the latter is the primary culprit and called for greater collaboration. Addressing the endocrinologists in the audience, he concluded, “We need your help. We need your help now.”

• “Imagine if someone had invented a pill that induced full and durable remission of type 2 diabetes in 80-95% of cases.” Bariatric surgery can provide this benefit, explained Dr. Pories. The procedure has safety comparable to a routine cholecystectomy (90-day mortality of 0.3%) and costs ~$18,000, an amount which is recovered in medication alone in two years time according to Dr. Pories. He did not specify bariatric surgery type during his presentation; however, we assume his discussion was focused on Roux-en-Y Gastric Bypass.
• Excessive requirement by insurance carriers exclude many patients from bariatric surgery. First, carriers require medical documentation of five years of obesity. Second, qualification requires documentation of six months of professional dietary supervision. Third, qualification is based on weight requirements that “make no sense.” Dr. Pories believes strongly that BMI is not an appropriate metric to deny access to bariatric surgery as it discriminates by age, gender, race, and fitness. To drive his point home, he described a 5’ 8” male with a BMI of 47 kg/m2, which would qualify the individual for bariatric surgery. You could never catch him though, said Dr. Pories, as the individual is also Eastern Carolina University’s fastest running back. Dr. Pories argued that the indication for metabolic surgery should be the same as the indication for other surgical procedures: when the disease can no longer be managed well by medical measures.
• Most people have never heard of the bariatric field. Said Dr. Pories, the failure to educate the public about bariatric surgery and the benefits of bariatric surgery for patients with diabetes is a major barrier to patient use.
• “It’s time for an endocrinology and metabolic surgery partnership.” Cardiologists collaborate with cardiac surgeons and neurologists with neurosurgeons, said Dr. Pories. Metabolic surgeons need the help of endocrinologists. Especially because of the substantial changes that patients go through following bariatric surgery, endocrinologist involvement becomes very important.
• For more reading on bariatric surgery, see our interview with Dr. David Cummings (University of Washington, Seattle, WA) at http://www.closeconcerns.com/knowledgebase/r/b406ae78.

DIABETES TECHNOLOGY AND THE HUMAN FACTOR

Bruce Buckingham, MD (Stanford University, Stanford, CA)

The charismatic Dr. Bruce Buckingham rounded out this year’s ATTD yearbook session with a presentation on the impact of patient attitude on type 2 diabetes treatment success. He described the “vicious circle” by which negative attitudes result in treatment neglect, and thus, more diabetes care failures. These failures only further perpetuate the patients’ negative attitudes, which recharge the circle. In a study of newly diagnosed patients with type 2 diabetes following short-term continuous subcutaneous insulin infusion treatment, patients who experienced remission (defined as being drug free for one year with fasting glucose <126 mg/dl and two hour glucose tolerance test <180 mg/dl) tended to have lower “negative attitude” scores and higher care ability scores (Chen et al., Diabetes Care 2012). Dr. Buckingham believes that an absent psychosocial support system for patients with type 2 diabetes could be contributing to these negative attitudes and poorer health outcomes. He concluded, “it is important to invest in the psychosocial support of patient with type 2 diabetes.” We are so glad to hear increasing focus in this area.

Session: Medical Treatment of Type 2 Diabetes – Are There Regional Differences?

MEDICAL TREATMENT OF T2D IN CHINA

Linong Ji, MD (Peking University Diabetes Center, Beijing, China)

Dr. Linong Ji ably demonstrated that the burden of diabetes in China is huge. Currently about 10% of Chinese people have diabetes, control of type 2 is poor, and the pattern of medical treatment is glucose centric. Guidelines are similar to IDF, with metformin as first line therapy. The only notable difference is the greater use of acarbose (27% of patients). Current hypoglycemic medications have the same effect in Asians and Caucasians, so it seems that China does not need a population specific drug for diabetes.

• In a 2007 study, it became clear that the diabetes prevalence in China is 9.7% for type 2 diabetes. Over 70% of people with type 2 diabetes also have other cardiovascular risk factors and as expected, their complications scale with the duration of diabetes. Forty-five percent of Chinese people with type 2 diabetes have an A1c less than 7%, and 31% have an A1c less than 6.5%. However, only 5% have A1c <6.5% and blood pressure and lipids at target. This data is taken from the China cardiometabolic registry from a set of n=25,460 type 2 patients.
• In China, 5% of type 2 patients are on diet/exercise, 50% are oral agents only, 15% insulin only, and 30% insulin + oral agents. Thirty eight percent take metformin, 29% take sulfonylureas, 27% take acarbose (different from Western countries). Almost no patients use incretins since they have only just launched and are not (yet) reimbursed.
• The current (2010) Chinese guidelines are similar to the current IDF treatment algorithm. Metformin is first line therapy, second line is an insulin secretagogue or acarbose. Third line is basal/premix insulin or a secretagogue/TZD/DPP-4/GLP-1. Fourth line is basal/bolus insulin therapy (or a move to basal/premix insulin).
• Although Chinese BMI at diagnosis is lower than Caucasians, the differences in drug effects between Asians and Caucasians at any BMI are much smaller than many people believe. In a study of n=33 newly diagnosed patients with type 2 diabetes, metformin had no difference in effectiveness across BMI groups. Acarbose reduced A1c by the same amount (~0.7%) in both Asians and Caucasians. The same finding holds for TZDs. Sitagliptin (Merck’s Januvia) appeared to reduce A1c by 1.0% in monotherapy with an Asian population, and exenatide twice daily (Amylin’s Byetta) and once weekly (Amylin’s Bydureon) appeared similar across the races (A1c -0.85% for twice daily, and a further -0.3% for once weekly). Dr. Ji commented that to date they have not found any relationship between BMI and the treatment efficacy of a drug.

Questions and Answers

Q: What is the value of traditional Chinese medicine (TCM) in diabetes?

A: We have compared a combination of fixed dose TCM plus glyburide versus glyburide alone. We found no hypoglycemic effect with TCM, but the risk of hypoglycemia did decline. There is also no evidence that Chinese herbs can be used as a weight loss agent.

MEDICAL TREATMENT OF T2D IN EUROPE

Cees Tack, MD, PhD (Radboud University Nijmegen, Nijmegen, The Netherlands)

Europe is very diverse and heterogeneous. There are large regional differences in healthcare delivery and results across the countries. There has been a rapid increase in diabetes prevalence in Europe over the past few decades, but this is partly because we are catching patients earlier. In fact, Europe’s population, while still growing, is likely past the point of peak growth, according to Dr. Cees Tack. Although there has been a gradual improvement in average A1c across Europe, the big problem is rising cost as a percentage of GDP. Costs are set to rise as the population ages in the absence of strong economic growth. Dr. Tack suggested that the solution is to enforce performance at the primary care level, particularly by the use of specialist nurses, who are more cost effective and have been shown to improve standards.

• There has been a rapid increase in diabetes prevalence in Europe over the past few decades, but Europe’s healthcare system is catching patients earlier. The evidence for this is that at diagnosis, hardly anyone has retinopathy any more. But, Dr. Tack is confident that there will be more patients in future – that’s because the population is ageing, there is likely to be an increase in obesity, there are still undiagnosed cases, and because people with diabetes will likely live longer. But Europe’s prevalence, although still growing, is likely past the point of peak growth rate, unlike Asia (for example).
• There has been a gradual improvement in average A1c in Europe, most likely because of guidelines and increased focus on optimizing therapy. There might also be an effect of earlier diagnosis. The UKPDS suggested that diabetes is a progressive disease; however, in the more recent ADVANCE trial, the control arm stayed stable for six years. This is probably because of a progressive improvement in optimizing glucose control at physician practices. The PANORAMA study showed a variety of control in EU countries, but the average isgood (around 7%) and is improving because reimbursement is increasingly based on following guidelines. Dr. Tack also noted that practices that are nurse led obtain lower A1c levels.
• The cost figures for healthcare are staggering, yet they are set to go up as a percentage of GDP, meaning that cost will become more and more of an important issue. The UK spends 9.4% of its GDP on healthcare and Germany 11.6%, compared with 17.6% in the US and 11.4% in Canada. Since there is an ageing population in Europe with no strong economic growth, healthcare costs are expected to increase. In diabetes, drugs are getting more expensive and long-term complications are costly.
• The key to good cost effective diabetes care is strict treatment protocols, enforcing the performance of primary care with quality indices, and utilizing specialist nurses wherever possible.

MEDICAL TREATMENT OF TYPE 2 DIABETES IN INDIA: THERAPIES AND TECHNOLOGIES 2013

Shashank Joshi, MD (Lilavati and Bhatia Hospital, Mumbai, India)

Dr. Shashank Joshi gave a high-speed, data-driven presentation on the Asian Indian phenotype and its implications for diabetes treatment. The burden of diabetes is especially sobering is India – approximately 62.4 million have diabetes and 77 million have prediabetes. Dr. Joshi posited that the “thin-fat” (i.e., higher truncal and abdominal adiposity) sarcopenic phenotype of Asian Indians make this ethnic group particularly susceptible to type 2 diabetes. To demonstrate this phenotypic discrepancy, Dr. Joshi showed a comparative body composition study in which Asian Indian males had body fat/BMI ratio of 1.34 vs. 1.02 for African Americans and 1.01 for Caucasians (Banerjee et al., J Clin Endocrinol Metab 1999). Myriad factors contribute to this phenotype (nutritional imbalance, physical inactivity, genetic predisposition, early-life adverse events), which in turn contribute to higher rates of insulin resistance in this population, a lower age at onset of type 2 diabetes, and a lower BMI threshold for diabetes. Taking this phenotype and higher carbohydrate loads into consideration, Dr. Joshi suggested that Asian Indians may require lower doses of DPP-4 inhibitors, GLP-1 analogs, and TZDs (with the caveat that more studies are needed). With a carbohydrate-rich diet, alpha glucosidase inhibitors also have a more potent effect. You need the right treatment for the right patient at the right time, said Dr. Joshi, but it also has to be affordable. The proposed Indian diabetes treatment algorithm is designed to take the latter into consideration as well.

• The proposed treatment algorithm starts with lifestyle and metformin. After which if A1c is greater than 7% and the patient can afford it and is obese, liraglutide is added to the therapy. If the patient can afford it and is non-obese, DPP-4 inhibitor is added. If the patient cannot afford liraglutide/DPP-4 inhibitor, a low dose SFU is added. If the patient remains uncontrolled on these therapy combinations, insulin is considered next.

Questions and Answers

Q: There is a difference in the type of grain consumption in Northern versus Southern India. Is there a difference in incidence of diabetes?

A: No, wheat is as bad as rice and both our cereals are refined.

Q: My question is in a high glycemic stress situation, would an SFU be appropriate or would it accelerate beta cell damage? And what are your thoughts on early introduction of insulin?

A: We have used insulin pumps even in patients with type 2 diabetes. The first part of your question is logical. If you use secretagogues, you could get beta cell burnout, but we need prospective data. In India secretagogues are still used because of the cost, though if patients can use gliptins that is a good choice.

MEDICAL TREATMENT FOR TYPE 2 DIABETES IN THE UNITED STATES: GOOD, BAD, OR UGLY?

Irl Hirsch, MD (University of Washington, Seattle, WA)

“Treatment for type 2 diabetes in the US is sometimes good, often bad, and invariably ugly,” said Dr. Irl Hirsch in his review of US’ healthcare system and type 2 diabetes care. His presentation began with broad discussion on healthcare costs for diabetes – in 2007, 20% of US healthcare dollars was spent caring for patients with diabetes and 10% was spent directly on diabetes and its complications (ADA, Diabetes Care 2008). The challenge in treating diabetes is compounded by fragmented and inconsistent healthcare structures. Dr. Hirsch explained that there is no “one system” for diabetes management; rather, different payers have different costs for drugs and services and different providers have different care approaches. For Americans with insurance, the cost of managing type 2 diabetes can be challenging or prohibitive. For Americans without insurance (53 million; 17.6% of the population), the cost is even more so. Necessarily, on both the state and federal level, discussion is ongoing as to the best approach to curb costs whilst improving care – Dr. Hirsch believes that accountable care organizations have the potential to incentivize value in healthcare systems. Certainly, creative approaches to address both cost and quality need to be considered and Dr. Hirsch predicts that in the type 2 diabetes arena, healthcare system innovation (more so than drug innovation) will be the focus of the next decade.

Questions and Answers

Q: In the US we’re unique in being an extremely litigious society and I think that needs to change.

A: Tort reform and concerns about malpractice – it is very different depending on the state you live in. In Florida it’s extremely litigious. Where I live now, not so much so. Medicare keeps track not just of physicians, but regions. Where I live in the Pacific Northwest, we are spending less on healthcare than other parts of the county and I think it is because of that.

Q: You predicted that healthcare innovation will be focused on system changes. I make the argument that behavior changes are even more important. Is the healthcare system going to help people self manage their diabetes?

A: I think that’s true. But there are caveats to that discussion and that has to do with the huge number of patients living in poverty where they don't have access to all the technologies and tools. In the end, from a system’s point of view, they cost more. But your point is well served and I do agree with it.

Session: Treatment or Cure T2D

INTERVENTIONAL APPROACHES TO TYPE 2 DIABETES

Dimitri Pournaras, PhD (Imperial College London, London, United Kingdom)

Dr. Dimitri Pournaras discussed many aspects of bariatric surgery, but focused on endoscopic alternatives to traditional metabolic surgery. He presented unpublished, encouraging one-year data on GI Dynamics’ EndoBarrier; he also conveyed enthusiasm for Aspire Bariatrics’ AspireAssist and for endoscopic vertical gastroplasty. To conclude he encouraged greater cooperation between surgeons and diabetologists; he also called for wider use of regimens that combine both surgery and medication.

• Dr. Pournaras briefly mentioned several studies of metabolic surgery’s efficacy and safety. For example, the Swedish Obesity Study has shown that metabolic surgery is effective at forestalling diabetes onset in high-risk patients (Carlsson et al., NEJM 2012) and preventing heart attacks (Romeo et al., Diabetes Care 2012), among other benefits. Surgery’s effects seem to involve the path of nutrients down the gut (rather than just caloric restriction), as seen in a small study of roux-en-Y gastric bypass surgery patients who were temporarily fed via gastrotomy (Pournaras et al., Surg Obes Relat Dis 2012).
• Endoscopic procedures tend to be less effective than roux-en-Y gastric bypass, but Dr. Pournaras suggested a few situations in which they can be particularly useful. He noted that many patients might want traditional metabolic surgery but have too low a BMI to receive it. (For such patients, Dr. Pournaras said, “I am sure that we can do more than say ‘come back when you are heavier.’ ”) Another indication is “bridge treatment” for patients who are too heavy for highly invasive procedures; endoscopic interventions might reduce these patients’ weight enough so that major surgery can be safely performed. He also suggested endoscopic therapy as a form of palliative care in homebound, terminally ill patients with extreme obesity (e.g., BMI ~70 kg/m2).
• The intragastric balloon is probably the most widely accepted endoscopic intervention for obesity, Dr. Pournaras said. As a reminder, the balloon is placed inside the stomach and filled with air and liquid up to a volume that patients feel fuller while eating less food. Dr. Pournaras showed unpublished data on 33 patients who, with the balloon, reduced mean BMI from 65 to 56 kg/m2. He said that balloons were “very good” for patients trying to lose weight in preparation for true bariatric surgery, but that they can cause complications. (He mentioned that sometimes patients feel too sick to drink anything.)Endoscopic vertical gastroplasty has yielded “promising results” – weight loss of roughly 10 kg. Dr. Pournaras noted that this technique involves using sutures to reduce the size of the stomach. It has been advanced by Massachusetts General Hospital and the Cleveland Clinic.
• Dr. Pournaras briefly mentioned Aspire Bariatrics’ AspireAssist Aspiration Therapy System, which he called “an excellent idea.” As a reminder, patients using the system wear a percutaneous endoscopic gastrotomy (PEG) tube, through which they aspirate (drain) roughly 30% of their caloric intake after meals. (For details on the AspireAssist, see our coverage of Dr. Katherine Crothall’s presentation at ATTD 2013.) Dr. Pournaras noted that one might expect “biochemical disturbances” from periodic draining of the stomach, but he said that these seem not to have occurred in clinical studies to date.
• Dr. Pournaras presented unpublished, one-year data from a pilot study of the EndoBarrier – GI Dynamics’ duodenal-jejunal liner, which prevents nutrients from contacting the foregut. The study was carried out in Brazil under the leadership of Dr. Ricardo Cohen (Oswaldo Cruz Hospital, Sao Paolo, Brazil), in collaboration with Imperial College London. It enrolled 16 patients with type 2 diabetes duration of two-to-10 years and A1c between 7.5% and 10.2%. All of the participants were taking metformin, and none were taking insulin or incretins.

  • Mean baseline A1c was slightly over 30 kg/m2; small (but statistically significant) reductions in mean BMI were observed at both 12 and 52 weeks.

• More striking was the decline in mean A1c from 8.6% at baseline to 7.5% at 52 weeks. Also of note, 62.5% of participants had A1c below 7.0% at 52 weeks. When the EndoBarrier was explanted, patients’ A1c rose, but not at a very sharp rate. Dr. Pournaras portrayed the slow rise as a relatively encouraging sign, and he attributed it to a legacy effect of good control while the EndoBarrier was implanted.
• Insulin secretion did not change with the EndoBarrier, as it does with roux- en-Y gastric bypass; however, insulin sensitivity improved during the first week after implantation – before any significant weight loss had occurred. Dr. Pournaras noted that food intake did not change; he reminded the audience that the study participants were already eating fairly low-calorie diets before implantation. During the panel discussion, Dr. Pournaras emphasized that these data are still quite new and that researchers are still figuring out why the EndoBarrier has its particular profile of metabolic effects.
• “At the moment we are treating metabolic surgery as a shotgun; we need to make it a laser beam.” Dr. Pournaras called for a redoubling of efforts to understand metabolic surgery’s effects, to advance the development of therapies that have less risk, with similar or greater efficacy. He also hopes that clinicians will become better at predicting which patients are likely to benefit from an intervention. In the interim, Dr. Pournaras advised his surgical colleagues to remain vigilant of safety concerns and to cooperate with diabetologists for multi- disciplinary interventions. He encouraged listeners to tell their funders that traditional surgery, endoscopy, and medications should all be offered to people with diabetes – after all, as he remarked, “We don’t ask cancer patients to choose between endoscopy and chemotherapy.”

MOVING BEYOND A1C – ROLE OF INCRETIN THERAPY IN IMPROVING A1C WITHOUT HYPOGLYCEMIA OR WEIGHT GAIN

Richard Bergenstal, MD (International Diabetes Center at Park Nicollet, Minneapolis, MN)

In the view of Dr. Richard Bergenstal, “moving beyond A1c” is a theme that runs throughout ATTD, with its emphasis on myriad new ways to characterize, measure, and improve diabetes control. He said that in today’s world, a glucose control therapy is expected not only to optimize A1c but also to minimize hypoglycemia and glycemic variability, to avoid weight gain (and ideally cause weight loss), and to improve quality of life. On that note, he said that GLP-1 receptor agonists consistently outperform other agents in aggregate metrics such as percentage of patients who achieve A1c of 7.0% without weight gain or hypoglycemia (Zinman et al., Diabetes Obes Metab 2011; Bergenstal et al., Diabetes Obes Metab 2013). (Dr. Bergenstal acknowledged that many of his colleagues oppose such composite endpoints, but he also noted that they seem to be the way of the future. According to proposed quality performance standards for diabetes management, accountable care organizations would be evaluated based on the percentage of patients who meet the target for all five of: A1c, blood pressure, LDL cholesterol, not smoking, and taking aspirin.) Of course, much remains unknown about the long-term safety of incretin agents, as highlighted just days before in a much-publicized database study suggesting that the drugs double patients’ odds of pancreatitis (Singh et al., JAMA Intern Med). Dr. Bergenstal seemed to agree with the joint ADA/AACE response to the paper, which cautioned patients and providers not to quit their drugs because of observational findings, limited as such studies inherently are – especially with large, long-term randomized controlled trials set to report in the relatively near term.

A PUBLIC HEALTH PERSPECTIVE ON THE COST/BENEFIT OF SURGERY FOR DIABETES

David Flum, MD, MPH (University of Washington, Seattle, WA)

Dr. David Flum invited each member of the audience to imagine that they were the nation’s “health czar” and to address two key questions about metabolic surgery: “Is it worth it?” and “Can we afford it?” Many modeling studies have indicated that metabolic surgery should be cost-effective or even cost- saving, given its myriad health benefits. However, real-world data have not shown great cost differences with surgery, suggesting that the models are flawed (Zingmond et al., JAMA 2005; Maciejewski et al., Arch Surg 2012; Weiner et al., JAMA Surg 2013). Dr. Flum suggested that future research should involve reconciling these discrepancies, understanding the impact of metabolic surgery within various health systems, modeling ramp-up costs (e.g., training enough surgeons to meet a large increase in demand), and weighing the tradeoffs of metabolic surgery and other healthcare expenditures.

PANEL DISCUSSION

Bruce Bode, MD (Emory University, Atlanta, GA); Dimitri D. Pournaras (Imperial College London, London, United Kingdom); Richard Bergenstal, MD (International Diabetes Center at Park Nicollet, Minneapolis, MN); David Flum, MD, MPH (University of Washington, Seattle, WA); Dr. Walter Pories (East Carolina University, Greenville, NC)

Q: Is it just absence of food that causes quick remission of diabetes in the first couple weeks after surgery?

Dr. Flum: Animal studies are looking at three main hypotheses about why surgery affects diabetes so quickly: exclusion of food in foregut, accelerated delivery of food to hindgut, and partial vagotomy. There are theories about bile salts, as you heard, but I think these fall into the gut-location categories. To your question, I would mention Dr. le Roux’s group’s study in which gastrotomy effectively turned diabetes on and off. It is a very exciting time to be in this field.

Dr. Pournaras: Bile acids seem to combine the proximal and distal gut hypotheses. The way I see it, bile salts may be a message from the proximal to the distal gut. It improves your insulin sensitivity but also your GLP-1 production.

Dr. Pories: We now think that the gut is a very carefully synchronized organ. If you interrupt that in any way, it seems to interrupt diabetes. You can move part of the distal jejunum up and have diabetes taken away.

Q: I run an adolescent obesity clinic. One of my patients is 15 years old and has BMI 45. She’s black and has insulin resistance. What would you recommend to such a patient?

Dr. Flum: LABS is a Framingham-like study of 5,000 patients with bariatric surgery to see the effect of risk factors on their lives. Dr. Pories and I are co-investigators. Tom Inge in Cincinnati is running a teen version of LABS to guide people like the patient you describe, but right now there is a paucity of data. Gastric bypass is typically thought of as an irreversible procedure … this may be a place where adjustable gastric banding has a real role to play. In some sub-cohorts, it is more effective than in the adult population.

There is also a Swedish study, similar in design to the SOS, that reported outcomes in obesity last year. Mainly these patients received bypasses; so far it is still in its early days, but it has shown that younger patients respond to surgery in a very similar way to adults. But one important question that you mentioned is, “what do you have to lose?” Her risk at the moment is extremely high. She probably won’t make it to 65 years old.

Dr. Pories: Teenagers who receive bariatric surgery tend to see remarkably better in terms of socioeconomics, performance in school, etc.

Comment: I worry more about my type 2 patients than my type 1s.

Dr. Bergenstal: We diabetologists have to rethink our algorithms maybe. I didn’t see surgery on there, but maybe that will change.

Dr. Flum: [Regarding the large hall’s sparse attendance] If this session had been on a drug with this profile, I think that there would be a lot of interest in the diabetological and endocrinological community.

Dr. Pories: It is also striking to me that we talk so much about the cost-effectiveness of this operation. We do not ask that question of hip replacement or cancer surgeries.

Dr. Flum: Or GLP-1 receptor agonists.

Q: Dr. Bergenstal, I have been studying the positive effects of GLP-1 receptor agonists on cognitive dysfunction in type 2 diabetes. Do you have anything to share from your personal studies?

Dr. Bergenstal: I am not sure whether this would reflect a direct effect of incretins or avoidance of hypoglycemia, which might be aggravating to cognitive dysfunction. I have no other specific insights. Do you have any, Dr. Bode?

Dr. Bode: Not that I’m aware of. Memory loss will be an adverse event in the ongoing cardiovascular outcomes trials, so hopefully a signal would be picked up, but maybe not.

Dr. Bode: How would you explain that the sleeve is almost as good as bypass from a weight- loss and diabetes perspective?

Dr. Flum: It is unclear if the time-course is as quick with the sleeve as with bypass. This is why Dr. Phil Schauer’s study is especially important. It did not look as good as bypass in that study, and is probably not as good as bypass. Its effects may be related to ghrelin, which is dramatically altered.

Dr. Pournaras: I think that the sleeve does exactly the opposite of what it was ‘supposed’ to do [i.e., make the stomach smaller so you eat less at a time]. You have quicker delivery of nutrients down your gut. If you have nutrients hitting faster, you are more likely to produce GLP-1. If you change the dynamics of nutrients and bile, do you get bile or food hitting the gut first, or is it a combination of the two? I definitely don’t think that it is because you have a smaller stomach.

Dr. Bode: A 50-year-old patient comes in with diabetes and a BMI of 45 kg/m2, and says “tell me doc, what do you think is best treatment for me?” They are 50 years old. What will you tell them?

Dr. Flum: We are surgeons. We would have a conversation about their goals. If they are trying to cure their diabetes, that to me is perfect case for surgery.

Dr. Pories: [Commenting on the session’s small audience] The overall attendance at this meeting is 2300 people. Yet when you talk about this technique that literally reverse disease at a diabetes session, it’s interesting to how little we talk to each other.

Dr. Bergenstal: We [diabetologists] are talking a lot more surgery now than we used to. It’s not a slam- dunk that it’s automatic, but we will have a discussion with patients and probably give them more time to think about it while they are still on their medications.

Dr. Flum: I think it’s on the ADA/EASD algorithm for patients with BMI at or above 40 kg/m2.

Dr. Bode: Yes, but patients who actually get surgery also tend to be ‘failing everything else.’ They’ve tried everything. My question is, do any of you use banding?

Dr. Flum: It varies by country. I don’t really see anyone putting in bands in the states anymore.

Dr. Pournaras: In the UK, we ask first, “do you want to have surgery,” then “what do you want to do.” There is level-one evidence that laparoscopic adjustable gastric banding is very good for diabetes.

Dr. Pories: Dr. Flum, it was interesting that in the example you gave us, the beginnings of cardiac surgery, the mentality was “if it’s really bad, then we’ll send it to the surgeon.”

Dr. Flum: As you play with it, the patient gets to be older and have inulin resistance, and it gets to be a more complex situation.

Dr. Pournaras: For patients with BMI 50 kg/m2, guidelines say that surgery is the primary model of care. We don’t actually do that on the whole, but that’s what the guidelines say.

Dr. Bode: When would you recommend sleeve gastrectomy instead of gastric bypass?

Dr. Flum: There is a risk profile that is in some ways better with the sleeve than with bypass. Some feel that post-surgical recovery is quicker. There is no clear advantage of the sleeve over bypass. Certainly we have more information about bypass.

Dr. Flum: And some insurance agents don’t feel that there is enough evidence for the sleeve.

Dr. Pournaras: With the sleeve, the long-term evidence is very limited. With bypass, you know that we have 40-year data.

Dr. Flum: The datasets on gastric bypass are more like 10-to-15 years old.

Dr. Pournaras: For the large studies, yes, but there are people alive who had gastric bypass 40 years ago. There are no data on beyond ten years with gastrectomy. You would not meet someone who had a gastrectomy more than 40 years ago.

Dr. Bode: This is a very important treatment, and I am sorry that there isn’t a bigger crowd here.

International Fair of New Technologies in Diabetes

ASPIRE BARIATRICS: ASPIRATION THERAPY – A NOVEL APPROACH TO WEIGHT LOSS

Katherine Crothall, PhD (CEO, Aspire Bariatrics, King of Prussia, PA)

Dr. Katherine Crothall gave a quick summary of Aspire Bariatrics’ Aspiration therapy, emphasizing its safety, efficacy, and favorable comparison to bariatric surgery. With Aspiration Therapy, patients “aspirate” (drain) a portion of their stomach contents into the toilet after each meal through an endoscopically-implanted percutaneous tube – the process drains ~30% of calories consumed and takes about 5-10 minutes. To date, 54 patients have had tubes implanted (20-minute outpatient procedure), and the safety profile has been positive: 100% implantation success, only 1/54 patients had difficulty tolerating the tube, no serious adverse events, and all that on top of a long history with PEG tubes (used for over 30 years). Weight loss with Aspire’s product is similar to conventional sleeve gastrectomy/banding: ~22% body weight loss at 52 weeks (50% excess weight loss) and comparable data at 104 weeks. The device has a CE Mark and approval in New Zealand, Saudi Arabia, and Israel (filed in Australia and Canada). Sales have begun in several countries. A 10-center, 175-patient US pivotal study is currently recruiting participants (ClinicalTrials.gov Identifier: NCT01766037) and expected to complete in July 2014. The safety and efficacy data to date looks encouraging – for us, one key question is patient perceptions of the device. Dr. Crothall addressed this quite well in her presentation, and we look forward to learning more once a greater number of individuals use the device.

• With Aspiration Therapy, patients “aspirate” (drain) a portion of their stomach contents into the toilet after each meal through an endoscopically implanted tube. Aspiration performed about twenty minutes after a meal will remove about a third of the calories consumed. The tube is implanted in the stomach, and leads to a “low-profile” port at the surface of the skin.
• Weight loss with Aspire’s product ~22% body weight loss at 52 weeks (50% excess weight loss) and comparable data at 104 weeks. In the feasibility study, there were no non-responders to Aspiration therapy:

• In clinical studies, the most common complications were abdominal discomfort and constipation/diarrhea. Dr. Crothall notes other less commonly reported risks (infection, anemia, and buried bumper syndrome) were generally resolved with medical care or tube replacement. As with PEG tubes, the body “heals” around the implanted tube, reducing susceptibility to infection. Two concerns are a reduction in serum iron (typically seen with weight loss) and hypokalemia – Aspire is recommending prophylactic use of potassium, proton pump inhibitors, and iron supplements (the latter only for patients with low iron). However, in Sweden, a lack of supplementation has not been a problem.
• Dr. Crothall highlighted that unlike many other weight loss procedures, Aspiration therapy is minimally invasive and completely reversible at any time. The AspireAssist can be removed at any time though a simple 15-minute non-invasive outpatient procedure. Removal is similar to the placement procedure, and is performed under conscious sedation (general anesthesia is not required). The A-Tube site usually closes naturally on its own afterwards.
• In preliminary type 2 diabetes data (n=6), A1c declined from 7.1% to 6.2% at 10 weeks. This is an impressive reduction in a fairly short time period – we wonder if Aspire could pursue a type 2 diabetes-specific indication like GI Dynamics. Given the challenges of obesity reimbursement (this is certainly changing, but it’s still early days), pursuing the diabetes route could be a promising approach for the company. We’d suspect hypoglycemia could be concern for insulin users, though certainly oral users could stand to benefit; from a payer perspective, the potential for diabetes remission would certainly make reimbursement attractive.
• Dr. Crothall remarked that patient acceptance of the device has been quite good. While the therapy may sound unusual, she emphasized taking the viewpoint of someone considering bariatric surgery (i.e., complications, irreversible, high cost, etc.). Dr. Crothall also mentioned that AspireAssist enables behavior change – it forces patients to eat slowly, to chew carefully, and drink water. Also, lifestyle modification program will be an integral part of the education process with aspiration therapy.
• While many patients say they’ll only use the device for one year, the majority end up continuing therapy. Dr. Crothall highlighted that this is entirely patient dependent. However, most patients recognize that obesity is a chronic problem, and certainly success with the device would encourage continued use beyond one year.
• There are a few patient populations that Aspiration therapy does not seem to work well for: those with highly chaotic lives, those who are unwilling to do what is recommended, and those with major family issues.

-- by Adam Brown, Joseph Shivers, Nathan Nakatsuka, Kira Maker, John Close, and Kelly Close